Micro-CT Based Experimental Liver Imaging Using a Nanoparticulate Contrast Agent: A Longitudinal Study in Mice

PubMed Central

Boll, Hanne; Nittka, Stefanie; Doyon, Fabian; Neumaier, Michael; Marx, Alexander; Kramer, Martin; Groden, Christoph; Brockmann, Marc A.

2011-01-01

Background Micro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging. Methodology ExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intravenously injected in C57BL/6J-mice. The distribution and time course of contrast enhancement were analysed by repeated micro-CT up to 6 months. Finally, mice developing liver metastases after intrasplenic injection of colon carcinoma cells underwent longitudinal micro-CT imaging after a single injection of ExiTron nano. Principal Findings After a single injection of ExiTron nano the contrast of liver and spleen peaked after 4–8 hours, lasted up to several months and was tolerated well by all mice. In addition, strong contrast enhancement of abdominal and mediastinal lymph nodes and the adrenal glands was observed. Within the first two hours after injection, particularly ExiTron nano 12000 provided pronounced contrast for imaging of vascular structures. ExiTron nano facilitated detection of liver metastases and provided sufficient contrast for longitudinal observation of tumor development over weeks. Conclusions The nanoparticulate contrast agents ExiTron nano 6000 and 12000 provide strong contrast of the liver, spleen, lymph nodes and adrenal glands up to weeks, hereby allowing longitudinal monitoring of pathological processes of these organs in small animals, with ExiTron nano 12000 being particularly optimized for angiography due to its very high initial vessel contrast. PMID:21984939

Peripheral Artery Disease

MedlinePlus

... This minimally invasive imaging exam relies on a contrast agent and x-rays to show blood flow in ... pinpoint any blockages that may be present. The contrast agent is injected through a tube or catheter that ...

Saline as the Sole Contrast Agent for Successful MRI-guided Epidural Injections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deli, Martin, E-mail: martin.deli@web.de; Fritz, Jan, E-mail: jfritz9@jhmi.edu; Mateiescu, Serban, E-mail: mateiescu@microtherapy.de

Purpose. To assess the performance of sterile saline solution as the sole contrast agent for percutaneous magnetic resonance imaging (MRI)-guided epidural injections at 1.5 T. Methods. A retrospective analysis of two different techniques of MRI-guided epidural injections was performed with either gadolinium-enhanced saline solution or sterile saline solution for documentation of the epidural location of the needle tip. T1-weighted spoiled gradient echo (FLASH) images or T2-weighted single-shot turbo spin echo (HASTE) images visualized the test injectants. Methods were compared by technical success rate, image quality, table time, and rate of complications. Results. 105 MRI-guided epidural injections (12 of 105 withmore » gadolinium-enhanced saline solution and 93 of 105 with sterile saline solution) were performed successfully and without complications. Visualization of sterile saline solution and gadolinium-enhanced saline solution was sufficient, good, or excellent in all 105 interventions. For either test injectant, quantitative image analysis demonstrated comparable high contrast-to-noise ratios of test injectants to adjacent body substances with reliable statistical significance levels (p < 0.001). The mean table time was 22 {+-} 9 min in the gadolinium-enhanced saline solution group and 22 {+-} 8 min in the saline solution group (p = 0.75). Conclusion. Sterile saline is suitable as the sole contrast agent for successful and safe percutaneous MRI-guided epidural drug delivery at 1.5 T.« less

The posterior transtriceps approach for elbow arthrography: a forgotten technique?

PubMed

Lohman, M; Borrero, C; Casagranda, B; Rafiee, B; Towers, J

2009-05-01

To evaluate the technical feasibility of performing elbow MR arthrography via a posterior approach through the triceps. The images of 19 patients with elbow MR arthrography via a posterior transtriceps approach were retrospectively studied. The injections were performed by four musculoskeletal radiologists, using fluoroscopic guidance and a 22- or 25-gauge needle. The fluoroscopic and subsequent MR images were reviewed by two musculoskeletal radiologists and evaluated for adequacy of joint capsular distention, degree and location of contrast leakage, and presence of gas bubbles. The injection was diagnostic in all 19 patients, with a sufficient amount of contrast agent seen in the elbow joint. No significant contrast leakage occurred in 12 patients who received injections of 8 cc or less of contrast agent, but moderate contrast leakage occurred in 6/7 patients who received injections of greater than 8 cc. Contrast leakage generally occurred within the triceps myotendinous junction. No gas bubbles were identified in the injected joints. Patients often present for MR arthrography of the elbow with medial or lateral elbow pain. Contrast leakage during a radiocapitellar approach may complicate evaluation of the lateral collateral ligament or the common extensor tendon origin. Transtriceps MR arthrography offers an alternative to the more commonly used radiocapitellar approach. With injected volumes not exceeding 8 cc, the risk of significant contrast leakage is small. An advantage of the transtriceps injection is that contrast leakage through the posterior needle tract does not interfere with evaluation of the lateral structures.

Early detection of osteoarthritis in rabbits using MRI with a double-contrast agent.

PubMed

Onishi, Okihiro; Ikoma, Kazuya; Kido, Masamitsu; Kabuto, Yukichi; Ueshima, Keiichiro; Matsuda, Ken-Ichi; Tanaka, Masaki; Kubo, Toshikazu

2018-03-13

Articular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent. We induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T 2 -calculated images were obtained before and after contrast agent injection into the knee. The signal intensity ratio (SIR) values on the proton density-weighted images were calculated by dividing the signal intensity of the articular cartilage by that of joint fluid. Six rabbits were examined using MRI at 2 (designated 2-w OA) and 4 weeks (4-w OA) after the operation. Histological examination was performed 4 weeks after the operation. One rabbit was histologically examined 2 weeks after the operation. The control consisted of six rabbits that were not subjected to the operation. The SIR values, T 2 values and the thicknesses of the cartilage of the 2-w OA, 4-w OA and the control before and after contrast agent injection were analyzed. The Mankin score and OARSI (Osteoarthritis Research Society International) score were used for the histological evaluation. Significant differences in the SIR and T 2 values of the medial and lateral condyles of the femur were found between the control and the 4-w OA only after contrast agent injection. No significant differences were found in the SIR and T 2 values before contrast agent injection between the control, the 2-w OA and 4-w OA. The thickness of the articular cartilage revealed no significant differences. In the histological assessment, the Mankin score and OARSI score sequentially increased from the control to the 4-w OA. We evaluated the SIR and T 2 values of the knees in a rabbit OA model and a control model using a new double-contrast agent. MRI with this agent enabled OA detection earlier than using conventional MRI.

Automatic and remote controlled ictal SPECT injection for seizure focus localization by use of a commercial contrast agent application pump.

PubMed

Feichtinger, Michael; Eder, Hans; Holl, Alexander; Körner, Eva; Zmugg, Gerda; Aigner, Reingard; Fazekas, Franz; Ott, Erwin

2007-07-01

In the presurgical evaluation of patients with partial epilepsy, the ictal single photon emission computed tomography (SPECT) is a useful noninvasive diagnostic tool for seizure focus localization. To achieve optimal SPECT scan quality, ictal tracer injection should be carried out as quickly as possible after the seizure onset and under highest safety conditions possible. Compared to the commonly used manual injection, an automatic administration of the radioactive tracer may provide higher quality standards for this procedure. In this study, therefore, we retrospectively analyzed efficiency and safety of an automatic injection system for ictal SPECT tracer application. Over a 31-month period, 26 patients underwent ictal SPECT by use of an automatic remote-controlled injection pump originally designed for CT-contrast agent application. Various factors were reviewed, including latency of ictal injection, radiation safety parameters, and ictal seizure onset localizing value. Times between seizure onset and tracer injection ranged between 3 and 48 s. In 21 of 26 patients ictal SPECT supported the localization of the epileptogenic focus in the course of the presurgical evaluation. In all cases ictal SPECT tracer injection was performed with a high degree of safety to patients and staff. Ictal SPECT by use of a remote-controlled CT-contrast agent injection system provides a high scan quality and is a safe and confirmatory presurgical evaluation technique in the epilepsy-monitoring unit.

Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET

PubMed Central

Swiercz, Rafal; Chiguru, Srinivas; Tahmasbi, Amir; Ramezani, Saleh M.; Hao, Guiyang; Challa, Dilip K.; Lewis, Matthew A.; Kulkarni, Padmakar V.; Sun, Xiankai; Ober, Raimund J.; Mason, Ralph P.; Ward, E. Sally

2015-01-01

Despite promise for the use of antibodies as molecular imaging agents in PET, their long in vivo half-lives result in poor contrast and radiation damage to normal tissue. This study describes an approach to overcome these limitations. Methods Mice bearing human epidermal growth factor receptor type 2 (HER2)–overexpressing tumors were injected with radiolabeled (124I, 125I) HER2-specific antibody (pertuzumab). Pertuzumab injection was followed 8 h later by the delivery of an engineered, antibody-based inhibitor of the receptor, FcRn. Biodistribution analyses and PET were performed at 24 and 48 h after pertuzumab injection. Results The delivery of the engineered, antibody-based FcRn inhibitor (or Abdeg, for antibody that enhances IgG degradation) results in improved tumor-to-blood ratios, reduced systemic exposure to radiolabel, and increased contrast during PET. Conclusion Abdegs have considerable potential as agents to stringently regulate antibody dynamics in vivo, resulting in increased contrast during molecular imaging with PET. PMID:24868106

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents.

PubMed

Anderson, Christian E; Donnola, Shannon B; Jiang, Yun; Batesole, Joshua; Darrah, Rebecca; Drumm, Mitchell L; Brady-Kalnay, Susann M; Steinmetz, Nicole F; Yu, Xin; Griswold, Mark A; Flask, Chris A

2017-08-16

Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI's ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast - Magnetic Resonance Fingerprinting (DC - MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This "multi-color" MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.

A modified commercial ultrasound scanner used for in vivo photoacoustic imaging of nude mice injected with non-targeted contrast agents

NASA Astrophysics Data System (ADS)

Jankovic, Ladislav; Shahzad, Khalid; Wang, Yao; Burcher, Michael; Scholle, Frank-Detlef; Hauff, Peter; Mofina, Sabine; Skobe, Mihaela

2008-02-01

Photoacoustic (PA) experiments were performed using a modified commercial ultrasound scanner equipped with an array transducer and a Nd:YAG pumped OPO laser. The contrast agent SIDAG (Bayer Schering Pharma AG, Germany), used to enhance the optical absorption, demonstrated an expected pharmacokinetic behavior of the dye in the tumor and in the bladder of the nude mice. A typical behavior in the tumor consisted of an initial linear increase in PA signal followed by an exponential decay. PA signal approached the pre-injection level after about one hour following the dye injection, which was consistent with the behavior for such contrast agents when used in other imaging modalities, such as fluorescence imaging. The in-vivo spectral PA data from the mouse bladder, conducted 1.5 hours after the dye injection, clearly demonstrated presence of the dye. The multi-spectral PA data was obtained at 760nm, 784nm and 850nm laser excitations. The PA intensities obtained at these three wavelengths accurately matched the dye absorption spectrum. In addition, in the kidney, a clearance organ for this contrast agent, both in-vivo and ex-vivo results demonstrated a significant increase (~ 40%) in the ratio of PA signal at 760nm (the peak of the dye absorption) relative to the signal at 850nm (<1% absorption), indicating significant amounts of the dye in this organ. Our initial results confirm the desired photoacoustic properties of the contrast agent, indicating its great potential to be used for imaging with a commercial array-based ultrasound scanner.

Modeling contrast agent flow in cerebral aneurysms: comparison of CFD with medical imaging

NASA Astrophysics Data System (ADS)

Rayz, Vitaliy; Vali, Alireza; Sigovan, Monica; Lawton, Michael; Saloner, David; Boussel, Loic

2016-11-01

PURPOSE: The flow in cerebral aneurysms is routinely assessed with X-ray angiography, an imaging technique based on a contrast agent injection. In addition to requiring a patient's catheterization and radiation exposure, the X-ray angiography may inaccurately estimate the flow residence time, as the injection alters the native blood flow patterns. Numerical modeling of the contrast transport based on MRI imaging, provides a non-invasive alternative for the flow diagnostics. METHODS: The flow in 3 cerebral aneurysms was measured in vivo with 4D PC-MRI, which provides time-resolved, 3D velocity field. The measured velocities were used to simulate a contrast agent transport by solving the advection-diffusion equation. In addition, the flow in the same patient-specific geometries was simulated with CFD and the velocities obtained from the Navier-Stokes solution were used to model the transport of a virtual contrast. RESULTS: Contrast filling and washout patterns obtained in simulations based on MRI-measured velocities were in agreement with those obtained using the Navier-Stokes solution. Some discrepancies were observed in comparison to the X-ray angiography data, as numerical modeling of the contrast transport is based on the native blood flow unaffected by the contrast injection. NIH HL115267.

High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media

PubMed Central

Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Roman, Brian B.; Jansen, Sanaz A.; Macleod, Kay; Conzen, Suzanne D.; Karczmar, Gregory S.

2014-01-01

The purpose of this study was to use high resolution 3D MRI to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12–20 weeks (n = 12), were used in this study. A 34G, 45° tip Hamilton needle with a 25uL Hamilton syringe was inserted into the tip of the nipple. Approximately 20–25uL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p < 0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p < 0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. PMID:25179139

A guide for effective anatomical vascularization studies: useful ex vivo methods for both CT and MRI imaging before dissection.

PubMed

Renard, Yohann; Hossu, Gabriela; Chen, Bailiang; Krebs, Marine; Labrousse, Marc; Perez, Manuela

2018-01-01

The objective of this study was to develop a simple and useful injection protocol for imaging cadaveric vascularization and dissection. Mixtures of contrast agent and cast product should provide adequate contrast for two types of ex vivo imaging (MRI and CT) and should harden to allow gross dissection of the injected structures. We tested the most popular contrast agents and cast products, and selected the optimal mixture composition based on their availability and ease of use. All mixtures were first tested in vitro to adjust dilution parameters of each contrast agent and to fine-tune MR imaging acquisition sequences. Mixtures were then injected in 24 pig livers and one human pancreas for MR and computed tomography (CT) imaging before anatomical dissection. Colorized latex, gadobutrol and barite mixture met the above objective. Mixtures composed of copper sulfate (CuSO 4 ) gadoxetic acid (for MRI) and iodine (for CT) gave an inhomogeneous signal or extravasation of the contrast agent. Agar did not harden sufficiently for gross dissection but appears useful for CT and magnetic resonance imaging (MRI) studies without dissection. Silicone was very hard to inject but achieved the goals of the study. Resin is particularly difficult to use but could replace latex as an alternative for corrosion instead of dissection. This injection protocol allows CT and MRI images to be obtained of cadaveric vascularization and anatomical casts in the same anatomic specimen. Post-imaging processing software allow easy 3D reconstruction of complex anatomical structures using this technique. Applications are numerous, e.g. surgical training, teaching methods, postmortem anatomic studies, pathologic studies, and forensic diagnoses. © 2017 Anatomical Society.

The Impact of Injector-Based Contrast Agent Administration on Bolus Shape and Magnetic Resonance Angiography Image Quality.

PubMed

Jost, Gregor; Endrikat, Jan; Pietsch, Hubertus

2017-01-01

To compare injector-based contrast agent (CA) administration with hand injection in magnetic resonance angiography (MRA). Gadobutrol was administered in 6 minipigs with 3 protocols: (a) hand injection (one senior technician), (b) hand injection (6 less-experienced technicians), and (c) power injector administration. The arterial bolus shape was quantified by test bolus measurements. A head and neck MRA was performed for quantitative and qualitative comparison of signal enhancement. A significantly shorter time to peak was observed for protocol C, whereas no significant differences between protocols were found for peak height and bolus width. However, for protocol C, these parameters showed a much lower variation. The MRA revealed a significantly higher signal-to-noise ratio for injector-based administration. A superimposed strong contrast of the jugular vein was found in 50% of the hand injections. Injector-based CA administration results in a more standardized bolus shape, a higher vascular contrast, and a more robust visualization of target vessels.

MRI and CT contrast media extravasation: A systematic review.

PubMed

Heshmatzadeh Behzadi, Ashkan; Farooq, Zerwa; Newhouse, Jeffery H; Prince, Martin R

2018-03-01

This systematic review combines data from multiple papers on contrast media extravasation to identify factors contributing to increased extravasation risk. Data were extracted from 17 papers reporting 2191 extravasations in 1,104,872 patients (0.2%) undergoing computed tomography (CT) or magnetic resonance imaging (MRI). Extravasation rates were 0.045% for gadolinium-based contrast agents (GBCA) and nearly 6-fold higher, 0.26% for iodinated contrast agents. Factors associated with increased contrast media extravasations included: older age, female gender, using an existing intravenous (IV) instead of placing a new IV in radiology, in-patient status, use of automated power injection, high injection rates, catheter location, and failing to warm up the more viscous contrast media to body temperature. Contrast media extravasation is infrequent but nearly 6 times less frequent with GBCA for MRI compared with iodinated contrast used in CT.

Comparison of transcutaneous contrast-enhanced ultrasound-guided injected hemostatic agents with traditional surgery treatment for liver, spleen and kidney trauma: a retrospective study.

PubMed

Wang, Dong; Lv, Faqin; Luo, Yukun; An, Lichun; Li, Junlai; Xie, Xia; Tian, Jiangke; Zhao, Weiyan; Tang, Jie

2012-10-01

There is lack of studies on the effectiveness of transcutaneous contrast-enhanced ultrasound-guided injections of hemostatic agents for liver. spleen and kidney trauma. We compared treatment by hemostatic agents to surgical treatment in a retrospective interventional human study. The study enrolled a total of 135 subjects from emergency unit of the Chinese People's Liberation Army General Hospital in Beijing. Within the cohort, 62 patients received contrast enhanced ultrasound-guided injection of hemostatic agents and the rest received surgical treatments. The injury severity score was lower in the hemostatic agent treatment group than surgical treatment group (p<0.05), but Glasgow coma scale scores did not reach statistical significance. The patients in the surgical treatment group had significantly higher hospital fees than those in the hemostatic treatment group (p<0.05), although the length of hospitalization did not significantly differ between two groups. Safety outcome variables pre- and post-treatment remained within normal limits in both groups. Hemostatic agents were more cost-effective than surgery to treat patients with liver, spleen and kidney trauma. However, given the limited sample size, subsequent studies drawing upon larger populations from multiple medical centers are necessary for follow-up.

High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media.

PubMed

Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Roman, Brian B; Jansen, Sanaz A; Macleod, Kay; Conzen, Suzanne D; Karczmar, Gregory S

2015-01-01

The purpose of this study was to use high resolution three-dimensional (3D) magnetic resonance imaging (MRI) to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12-20 weeks (n=12), were used in this study. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple. Approximately 20-25μL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p<0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p<0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents.

PubMed

Runge, Val M

2017-06-01

For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was convincing evidence of gadolinium deposition in the brain months after injection of these linear agents. Primovist/Eovist (gadoxetic acid disodium) will remain available, being used at a lower dose for liver imaging, because it meets an important diagnostic need. In addition, a formulation of Magnevist for intra-articular injection will remain available because of its very low gadolinium concentration.

Renal contrast-enhanced MR angiography: timing errors and accurate depiction of renal artery origins.

PubMed

Schmidt, Maria A; Morgan, Robert

2008-10-01

To investigate bolus timing artifacts that impair depiction of renal arteries at contrast material-enhanced magnetic resonance (MR) angiography and to determine the effect of contrast agent infusion rates on artifact generation. Renal contrast-enhanced MR angiography was simulated for a variety of infusion schemes, assuming both correct and incorrect timing between data acquisition and contrast agent injection. In addition, the ethics committee approved the retrospective evaluation of clinical breath-hold renal contrast-enhanced MR angiographic studies obtained with automated detection of contrast agent arrival. Twenty-two studies were evaluated for their ability to depict the origin of renal arteries in patent vessels and for any signs of timing errors. Simulations showed that a completely artifactual stenosis or an artifactual overestimation of an existing stenosis at the renal artery origin can be caused by timing errors of the order of 5 seconds in examinations performed with contrast agent infusion rates compatible with or higher than those of hand injections. Lower infusion rates make the studies more likely to accurately depict the origin of the renal arteries. In approximately one-third of all clinical examinations, different contrast agent uptake rates were detected on the left and right sides of the body, and thus allowed us to confirm that it is often impossible to optimize depiction of both renal arteries. In three renal arteries, a signal void was found at the origin in a patent vessel, and delayed contrast agent arrival was confirmed. Computer simulations and clinical examinations showed that timing errors impair the accurate depiction of renal artery origins. (c) RSNA, 2008.

MRI in ocular drug delivery

PubMed Central

Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

2008-01-01

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

[Development of Biliary Contrast Agents Remote Pushing Device].

PubMed

Zhu, Haoyang; Dong, Dinghui; Luo, Yu; Ren, Fenggang; Zhang, Jing; Tan, Wenjun; Shi, Aihua; Hu, Liangshuo; Wu, Rongqian; Lyu, Yi

2018-01-30

A biliary contrast agents pushing device, including a syringe pushing system and a remote controller is introduced. The syringe pushing system comprises an injector card slot, a support platform and an injection bolus fader. A 20 mL syringe can be fitted on the syringe pushing system and kept with the ground about 30 degree. This system can perform air bubble pumping back and contrast agents bolus injection as well as speed adjustment. Remote controller is an infrared remote control which can start and stop the syringe pushing system. With this device, the remote controlled cholangiography technology can be achieved, which can not only protect doctors from X-ray radiation but also improve the traditional T-tube cholangiography and the contrast effect, reduce postoperative complications in patients as well. The application of this device will improve the current diagnosis and treatment system, the device will benefit the majority of doctors and patients.

MRI and CT contrast media extravasation

PubMed Central

Heshmatzadeh Behzadi, Ashkan; Farooq, Zerwa; Newhouse, Jeffery H.; Prince, Martin R.

2018-01-01

Abstract Background: This systematic review combines data from multiple papers on contrast media extravasation to identify factors contributing to increased extravasation risk. Methods: Data were extracted from 17 papers reporting 2191 extravasations in 1,104,872 patients (0.2%) undergoing computed tomography (CT) or magnetic resonance imaging (MRI). Results: Extravasation rates were 0.045% for gadolinium-based contrast agents (GBCA) and nearly 6-fold higher, 0.26% for iodinated contrast agents. Factors associated with increased contrast media extravasations included: older age, female gender, using an existing intravenous (IV) instead of placing a new IV in radiology, in-patient status, use of automated power injection, high injection rates, catheter location, and failing to warm up the more viscous contrast media to body temperature. Conclusion: Contrast media extravasation is infrequent but nearly 6 times less frequent with GBCA for MRI compared with iodinated contrast used in CT. PMID:29489663

Evaluation of optimized magnetic resonance perfusion imaging scanning time window after contrast agent injection for differentiating benign and malignant breast lesions

PubMed Central

Dong, Jie; Wang, Dawei; Ma, Zhenshen; Deng, Guodong; Wang, Lanhua; Zhang, Jiandong

2017-01-01

The aim of the study was evaluate the 3.0 T magnetic resonance (MR) perfusion imaging scanning time window following contrast injection for differentiating benign and malignant breast lesions and to determine the optimum scanning time window for increased scanner usage efficiency and reduced diagnostic adverse risk factors. A total of 52 women with breast abnormalities were selected for conventional MR imaging and T1 dynamic-enhanced imaging. Quantitative parameters [volume transfer constant (Ktrans), rate constant (Kep) and extravascular extracellular volume fraction (Ve)] were calculated at phases 10, 20, 30, 40 and 50, which represented time windows at 5, 10, 15, 20 and 25 min, respectively, following injection of contrast agent. The association of the parameters at different phases with benign and malignant tumor diagnosis was analyzed. MR perfusion imaging was verified as an effective modality in the diagnosis of breast malignancies and the best scanning time window was identified: i) Values of Ktrans and Kep at all phases were statistically significant in differentiating benign and malignant tumors (P<0.05), while the value of Ve had statistical significance only at stage 10, but not at any other stages (P>0.05); ii) values of Ve in benign tumors increased with phase number, but achieved no obvious changes at different phases in malignant tumors; iii) the optimum scanning time window of breast perfusion imaging with 3.0 T MR was between phases 10 and 30 (i.e., between 5 and 15 min after contrast agent injection). The variation trend of Ve values at different phases may serve as a diagnostic reference for differentiating benign and malignant breast abnormalities. The most efficient scanning time window was indicated to be 5 min after contrast injection, based on the observation that the Ve value only had statistical significance in diagnosis at stage 10. However, the optimal scanning time window is from 5 to 15 min following the injection of contrast agent, since that the variation trend of Ve is able to serve as a diagnostic reference. PMID:28450944

Evaluation of optimized magnetic resonance perfusion imaging scanning time window after contrast agent injection for differentiating benign and malignant breast lesions.

PubMed

Dong, Jie; Wang, Dawei; Ma, Zhenshen; Deng, Guodong; Wang, Lanhua; Zhang, Jiandong

2017-03-01

The aim of the study was evaluate the 3.0 T magnetic resonance (MR) perfusion imaging scanning time window following contrast injection for differentiating benign and malignant breast lesions and to determine the optimum scanning time window for increased scanner usage efficiency and reduced diagnostic adverse risk factors. A total of 52 women with breast abnormalities were selected for conventional MR imaging and T1 dynamic-enhanced imaging. Quantitative parameters [volume transfer constant (K trans ), rate constant (K ep ) and extravascular extracellular volume fraction (V e )] were calculated at phases 10, 20, 30, 40 and 50, which represented time windows at 5, 10, 15, 20 and 25 min, respectively, following injection of contrast agent. The association of the parameters at different phases with benign and malignant tumor diagnosis was analyzed. MR perfusion imaging was verified as an effective modality in the diagnosis of breast malignancies and the best scanning time window was identified: i) Values of K trans and K ep at all phases were statistically significant in differentiating benign and malignant tumors (P<0.05), while the value of V e had statistical significance only at stage 10, but not at any other stages (P>0.05); ii) values of V e in benign tumors increased with phase number, but achieved no obvious changes at different phases in malignant tumors; iii) the optimum scanning time window of breast perfusion imaging with 3.0 T MR was between phases 10 and 30 (i.e., between 5 and 15 min after contrast agent injection). The variation trend of V e values at different phases may serve as a diagnostic reference for differentiating benign and malignant breast abnormalities. The most efficient scanning time window was indicated to be 5 min after contrast injection, based on the observation that the V e value only had statistical significance in diagnosis at stage 10. However, the optimal scanning time window is from 5 to 15 min following the injection of contrast agent, since that the variation trend of V e is able to serve as a diagnostic reference.

Comparison of arterial input functions measured from ultra-fast dynamic contrast enhanced MRI and dynamic contrast enhanced computed tomography in prostate cancer patients

NASA Astrophysics Data System (ADS)

Wang, Shiyang; Lu, Zhengfeng; Fan, Xiaobing; Medved, Milica; Jiang, Xia; Sammet, Steffen; Yousuf, Ambereen; Pineda, Federico; Oto, Aytekin; Karczmar, Gregory S.

2018-02-01

The purpose of this study was to evaluate the accuracy of arterial input functions (AIFs) measured from dynamic contrast enhanced (DCE) MRI following a low dose of contrast media injection. The AIFs measured from DCE computed tomography (CT) were used as ‘gold standard’. A total of twenty patients received CT and MRI scans on the same day. Patients received 120 ml Iohexol in DCE-CT and a low dose of (0.015 mM kg-1) of gadobenate dimeglumine in DCE-MRI. The AIFs were measured in the iliac artery and normalized to the CT and MRI contrast agent doses. To correct for different temporal resolution and sampling periods of CT and MRI, an empirical mathematical model (EMM) was used to fit the AIFs first. Then numerical AIFs (AIFCT and AIFMRI) were calculated based on fitting parameters. The AIFMRI was convolved with a ‘contrast agent injection’ function (AIFMRICON ) to correct for the difference between MRI and CT contrast agent injection times (~1.5 s versus 30 s). The results show that the EMMs accurately fitted AIFs measured from CT and MRI. There was no significant difference (p  >  0.05) between the maximum peak amplitude of AIFs from CT (22.1  ±  4.1 mM/dose) and MRI after convolution (22.3  ±  5.2 mM/dose). The shapes of the AIFCT and AIFMRICON were very similar. Our results demonstrated that AIFs can be accurately measured by MRI following low dose contrast agent injection.

A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging.

PubMed

Mehnert, Ulrich; Boy, Sönke; Schmid, Marius; Reitz, André; von Hessling, Alexander; Hodler, Juerg; Schurch, Brigitte

2009-06-01

Although botulinum neurotoxin type A (BoNT/A) intradetrusor injections are a recommended therapy for neurogenic detrusor overactivity (NDO), refractory to antimuscarinic drugs, a standardisation of injection technique is missing. Furthermore, some basic questions are still unanswered, as where the toxin solution exactly spreads after injection. Therefore, we investigated the distribution of the toxin solution after injection into the bladder wall, using magnet resonance imaging (MRI). Six patients with NDO were recruited. Three of six patients received 300 U of BoNT/A + contrast agent distributed over 30 injection sites (group 1). The other three patients received 300 U of BoNT/A + contrast agent distributed over 10 injection sites (group 2). Immediately after injection, MRI of the pelvis was performed. The volume of the detrusor and the total volume of contrast medium inside and outside the bladder wall were calculated. In all patients, a small volume (mean 17.6%) was found at the lateral aspects of the bladder dome in the extraperitoneal fat tissue, whereas 82.4% of the injected volume reached the target area (detrusor). In both groups there was a similar distribution of the contrast medium in the target area. A mean of 33.3 and 25.3% of the total detrusor volume was covered in group 1 and 2, respectively. Six weeks after injection, five of six patients were continent and showed no detrusor overactivity in the urodynamic follow-up. No systemic side effects were observed. Our results provide morphological arguments that the currently used injection techniques are appropriate and safe.

VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-07-01

Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics. © The Author(s) 2014.

Synchrotron-based intra-venous K-edge digital subtraction angiography in a pig model: a feasibility study.

PubMed

Schültke, Elisabeth; Fiedler, Stefan; Nemoz, Christian; Ogieglo, Lissa; Kelly, Michael E; Crawford, Paul; Esteve, Francois; Brochard, Thierry; Renier, Michel; Requardt, Herwig; Le Duc, Geraldine; Juurlink, Bernhard; Meguro, Kotoo

2010-03-01

K-edge digital subtraction angiography (KEDSA) combined with the tunability of synchrotron beam yields an imaging technique that is highly sensitive to low concentrations of contrast agents. Thus, contrast agent can be administered intravenously, obviating the need for insertion of a guided catheter to deliver a bolus of contrast agent close to the target tissue. With the high-resolution detectors used at synchrotron facilities, images can be acquired at high spatial resolution. Thus, the KEDSA appears particularly suited for studies of neurovascular pathology in animal models, where the vascular diameters are significantly smaller than in human patients. This feasibility study was designed to test the suitability of KEDSA after intravenous injection of iodine-based contrast agent for use in a pig model. Four adult male pigs were used for our experiments. Neurovascular angiographic images were acquired using KEDSA with a solid state Germanium (Ge) detector at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. After intravenous injection of 0.9 ml/kg iodinated contrast agent (Xenetix), the peak iodine concentrations in the internal carotid and middle cerebral arteries reached 35 mg/ml. KEDSA images in radiography mode allowed the visualization of intracranial arteries of less than 1.5mm diameter. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Preclinical evaluation of a novel cyanine dye for tumor imaging with in vivo photoacoustic imaging.

PubMed

Temma, Takashi; Onoe, Satoru; Kanazaki, Kengo; Ono, Masahiro; Saji, Hideo

2014-09-01

Photoacoustic imaging (PA imaging or PAI) has shown great promise in the detection and monitoring of cancer. Although nanocarrier-based contrast agents have been studied for use in PAI, small molecule contrast agents are required due to their ease of preparation, costeffectiveness, and low toxicity. Here, we evaluated the usefulness of a novel cyanine dye IC7-1-Bu as a PAI contrast agent without conjugated targeting moieties for in vivo tumor imaging in a mice model. Basic PA characteristics of IC7-1-Bu were compared with indocyanine green (ICG), a Food and Drug Administration approved dye, in an aqueous solution. We evaluated the tumor accumulation profile of IC7-1-Bu and ICG by in vivo fluorescence imaging. In vivo PAI was then performed with a photoacoustic tomography system 24 and 48 h after intravenous injection of IC7-1-Bu into tumor bearing mice. IC7-1-Bu showed about a 2.3-fold higher PA signal in aqueous solution compared with that of ICG. Unlike ICG, IC7-1-Bu showed high tumor fluorescence after intravenous injection. In vivo PAI provided a tumor to background PA signal ratio of approximately 2.5 after intravenous injection of IC7-1-Bu. These results indicate that IC7-1-Bu is a promising PAI contrast agent for cancer imaging without conjugation of targeting moieties.

Poly(iohexol) nanoparticles as contrast agents for in vivo X-ray computed tomography imaging.

PubMed

Yin, Qian; Yap, Felix Y; Yin, Lichen; Ma, Liang; Zhou, Qin; Dobrucki, Lawrence W; Fan, Timothy M; Gaba, Ron C; Cheng, Jianjun

2013-09-18

Biocompatible poly(iohexol) nanoparticles, prepared through cross-linking of iohexol and hexamethylene diisocyanate followed by coprecipitation of the resulting cross-linked polymer with mPEG-polylactide, were utilized as contrast agents for in vivo X-ray computed tomography (CT) imaging. Compared to conventional small-molecule contrast agents, poly(iohexol) nanoparticles exhibited substantially protracted retention within the tumor bed and a 36-fold increase in CT contrast 4 h post injection, which makes it possible to acquire CT images with improved diagnosis accuracy over a broad time frame without multiple administrations.

Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging.

PubMed

Kim, Dongkyu; Park, Sangjin; Lee, Jae Hyuk; Jeong, Yong Yeon; Jon, Sangyong

2007-06-20

Current computed tomography (CT) contrast agents such as iodine-based compounds have several limitations, including short imaging times due to rapid renal clearance, renal toxicity, and vascular permeation. Here, we describe a new CT contrast agent based on gold nanoparticles (GNPs) that overcomes these limitations. Because gold has a higher atomic number and X-ray absorption coefficient than iodine, we expected that GNPs can be used as CT contrast agents. We prepared uniform GNPs ( approximately 30 nm in diameter) by general reduction of HAuCl4 by boiling with sodium citrate. The resulting GNPs were coated with polyethylene glycol (PEG) to impart antibiofouling properties, which extends their lifetime in the bloodstream. Measurement of the X-ray absorption coefficient in vitro revealed that the attenuation of PEG-coated GNPs is 5.7 times higher than that of the current iodine-based CT contrast agent, Ultravist. Furthermore, when injected intravenously into rats, the PEG-coated GNPs had a much longer blood circulation time (>4 h) than Ultravist (<10 min). Consequently, CT images of rats using PEG-coated GNPs showed a clear delineation of cardiac ventricles and great vessels. On the other hand, relatively high levels of GNPs accumulated in the spleen and liver, which contain phagocytic cells. Intravenous injection of PEG-coated GNPs into hepatoma-bearing rats resulted in a high contrast ( approximately 2-fold) between hepatoma and normal liver tissue on CT images. These results suggest that PEG-coated GNPs can be useful as a CT contrast agent for a blood pool and hepatoma imaging.

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging.

PubMed

Longo, Dario Livio; Moustaghfir, Fatima Zzahra; Zerbo, Alexandre; Consolino, Lorena; Anemone, Annasofia; Bracesco, Martina; Aime, Silvio

2017-06-15

Chemical Exchange Saturation Transfer (CEST) approach is a novel tool within magnetic resonance imaging (MRI) that allows visualization of molecules possessing exchangeable protons with water. Many molecules, employed as excipients for the formulation of finished drug products, are endowed with hydroxyl, amine or amide protons, thus can be exploitable as MRI-CEST contrast agents. Their high safety profiles allow them to be injected at very high doses. Here we investigated the MRI-CEST properties of several excipients (ascorbic acid, sucrose, N-acetyl-d-glucosamine, meglumine and 2-pyrrolidone) and tested them as tumor-detecting agents in two different murine tumor models (breast and melanoma cancers). All the investigated molecules showed remarkable CEST contrast upon i.v. administration in the range 1-3ppm according to the type of mobile proton groups. A marked increase of CEST contrast was observed in tumor regions up to 30min post injection. The combination of marked tumor contrast enhancement and lack of toxicity make these molecules potential candidates for the diagnosis of tumors within the MRI-CEST approach. Copyright © 2017 Elsevier B.V. All rights reserved.

XFM demonstrates preferential accumulation of a vanadyl-based MRI contrast agent in murine colonic tumors

PubMed Central

Mustafi, Devkumar; Ward, Jesse; Dougherty, Urszula; Bissonnette, Marc; Hart, John; Vogt, Stefan; Karczmar, Gregory S.

2016-01-01

Contrast agents that specifically enhance cancers on MRI would allow earlier detection. Vanadyl-based chelates (VCs) selectively enhance rodent cancers on MRI, suggesting selective uptake of VCs by cancers. Here we report X-ray fluorescence microscopy (XFM) of VC uptake by murine colon cancer. Colonic tumors in mice treated with azoxymethane/dextran sulfate sodium were identified by MRI. Then a gadolinium-based contrast agent and a VC were injected I.V.; mice were sacrificed and colons sectioned. VC distribution was sampled at 120 minutes after injection to evaluate the long term accumulation. Gadolinium distribution was sampled at 10 minutes after injection due to its rapid washout. XFM was performed on 72 regions of normal and cancerous colon from 5 normal mice and 4 cancer-bearing mice. XFM showed that all gadolinium was extracellular with similar concentrations in colon cancers and normal colon. In contrast, the average VC concentration was 2-fold higher in cancers vs. normal tissue (p<0.002). Cancers also contained numerous ‘hot spots’ with intracellular VC concentrations 6-fold higher than the concentration in normal colon (p<0.0001). No ‘hot spots’ were detected in normal colon. This is the first direct demonstration that VCs selectively accumulate in cancer cells, and thus may improve cancer detection. PMID:25813904

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Improved Peritoneal Cavity and Abdominal Organ Imaging Using a Biphasic Contrast Agent Protocol and Spectral Photon Counting Computed Tomography K-Edge Imaging.

PubMed

Si-Mohamed, Salim; Thivolet, Arnaud; Bonnot, Pierre-Emmanuel; Bar-Ness, Daniel; Képénékian, Vahan; Cormode, David P; Douek, Philippe; Rousset, Pascal

2018-05-23

To validate in vitro the capability of a high-spatial-resolution prototype spectral photon-counting computed tomography (SPCCT) scanner to differentiate between 2 contrast agents and to assess in vivo the image quality and the feasibility to image the peritoneal cavity in rats using the 2 contrast agents simultaneously within the vascular and peritoneal compartments. The authors performed SPCCT imaging (100 mAs, 120 kVp) with energy bin thresholds set to 30, 51, 64, 72, and 85 keV in vitro on a custom-made polyoxymethylene cylindrical phantom consisting of tubes with dilutions of both contrast agents and in vivo on 2 groups of adult rats using 2 injection protocols. Approval from the institutional animal ethics committee was obtained. One group received macrocylic gadolinium chelate intraperitoneal (IP) and iodine intravenous (IV) injections (protocol A, n = 3), whereas the second group received iodine IP and gadolinium IV (protocol B, n = 3). Helical scans were performed 35 minutes after IP injection and 20 seconds after IV injection. The SPCCT and contrast material images, that is, iodine and gadolinium maps, were reconstructed with a field of view of 160 mm, an isotropic voxel size of 250 μm, and a matrix size of 640 × 640 pixels using a soft reconstruction kernel. The SPCCT images were reconstructed with 2 different spatial resolutions to compare the image quality (sharpness, diagnostic quality, and organ visualization) of SPCCT (250 μm) with single-energy computed tomography (CT) (600 μm). Two radiologists evaluated the peritoneal opacification index in 13 regions (score = 0-3 per region) on each type of image. Concentrations of contrast agents were measured in the organs of interest. In vitro, the concentration measurements correlated well with the expected concentrations. The linear regressions both had R values of 0.99, slopes of 0.84 and 0.87, and offsets at -0.52 and -0.38 mg/mL for iodine and gadolinium, respectively. In vivo, the SPCCT images were of better diagnostic quality, with increased sharpness compared with the CT-like images (P < 0.0001). Intraperitoneal diffusion was excellent, with similar peritoneal opacification index on SPCCT images and overlay of contrast material maps (P = 1) without a significant difference between protocol A (37.0 ± 1.7) and protocol B (35.3 ± 1.5) (P = 0.34). Only the contrast material maps demonstrated clear visual separation of the contrast agents, allowing specific quantification of the physiological enhancement in the liver, spleen, and kidney and the urinary clearance in the renal pelvis and bladder. Renal excretion of the contrast agents injected IP was observed and was consistent with blood diffusion. Spectral photon-counting CT can be used to perform a complete peritoneal dual-contrast protocol, enabling a good assessment of the peritoneal cavity and abdominal organs in rats.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Biofilm imaging in porous media by laboratory X-Ray tomography: Combining a non-destructive contrast agent with propagation-based phase-contrast imaging tools.

PubMed

Carrel, Maxence; Beltran, Mario A; Morales, Verónica L; Derlon, Nicolas; Morgenroth, Eberhard; Kaufmann, Rolf; Holzner, Markus

2017-01-01

X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent-biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development and bioclogging mechanisms in porous materials and the obtained biofilm morphology could be an ideal basis for 3D numerical calculations of hydrodynamic conditions to investigate biofilm-flow coupling.

The potential for neurovascular intravenous angiography using K-edge digital subtraction angiography

NASA Astrophysics Data System (ADS)

Schültke, E.; Fiedler, S.; Kelly, M.; Griebel, R.; Juurlink, B.; LeDuc, G.; Estève, F.; Le Bas, J.-F.; Renier, M.; Nemoz, C.; Meguro, K.

2005-08-01

Background: Catheterization of small-caliber blood vessels in the central nervous system can be extremely challenging. Alternatively, intravenous (i.v.) administration of contrast agent is minimally invasive and therefore carries a much lower risk for the patient. With conventional X-ray equipment, volumes of contrast agent that could be safely administered to the patient do not allow acquisition of high-quality images after i.v. injection, because the contrast bolus is extremely diluted by passage through the heart. However, synchrotron-based digital K-edge subtraction angiography does allow acquisition of high-quality images after i.v. administration of relatively small doses of contrast agent. Materials and methods: Eight adult male New Zealand rabbits were used for our experiments. Animals were submitted to both angiography with conventional X-ray equipment and synchrotron-based digital subtraction angiography. Results: With conventional X-ray equipment, no contrast was seen in either cerebral or spinal blood vessels after i.v. injection of iodinated contrast agent. However, using K-edge digital subtraction angiography, as little as 1 ml iodinated contrast agent, when administered as i.v. bolus, yielded images of small-caliber blood vessels in the central nervous system (both brain and spinal cord). Conclusions: If it would be possible to image blood vessels of the same diameter in the central nervous system of human patients, the synchrotron-based technique could yield high-quality images at a significantly lower risk for the patient than conventional X-ray imaging. Images could be acquired where catheterization of feeding blood vessels has proven impossible.

A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite.

PubMed

Sonoda, Akinaga; Nitta, Norihisa; Tsuchiya, Keiko; Nitta-Seko, Ayumi; Ohta, Shinichi; Otani, Hideji; Murata, Kiyoshi

2016-12-01

Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd‑based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. The present study evaluated whether the degree of charge alters the blood‑pooling time. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADM‑, CMEADM2‑, CMEADM+ (surface charges: ‑10.4, ‑41.0 and +9.6 mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO; ‑11.5 mV). The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel = (SI post‑contrast ‑ SI pre‑contrast / SI pre‑contrast) x 100. Following injection with the CMEADMs, but not with USPIO, the in vivo pooling time was prolonged to >300 min. No significant differences were attributable to the electric charge among the CMEADM‑, CMEADM2‑ or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Taken together, all three differently‑charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.

Development of Bifunctional Gadolinium-Labeled Superparamagnetic Nanoparticles (Gd-MnMEIO) for In Vivo MR Imaging of the Liver in an Animal Model.

PubMed

Kuo, Yu-Ting; Chen, Chiao-Yun; Liu, Gin-Chung; Wang, Yun-Ming

2016-01-01

Liver tumors are common and imaging methods, particularly magnetic resonance imaging (MRI), play an important role in their non-invasive diagnosis. Previous studies have shown that detection of liver tumors can be improved by injection of two different MR contrast agents. Here, we developed a new contrast agent, Gd-manganese-doped magnetism-engineered iron oxide (Gd-MnMEIO), with enhancement effects on both T1- and T2-weighted MR images of the liver. A 3.0T clinical MR scanner equipped with transmit/receiver coil for mouse was used to obtain both T1-weighted spoiled gradient-echo and T2-weighted fast spin-echo axial images of the liver before and after intravenous contrast agent injection into Balb/c mice with and without tumors. After pre-contrast scanning, six mice per group were intravenously injected with 0.1 mmol/kg Gd-MnMEIO, or the control agents, i.e., Gd-DTPA or SPIO. The scanning time points for T1-weighted images were 0.5, 5, 10, 15, 20, 25, and 30 min after contrast administration. The post-enhanced T2-weighted images were then acquired immediately after T1-weighted acquisition. We found that T1-weighted images were positively enhanced by both Gd-DTPA and Gd-MnMEIO and negatively enhanced by SPIO. The enhancement by both Gd-DTPA and Gd-MnMEIO peaked at 0.5 min and gradually declined thereafter. Gd-MnMEIO (like Gd-DTPA) enhanced T1-weighted images and (like SPIO) T2-weighted images. Marked vascular enhancement was clearly visible on dynamic T1-weighted images with Gd-MnMEIO. In addition, the T2 signal was significantly decreased at 30 min after administration of Gd-MnMEIO. Whereas the effects of Gd-MnMEIO and SPIO on T2-weighted images were similar (p = 0.5824), those of Gd-MnMEIO and Gd-DTPA differed, with Gd-MnMEIO having a significant T2 contrast effect (p = 0.0086). Our study confirms the feasibility of synthesizing an MR contrast agent with both T1 and T2 shortening effects and using such an agent in vivo. This agent enables tumor detection and characterization in single liver MRI sections.

[Experiences with power-injectable port systems: complications, patient satisfaction and clinical benefit].

PubMed

Chang, D-H; Kabbasch, C; Bovenschulte, H; Libicher, M; Maintz, D; Bangard, C

2013-05-01

Evaluation of complications, patient satisfaction and clinical benefit of port systems with authorization for high pressure injection of contrast agent during CT/MR examinations. Ultrasound-guided insertions of central venous port catheters were performed through the lateral subclavian vein at a university teaching hospital. The radiological information system (HIS/RIS) was used to evaluate technical success and complication rates. Assessment of patient satisfaction and clinical benefit was carried out by a questionnaire during a telephone call 6 months after implantation of the port system. A total of 195 port systems in 193 patients were implanted. The catheter remained in place for a mean duration of 169 days (overall 29,210 catheter days). The technical success rate was 99.5 % and the overall complication rate was 17.4 % (24/138; 0.82 per 1000 catheter days). Follow-up revealed 13 early port explantations (9 %). Most of the patients reported high satisfaction in general (satisfied/very satisfied: 94 %). 34/209 contrast-enhanced CT/MRT scans (16 %) were performed using the port for contrast media injection. There were no complications during or after administration of contrast agent via the port system. The Powerport system is a safe alternative for peripheral i. v. contrast media injection during CT/MR scans, but has been infrequently used. Most patients reported high overall satisfaction with the port system. © Georg Thieme Verlag KG Stuttgart · New York.

Biofilm imaging in porous media by laboratory X-Ray tomography: Combining a non-destructive contrast agent with propagation-based phase-contrast imaging tools

PubMed Central

Beltran, Mario A.; Morales, Verónica L.; Derlon, Nicolas; Morgenroth, Eberhard; Kaufmann, Rolf; Holzner, Markus

2017-01-01

X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent—biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development and bioclogging mechanisms in porous materials and the obtained biofilm morphology could be an ideal basis for 3D numerical calculations of hydrodynamic conditions to investigate biofilm-flow coupling. PMID:28732010

Contrast-enhanced voiding urosonography: in vitro evaluation of a second-generation ultrasound contrast agent for in vivo optimization.

PubMed

Back, Susan J; Edgar, J Christopher; Canning, Douglas A; Darge, Kassa

2015-09-01

Pediatric contrast-enhanced ultrasound (CEUS) is primarily performed outside the United States where a track record for safety in intravenous and intravesical applications has been established. Contrast-enhanced voiding urosonography (ceVUS) has also been shown to have a much higher rate of vesicoureteral reflux detection compared to voiding cystourethrography. US contrast agents available in the United States differ from those abroad. Optison® (GE Healthcare, Princeton, NJ) is such an US contrast agent. While Optison® has similar characteristics to other second-generation agents, it has never been used for ceVUS. In vitro optimization of dose and imaging parameters as well as assessment of contrast visualization when delivered in conditions similar to ceVUS are necessary starting points prior to in vivo applications. To optimize the intravesical use of Optison® in vitro for ceVUS before its use in pediatric studies. The experimental design simulated intravesical use. Using 9- and 12-MHz linear transducers, we scanned 20-mL syringes varying mechanical index, US contrast agent concentration (0.25%, 0.5%, 1.0%), solvent (saline, urine, radiographic contrast agent) and time out of refrigeration. We evaluated mechanical index settings and contrast duration, optimized the contrast dose, measured the effect of urine and radiographic contrast agent, and the impact of length of time of contrast outside of the refrigerator on US contrast appearance. We scanned 50-ml saline bags to assess the appearance and duration of US contrast with different delivery systems (injection vs. infusion). Consistent contrast visualization was achieved at a mechanical index of 0.06-0.17 and 0.11-0.48 for the L9 and L12 MHz transducers (P < 0.01), respectively. Thus, it was necessary to increase the mechanical index for better contrast visualization of the microbubbles with a higher transducer frequency. The lowest mechanical index for earliest visible microbubble destruction was 0.21 for the 9 MHz and 0.39 for the 12 MHz (P < 0.01) transducers. The 0.5% US contrast agent volume to bladder filling was the most optimal. At this concentration, the mean time to visualize homogenous contrast was 2 min and destruction of approximately half of the microbubbles in the field of view occurred in 7.8 min using the 9-MHz transducer. During contrast infusion, the contrast dose needed to be reduced to 0.12% for maintenance of optimal visualization of microbubbles. There was no deleterious effect on the visualization of contrast in the presence of urine or radiographic contrast agent. Infusion of the US contrast agent speeded visualization of homogeneous enhancement compared with injection. Time outside refrigeration did not affect contrast performance. Transducer mechanical index settings need to be optimized. A very low dose of the US contrast agent Optison® will suffice for intravesical application, i.e. 0.12% to 0.50% of the bladder filling volume. The presence of urine or radiographic contrast agent did not compromise contrast visualization. The best mode of administration is the infusion method due to fast homogenous distribution at the lowest dose of 0.12%. Leaving the US contrast agent outside the refrigerator for an hour does not affect the microbubbles.

GI Radiographic Tests

MedlinePlus

... the body in various directions. A non-iodine contrast agent, usually gadolinium, is injected at the time of the exam. This test is performed to evaluate intra-abdominal organs, such ... large volumes of oral contrast to evaluate the small intestine. This is a ...

4-D spatiotemporal analysis of ultrasound contrast agent dispersion for prostate cancer localization: a feasibility study.

PubMed

Schalk, Stefan G; Demi, Libertario; Smeenge, Martijn; Mills, David M; Wallace, Kirk D; de la Rosette, Jean J M C H; Wijkstra, Hessel; Mischi, Massimo

2015-05-01

Currently, nonradical treatment for prostate cancer is hampered by the lack of reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently shown great potential as a prostate cancer imaging technique. CUDI estimates the local dispersion of intravenously injected contrast agents, imaged by transrectal dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes related to tumor growth. The best CUDI results have so far been obtained by similarity analysis of the contrast kinetics in neighboring pixels. To date, CUDI has been investigated in 2-D only. In this paper, an implementation of 3-D CUDI based on spatiotemporal similarity analysis of 4-D DCE-US is described. Different from 2-D methods, 3-D CUDI permits analysis of the entire prostate using a single injection of contrast agent. To perform 3-D CUDI, a new strategy was designed to estimate the similarity in the contrast kinetics at each voxel, and data processing steps were adjusted to the characteristics of 4-D DCE-US images. The technical feasibility of 4-D DCE-US in 3-D CUDI was assessed and confirmed. Additionally, in a preliminary validation in two patients, dispersion maps by 3-D CUDI were quantitatively compared with those by 2-D CUDI and with 12-core systematic biopsies with promising results.

Preclinical Studies of a Kidney Safe Iodinated Contrast Agent.

PubMed

Rowe, Elizabeth S; Rowe, Vernon D; Biswas, Sangita; Mosher, Gerold; Insisienmay, Lovella; Ozias, Marlies K; Gralinski, Michael R; Hunter, John; Barnett, James S

2016-09-01

Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the use of iodinated contrast agents. This problem is particularly acute in interventional neurology and interventional cardiology, probably due to the intra-arterial route of injection, high contrast volumes, and preexisting risk factors of these patients. In an attempt to develop a contrast agent that is less damaging to the kidneys, we have studied the effects of adding a small amount of the substituted cyclodextrin, sulfobutyl-ether-β-cyclodextrin (SBECD), to iohexol in rodent models of renal toxicity. Renally compromised mice and rats were injected with iohexol and iohexol-SBECD via the tail vein. The renal pathology, creatinine clearance, and survival benefits of iohexol-SBECD were studied. The safety of direct intra-arterial injection of the iohexol-SBECD formulation was studied in a dog heart model system. Mechanism of action studies in cell culture model using a human kidney cell line was performed using flow cytometry. Nephrotoxicity was significantly reduced using iohexol-SBECD compared to iohexol alone, at mole ratios of iohexol:SBECD of 1:0.025. SBECD increased survival from 50% to 88% in a rat survival study. In the dog heart model, iohexol-SBECD was safe. Cell culture studies suggest that SBECD interferes with the early stages of contrast-induced apoptosis in a human renal cell line. We have shown that the addition of a small amount of SBECD (one molecule of SBECD per 40 iohexol molecules) significantly protects rodent kidneys from CI-AKI. Further development of this new formulation of iodinated contrast is warranted. © 2016 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA

PubMed Central

Liu, Xiaoli; Madhankumar, Achuthamangalam B.; Miller, Patti A.; Duck, Kari A.; Hafenstein, Susan; Rizk, Elias; Slagle-Webb, Becky; Sheehan, Jonas M.; Connor, James R.; Yang, Qing X.

2016-01-01

Background Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity. Methods The targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically. Results The average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI. Conclusions IL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI. PMID:26519740

Biocompatible astaxanthin as novel contrast agent for biomedical imaging.

PubMed

Nguyen, Van Phuc; Park, Suhyun; Oh, Junghwan; Wook Kang, Hyun

2017-08-01

Photoacoustic imaging (PAI) is a hybrid imaging modality with high resolution and sensitivity that can be beneficial for cancer staging. Due to insufficient endogenous photoacoustic (PA) contrast, the development of exogenous agents is critical in targeting cancerous tumors. The current study demonstrates the feasibility of marine-oriented material, astaxanthin, as a biocompatible PA contrast agent. Both silicon tubing phantoms and ex vivo bladder tissues are tested at various concentrations (up to 5 mg/ml) of astaxanthin to quantitatively explore variations in PA responses. A Q-switched Nd : YAG laser (λ = 532 nm) in conjunction with a 5 MHz ultrasound transducer is employed to generate and acquire PA signals from the samples. The phantom results presented that the PA signal amplitudes increase linearly with the astaxanthin concentrations (threshold detection = 0.31 mg/ml). The tissue injected with astaxanthin yields up to 16-fold higher PA signals, compared with that with saline. Due to distribution of the injected astaxanthin, PAI can image the margin of astaxanthin boles as well as quantify their volume in 3D reconstruction. Further investigations on selective tumor targeting are required to validate astaxanthin as a potential biocompatible contrast agent for PAI-assisted bladder cancer detection. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ocular pharmacokinetic study using T₁ mapping and Gd-chelate- labeled polymers.

PubMed

Shi, Xianfeng; Liu, Xin; Wu, Xueming; Lu, Zheng-Rong; Li, S Kevin; Jeong, Eun-Kee

2011-12-01

Recent advances in drug discovery have led to the development of a number of therapeutic macromolecules for treatment of posterior eye diseases. We aimed to investigate the clearance of macromolecular contrast probes (polymers conjugated with Gd-chelate) in the vitreous after intravitreal injections with the recently developed ms-DSEPI-T12 MRI and to examine the degradation of disulfide-containing biodegradable polymers in the vitreous humor in vivo. Intravitreal injections of model contrast agents poly[N-(2-hydroxypropyl)methacrylamide]-GG-1,6-hexanediamine-(Gd-DO3A), biodegradable (Gd-DTPA)-cystine copolymers, and MultiHance were performed in rabbits; their distribution and elimination from the vitreous after injections were determined by MRI. Times for macromolecular contrast agents to decrease to half their initial concentrations in the vitreous ranged from 0.4-1.3 days post-injection. Non-biodegradable polymers demonstrated slower vitreal clearance than those of disulfide-biodegradable polymers. Biodegradable polymers had similar clearance as MultiHance. Usefulness of T(1) mapping and ms-DSEPI-T12 MRI to study ocular pharmacokinetics was demonstrated. Results suggest an enzymatic degradation mechanism for the disulfide linkage in polymers in the vitreous leading to breakup of polymers in vitreous humor over time.

Validation of diffuse optical tomography using a bi-functional optical-MRI contrast agent and a hybrid MRI-DOT system

NASA Astrophysics Data System (ADS)

Luk, Alex T.; Lin, Yuting; Grimmond, Brian; Sood, Anup; Uzgiris, Egidijus E.; Nalcioglu, Orhan; Gulsen, Gultekin

2013-03-01

Since diffuse optical tomography (DOT) is a low spatial resolution modality, it is desirable to validate its quantitative accuracy with another well-established imaging modality, such as magnetic resonance imaging (MRI). In this work, we have used a polymer based bi-functional MRI-optical contrast agent (Gd-DTPA-polylysine-IR800) in collaboration with GE Global Research. This multi-modality contrast agent provided not only co-localization but also the same kinetics, to cross-validate two imaging modalities. Bi-functional agents are injected to the rats and pharmacokinetics at the bladder are recovered using both optical and MR imaging. DOT results are validated using MRI results as "gold standard"

Nonpharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury

PubMed Central

Eiam-Ong, Somchai

2014-01-01

Contrast-induced AKI (CI-AKI) has been one of the leading causes for hospital-acquired AKI and is associated with independent risk for adverse clinical outcomes including morbidity and mortality. The aim of this review is to provide a brief summary of the studies that focus on nonpharmacological strategies to prevent CI-AKI, including routine identification of at-risk patients, use of appropriate hydration regimens, withdrawal of nephrotoxic drugs, selection of low-osmolar contrast media or isoosmolar contrast media, and using the minimum volume of contrast media as possible. There is no need to schedule dialysis in relation to injection of contrast media or injection of contrast agent in relation to dialysis program. Hemodialysis cannot protect the poorly functioning kidney against CI-AKI. PMID:24795882

Surface impact on nanoparticle-based magnetic resonance imaging contrast agents

PubMed Central

Zhang, Weizhong; Liu, Lin; Chen, Hongmin; Hu, Kai; Delahunty, Ian; Gao, Shi; Xie, Jin

2018-01-01

Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in the clinic. To improve imaging quality, MRI contrast agents, which can modulate local T1 and T2 relaxation times, are often injected prior to or during MRI scans. However, clinically used contrast agents, including Gd3+-based chelates and iron oxide nanoparticles (IONPs), afford mediocre contrast abilities. To address this issue, there has been extensive research on developing alternative MRI contrast agents with superior r1 and r2 relaxivities. These efforts are facilitated by the fast progress in nanotechnology, which allows for preparation of magnetic nanoparticles (NPs) with varied size, shape, crystallinity, and composition. Studies suggest that surface coatings can also largely affect T1 and T2 relaxations and can be tailored in favor of a high r1 or r2. However, the surface impact of NPs has been less emphasized. Herein, we review recent progress on developing NP-based T1 and T2 contrast agents, with a focus on the surface impact. PMID:29721097

Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years.

PubMed

Kromrey, Marie-Luise; Liedtke, Kim Rouven; Ittermann, Till; Langner, Sönke; Kirsch, Michael; Weitschies, Werner; Kühn, Jens-Peter

2017-02-01

To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey. Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5 years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (0.15 mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up. No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios. Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol. • Gadobutrol does not lead to neuronal signal alterations after 5 years. • Neuronal deposition of macrocyclic contrast agent could not be confirmed. • Macrocyclic contrast agents in a proven dosage are safe.

Gadolinium-enhanced MR images of the growing piglet skeleton: ionic versus nonionic contrast agent.

PubMed

Menezes, Nina M; Olear, Elizabeth A; Li, Xiaoming; Connolly, Susan A; Zurakowski, David; Foley, Mary; Shapiro, Frederic; Jaramillo, Diego

2006-05-01

To determine whether there are differences in the distribution of ionic and nonionic gadolinium-based contrast agents by evaluating contrast enhancement of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis in the knees of normal piglets. Following approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with gradient-echo MR imaging was quantified and compared (Student t test) by means of enhancement ratios. Distribution of contrast material was assessed and compared (Student t test) by means of T1 measurements obtained before and at three 15-minute intervals after contrast agent administration. The relative visibility of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis was qualitatively assessed by two observers and compared (Wilcoxon signed rank test). Differences in matrix content and cellularity that might explain the imaging findings were studied at histologic evaluation. Enhancement ratios were significantly higher for gadoteridol than for gadopentetate dimeglumine in the physis, epiphyseal cartilage, and secondary ossification center (P < .05). After contrast agent administration, T1 values decreased sharply for both agents-but more so for gadoteridol. Additionally, there was less variability in T1 values across structures with this contrast agent. Gadoteridol resulted in greater visibility of the physis, while gadopentetate dimeglumine resulted in greater contrast between the physis and metaphysis (P < .05). The results suggest different roles for the two gadolinium-based contrast agents: The nonionic contrast medium is better suited for evaluating perfusion and anatomic definition in the immature skeleton, while the ionic contrast medium is better for evaluating cartilage fixed-charge density. (c) RSNA, 2006.

A Cadaveric Study on Sacroiliac Joint Injection

PubMed Central

Zou, Yu-Cong; Li, Yi-Kai; Yu, Cheng-Fu; Yang, Xian-Wen; Chen, Run-Qi

2015-01-01

The scope of this study was to explore the possibility as well as the feasibility of sacroiliac joint injection following simple X-ray clip location. For the cadaveric study, 10 fixed sacroiliac joint (SIJ) sectional specimens, 4 dried cadaveric pelvises and 21 embalmed adult cadaveric pelvises were dissected, followed by an injection of contrast agent into the joint. The irrigation of the agent was observed through CT scanning. For the radiologic study, 188 CT scans of ankylosing spondylitis patients (143 male, 45 female) were collected from 2010 to 2012, in Nanfang Hospital. What was measured was (1) Distance between the posterior midline and sagittal synovium; (2) Length of the sagittal synovium; (3) Distance between the midpoint of the sagittal synovium and posterior superior iliac spine; and (4) Distance between the superficial skin vertical to the sagittal synovium point were measured. For the practice-based study: 20 patients (17 males and 3 females) with early ankylosing spondylitis, from Nanfang Hospital affiliated with Southern Medical University were recruited, and sacroiliac joint unguided injections were done on the basis of the cadaveric and radiologic study. Only the inferior 1/3rd portion parallel to the posterior midline could be injected into since the superior 2/3rd portion were filled with interosseous ligaments. Thirteen of the 20 patients received successful injections as identified by CT scan using the contrast agent. Sacroiliac joint injection following simple X-ray clip location is possible and feasible if the operation is performed by trained physicians familiar with the sacroiliac joint and its surrounding anatomic structures. PMID:25692437

SU-F-T-664: The Efficacy of Gold Nanoparticles as Contrast Agents in Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Y; Zhang, Y; Sajo, E

Purpose: Micro-Computed Tomography (micro-CT) has been widely used as a non-invasive, high-resolution imaging modality in preclinical research. However, tumors cannot be well distinguished, since their density are similar to those of surrounding tissues, and the tumors’ natural contrast is very low. The benefits of using Gold Nanoparticles (AuNPs) as a promising high atomic weight contrast agent have been published in recent years. The aim of this study is to investigate the efficacy of AuNPs as contrast agents using different energy x-rays. Methods: The left flank of an immune-compromised athymic nude mouse was implanted with subcutaneous xenograft model of human lungmore » cancer line, A549 cells (from ATCC). After 14 days, this mouse was imaged with dual energy cone-beam micro-CT. The selected energies were 45 kVp and 65 kVp. 10µg AuNPs (200 µg/ml concentration) approximately 12 nm in size were injected subcutaneously into the tumor. The mouse was imaged 0, 3 and 24 hours post-injection. During scanning, this mouse was anesthetized. All projection raw data have been optimized and then images were reconstructed with the FDK Algorithm. Results: Based on images, at 0 hour, AuNPs provided obvious contrast no matter which energy selected, 45 kVp or 65 kVp; and using 45 kVp X-ray, AuNps showed greater contrast. After 3 hours or evenand longer, AuNPs distributed throughout the whole body of mouse, and they were not shown clearly shown in the images. Conclusion: In this study, we investigated the efficacy of AuNPs as image contrast agents at different energies with dual-energy micro-CT, using 200µg/mL of AuNPs. Sufficiently high concentrations of AuNPs are needed to be able to track intratumoral distribution. Images showed good contrast immediately following the administration of the agent but results were poor after 3 hours.« less

Multi-slice computed tomography 5-minute delayed scan is superior to immediate scan after contrast media application in characterization of intracranial tuberculosis.

PubMed

Hou, Dailun; Qu, Huifang; Zhang, Xu; Li, Ning; Liu, Cheng; Ma, Xiangxing

2014-09-02

The aim of this study was to determine whether the diagnosis of intracranial tuberculosis (TB) can be improved when multi-slice computed tomography (MSCT) scans are taken with a 5-min delay after contrast media application. Pre- and post-contrast CT scans of the head were obtained from 30 patients using a 16-slice spiral CT. Dual-phase acquisition was performed immediately and 5 min after contrast agent injection. Diagnostic values of different images were compared using a scoring system applied by 2 experienced radiologists. We found 526 lesions in 30 patients, including 22 meningeal thickenings, 235 meningeal tuberculomas/tubercles, and 269 parenchymal tuberculomas/tubercles. Images obtained with 5-min delayed scan time were superior in terms of lesion size and meningeal thickening outlining in all disease types (P<0.01). The ability to distinguish between vascular sections from the cerebral sulcus and tubercle was also improved (P<0.01). Image acquisition with 5-min delay after contrast agent injection should be performed as a standard scanning protocol to diagnose intracranial TB.

Effect of Anesthesia Carrier Gas on In-Vivo Circulation Times of Ultrasound Microbubble Contrast Agents in Rats

PubMed Central

Mullin, Lee; Gessner, Ryan; Kwan, James; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. PMID:21246710

Ocular Pharmacokinetic Study Using T1 Mapping and Gd-Chelate-Labeled Polymers

PubMed Central

Shi, Xianfeng; Liu, Xin; Wu, Xueming; Lu, Zheng-Rong; Li, S. Kevin

2011-01-01

Purpose Recent advances in drug discovery have led to the development of a number of therapeutic macromolecules for treatment of posterior eye diseases. We aimed to investigate the clearance of macromolecular contrast probes (polymers conjugated with Gd-chelate) in the vitreous after intravitreal injections with the recently developed ms-DSEPI-T12 MRI and to examine the degradation of disulfide-containing biodegradable polymers in the vitreous humor in vivo. Methods Intravitreal injections of model contrast agents poly[N-(2-hydroxypropyl)methacrylamide]-GG-1,6-hexanediamine-(Gd-DO3A), biodegradable (Gd-DTPA)-cystine copolymers, and MultiHance were performed in rabbits; their distribution and elimination from the vitreous after injections were determined by MRI. Results Times for macromolecular contrast agents to decrease to half their initial concentrations in the vitreous ranged from 0.4–1.3 days post-injection. Non-biodegradable polymers demonstrated slower vitreal clearance than those of disulfide-biodegradable polymers. Biodegradable polymers had similar clearance as MultiHance. Conclusions Usefulness of T1 mapping and ms-DSEPI-T12 MRI to study ocular pharmacokinetics was demonstrated. Results suggest an enzymatic degradation mechanism for the disulfide linkage in polymers in the vitreous leading to breakup of polymers in vitreous humor over time. PMID:21691891

WE-FG-207B-01: BEST IN PHYSICS (IMAGING): Abdominal CT with Three K-Edge Contrast Materials Using a Whole-Body Photon-Counting Scanner: Initial Results of a Large Animal Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lakshmanan, M; Symons, R; Cork, T

Purpose: To demonstrate the feasibility of in vivo three-material decomposition techniques using photon-counting CT (PCCT) with possible advantage of resolving arterial and venous flow of an organ simultaneously. Methods: Abdominal PCCT scans were acquired using a prototype whole-body PCCT with four energy thresholds (25/50/75/90keV) in a canine. Bismuth subsalicylate (60 mg) was administered orally one day prior to scanning. Immediately prior to CT scan, gadoteric acid (60 ml, Dotarem, Guerbet) was intravenously injected, followed in ten minutes by a 20mL injection of iodinated contrast (iopamidol 370 mg/mL, Bracco). Scans were acquired every ∼20 seconds, starting from the time of iodinemore » injection. Linear material decomposition was performed using the least mean squares method to create concentration maps of iodine, gadolinium, and bismuth. The method was calibrated to vials with known concentrations of materials placed next to the animal. The accuracy of this method was tested on vials with known concentrations. Results: The material decomposition algorithm’s accuracy was confirmed to be within ±4mM in the test vials. In the animal, we could estimate the concentration of gadolinium in delayed-enhanced phase (10 minutes post-injection) in the abdomen. We could follow the wash-in and wash-out of iodine in arterial, venous, and excretory flow of the kidneys (20s, 80s, and 120s post-iodine injection) while gadolinium was present in the delayed-enhanced phase. Bismuth, which was used as a contrast agent for the gastro-intestinal tract, was easily differentiable from the other two contrast agents in the small intestine. Conclusion: This study shows the feasibility of using photon-counting CT with four energy thresholds to differentiate three k-edge contrast agents in vivo. This can potentially reduce radiation dose to patients by combining arterial and venous phases into a single acquisition.« less

Quantitative analysis applied to contrast medium extravasation by using the computed-tomography number within the region of interest

NASA Astrophysics Data System (ADS)

Lee, Jae-Seung; Im, In-Chul; Kim, Moon-Jib; Goo, Eun-Hoe; Kim, Sun-Ju; Kim, Kwang; Kwak, Byung-Joon

2014-02-01

The present study was carried out to present a method to analyze extravasation quantitatively by measuring the computed tomography (CT) number after determining the region of interest (ROI) in the CT images obtained from patients suspected of extravasation induced by contrast medium auto-injection. To achieve this, we divided the study subjects into a group of patients who incurred extravasation and a group of patients who underwent routine scans without incurring extravasation. The CT numbers at IV sites were obtained as reference values, and CT numbers at extravasation sites and hepatic portal veins, respectively, were obtained as relative values. Thereupon, the predicted time for extravasation ( T EP ) and the predicted ratio for extravasation ( R EP ) of an extravasation site were obtained and analyzed quantitatively. In the case of extravasation induced by a dual auto-injector, the values of the CT numbers were confirmed to be lower and the extravasation site to be enlarged when compared to the extravasation induced by a single autoinjector. This is because the physiological saline introduced after the injection of the contrast agent diluted the concentration of the extravasated contrast agent. Additionally, the T EP caused by the auto-injector was about 40 seconds, and we could perform a precise quantitative assessment of the site suspected of extravasation. In conclusion, the dual auto-injection method, despite its advantage of reducing the volume of contrast agent and improving the quality of images for patients with good vascular integrity, was judged to be likely to increase the risk of extravasation and aggravate outcomes for patients with poor vascular integrity by enlarging extravasation sites.

[Diagnosis of cerebral metastasis with standard dose gadobutrol vs. a high dose protocol. Intraindividual evaluation of a phase II high dose study].

PubMed

Vogl, T J; Friebe, C E; Balzer, T; Mack, M G; Steiner, S; Schedel, H; Pegios, W; Lanksch, W; Banzer, D; Felix, R

1995-08-01

To assess the effectiveness and safety of normal and high doses of Gadobutrol versus a standard dose of Gadolinium DTPA in the MR evaluation of patients with brain metastases. In a clinical phase-II study 20 patients who had been diagnosed as having brain metastases with CT or MRT were studied prospectively with Gadobutrol, a new nonionic, low osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg body weight and an additional dose of 0.2 mmol/kg Gadobutrol 10 min later. Spin-echo images were obtained before and after the two applications of Gadobutrol. Dynamic scanning (Turbo-FLASH) was performed for 3 min after each injection of the contrast agent. Both quantitative and qualitative data were intraindividually evaluated. The primary tumor was a bronchial carcinoma in 11 cases; in 9 other cases there were different primary tumors. Forty-eight hours after the use of Gadobutrol there were no adverse signs in the clinical examination, vital signs or blood and urine chemistry. Statistical analysis (Friedman test and Wilcoxon test) of the C/N ratios between tumor and white matter, percentage enhancement, and visual assessment rating revealed statistically significant superiority of high-dose Gadobutrol injection in comparison to the standard dose. The percentage enhancement increased on average from 104% after 0.1 mmol/kg to 162% after 0.3 mmol/kg Gadobutrol. Qualitative delineation and contrast of the lesions increased significantly. The use of high-dose Gadobutrol improved the detection of 36 additional lesions in 6 patients. The first in vivo results prove the excellent contrast capacity of the nonionic contrast agent Gadobutrol for the diagnosis of intracerebral metastases.

Imaging of paediatric splenic injury with contrast-enhanced ultrasonography.

PubMed

Oldenburg, Anja; Hohmann, Joachim; Skrok, Jan; Albrecht, Thomas

2004-04-01

We report two children who sustained traumatic parenchymal splenic injury and were monitored with contrast-enhanced ultrasound (CEUS). In both cases, unenhanced US failed to diagnose splenic haematoma, but the injury was well demonstrated after injection of contrast agent. In one case agreement with CT was excellent; in the other, CT was not performed due to the comprehensive information provided by CEUS.

MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA.

PubMed

Liu, Xiaoli; Madhankumar, Achuthamangalam B; Miller, Patti A; Duck, Kari A; Hafenstein, Susan; Rizk, Elias; Slagle-Webb, Becky; Sheehan, Jonas M; Connor, James R; Yang, Qing X

2016-05-01

Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity. The targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically. The average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI. IL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

In vivo tumor characterization using both MR and optical contrast agents with a hybrid MRI-DOT system

NASA Astrophysics Data System (ADS)

Lin, Yuting; Ghijsen, Michael; Thayer, David; Nalcioglu, Orhan; Gulsen, Gultekin

2011-03-01

Dynamic contrast enhanced MRI (DCE-MRI) has been proven to be the most sensitive modality in detecting breast lesions. Currently available MR contrast agent, Gd-DTPA, is a low molecular weight extracellular agent and can diffuse freely from the vascular space into interstitial space. Due to this reason, DCE-MRI has low sensitivity in differentiating benign and malignant tumors. Meanwhile, diffuse optical tomography (DOT) can be used to provide enhancement kinetics of an FDA approved optical contrast agent, ICG, which behaves like a large molecular weight optical agent due to its binding to albumin. The enhancement kinetics of ICG may have a potential to distinguish between the malignant and benign tumors and hence improve the specificity. Our group has developed a high speed hybrid MRI-DOT system. The DOT is a fully automated, MR-compatible, multi-frequency and multi-spectral imaging system. Fischer-344 rats bearing subcutaneous R3230 tumor are injected simultaneously with Gd-DTPA (0.1nmol/kg) and IC-Green (2.5mg/kg). The enhancement kinetics of both contrast agents are recorded simultaneously with this hybrid MRI-DOT system and evaluated for different tumors.

Ultrasound guidance to perform intra-articular injection of gadolinium-based contrast material for magnetic resonance arthrography as an alternative to fluoroscopy: the time is now.

PubMed

Messina, Carmelo; Banfi, Giuseppe; Aliprandi, Alberto; Mauri, Giovanni; Secchi, Francesco; Sardanelli, Francesco; Sconfienza, Luca Maria

2016-05-01

Magnetic resonance (MR) imaging has been definitively established as the reference standard in the evaluation of joints in the body. Similarly, magnetic resonance arthrography has emerged as a technique that has been proven to increase significantly the diagnostic performance if compared with conventional MR imaging, especially when dealing with fibrocartilage and articular cartilage abnormalities. Diluted gadolinium can be injected in the joint space using different approaches: under palpation using anatomic landmarks or using an imaging guidance, such as fluoroscopy, computed tomography, or ultrasound. Fluoroscopy has been traditionally used, but the involvement of ionizing radiation should represent a remarkable limitation of this modality. Conversely, ultrasound has emerged as a feasible, cheap, quick, and radiation-free modality that can be used to inject joints, with comparable accuracy of fluoroscopy. In the present paper, we discuss the advantages and disadvantages of using fluoroscopy or ultrasound in injecting gadolinium-based contrast agents in joints to perform magnetic resonance arthrography, also in view of the new EuroSAFE Imaging initiative promoted by the European Society of Radiology and the recent updates to the European Atomic Energy Community 2013/59 directive on the medical use of ionizing radiation. • Intra-articular contrast agent injection can be performed using different imaging modalities • Fluoroscopy is widely used, but uses ionizing radiation • Ultrasound is an accurate, quick, and radiation-free modality for joint injection • X-rays should be avoided when other radiation-free modalities can be used.

Normal saline as a natural intravascular contrast agent for dynamic perfusion-weighted MRI of the brain: Proof of concept at 1.5T.

PubMed

Jara, Hernán; Mian, Asim; Sakai, Osamu; Anderson, Stephan W; Horn, Mitchel J; Norbash, Alexander M; Soto, Jorge A

2016-12-01

Gadolinium-based contrast agents have associated risks. Normal saline (NS) is a nontoxic sodium chloride water solution that can significantly increase the magnetic resonance imaging (MRI) relaxation times of blood via transient hemodilution (THD). The purpose of this pilot study was to test in vivo in the head the potential of normal saline as a safer, exogenous perfusion contrast agent. This Health Insurance Portability and Accountability Act (HIPAA)-compliant prospective study was approved by the local Institutional Review Board (IRB): 12 patients were scanned with T 1 -weighted inversion recovery turbo spin echo pulse sequence at 1.5T. The dynamic inversion recovery pulse sequence was run before, during, and after the NS injection for up to 5 minutes: 100 ml of NS was power-injected via antecubital veins at 3-4 ml/s. Images were processed to map maximum enhancement area-under-the-curve, time-to-peak, and mean-transit-time. These maps were used to identify the areas showing significant NS injection-related signal and to generate enhancement time curves. Hardware and pulse sequence stability were studied via phantom experimentation. Main features of the time curves were tested against theoretical modeling of THD signal effects using inversion recovery pulse sequences. Pearson correlation coefficient (R) mapping was used to differentiate genuine THD effects from motion confounders and noise. The scans of 8 out of 12 patients showed NS injection-related effects that correlate in magnitude with tissue type (gray matter ∼15% and white matter ∼3%). Motion artifacts prevented ascertaining NS signal effects in the remaining four patients. Positive and negative time curves were observed in vivo and this dual THD signal polarity was also observed in the theoretical simulations. R-histograms that were approximately constant in the range 0.1 < |R| < 0.8 and leading to correlation fractions of F corr (|R| > 0.5) = 0.45 and 0.59 were found to represent scans with genuine THD signal effects. A measurable perfusion effect in brain tissue was demonstrated in vivo using NS as an injectable intravascular contrast agent. J. Magn. Reson. Imaging 2016;44:1580-1591. © 2016 International Society for Magnetic Resonance in Medicine.

Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-01-01

Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

A new contrast agent for radiological and dissection studies of the arterial network of anatomic specimens.

PubMed

Bulla, A; Casoli, C; Farace, F; Mazzarello, V; De Luca, L; Rubino, C; Montella, A

2014-01-01

The aim of the present study is to propose a new contrast agent that can be easily applied both to CT and dissection studies to replace lead oxide based formulas for comparative anatomical analyses of the vascularisation of cadaveric specimens. The infusion material was an epoxy resin, especially modified by the addition of barium sulphate to enhance its radiopacity. The final copolymer was toxicologically safe. To test the properties of the new material, several cadaveric limb injections were performed. The injected specimens were both CT scanned to perform 3D vascular reconstructions and dissected by anatomical planes. There was a perfect correspondence between the image studies and the dissections: even the smallest arteries on CT scan can be identified on the specimen and vice versa. The properties of the epoxy allowed an easy dissection of the vessels. The new imaging techniques available today, such as CT scan, can evaluate the vascular anatomy in high detail and 3D. This new contrast agent may help realising detailed vascular studies comparing CT scan results with anatomical dissections. Moreover, it may be useful for teaching surgical skills in the field of plastic surgery.

Prevention of polydimethylsiloxane microsphere migration using a mussel-inspired polydopamine coating for potential application in injection therapy.

PubMed

Chung, Eun-Jae; Jun, Dae-Ryong; Kim, Dong-Wook; Han, Mi-Jung; Kwon, Tack-Kyun; Choi, Sung-Wook; Kwon, Seong Keun

2017-01-01

The use of injectable bulking agents is a feasible alternative procedure for conventional surgical therapy. In this study, poly(dimethylsiloxane) (PDMS) microspheres coated with polydopamine (PDA) were developed as a potential injection agent to prevent migration in vocal fold. Uniform PDMS microspheres are fabricated using a simple fluidic device and then coated with PDA. Cell attachment test reveals that the PDA-coated PDMS (PDA-PDMS) substrate favors cell adhesion and attachment. The injected PDA-PDMS microspheres persist without migration on reconstructed axial CT images, whereas, pristine PDMS locally migrates over a period of 12 weeks. The gross appearance of the implants retrieved at 4, 8, 12 and 34 weeks indicates that the PDA-PDMS group maintained their original position without significant migration until 34 weeks after injection. By contrast, there is diffuse local migration of the pristine PDMS group from 4 weeks after injection. The PDA-coated PDMS microspheres can potentially be used as easily injectable, non-absorbable filler without migration.

Prevention of polydimethylsiloxane microsphere migration using a mussel-inspired polydopamine coating for potential application in injection therapy

PubMed Central

Kim, Dong-Wook; Han, Mi-Jung; Kwon, Tack-Kyun; Choi, Sung-Wook

2017-01-01

The use of injectable bulking agents is a feasible alternative procedure for conventional surgical therapy. In this study, poly(dimethylsiloxane) (PDMS) microspheres coated with polydopamine (PDA) were developed as a potential injection agent to prevent migration in vocal fold. Uniform PDMS microspheres are fabricated using a simple fluidic device and then coated with PDA. Cell attachment test reveals that the PDA-coated PDMS (PDA-PDMS) substrate favors cell adhesion and attachment. The injected PDA-PDMS microspheres persist without migration on reconstructed axial CT images, whereas, pristine PDMS locally migrates over a period of 12 weeks. The gross appearance of the implants retrieved at 4, 8, 12 and 34 weeks indicates that the PDA-PDMS group maintained their original position without significant migration until 34 weeks after injection. By contrast, there is diffuse local migration of the pristine PDMS group from 4 weeks after injection. The PDA-coated PDMS microspheres can potentially be used as easily injectable, non-absorbable filler without migration. PMID:29095854

Evaluation of joint effusion in rabbits by color Doppler, power Doppler, and contrast-enhanced power Doppler ultrasonography.

PubMed

Lim, Gye-Yeon; Im, Soo Ah; Jung, Won Sang; Lee, Jae Mun; Lee, Ah Won

2005-09-01

The aim of this prospective study was to evaluate the diagnostic value of power Doppler ultrasonography (PDUS) and contrast-enhanced PDUS (CEPDUS) in the depiction and characterization of experimentally induced arthritis in the rabbit. Thirty rabbits were divided into three groups consisting of one control group (saline injection group) and two experimental groups: a suppurative arthritis group and a chemically induced synovitis group. The same amount (1 ml) of each agent was directly injected into the right hip joint. Serial color Doppler ultrasound (CDUS), PDUS, and CEPDUS images were obtained before and after injection. We observed that all of the infected knees in the suppurative arthritis group with Staphylococcus aureus demonstrated an increased signal on PDUS after inoculation. A minimal power Doppler signal was presented in the chemically induced synovitis group with talc injection, but none of the control knees demonstrated any increased signals. CEPDUS was the most sensitive imaging modality for evaluating the increase of blood flows in suppurative arthritis and was subsequently followed by PDUS and CDUS. The increased signals obtained with PDUS represent increased local blood flows; therefore, this technique can be used for evaluating the degree of inflammation. Furthermore, using the contrast agent enhances the sensitivity of PDUS, and it can even be useful for differentiating borderline cases. Copyright 2005 Wiley Periodicals, Inc

Gross, Histologic, and Computed Tomographic Anatomy of the Lacrimal System of Snakes

PubMed Central

Souza, Nicole M.; Maggs, David J.; Park, Shin Ae; Puchalski, Sarah; Reilly, Christopher M.; Paul-Murphy, Joanne; Murphy, Christopher J.

2014-01-01

Objective To describe the lacrimal system of snakes using contrast micro-computed tomography (micro-CT) with 3-dimensional reconstruction, fluorescein passage (“Jones”) testing, histology, and gross dissection. Animals studied One Royal Python and 19 snake cadavers representing 10 species. Procedures Direct observation following injection of fluorescein into the subspectacular space, micro-CT following injection of 3 contrast agents into the subspectacular space, gross dissection following injection of latex into the subspectacular space, and histopathology. Results Injection of fluorescein confirmed patency but not course of the lacrimal duct. Barium enabled clear visualization of the lacrimal duct whereas two iodinated contrast agents proved inadequate. Collectively, micro-CT, anatomic dissections, and histology suggest tears are produced by a single, large, serous, retrobulbar gland, released into the subspectacular space via several ductules, and drained through a single punctum originating in the ventronasal subspectacular space and the lacrimal duct taking one of 3 routes of variable tortuosity before opening into the oral cavity in close association with the opening of the duct of the vomeronasal organ. Conclusions The ophidian lacrimal duct has a generally tortuous course and the details of its anatomy is species variable. The tortuous course of the duct likely predisposes snakes to duct occlusion and must be considered when planning medical and surgical interventions in snakes with pseudobuphthalmos and subspectacular abscessation. PMID:24862081

Ferrimagnetic susceptibility contrast agents.

PubMed

Bach-Gansmo, T

1993-01-01

Contrast agents based on superparamagnetic particles have been in clinical development for more than 5 years, and the complexity of their effects is still not elucidated. The relaxivities are frequently used to give an idea of their efficacy, but these parameters can only be used if they are concentration independent. For large superparamagnetic systems, the evolution of the transverse magnetization is biexponential, after an initial loss of magnetization. Both these characteristics of large superparamagnetic systems should lead to prudence in using the relaxivities as indicators of contrast medium efficacy. Susceptibility induced artefacts have been associated with the use of superparamagnetic contrast agents since the first imaging evaluation took place. The range of concentrations where good contrast effect was achieved without inducing artefacts, as well as blurring and metal artefacts were evaluated. The influence of motion on the induction of artefacts was studied, and compared to the artefacts induced by a paramagnetic agent subject to motion. With a suitable concentration of a negative contrast agent, a signal void could be achieved in the region prone to motion, and no artefacts were induced. If the concentration was too high, a displacement of the region close to the contrast agent was observed. The artefacts occurred in a volume surrounding the contrast agent, i.e., also outside the imaging plane. In comparison a positive, paramagnetic contrast agent induced heavy artefacts in the phase encoding direction, appearing as both high intensity regions and black holes, in a mosaic pattern. Clinical trials of the oral contrast agent OMP for abdominal MR imaging showed this agent to be safe and efficacious. OMP increased the diagnostic efficacy of abdominal MR imaging in 2 of 3 cases examined, with a significant decrease in motion artefacts. Susceptibility contrast agents may also be of use in the evaluation of small lesions in the liver. Particulate material injected i.v. will be targeted to the liver and spleen by way of the mononuclear phagocyte system (MPS). Small particles, without specific receptor affinities were targeted to the hepatocytes and the MPS. The distribution correlated with a high efficiency as a contrast agent, whereas no correlation to in vitro relaxation rates and relaxivities could be found. Superparamagnetic particles have important possibilities as contrast agents. The identification of in vitro properties of these agents may help the comparison of various agents before in vivo imaging.

Radioprotection and contrast agent use in pediatrics: what, how, and when.

PubMed

Lancharro Zapata, Á M; Rodríguez, C Marín

2016-05-01

It is essential to minimize exposure to ionizing radiation in children for various reasons. The risk of developing a tumor from exposure to a given dose of radiation is greater in childhood. Various strategies can be used to reduce exposure to ionizing radiation. It is fundamental to avoid unnecessary tests and tests that are not indicated, to choose an alternative test that does not use ionizing radiation, and/or to take a series of measures that minimize the dose of radiation that the patient receives, such as avoiding having to repeat tests, using the appropriate projections, using shields, adjusting the protocol (mAs, Kv, or pitch) to the patient's body volume, etc… When contrast agents are necessary, intracavitary ultrasound agents can be used, although the use of ultrasound agents is also being extended to include intravenous administration. In fluoroscopy, contrast agents with low osmolarity must be used, as in CT where we must adjust the dose and speed of injection to the patient's weight and to the caliber of the peripheral line, respectively. In MRI, only three types of contrast agents have been approved for pediatric use. It is sometimes necessary to use double doses or organ-specific contrast agents in certain clinical situations; the safety of contrast agents for these indications has not been proven, so they must be used off label. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Contrast-enhanced peripheral MRA: technique and contrast agents.

PubMed

Nielsen, Yousef W; Thomsen, Henrik S

2012-09-01

In the last decade contrast-enhanced magnetic resonance angiography (CE-MRA) has gained wide acceptance as a valuable tool in the diagnostic work-up of patients with peripheral arterial disease. This review presents current concepts in peripheral CE-MRA with emphasis on MRI technique and contrast agents. Peripheral CE-MRA is defined as an MR angiogram of the arteries from the aortic bifurcation to the feet. Advantages of CE-MRA include minimal invasiveness and lack of ionizing radiation. The basic technique employed for peripheral CE-MRA is the bolus-chase method. With this method a paramagnetic MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic field strength of the MRI system, receiver coil configuration, use of parallel imaging, contrast bolus timing technique, and k-space filling strategies. Furthermore, it is possible to optimize peripheral CE-MRA using venous compression techniques, hybrid scan protocols, time-resolved imaging, and steady-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Using optimized technique and a stable MRI contrast agent, peripheral CE-MRA is a safe procedure with diagnostic accuracy close to that of conventional catheter X-ray angiography.

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

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Jeong, Sang Young; Kim, Hyo Jeong; Kwak, Byung-Kook; Lee, Ha-Young; Seong, Hasoo; Shin, Byung Cheol; Yuk, Soon Hong; Hwang, Sung-Joo; Cho, Sun Hang

2010-12-01

Biocompatible poly-[ N-(2-hydroxyethyl)- d, l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

Mass diffusion coefficient measurement for vitreous humor using FEM and MRI

NASA Astrophysics Data System (ADS)

Rattanakijsuntorn, Komsan; Penkova, Anita; Sadha, Satwindar S.

2018-01-01

In early studies, the ‘contour method’ for determining the diffusion coefficient of the vitreous humor was developed. This technique relied on careful injection of an MRI contrast agent (surrogate drug) into the vitreous humor of fresh bovine eyes, and tracking the contours of the contrast agent in time. In addition, an analytical solution was developed for the theoretical contours built on point source model for the injected surrogate drug. The match between theoretical and experimental contours as a least square fit, while floating the diffusion coefficient, led to the value of the diffusion coefficient. This method had its limitation that the initial injection of the surrogate had to be spherical or ellipsoidal because of the analytical result based on the point-source model. With a new finite element model for the analysis in this study, the technique is much less restrictive and handles irregular shapes of the initial bolus. The fresh bovine eyes were used for drug diffusion study in the vitreous and three contrast agents of different molecular masses: gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA, 938 Da), non-ionic gadoteridol (Prohance, 559 Da), and bovine albumin conjugated with gadolinium (Galbumin, 74 kDa) were used as drug surrogates to visualize the diffusion process by MRI. The 3D finite element model was developed to determine the diffusion coefficients of these surrogates with the images from MRI. This method can be used for other types of bioporous media provided the concentration profile can be visualized (by methods such as MRI or fluorescence).

Migration of iron-labeled KHYG-1 natural killer cells to subcutaneous tumors in nude mice, as detected by magnetic resonance imaging.

PubMed

Mallett, Christiane L; McFadden, Catherine; Chen, Yuhua; Foster, Paula J

2012-07-01

A novel cell line of cytotoxic natural killer (NK) cells, KHYG-1, was examined in vivo for immunotherapy against prostate cancer. The feasibility of using magnetic resonance imaging (MRI) tracking to monitor the fate of injected NK cells following intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c.) administration was assessed. PC-3M human prostate cancer cells were injected s.c. into the flank of nude mice (day 0). KHYG-1 NK cells were labeled with an iron oxide contrast agent and injected s.c., i.v. or i.p. on day 8. Mice were imaged by MRI on days 7, 9 and 12. Tumor sections were examined with fluorescence microscopy and immunohistologic staining for NK cells. NK cells were detected in the tumors by histology after all three administration routes. NK cells and fluorescence from the iron label were co-localized. Signal loss was seen in the areas around the tumors and between the tumor lobes in the s.c. group. We are the first to label this cell line of NK cells with an iron oxide contrast agent. Accumulation of NK cells was visualized by MRI after s.c. injection but not after i.v. and i.p. injection.

Biocompatible and high-performance amino acids-capped MnWO4 nanocasting as a novel non-lanthanide contrast agent for X-ray computed tomography and T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Dong, Kai; Liu, Zhen; Liu, Jianhua; Huang, Sa; Li, Zhenhua; Yuan, Qinghai; Ren, Jinsong; Qu, Xiaogang

2014-01-01

In the present work, a novel non-lanthanide dual-modality contrast agent, manganese tungstate (MnWO4), has been successfully constructed by a facile and versatile hydrothermal route. With the merits of a high atomic number and a well-positioned K-edge energy of tungsten, our well-prepared non-lanthanide nanoprobes provide a higher contrast efficacy than routine iodine-based agents in clinics. Additionally, the presence of Mn in these nanoparticles endow them with excellent T1-weighted MR imaging capabilities. As an alternative to T2-weighted MRI and CT dual-modality contrast agents, the nanoprobes can provide a positive contrast signal, which prevents confusion with the dark signals from hemorrhage and blood clots. To the best of our knowledge, this is the first report that a non-lanthanide imaging nanoprobe is applied for CT and T1-weighted MRI simultaneously. Moreover, comparing with gadolinium-based T1-weighted MRI and CT dual-modality contrast agents that were associated with nephrogenic systemic fibrosis (NSF), our contrast agents have superior biocompatibility, which is proved by a detailed study of the pharmacokinetics, biodistribution, and in vivo toxicology. Together with excellent dispersibility, high biocompatibility and superior contrast efficacy, these nanoprobes provide detailed and complementary information from dual-modality imaging over traditional single-mode imaging and bring more opportunities to the new generation of non-lanthanide nanoparticulate-based contrast agents.In the present work, a novel non-lanthanide dual-modality contrast agent, manganese tungstate (MnWO4), has been successfully constructed by a facile and versatile hydrothermal route. With the merits of a high atomic number and a well-positioned K-edge energy of tungsten, our well-prepared non-lanthanide nanoprobes provide a higher contrast efficacy than routine iodine-based agents in clinics. Additionally, the presence of Mn in these nanoparticles endow them with excellent T1-weighted MR imaging capabilities. As an alternative to T2-weighted MRI and CT dual-modality contrast agents, the nanoprobes can provide a positive contrast signal, which prevents confusion with the dark signals from hemorrhage and blood clots. To the best of our knowledge, this is the first report that a non-lanthanide imaging nanoprobe is applied for CT and T1-weighted MRI simultaneously. Moreover, comparing with gadolinium-based T1-weighted MRI and CT dual-modality contrast agents that were associated with nephrogenic systemic fibrosis (NSF), our contrast agents have superior biocompatibility, which is proved by a detailed study of the pharmacokinetics, biodistribution, and in vivo toxicology. Together with excellent dispersibility, high biocompatibility and superior contrast efficacy, these nanoprobes provide detailed and complementary information from dual-modality imaging over traditional single-mode imaging and bring more opportunities to the new generation of non-lanthanide nanoparticulate-based contrast agents. Electronic supplementary information (ESI) available: TEM images of MnWO4 nanoparticles synthesized at pH = 7, 180 °C pH = 9, 180 °C pH = 6, 200 °C with various amino acid molecules as capped agents, survey XPS spectra, FTIR spectrum of glycine capped MnWO4 nanorods, photos of glycine capped MnWO4 nanorods in various solutions including PBS, DMEM cell medium, and FBS, in vivo coronal view CT images of a rat before and after intravenous injection of iobitridol at different timed intervals, in vivo CT imaging of the rat one month after intravenous injection of MnWO4 nanorods, CT values of the heart, liver, spleen and kidney of a rat before and after intravenous administration of MnWO4 nanorods and iobitridol at different time intervals, hematology analysis and blood biochemical assay. See DOI: 10.1039/c3nr05455a

Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

PubMed

Wan, Chuanling; Xue, Rong; Zhan, Youyang; Wu, Yijie; Li, Xiaojing; Pei, Fengkui

2017-09-01

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg -1 body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from the injury induced by gadolinium-based contrast agents.

Indirect MR lymphangiography of the head and neck using conventional gadolinium contrast: A pilot study in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loo, Billy W.; Draney, Mary T.; Sivanandan, Ranjiv

2006-10-01

Purpose: To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using interstitial injection of conventional gadolinium contrast (gadoteridol and gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head-and-neck sites. Methods and Materials: We performed head-and-neck MR-LAG in 5 healthy volunteers, with injection of dermal and mucosal sites. We evaluated the safety of the procedure, the patterns of enhancement categorized by injection site and nodal level, the time course of enhancement, the optimal concentration and volume of contrast, and the optimal imaging sequence. Results: The worst side effects of interstitial contrast injection were brief, mild pain and swelling at the injected sitesmore » that were self-limited. MR-LAG resulted in consistent visualization of the primary lymphatic drainage pattern specific to each injected site, which was reproducible on repeated examinations. The best enhancement was obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted, imaging within 5-15 min of injection, and a three-dimensional fast spoiled gradient echo sequence with magnetization transfer. Conclusions: We found head-and-neck MR-LAG to be a safe, convenient imaging method that provides functional information about the lymphatic drainage of injected sites. Applied to head-and-neck cancer, it has the potential to identify sites at highest risk of occult metastatic spread for radiotherapy or surgical planning, and possibly to visualize micrometastases.« less

Impact of myocardial contrast echocardiography on vascular permeability: an in vivo dose response study of delivery mode, pressure amplitude and contrast dose.

PubMed

Li, Peng; Cao, Lu-qin; Dou, Chun-Yan; Armstrong, William F; Miller, Douglas

2003-09-01

An in vivo rat model of myocardial contrast echocardiography (MCE) was defined and used to examine the dose range response of microvascular permeabilization and premature ventricular contractions (PVCs) with respect to method of imaging, peak rarefactional pressure amplitude (PRPA) and agent dose. A left ventricular short axis view was obtained on anesthetized rats at 1.7 MHz using a diagnostic ultrasound system with simultaneous ECG recording. Evans blue dye, a marker for microvascular leakage, and a bolus of Optison were injected i.v. Counts of PVCs were made from video tape during the 3 min of MCE. Hearts were excised 5 min after imaging and petechial hemorrhages, Evans blue colored area and Evans blue content were determined. No PVCs or microvascular leakage were seen in rats imaged without contrast agent followed by contrast agent injection without imaging. When PVCs were detected during MCE, petechial hemorrhages and Evans blue leakage were also found in the myocardium. Triggering 1:4 at end-systole produced the most PVCs per frame and most microvascular leakage, followed by end-systole 1:1, continuous scanning and end-diastole triggering 1:1. All effects increased with increasing Optison dosage in the range 25 to 500 microL kg(-1). Ultrasound PRPA was important, with apparent thresholds for PVCs at 1.0 MPa and for petechiae at 0.54 MPa. PVCs, petechial hemorrhages and microvascular leakage in the myocardium occur as a result of MCE in rats.

Ultrasound contrast agents for bleeding detection and acoustic hemostasis

NASA Astrophysics Data System (ADS)

Zderic, Vesna; Luo, Wenbo; Brayman, Andrew; Crum, Lawrence; Vaezy, Shahram

2005-04-01

Objective: To investigate the application of ultrasound contrast agents (UCA) in improving both therapeutic and diagnostic aspects of ultrasound-guided High Intensity Focused Ultrasound (HIFU) therapy. Methods: Incisions (3 cm long, 0.5 cm deep) were made in rabbit livers (in anterior surface for HIFU treatment, or posterior surface for bleeding detection). UCA Optison (~0.1 ml/kg) was injected into mesenteric vein or ear vein. A HIFU applicator (5.5 MHz, 6400 W/cm2) was scanned manually over the incision until hemostasis was achieved. Occult bleeding was monitored with Doppler ultrasound. Results: The presence of Optison produced 37% reduction in hemostasis times normalized to initial bleeding rates. Gross and histological observations showed similar appearance of HIFU lesions produced in the presence of Optison and control HIFU lesions. The temperature reached 100°C in both HIFU only and HIFU+UCA treatments. Tension strength of hemostatic liver incisions was 0.9+/-0.5 N. Almost no bleeding could be detected before Optison injection. First appearance of contrast enhancement localized at the bleeding site was 15 s after Optison injection, and lasted for ~50 s. Conclusion: The presence of UCA during HIFU treatment of liver incisions resulted in shortening of HIFU application times and better visualization of bleeding sites.

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

PubMed Central

2010-01-01

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd. PMID:21170410

Pharmacokinetics and Magnetic Resonance Imaging of Biodegradable Macromolecular Blood-Pool Contrast Agent PG-Gd in Non-Human Primates: A Pilot Study

PubMed Central

Tian, Mei; Wen, Xiaoxia; Jackson, Edward F.; Ng, Chaan; Uthamanthil, Rajesh; Liang, Dong; Gelovani, Juri G.; Li, Chun

2012-01-01

The purpose of this study was to evaluate poly(L-glutamic acid)-benzyl-DTPA-Gd (PG-Gd), a new biodegradable macromolecular magnetic resonance imaging contrast agent, for its pharmacokinetics and MRI enhancement in nonhuman primates. Studies were performed in rhesus monkeys at intravenous doses of 0.01, 0.02, and 0.08 mmol Gd/kg. T1-weighted MR images were acquired at 1.5T using fast spoiled gradient recalled echo and fast spin echo imaging protocols. The small-molecule contrast agent Magnevist was used as a control. PG-Gd in the monkey showed a bi-exponential disposition. The initial blood concentrations within 2 hours of PG-Gd administration were much higher than for those of Magnevist. The high blood concentration of PG-Gd was consistent with the MR imaging data, which showed prolonged circulation of PG-Gd in the blood pool. Enhancement of blood vessels and organs with a high blood perfusion (heart, liver, and kidney) was clearly visualized at 2 hours after contrast injection at the three doses used. A greater than proportional increase of the area under the blood concentration-time curve was observed when the administered single dose was increased from 0.01 mmol/kg to 0.08 mmol/kg. By 2 days after PG-Gd injection, the contrast agent was mostly cleared from all major organs, including kidney. The mean residence time was 15 hours at the 0.08 mmol/kg dose. A similar pharmacokinetic profile was observed in mice, with a mean residence time of 5.4 hours and a volume of distribution at steady-state of 85.5 mL/kg, indicating that the drug was mainly distributed in the blood compartment. Based on this pilot study, further investigations on potential systemic toxicity of PG-Gd in both rodents and large animals are needed before testing this agent in humans. PMID:21861289

Assessment of contrast enhanced respiration managed cone-beam CT for image guided radiotherapy of intrahepatic tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Nikolaj K. G., E-mail: nkyj@regionsjaelland.dk; Stewart, Errol; Imaging Research Lab, Robarts Research Institute, London, Ontario N6A 5B7

2014-05-15

Purpose: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy. Methods: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection. The acquired CBCT images were registeredmore » to the planning CT to determine alignment accuracy and dosimetric impact. The authors developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols. The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma. Results: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm. This was reduced to 2.8 mm when both techniques were employed. Tumors were not visualized in clinical CBCT images of human subjects. Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects. Different patients were found to require different contrast injections to maximize tumor contrast. Conclusions: Based on the authors’ animal study, respiration managed contrast enhanced CBCT improves IGRT significantly. Contrast enhanced CBCT benefits from patient specific tracer kinetics determined from DCE-CT.« less

Novel route synthesis of porous and solid gold nanoparticles for investigating their comparative performance as contrast agent in computed tomography scan and effect on liver and kidney function.

PubMed

Aziz, Farooq; Ihsan, Ayesha; Nazir, Aalia; Ahmad, Ishaq; Bajwa, Sadia Zafar; Rehman, Asma; Diallo, Abdoulaye; Khan, Waheed S

2017-01-01

Gold nanoparticles (GNPs) with dimension in the range of 1-100 nm have a prominent role in a number of biomedical applications like imaging, drug delivery, and cancer therapy owing to their unique optical features and biocompatibility. In this work, we report a novel technique for the synthesis of two types of GNPs namely porous gold nanoparticles (PGNPs) and solid gold nanoparticles (SGNPs). PGNPs of size 35 nm were fabricated by reduction of gold (III) solution with lecithin followed by addition of L-ascorbic acid and tri-sodium citrate, whereas SGNPs with a dimension of 28 nm were prepared by reflux method using lecithin as a single reducing agent. Comparative studies using PGNPs (λ max 560 nm) and SGNPs (λ max 548 nm) were conducted for evaluating their use as a contrast agent. These studies reveled that in direct computed tomography scan, PGNPs exhibited brighter contrast (45 HU) than SGNPs (26 HU). To investigate the effect of PGNPs and SGNPs on the liver and kidney profile, male rabbits were intravenously injected with an equal dose of 1 mg/kg weight of PGNPs and SGNPs. The effect on biochemical parameters was evaluated 72 hours after intravenous (IV) injection including liver function profile, renal (kidney) function biomarker, random blood glucose value, and cholesterol level. During one comparison of contrast in CT scan, PGNPs showed significantly enhanced contrast in whole-rabbit and organ CT scan as compared to SGNPs 6 hours after injection. Our findings suggested that the novel PGNPs enhance CT scan image with higher efficacy as compared to SGNPs. The results showed that IV administration of synthesized PGNPs increases the levels of aspartate aminotransferase (AST), alkaline phosphate (ALP), serum creatinine, and blood glucose, whereas that of SGNPs increases the levels of AST, ALP, and blood glucose.

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. Copyright © 2015 John Wiley & Sons, Ltd.

Development of a platform for co-registered ultrasound and MR contrast imaging in vivo

NASA Astrophysics Data System (ADS)

Chandrana, Chaitanya; Bevan, Peter; Hudson, John; Pang, Ian; Burns, Peter; Plewes, Donald; Chopra, Rajiv

2011-02-01

Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.

Development of silica-encapsulated silver nanoparticles as contrast agents intended for dual-energy mammography.

PubMed

Karunamuni, Roshan; Naha, Pratap C; Lau, Kristen C; Al-Zaki, Ajlan; Popov, Anatoliy V; Delikatny, Edward J; Tsourkas, Andrew; Cormode, David P; Maidment, Andrew D A

2016-09-01

Dual-energy (DE) mammography has recently entered the clinic. Previous theoretical and phantom studies demonstrated that silver provides greater contrast than iodine for this technique. Our objective was to characterize and evaluate in vivo a prototype silver contrast agent ultimately intended for DE mammography. The prototype silver contrast agent was synthesized using a three-step process: synthesis of a silver core, silica encapsulation and PEG coating. The nanoparticles were then injected into mice to determine their accumulation in various organs, blood half-life and dual-energy contrast. All animal procedures were approved by the institutional animal care and use committee. The final diameter of the nanoparticles was measured to be 102 (±9) nm. The particles were removed from the vascular circulation with a half-life of 15 min, and accumulated in macrophage-rich organs such as the liver, spleen and lymph nodes. Dual-energy subtraction techniques increased the signal difference-to-noise ratio of the particles by as much as a factor of 15.2 compared to the single-energy images. These nanoparticles produced no adverse effects in mice. Silver nanoparticles are an effective contrast agent for dual-energy x-ray imaging. With further design improvements, silver nanoparticles may prove valuable in breast cancer screening and diagnosis. • Silver has potential as a contrast agent for DE mammography. • Silica-coated silver nanoparticles are biocompatible and suited for in vivo use. • Silver nanoparticles produce strong contrast in vivo using DE mammography imaging systems.

Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes.

PubMed

Mahmoudi, Morteza; Tachibana, Atsushi; Goldstone, Andrew B; Woo, Y Joseph; Chakraborty, Papia; Lee, Kayla R; Foote, Chandler S; Piecewicz, Stephanie; Barrozo, Joyce C; Wakeel, Abdul; Rice, Bradley W; Bell Iii, Caleb B; Yang, Phillip C

2016-06-06

Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.

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 diffusion in magnetic field gradients due to susceptibility differences and cross-relaxation were considered as possible explanations for the findings. From the relaxivity results it follows that unless actual tissue relaxivities are used, estimates of tissue magnetopharmaceutical concentration made from enhancement of MR signal will be significantly in error, as will derived estimates of clinically useful parameters such as tissue perfusion.

Analysis of tracer transit in rat brain after carotid artery and femoral vein administrations using linear system theory.

PubMed

Rudin, M; Beckmann, N; Sauter, A

1997-01-01

Determination of tissue perfusion rates by MRI bolus tracking methods relies on the central volume principle which states that tissue blood flow is given by the tissue blood volume divided by the mean tracer transit time (MTT). Accurate determination of the MTT requires knowledge of the arterial input function which in MRI experiments is usually not known, especially when using small animals. The problem of unknown arterial input can be circumvented in animal experiments by directly injecting the contrast agent into a feeding artery of the tissue of interest. In the present article the passage of magnetite nanoparticles through the rat cerebral cortex is analyzed after injection into the internal carotid artery. The results are discussed in the framework of linear system theory using a one-compartment model for brain tissue and by using the well characterized gamma-variate function to describe the tissue concentration profile of the contrast agent. The results obtained from the intra-arterial tracer administration experiments are then compared with the commonly used intra-venous injection of the contrast agent in order to estimate the contribution of the peripheral circulation to the MTT values in the latter case. The experiments were analyzed using a two-compartment model and the gamma-variate function. As an application perfusion rates in normal and ischemic cerebral cortex of hypertensive rats were estimated in a model of focal cerebral ischemia. The results indicate that peripheral circulation has a significant influence on the MTT values and thus on the perfusion rates, which cannot be neglected.

Utility of a prototype liposomal contrast agent for x-ray imaging of breast cancer: a proof of concept using micro-CT in small animals

NASA Astrophysics Data System (ADS)

Badea, C. T.; Samei, E.; Ghaghada, K.; Saunders, R.; Yuan, H.; Qi, Y.; Hedlund, L. W.; Mukundan, S.

2008-03-01

Imaging tumor angiogenesis in small animals is extremely challenging due to the size of the tumor vessels. Consequently, both dedicated small animal imaging systems and specialized intravascular contrast agents are required. The goal of this study was to investigate the use of a liposomal contrast agent for high-resolution micro-CT imaging of breast tumors in small animals. A liposomal blood pool agent encapsulating iodine with a concentration of 65.5 mg/ml was used with a Duke Center for In Vivo Microscopy (CIVM) prototype micro-computed tomography (micro-CT) system to image the R3230AC mammary carcinoma implanted in rats. The animals were injected with equivalent volume doses (0.02 ml/kg) of contrast agent. Micro-CT with the liposomal blood pool contrast agent ensured a signal difference between the blood and the muscle higher than 450 HU allowing the visualization of the tumors 3D vascular architecture in exquisite detail at 100-micron resolution. The micro-CT data correlated well with the histological examination of tumor tissue. We also studied the ability to detect vascular enhancement with limited angle based reconstruction, i.e. tomosynthesis. Tumor volumes and their regional vascular percentage were estimated. This imaging approach could be used to better understand tumor angiogenesis and be the basis for evaluating anti-angiogenic therapies.

Contrast-Enhanced Sonography Depicts Spontaneous Ovarian Cancer at Early Stages in a Preclinical Animal Model

PubMed Central

Barua, Animesh; Bitterman, Pincas; Bahr, Janice M.; Basu, Sanjib; Sheiner, Eyal; Bradaric, Michael J.; Hales, Dale B.; Luborsky, Judith L.; Abramowicz, Jacques S.

2011-01-01

Objective Our goal was to examine the feasibility of using laying hens, a preclinical model of human spontaneous ovarian cancer, in determining the kinetics of an ultrasound contrast agent indicative of ovarian tumor-associated neoangiogenesis in early-stage ovarian cancer. Methods Three-year-old White Leghorn laying hens with decreased ovarian function were scanned before and after intravenous injection of a human serum albumin–perflutren contrast agent at a dose of 5 µL/kg body weight. Gray scale morphologic characteristics, Doppler indices, the arrival time, peak intensity, and wash-out of the contrast agent were recorded and archived on still images and video clips. Hens were euthanized thereafter; sonographic predictions were compared at gross examination; and ovarian tissues were collected. Archived clips were analyzed to determine contrast parameters and Doppler intensities of vessels. A time-intensity curve per hen was drawn, and the area under the curve was derived. Tumor types and the density of ovarian microvessels were determined by histologic examination and immunohistochemistry and compared to sonographic predictions. Results The contrast agent significantly (P < .05) enhanced the visualization of microvessels, which was confirmed by immunohistochemistry. Contrast parameters, including the time of wash-out and area under the curve, were significantly different (P < .05) between ovaries of normal hens and hens with ovarian cancer and correctly detected cancer at earlier stages than the time of peak intensity. Conclusions The laying hen may be a useful animal model for determining ovarian tumor-associated vascular kinetics diagnostic of early-stage ovarian cancer using a contrast agent. This model may also be useful for testing the efficacy of different contrast agents in a preclinical setting. PMID:21357555

Immediate reactions following iodinated contrast media injection: a study of 38 cases.

PubMed

Dewachter, Pascale; Laroche, Dominique; Mouton-Faivre, Claudie; Bloch-Morot, Evelyne; Cercueil, Jean-Pierre; Metge, Liliane; Carette, Marie-France; Vergnaud, Marie-Claude; Clément, Olivier

2011-03-01

To investigate the pathomechanisms involved in cases of immediate hypersensitivity reactions occurring after the administration of iodinated contrast media. Patients having presented clinical signs of immediate hypersensitivity suggesting allergy after iodinated contrast medium were investigated. Histamine and tryptase concentrations were measured, and/or skin tests were performed. Patients with positive skin tests to the culprit contrast agent were classified as IgE-mediated allergic hypersensitivity (Group I) and patients with negative skin tests as non-allergic hypersensitivity (Group II). 38 patients were included. Most reactions appeared after non-ionic (n = 32). Reactions were more frequently severe following ionic than non-ionic (p = 0.014). Skin testing was not performed in 11 patients. Skin tests with the culprit contrast agent were negative in 26% of the patients (Group II, n = 7) whereas they were found positive with the contrast agent in 73% of the patients (Group I, n = 19). Latex-induced reaction was diagnosed in one patient, and was consequently excluded from the cohort. In Group I, the frequency of cross-reactivity with the other commercialized iodinated contrast media was low (7%). Cardiovascular signs were present in Group I (52.6%, n = 10), and absent in Group II (p = 0.023). Histamine and tryptase concentrations were higher in patients who had cardiovascular signs (p < 0.02). Immediate reactions with clinical signs suggesting allergy along with positive skin tests with the administered contrast agent confirm immediate allergic hypersensitivity (anaphylaxis) to this agent. Consequently, the culprit contrast agent should be definitely avoided as well as cross-reactive ICM in order to prevent further recurrences. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2016-01-01

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

Comparison of Different Contrast Agents in Detecting Cardiac Right-to-Left Shunt in Patients with a Patent Foramen Ovale during Contrast-Transthoracic Echocardiography

PubMed Central

Zhao, Enfa; Cheng, Gesheng; Wang, Yingli

2017-01-01

The aim of this study is to evaluate the ability of two different contrast agents to detect cardiac right-to-left shunting in patients with a patent foramen ovale during contrast transthoracic echocardiography and transesophageal echocardiography. Eighty-four patients who had migraines or experienced cryptogenic stroke were prospectively enrolled. Contrast echocardiography of the right portion of the heart was performed using an injection of either (i) 8 ml of agitated saline, 1 ml of blood, and 1 ml of air (ASB) or (ii) 4 ml of vitamin B6 and 6 ml of sodium bicarbonate solution (VSBS). All patients underwent contrast echocardiography with different contrast agents successively before undergoing transesophageal echocardiography. The diagnostic sensitivity of VSBS and ASB for cardiac shunting diagnosis was 94.23% and 78.85%, respectively. The diagnostic sensitivity in the VSBS group was significantly higher than that in the ASB group (χ2 = 5.283, P = 0.022). The observed semiquantitative shunt grading suggests that the positive rate in the VSBS group was higher than that in the ASB group (Z = −1.998, P = 0.046). The use of vitamin B6 and sodium bicarbonate solution as a TTE contrast agent yielded a high sensitivity compared with ASB. However, further trials with large sample size are required to confirm this finding. PMID:29333447

Vena Cava 3D Contrast-Enhanced MR Venography: A Pictorial Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin Jiang; Zhou Kangrong; Chen Zuwang

Three-dimensional contrast-enhanced magnetic resonance venography (CE MRV) is a sensitive and accurate method for diagnosing vena cava pathologies. The commonly used indirect approach involves a nondiluted gadolinium contrast agent injected into an upper limb vein or, occasionally, a pedal vein for assessment of the superior or inferior vena cava. In our studies, a coronal 3D fast multi-planar spoiled gradient-echo acquisition was used. A pre-contrast scan was obtained to ensure correct coverage of the region of interest. We initiated contrast-enhanced acquisition 15 sec after the start of contrast agent injection and performed the procedure twice. The image sets were obtained duringmore » two 20-30-sec breath hold, with a breathing rest of 5-6 sec, to obtain the first-pass and delayed arteriovenous phases. For patients with Budd-Chiari syndrome, a third acquisition coinciding with late venous phase was collected to visualize the hepatic veins, which was carried out by one additional acquisition after a 5-6-sec breathing time. This review describes the clinical application of 3D CE MRV in vena cava congenital anomalies, superior and inferior vena cava syndrome, Budd-Chiari syndrome, peripheral vein thrombosis extending to the vena cava, pre-operational evaluation in portosystemic shunting and post-surgical follow-up, and road-mapping for the placement and evaluation of complications of central venous devices.« less

Contrast-enhanced endoscopic ultrasonography in digestive diseases.

PubMed

Hirooka, Yoshiki; Itoh, Akihiro; Kawashima, Hiroki; Ohno, Eizaburo; Itoh, Yuya; Nakamura, Yosuke; Hiramatsu, Takeshi; Sugimoto, Hiroyuki; Sumi, Hajime; Hayashi, Daijiro; Ohmiya, Naoki; Miyahara, Ryoji; Nakamura, Masanao; Funasaka, Kohei; Ishigami, Masatoshi; Katano, Yoshiaki; Goto, Hidemi

2012-10-01

Contrast-enhanced endoscopic ultrasonography (CE-EUS) was introduced in the early 1990s. The concept of the injection of carbon dioxide microbubbles into the hepatic artery as a contrast material (enhanced ultrasonography) led to "endoscopic ultrasonographic angiography". After the arrival of the first-generation contrast agent, high-frequency (12 MHz) EUS brought about the enhancement of EUS images in the diagnosis of pancreatico-biliary diseases, upper gastrointestinal (GI) cancer, and submucosal tumors. The electronic scanning endosonoscope with both radial and linear probes enabled the use of high-end ultrasound machines and depicted the enhancement of both color/power Doppler flow-based imaging and harmonic-based imaging using second-generation contrast agents. Many reports have described the usefulness of the differential diagnosis of pancreatic diseases and other abdominal lesions. Quantitative evaluation of CE-EUS images was an objective method of diagnosis using the time-intensity curve (TIC), but it was limited to the region of interest. Recently developed Inflow Time Mapping™ can be generated from stored clips and used to display the pattern of signal enhancement with time after injection, offering temporal difference of contrast agents and improved tumor characterization. On the other hand, three-dimensional CE-EUS images added new information to the literature, but lacked positional information. Three-dimensional CE-EUS with accurate positional information is awaited. To date, most reports have been related to pancreatic lesions or lymph nodes. Hemodynamic analysis might be of use for diseases in other organs: upper GI cancer diagnosis, submucosal tumors, and biliary disorders, and it might also provide functional information. Studies of CE-EUS in diseases in many other organs will increase in the near future.

Tumor characterization in small animals using magnetic resonance-guided dynamic contrast enhanced diffuse optical tomography

NASA Astrophysics Data System (ADS)

Lin, Yuting; Thayer, Dave; Nalcioglu, Orhan; Gulsen, Gultekin

2011-10-01

We present a magnetic resonance (MR)-guided near-infrared dynamic contrast enhanced diffuse optical tomography (DCE-DOT) system for characterization of tumors using an optical contrast agent (ICG) and a MR contrast agent [Gd-diethylenetriaminepentaacetic acid (DTPA)] in a rat model. Both ICG and Gd-DTPA are injected and monitored simultaneously using a combined MRI-DOT system, resulting in accurate co-registration between two imaging modalities. Fisher rats bearing R3230 breast tumor are imaged using this hybrid system. For the first time, enhancement kinetics of the exogenous contrast ICG is recovered from the DCE-DOT data using MR anatomical a priori information. As tumors grow, they undergo necrosis and the tissue transforms from viable to necrotic. The results show that the physiological changes between viable and necrotic tissue can be differentiated more accurately based on the ICG enhancement kinetics when MR anatomical information is utilized.

Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?

PubMed

De Stasio, Gelsomina; Rajesh, Deepika; Casalbore, Patrizia; Daniels, Matthew J; Erhardt, Robert J; Frazer, Bradley H; Wiese, Lisa M; Richter, Katherine L; Sonderegger, Brandon R; Gilbert, Benjamin; Schaub, Sebastien; Cannara, Rachel J; Crawford, John F; Gilles, Mary K; Tyliszczak, Tolek; Fowler, John F; Larocca, Luigi M; Howard, Steven P; Mercanti, Delio; Mehta, Minesh P; Pallini, Roberto

2005-06-01

Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific (157)Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents. Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0-72 hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA. In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA. Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.

Intratympanic Iodine Contrast Injection Diffuses Across the Round Window Membrane Allowing for Perilymphatic CT Volume Acquisition Imaging

PubMed Central

Abt, Nicholas B.; Lehar, Mohamed; Guajardo, Carolina Trevino; Penninger, Richard T.; Ward, Bryan K.; Pearl, Monica S.; Carey, John P.

2016-01-01

Hypothesis Whether the RWM is permeable to iodine-based contrast agents (IBCA) is unknown; therefore, our goal was to determine if IBCAs could diffuse through the RWM using CT volume acquisition imaging. Introduction Imaging of hydrops in the living human ear has attracted recent interest. Intratympanic (IT) injection has shown gadolinium's ability to diffuse through the round window membrane (RWM), enhancing the perilymphatic space. Methods Four unfixed human cadaver temporal bones underwent intratympanic IBCA injection using three sequentially studied methods. The first method was direct IT injection. The second method used direct RWM visualization via tympanomeatal flap for IBCA-soaked absorbable gelatin pledget placement. In the third method, the middle ear was filled with contrast after flap elevation. Volume acquisition CT images were obtained immediately post-exposure, and at 1, 6, and 24 hour intervals. Post-processing was accomplished using color ramping and subtraction imaging. Results Following the third method, positive RWM and perilymphatic enhancement were seen with endolymph sparing. Gray scale and color ramp multiplanar reconstructions displayed increased signal within the cochlea compared to pre-contrast imaging. The cochlea was measured for attenuation differences compared to pure water, revealing a pre-injection average of −1,103 HU and a post-injection average of 338 HU. Subtraction imaging shows enhancement remaining within the cochlear space, Eustachian tube, middle ear epithelial lining, and mastoid. Conclusions Iohexol iodine contrast is able to diffuse across the RWM. Volume acquisition CT imaging was able to detect perilymphatic enhancement at 0.5mm slice thickness. The clinical application of IBCA IT injection appears promising but requires further safety studies. PMID:26859543

Preliminary Results on Different Impedance Contrast Agents for Pulmonary Perfusion Imaging with Electrical Impedance Tomography

NASA Astrophysics Data System (ADS)

Nguyen, D. T.; Kosobrodov, R.; Barry, M. A.; Chik, W.; Pouliopoulos, J.; Oh, T. I.; Thiagalingam, A.; McEwan, A.

2013-04-01

Recent studies in animal models suggest that the use of small volume boluses of NaCl as an impedance contrast agent can significantly improve pulmonary perfusion imaging by Electrical Impedance Tomography (EIT). However, these studies used highly concentrated NaCl solution (20%) which may have adverse effects on the patients. In a pilot experiment, we address this problem by comparing a number of different Impedance Contrast Boluses (ICBs). Conductivity changes in the lungs of a sheep after the injection of four different ICBs were compared, including three NaCl-based ICBs and one glucose-based ICB. The following procedure was followed for each ICB. Firstly, ventilation was turned off to provide an apneic window of approximately 40s to image the conductivity changes due to the ICB. Each ICB was then injected through a pig-tail catheter directly into the right atrium. EIT images were acquired throughout the apnea to capture the conductivity change. For each ICB, the experiment was repeated three times. The three NaCl-based ICB exhibited similar behaviour in which following the injection of each of these ICBs, the conductivity of each lung predictably increased. The effect of the ICB of 5% glucose solution was inconclusive. A small decrease in conductivity in the left lung was observed in two out of three cases and none was discernible in the right lung.

Optoacoustic tomography in preclinical research: in vivo distribution of highly purified PEG-coated gold nanorods

NASA Astrophysics Data System (ADS)

Su, Richard; Liopo, Anton; Brecht, Hans-Peter; Ermilov, Sergey; Larin, Kirill; Oraevsky, Alexander A.

2011-07-01

We report on the optoacoustic (OA) imaging of the whole mouse body using a biocompatible contrast agent - highly purified, pegylated gold nanorods (GNR) - which has strong optical absorption in the near-infrared region and low level of toxicity. In vitro toxicity studies showed no significant change in survival rates of the cultured normal epithelium IEC-6 cells when incubated for 24 hours with up to 1 nM of GNR. In vivo toxicity studies in nude mice showed no pathological changes in liver 1 month after the IV injection of GNR with intra-body concentration around 0.25-0.50 nM. In order to study the enhancement of the OA contrast and accumulation of GNR in different tissues, we performed 3D OA imaging of live nude mice with IV-injected GNR. The enhancement of the OA contrast in comparison with the images of the untreated mice was visible starting 1 hour after the GNR injection. The OA contrast of kidneys, liver, and spleen peaked at about 2-3 days after the administration of the GNR, and then was gradually reducing.

Novel Approaches for Targeting Antiviral Agents in the Treatment of Arena-, Bunya-, Flavi-, and Retroviral

DTIC Science & Technology

1990-06-01

An additional group of mice was injected with Propionibacterium acnes (70 mg/kg) as a positive control. As illustrated in Table 5 no significant...macrophage cytotoxicity was observed in any of the groups. Macrophages from mice injected with P. acnes exhibited the expectected anti-tumor cytotoxic...peritoneal macrophages cytotoxic. In contrast P. acnes was highly effective. C.3.13 Peritoneal exudate cell phagocytosis following treatment with free or

Minimally Invasive Monitoring of Chronic Central Venous Catheter Patency in Mice Using Digital Subtraction Angiography (DSA)

PubMed Central

Figueiredo, Giovanna; Fiebig, Teresa; Kirschner, Stefanie; Nikoubashman, Omid; Kabelitz, Lisa; Othman, Ahmed; Nonn, Andrea; Kramer, Martin; Brockmann, Marc A.

2015-01-01

Background Repetitive administration of medication or contrast agents is frequently performed in mice. The introduction of vascular access mini-ports (VAMP) for mice allows long-term vascular catheterization, hereby eliminating the need for repeated vessel puncture. With catheter occlusion being the most commonly reported complication of chronic jugular vein catheterization, we tested whether digital subtraction angiography (DSA) can be utilized to evaluate VAMP patency in mice. Methods Twenty-three mice underwent catheterization of the jugular vein and subcutaneous implantation of a VAMP. The VAMP was flushed every second day with 50 μL of heparinized saline solution (25 IU/ml). DSA was performed during injection of 100 μL of an iodine based contrast agent using an industrial X-ray inspection system intraoperatively, as well as 7±2 and 14±2 days post implantation. Results DSA allowed localization of catheter tip position, to rule out dislocation, kinking or occlusion of a microcatheter, and to evaluate parent vessel patency. In addition, we observed different ante- and retrograde collateral flow patterns in case of jugular vein occlusion. More exactly, 30% of animals showed parent vessel occlusion after 7±2 days in our setting. At this time point, nevertheless, all VAMPs verified intravascular contrast administration. After 14±2 days, intravascular contrast injection was verified in 70% of the implanted VAMPs, whereas at this point of time 5 animals had died or were sacrificed and in 2 mice parent vessel occlusion hampered intravascular contrast injection. Notably, no occlusion of the catheter itself was observed. Conclusion From our observations we conclude DSA to be a fast and valuable minimally invasive tool for investigation of catheter and parent vessel patency and for anatomical studies of collateral blood flow in animals as small as mice. PMID:26098622

In vivo comparison of delayed gadolinium-enhanced MRI of cartilage and delayed quantitative CT arthrography in imaging of articular cartilage.

PubMed

Hirvasniemi, J; Kulmala, K A M; Lammentausta, E; Ojala, R; Lehenkari, P; Kamel, A; Jurvelin, J S; Töyräs, J; Nieminen, M T; Saarakkala, S

2013-03-01

To compare delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and delayed quantitative computed tomography (CT) arthrography (dQCTA) to each other, and their association to arthroscopy. Additionally, the relationship between dGEMRIC with intravenous (dGEMRIC(IV)) and intra-articular contrast agent administration (dGEMRIC(IA)) was determined. Eleven patients with knee pain were scanned at 3 T MRI and 64-slice CT before arthroscopy. dQCTA was performed at 5 and 45 min after intra-articular injection of ioxaglate. Both dGEMRIC(IV) and dGEMRIC(IA) were performed at 90 min after gadopentetate injection. dGEMRIC indices and change in relaxation rates (ΔR(1)) were separately calculated for dGEMRIC(IV) and dGEMRIC(IA). dGEMRIC and dQCTA parameters were calculated for predetermined sites at the knee joint that were International Cartilage Repair Society (ICRS) graded in arthroscopy. dQCTA normalized with the contrast agent concentration in synovial fluid (SF) and dGEMRIC(IV) correlated significantly, whereas dGEMRIC(IA) correlated with the normalized dQCTA only when dGEMRIC(IA) was also normalized with the contrast agent concentration in SF. Correlation was strongest between normalized dQCTA at 45 min and ΔR(1,IV) (r(s) = 0.72 [95% CI 0.56-0.83], n = 49, P < 0.01) and ΔR(1,IA) normalized with ΔR(1) in SF (r(s) = 0.70 [0.53-0.82], n = 52, P < 0.01). Neither dGEMRIC nor dQCTA correlated with arthroscopic grading. dGEMRIC(IV) and non-normalized dGEMRIC(IA) were not related while ΔR(1,IV) correlated with normalized ΔR(1,IA) (r(s) = 0.52 [0.28-0.70], n = 50, P < 0.01). This study suggests that dQCTA is in best agreement with dGEMRIC(IV) at 45 min after CT contrast agent injection. dQCTA and dGEMRIC were not related to arthroscopy, probably because the remaining cartilage is analysed in dGEMRIC and dQCTA, whereas in arthroscopy the absence of cartilage defines the grading. The findings indicate the importance to take into account the contrast agent concentration in SF in dQCTA and dGEMRIC(IA). Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Spin-lock imaging of exogenous exchange-based contrast agents to assess tissue pH.

PubMed

Zu, Zhongliang; Li, Hua; Jiang, Xiaoyu; Gore, John C

2018-01-01

Some X-ray contrast agents contain exchangeable protons that give rise to exchange-based effects on MRI, including chemical exchange saturation transfer (CEST). However, CEST has poor specificity to explicit exchange parameters. Spin-lock sequences at high field are also sensitive to chemical exchange. Here, we evaluate whether spin-locking techniques can detect the contrast agent iohexol in vivo after intravenous administration, and their potential for measuring changes in tissue pH. Two metrics of contrast based on R 1ρ , the spin lattice relaxation rate in the rotating frame, were derived from the behavior of R 1ρ at different locking fields. Solutions containing iohexol at different concentrations and pH were used to evaluate the ability of the two metrics to quantify exchange effects. Images were also acquired from rat brains bearing tumors before and after intravenous injections of iohexol to evaluate the potential of spin-lock techniques for detecting the agent and pH variations. The two metrics were found to depend separately on either agent concentration or pH. Spin-lock imaging may therefore provide specific quantification of iohexol concentration and the iohexol-water exchange rate, which reports on pH. Spin-lock techniques may be used to assess the dynamics of intravenous contrast agents and detect extracellular acidification. Magn Reson Med 79:298-305, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

EGFR-directed Affibody for fluorescence-guided glioma surgery: time-dose analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ribeiro de Souza, Ana Luiza; Marra, Kayla; Gunn, Jason R.; Elliott, Jonathan T.; Samkoe, Kimberley S.; Paulsen, Keith D.; Draney, Daniel R.; Feldwisch, Joachim

2016-03-01

The key to fluorescence guided surgical oncology is the ability to create specific contrast between normal and glioma tissue. The blood brain barrier that limits the delivery of substances to the normal brain is broken in tumors, allowing accumulation of agents in the tumor interior. However, for a clinical success, imaging agents should be in the infiltrative edges to minimize the resection of normal brain while enable the removal of tumor. The aberrant overexpression and/or activation of EGFR is associated with many types of cancers, including glioblastoma and the injection of a fluorescent molecule targeted to these receptors would improve tumor contrast during fluorescence guided surgery. Affibody molecules have intentional medium affinity and high potential specificity, which are the desirable features of a good surgical imaging agent. The aim of this study was evaluate the brain/glioma uptake of ABY029 labeled with near-infrared dye IRDye800CW after intravenous injection. Rats were either inoculated with orthotopic implantations of U251 human glioma cell line or PBS (shams control) in the brain. The tumors were allowed to grow for 2-3 weeks before carrying out fluorescent tracer experiments. Fluorescent imaging of ex vivo brain slices from rats was acquired at different time points after infection of fluorescently labeled EGFR-specific affibody to verify which time provided maximal contrast tumor to normal brain. Although the tumor was most clearly visualized after 1h of IRDye800CW-labeled ABY029 injection, the tumor location could be identified from the background after 48h. These results suggest that the NIR-labeled affibody examined shows excellent potential to increase surgical visualization for confirmed EGFR positive tumors.

Cytotoxic Effects of Nonionic Iodinated Contrast Agent on Human Adipose-derived Mesenchymal Stem Cells.

PubMed

Wu, Tao; Nie, Hai; Dietz, Allan B; Salek, David R; Smith, Jay; van Wijnen, Andre J; Qu, Wenchun

2018-05-31

Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections and the effects of these agents on MSCs represents a gap in knowledge. To investigate the biological effects of contrast media that are co-injected with MSCs. Prospective observational study. Academic medical center. Patient-derived clinical-grade culture expanded MSCs. Iohexol(Omnipaque300) was reduced to 12.5%, 25%, 50% and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate buffered saline (PBS) as control group. We examined cytotoxicity of Iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR) of related genes were analyzed immediately after exposure (day 0) and after two days of exposure (day 2). Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief 30min exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs. CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during mesenchymal stem cell therapy for disc degenerative diseases. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

In vivo photothermal optical coherence tomography of gold nanorods in the mouse eye (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lapierre-Landry, Maryse; Gordon, Andrew Y.; Penn, John S.; Skala, Melissa C.

2017-02-01

Optical coherence tomography (OCT) has become standard in retinal imaging at the pre-clinical and clinical level by allowing non-invasive, three-dimensional imaging of the tissue structure. However, OCT lacks specificity to contrast agents that could be used for in vivo molecular imaging. We have performed in vivo photothermal optical coherence tomography (PT-OCT) of targeted gold nanorods in the mouse retina after the mice were injected systemically with the contrast agent. To our knowledge, we are the first to perform PT-OCT in the eye and image targeted gold nanorods with this technology. As a model of age-related wet macular degeneration, lesions were induced by laser photocoagulation in each mouse retina (n=12 eyes). Untargeted and targeted (anti-mouse CD102 antibody, labeling neovasculature) gold nanorods (peak absorption λ=750nm) were injected intravenously by tail-vein injection five days after lesion induction, and imaged the same day with PT-OCT. Our instrument is a spectral domain OCT system (λ=860nm) with a Titanium:Sapphire laser (λ=750nm) added to the beam path using a 50:50 coupler to heat the gold nanorods. We acquired PT-OCT volumes of one lesion per mouse eye. There was a significant increase in photothermal intensity per unit area of the lesion in the targeted gold nanorods group versus the saline control group and the untargeted gold nanorods group. This experiment demonstrates the feasibility of PT-OCT to image the distribution of molecular contrast agents in the mouse retina, including in highly scattering lesions. In the future we will use this method to identify new biomarkers linked with retinal disease.

Patent foramen ovale: diagnosis with multidetector CT--comparison with transesophageal echocardiography.

PubMed

Kim, Young Jin; Hur, Jin; Shim, Chi-Young; Lee, Hye-Jeong; Ha, Jong-Won; Choe, Kyu Ok; Heo, Ji Hoe; Choi, Eui-Young; Choi, Byoung Wook

2009-01-01

To evaluate the clinical feasibility and accuracy of 64-section multidetector computed tomography (CT) compared with transesophageal echocardiography (TEE) for diagnosis of a patent foramen ovale (PFO). Institutional review board approval was obtained for this retrospective study. The study included 152 consecutive stroke patients (mean age, 61.7 years; 98 men, 54 women) who underwent both cardiac multidetector CT and TEE. Electrocardiographically gated cardiac CT was performed with a 64-section CT scanner by using a saline-chaser contrast agent injection technique. A contrast agent jet from the contrast agent-filled left atrium (LA) to the saline-filled right atrium (RA) and channel-like appearance of the interatrial septum (IAS) were evaluated on axial and oblique sagittal CT images. Two-dimensional and Doppler TEE were performed to detect PFO. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT were obtained with TEE as the reference standard. A PFO was present in 26 patients at TEE. On CT images, a left-to-right contrast agent jet toward the inferior vena cava was noted in 21 patients (sensitivity, 73.1%; specificity, 98.4%; PPV, 90.5%; NPV, 94.7%). Channel-like appearance of the IAS was detected in 38 patients (sensitivity, 76.9%; specificity, 85.7%; PPV, 52.6%; NPV, 94.7%). Channel-like appearance of the IAS was noted in all patients who had a contrast agent jet. A contrast agent jet from LA to RA toward the inferior vena cava with channel-like appearance of the IAS on CT images confirms the presence of a PFO. (c) RSNA, 2008.

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 magnetic resonance imaging. Experiments have already been performed with Yb-DTPA in animals, and it appears to have a lower toxicity than that of Gd-DTPA. Reported animal experiments with Gd-DOTA contrast agent show no toxicity at all.

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 was revealed by DCE-MRI using GDCC-40. The region of the tumor with suspicious uptake of GDCC-40 could be correlated to the residual tumor. With only minimum tissue accumulation, BMCA have applications in blood pool imaging, cancer diagnosis, and efficacy assessment of anticancer treatment. Therefore, BMCA are promising for clinical applications.

Comparison of first pass bolus AIFs extracted from sequential 18F-FDG PET and DSC-MRI of mice

NASA Astrophysics Data System (ADS)

Evans, Eleanor; Sawiak, Stephen J.; Ward, Alexander O.; Buonincontri, Guido; Hawkes, Robert C.; Adrian Carpenter, T.

2014-01-01

Accurate kinetic modelling of in vivo physiological function using positron emission tomography (PET) requires determination of the tracer time-activity curve in plasma, known as the arterial input function (AIF). The AIF is usually determined by invasive blood sampling methods, which are prohibitive in murine studies due to low total blood volumes. Extracting AIFs from PET images is also challenging due to large partial volume effects (PVE). We hypothesise that in combined PET with magnetic resonance imaging (PET/MR), a co-injected bolus of MR contrast agent and PET ligand can be tracked using fast MR acquisitions. This protocol would allow extraction of a MR AIF from MR contrast agent concentration-time curves, at higher spatial and temporal resolution than an image-derived PET AIF. A conversion factor could then be applied to the MR AIF for use in PET kinetic analysis. This work has compared AIFs obtained from sequential DSC-MRI and PET with separate injections of gadolinium contrast agent and 18F-FDG respectively to ascertain the technique‧s validity. An automated voxel selection algorithm was employed to improve MR AIF reproducibility. We found that MR and PET AIFs displayed similar character in the first pass, confirmed by gamma variate fits (p<0.02). MR AIFs displayed reduced PVE compared to PET AIFs, indicating their potential use in PET/MR studies.

Comparison of first pass bolus AIFs extracted from sequential 18F-FDG PET and DSC-MRI of mice.

PubMed

Evans, Eleanor; Sawiak, Stephen J; Ward, Alexander O; Buonincontri, Guido; Hawkes, Robert C; Carpenter, T Adrian

2014-01-11

Accurate kinetic modelling of in vivo physiological function using positron emission tomography (PET) requires determination of the tracer time-activity curve in plasma, known as the arterial input function (AIF). The AIF is usually determined by invasive blood sampling methods, which are prohibitive in murine studies due to low total blood volumes. Extracting AIFs from PET images is also challenging due to large partial volume effects (PVE). We hypothesise that in combined PET with magnetic resonance imaging (PET/MR), a co-injected bolus of MR contrast agent and PET ligand can be tracked using fast MR acquisitions. This protocol would allow extraction of a MR AIF from MR contrast agent concentration-time curves, at higher spatial and temporal resolution than an image-derived PET AIF. A conversion factor could then be applied to the MR AIF for use in PET kinetic analysis. This work has compared AIFs obtained from sequential DSC-MRI and PET with separate injections of gadolinium contrast agent and 18 F-FDG respectively to ascertain the technique's validity. An automated voxel selection algorithm was employed to improve MR AIF reproducibility. We found that MR and PET AIFs displayed similar character in the first pass, confirmed by gamma variate fits (p<0.02). MR AIFs displayed reduced PVE compared to PET AIFs, indicating their potential use in PET/MR studies.

Comparison of effects of isotonic sodium chloride with diltiazem in prevention of contrast-induced nephropathy.

PubMed

Beyazal, Hatice; Caliskan, Zuhal; Utaç, Cengiz

2014-04-01

Contrast-induced nephropathy (CIN) significantly increases the morbidity and mortality of patients. The aim of this study is to investigate and compare the protective effects of isotonic sodium chloride with sodium bicarbonate infusion and isotonic sodium chloride infusion with diltiazem, a calcium channel blocker, in preventing CIN. Our study included patients who were administered 30-60 mL of iodinated contrast agent for percutaneous coronary angiography (PCAG), all with creatinine values between 1.1 and 3.1 mg/dL. Patients were divided into three groups and each group had 20 patients. The first group of patients was administered isotonic sodium chloride; the second group was administered a solution that of 5% dextrose and sodium bicarbonate, while the third group was administered isotonic sodium chloride before and after the contrast injection. The third group received an additional injection of diltiazem the day before and first 2 days after the contrast injection. All of the patients' plasma blood urea nitrogen (BUN) and creatinine levels were measured on the second and seventh day after the administration of intravenous contrast material. The basal creatinine levels were similar for all three groups (p > 0.05). Among a total of 60 patients included in the study, 16 patients developed acute renal failure (ARF) on the second day after contrast material was injected (26.6%). The number of patients who developed ARF on the second day after the injection in the first group was five (25%), in the second group was six (30%) and the third group was five (25%) (p > 0.05). There was no significant difference between isotonic sodium chloride, sodium bicarbonate and isotonic sodium chloride with diltiazem application in prevention of CIN.

A theranostic dental pulp capping agent with improved MRI and CT contrast and biological properties.

PubMed

Mastrogiacomo, S; Güvener, N; Dou, W; Alghamdi, H S; Camargo, W A; Cremers, J G O; Borm, P J A; Heerschap, A; Oosterwijk, E; Jansen, J A; Walboomers, X F

2017-10-15

Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by µCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications. In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a theranostic pulp capping material have been developed and tested in an in vivo animal model. Our promising results in term of imaging contrast enhancement and of induction of new dentin formation, open a new scenario in the development of innovative dental materials. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

High-resolution motion compensated MRA in patients with congenital heart disease using extracellular contrast agent at 3 Tesla.

PubMed

Dabir, Darius; Naehle, Claas Philip; Clauberg, Ralf; Gieseke, Juergen; Schild, Hans H; Thomas, Daniel

2012-10-29

Using first-pass MRA (FP-MRA) spatial resolution is limited by breath-hold duration. In addition, image quality may be hampered by respiratory and cardiac motion artefacts. In order to overcome these limitations an ECG- and navigator-gated high-resolution-MRA sequence (HR-MRA) with slow infusion of extracellular contrast agent was implemented at 3 Tesla for the assessment of congenital heart disease and compared to standard first-pass-MRA (FP-MRA). 34 patients (median age: 13 years) with congenital heart disease (CHD) were prospectively examined on a 3 Tesla system. The CMR-protocol comprised functional imaging, FP- and HR-MRA, and viability imaging. After the acquisition of the FP-MRA sequence using a single dose of extracellular contrast agent the motion compensated HR-MRA sequence with isotropic resolution was acquired while injecting the second single dose, utilizing the timeframe before viability imaging. Qualitative scores for image quality (two independent reviewers) as well as quantitative measurements of vessel sharpness and relative contrast were compared using the Wilcoxon signed-rank test. Quantitative measurements of vessel diameters were compared using the Bland-Altman test. The mean image quality score revealed significantly better image quality of the HR-MRA sequence compared to the FP-MRA sequence in all vessels of interest (ascending aorta (AA), left pulmonary artery (LPA), left superior pulmonary vein (LSPV), coronary sinus (CS), and coronary ostia (CO); all p < 0.0001). In comparison to FP-MRA, HR-MRA revealed significantly better vessel sharpness for all considered vessels (AA, LSPV and LPA; all p < 0.0001). The relative contrast of the HR-MRA sequence was less compared to the FP-MRA sequence (AA: p <0.028, main pulmonary artery: p <0.004, LSPV: p <0.005). Both, the results of the intra- and interobserver measurements of the vessel diameters revealed closer correlation and closer 95 % limits of agreement for the HR-MRA. HR-MRA revealed one additional clinical finding, missed by FP-MRA. An ECG- and navigator-gated HR-MRA-protocol with infusion of extracellular contrast agent at 3 Tesla is feasible. HR-MRA delivers significantly better image quality and vessel sharpness compared to FP-MRA. It may be integrated into a standard CMR-protocol for patients with CHD without the need for additional contrast agent injection and without any additional examination time.

Phase contrast imaging of preclinical portal vein embolization with CO2 microbubbles.

PubMed

Tang, Rongbiao; Yan, Fuhua; Yang, Guo Yuan; Chen, Ke Min

2017-11-01

Preoperative portal vein embolization (PVE) is employed clinically to avoid postoperative liver insufficiency. Animal models are usually used to study PVE in terms of mechanisms and pathophysiological changes. PVE is formerly monitored by conventional absorption contrast imaging (ACI) with iodine contrast agent. However, the side effects induced by iodine can give rise to animal damage and death. In this study, the feasibility of using phase contrast imaging (PCI) to show PVE using homemade CO 2 microbubbles in living rats has been investigated. CO 2 gas was first formed from the reaction between citric acid and sodium bicarbonate. The CO 2 gas was then encapsulated by egg white to fabricate CO 2 microbubbles. ACI and PCI of CO 2 microbubbles were performed and compared in vitro. An additional increase in contrast was detected in PCI. PCI showed that CO 2 microbubbles gradually dissolved over time, and the remaining CO 2 microbubbles became larger. By PCI, the CO 2 microbubbles were found to have certain stability, suggesting their potential use as embolic agents. CO 2 microbubbles were injected into the main portal trunk to perform PVE in living rats. PCI exploited the differences in the refractive index and facilitated clear visualization of the PVE after the injection of CO 2 microbubbles. Findings from this study suggest that homemade CO 2 microbubbles-based PCI is a novel modality for preclinical PVE research.

Optimization of image quality in pulmonary CT angiography with low dose of contrast material

NASA Astrophysics Data System (ADS)

Assi, Abed Al Nasser; Abu Arra, Ali

2017-06-01

Aim: The aim of this study was to compare objective image quality data for patient pulmonary embolism between a conventional pulmonary CTA protocol with respect to a novel acquisition protocol performed with optimize radiation dose and less amount of iodinated contrast medium injected to the patients during PE scanning. Materials and Methods: Sixty- four patients with Pulmonary Embolism (PE) possibility, were examined using angio-CT protocol. Patients were randomly assigned to two groups: A (16 women and 16 men, with age ranging from 19-89 years) mean age, 62 years with standard deviation 16; range, 19-89 years) - injected contrast agent: 35-40 ml. B (16 women and 16 men, with age ranging from 28-86 years) - injected contrast agent: 70-80 ml. Other scanning parameters were kept constant. Pulmonary vessel enhancement and image noise were quantified; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Subjective vessel contrast was assessed by two radiologists in consensus. Result: A total of 14 cases of PE (22 %) were found in the evaluated of subjects (nine in group A, and five in group B). All PE cases were detected by the two readers. There was no significant difference in the size or location of the PEs between the two groups, the average image noise was 14 HU for group A and 19 HU for group B. The difference was not statistically significant (p = 0.09). Overall, the SNR and CNR were slightly higher on group B (24.4 and 22.5 respectively) compared with group A (19.4 and 16.4 respectively), but those differences were not statistically significant (p = 0.71 and p = 0.35, respectively). Conclusion and Discussion: Both groups that had been evaluated by pulmonary CTA protocol allow similar image quality to be achieved as compared with each other's, with optimize care dose for both protocol and contrast volume were reduced by 50 % in new protocol comparing to the conventional protocol.

X-ray computed tomography imaging of a tumor with high sensitivity using gold nanoparticles conjugated to a cancer-specific antibody via polyethylene glycol chains on their surface

NASA Astrophysics Data System (ADS)

Nakagawa, Tomohiko; Gonda, Kohsuke; Kamei, Takashi; Cong, Liman; Hamada, Yoh; Kitamura, Narufumi; Tada, Hiroshi; Ishida, Takanori; Aimiya, Takuji; Furusawa, Naoko; Nakano, Yasushi; Ohuchi, Noriaki

2016-01-01

Contrast agents are often used to enhance the contrast of X-ray computed tomography (CT) imaging of tumors to improve diagnostic accuracy. However, because the iodine-based contrast agents currently used in hospitals are of low molecular weight, the agent is rapidly excreted from the kidney or moves to extravascular tissues through the capillary vessels, depending on its concentration gradient. This leads to nonspecific enhancement of contrast images for tissues. Here, we created gold (Au) nanoparticles as a new contrast agent to specifically image tumors with CT using an enhanced permeability and retention (EPR) effect. Au has a higher X-ray absorption coefficient than does iodine. Au nanoparticles were supported with polyethylene glycol (PEG) chains on their surface to increase the blood retention and were conjugated with a cancer-specific antibody via terminal PEG chains. The developed Au nanoparticles were injected into tumor-bearing mice, and the distribution of Au was examined with CT imaging, transmission electron microscopy, and elemental analysis using inductively coupled plasma optical emission spectrometry. The results show that specific localization of the developed Au nanoparticles in the tumor is affected by a slight difference in particle size and enhanced by the conjugation of a specific antibody against the tumor.

Tc-99m Labeled carrier for imaging

DOEpatents

Henze, Eberhard

1984-01-01

Novel radionuclide imaging agents, having particular application for lymphangiography are provided by non-covalently binding Tc-99m to a pharmaceutically acceptable cross-linked polysaccharide. Upon injection of the Tc-99m labeled polysaccharide into the blood stream, optimum contrast can be obtained within one hour.

Ultra-high-field (9.4 T) MRI Analysis of Contrast Agent Transport Across the Blood-Perilymph Barrier and Intrastrial Fluid-Blood Barrier in the Mouse Inner Ear.

PubMed

Counter, S Allen; Nikkhou-Aski, Sahar; Damberg, Peter; Berglin, Cecilia Engmér; Laurell, Göran

2017-08-01

Effective paramagnetic contrast agent for the penetration of the perilymphatic spaces of the scala tympani, scala vestibuli, and scala media of the mouse inner ear can be determined using intravenous injection of various gadolinium (Gd) complexes and ultra-high-field magnetic resonance imaging (MRI) at 9.4 Tesla. A number of contrast agents have been explored in experimental high-field MRI to determine the most effective Gd complex for ideal signal-to-noise ratio and maximal visualization of the in vivo mammalian inner ear in analyzing the temporal and spatial parameters involved in drug penetration of the blood-perilymph barrier and intrastrial fluid-blood barrier in the mouse model using MRI. Gadoteric acid (Dotarem), Gadobutrol (Gadovist), Gadodiamide (Omniscan), Gadopent acid (Magnevist), and Mangafodipir (Teslascan) were administered intravenously using the tail vein of 60 Balb/C mice. High-resolution T1 images of drug penetration were acquired with a horizontal 9.4 T Agilent magnet after intravenously injection. Signal intensity was used as a metric of temporal and spatial parameters of drug delivery and penetration of the perilymphatic and endolymphatic spaces. ANOVA analysis of the area under the curve of intensity enhancement in perilymph revealed a significant difference (p < 0.05) in the scalae uptake using different contrast agents (F (3,25) = 3.54, p = 0.029). The Gadoteric acid complex Dotarem was found to be the most effective Gd compound in terms of rapid, morphological enhancement for analysis of the temporal, and spatial distribution in the perilymphatic space of the inner ear. Gadoteric acid (Dotarem) demonstrated efficacy as a contrast agent for enhanced visualization of the perilymphatic spaces of the inner ear labyrinthine in the mouse, including the scala tympani and scala vestibuli of the cochlea, and the semicircular canals of the vestibular apparatus. These findings may inform the clinical application of Gd compounds in patients with inner ear fluid disorders and vertigo.

Photoacoustic contrast imaging of biological tissues with nanodiamonds fabricated for high near-infrared absorbance

PubMed Central

Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Su, Long-Jyun; Ren, Shenqiang; Chang, Huan-Cheng; Yang, Xinmai

2013-01-01

Abstract. Radiation-damaged nanodiamonds (DNDs) are potentially ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their low toxicity and high optical absorbance. PA imaging contrast agents have been limited to quantum dots and gold particles, since most existing carbon-based nanoparticles, including fluorescent nanodiamonds, do not have sufficient optical absorption in the near-infrared (NIR) range. A new DND by He+ ion beam irradiation with very high NIR absorption was synthesized. These DNDs produced a 71-fold higher PA signal on a molar basis than similarly dimensioned gold nanorods, and 7.1 fmol of DNDs injected into rodents could be clearly imaged 3 mm below the skin surface with PA signal enhancement of 567% using an 820-nm laser wavelength. PMID:23400417

US appearance of partial-thickness supraspinatus tendon tears: Application of the string theory. Pictorial essay.

PubMed

Guerini, H; Fermand, M; Godefroy, D; Feydy, A; Chevrot, A; Morvan, G; Gault, N; Drapé, J L

2012-02-01

The supraspinatus tendon is composed of 5 different layers consisting of intertwining bundles. On a front portion of the tendon, the layers become coated bundles which insert on the trochanter. At the insertion, the superficial or bursal surface of the tendon corresponding to the tendon fibers in contact with the subacromial bursa can be distinguished from the deep surface corresponding to the fibers in contact with the glenohumeral joint. A tendon tear may involve partial or total disruption of the tendon fibers and is called full-thickness tear if it affects the entire tendon, and partial-thickness tear if it involves only part of the tendon. Partial-thickness tears of the supraspinatus tendon include lesions of the superficial, deep and central surface or tendon delamination.A contrast enhanced examination requires injection of contrast agent into the joint (arthrography followed by computed tomography (CT) or magnetic resonance imaging (MRI)) to study the deep surface, and injection into the subacromial bursa (bursography followed by CT) to study the superficial surface. MRI and ultrasound (US) examination allow the study of these different tendon layers without the use of contrast agent (which is not possible at CT).

Carbon Dioxide Angiography: Scientific Principles and Practice

PubMed Central

Cho, Kyung Jae

2015-01-01

Carbon dioxide (CO2) is a colorless, odorless gas which occurs naturally in the atmosphere and human body. With the advent of digital subtraction angiography, the gas has been used as a safe and useful alternative contrast agent in both arteriography and venography. Because of its lack of renal toxicity and allergic potential, CO2 is a preferred contrast agent in patients with renal failure or contrast allergy, and particularly in patients who require large volumes of contrast medium for complex endovascular procedures. Understanding of the unique physical properties of CO2 (high solubility, low viscosity, buoyancy, and compressibility) is essential in obtaining a successful CO2 angiogram and in guiding endovascular intervention. Unlike iodinated contrast material, CO2 displaces the blood and produces a negative contrast for digital subtraction imaging. Indications for use of CO2 as a contrast agent include: aortography and runoff, detection of bleeding, renal transplant arteriography, portal vein visualization with wedged hepatic venous injection, venography, arterial and venous interventions, and endovascular aneurysm repair. CO2 should not be used in the thoracic aorta, the coronary artery, and cerebral circulation. Exploitation of CO2 properties, avoidance of air contamination and facile catheterization technique are important to the safe and effective performance of CO2 angiography and CO2-guided endovascular intervention. PMID:26509137

Dual-contrast agent photon-counting computed tomography of the heart: initial experience.

PubMed

Symons, Rolf; Cork, Tyler E; Lakshmanan, Manu N; Evers, Robert; Davies-Venn, Cynthia; Rice, Kelly A; Thomas, Marvin L; Liu, Chia-Ying; Kappler, Steffen; Ulzheimer, Stefan; Sandfort, Veit; Bluemke, David A; Pourmorteza, Amir

2017-08-01

To determine the feasibility of dual-contrast agent imaging of the heart using photon-counting detector (PCD) computed tomography (CT) to simultaneously assess both first-pass and late enhancement of the myocardium. An occlusion-reperfusion canine model of myocardial infarction was used. Gadolinium-based contrast was injected 10 min prior to PCD CT. Iodinated contrast was infused immediately prior to PCD CT, thus capturing late gadolinium enhancement as well as first-pass iodine enhancement. Gadolinium and iodine maps were calculated using a linear material decomposition technique and compared to single-energy (conventional) images. PCD images were compared to in vivo and ex vivo magnetic resonance imaging (MRI) and histology. For infarct versus remote myocardium, contrast-to-noise ratio (CNR) was maximal on late enhancement gadolinium maps (CNR 9.0 ± 0.8, 6.6 ± 0.7, and 0.4 ± 0.4, p < 0.001 for gadolinium maps, single-energy images, and iodine maps, respectively). For infarct versus blood pool, CNR was maximum for iodine maps (CNR 11.8 ± 1.3, 3.8 ± 1.0, and 1.3 ± 0.4, p < 0.001 for iodine maps, gadolinium maps, and single-energy images, respectively). Combined first-pass iodine and late gadolinium maps allowed quantitative separation of blood pool, scar, and remote myocardium. MRI and histology analysis confirmed accurate PCD CT delineation of scar. Simultaneous multi-contrast agent cardiac imaging is feasible with photon-counting detector CT. These initial proof-of-concept results may provide incentives to develop new k-edge contrast agents, to investigate possible interactions between multiple simultaneously administered contrast agents, and to ultimately bring them to clinical practice.

In vivo transport of Gd-DTPA2- into human meniscus and cartilage assessed with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC)

PubMed Central

2014-01-01

Background Impaired stability is a risk factor in knee osteoarthritis (OA), where the whole joint and not only the joint cartilage is affected. The meniscus provides joint stability and is involved in the early pathological progress of OA. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been used to identify pre-radiographic changes in the cartilage in OA, but has been used less commonly to examine the meniscus, and then using only a double dose of the contrast agent. The purpose of this study was to enable improved early OA diagnosis by investigate the temporal contrast agent distribution in the meniscus and femoral cartilage simultaneously, in healthy volunteers, using 3D dGEMRIC at two different doses of the contrast agent Gd-DTPA2-. Methods The right knee in 12 asymptomatic volunteers was examined using a 3D Look-Locker sequence on two occasions after an intravenous injection of a double or triple dose of Gd-DTPA2- (0.2 or 0.3 mmol/kg body weight). The relaxation time (T1) and relaxation rate (R1 = 1/T1) were measured in the meniscus and femoral cartilage before, and 60, 90, 120 and 180 minutes after injection, and the change in relaxation rate (ΔR1) was calculated. Paired t-test and Analysis of Variance (ANOVA) were used for statistical evaluation. Results The triple dose yielded higher concentrations of Gd-DTPA2- in the meniscus and cartilage than the double dose, but provided no additional information. The observed patterns of ΔR1 were similar for double and triple doses of the contrast agent. ΔR1 was higher in the meniscus than in femoral cartilage in the corresponding compartments at all time points after injection. ΔR1 increased until 90-180 minutes in both the cartilage and the meniscus (p < 0.05), and was lower in the medial than in the lateral meniscus at all time points (p < 0.05). A faster increase in ΔR1 was observed in the vascularized peripheral region of the posterior medial meniscus, than in the avascular central part of the posterior medial meniscus during the first 60 minutes (p < 0.05). Conclusion It is feasible to examine undamaged meniscus and cartilage simultaneously using dGEMRIC, preferably 90 minutes after the injection of a double dose of Gd-DTPA2- (0.2 mmol/kg body weight). PMID:25005036

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.

Localizing Visual Function in the Brain

DTIC Science & Technology

1992-08-13

fec, 93-16707 FIELO GROUP SUB. GR. 9. AUSTRACT lCadouhn as en wierg if wcooemar end idenatfy 67 bloeS squoIbofD A three day meeting, held in Rochester...were unaware of using radiolabelled agents or optical imaging in macaque monkeys. This meeting introduced many scientists to other researchers and...paramagnetic contrast agent injected into a vein. The relative blood volume in a slice of the brain can thus be deduced, and changes in blood volume

Feasibility study of Fe3O4/TaO x nanoparticles as a radiosensitizer for proton therapy

NASA Astrophysics Data System (ADS)

Ahn, Sang Hee; Lee, Nohyun; Choi, Changhoon; Shin, Sung Won; Han, Youngyih; Park, Hee Chul

2018-06-01

We investigated the feasibility of using multifunctional Fe3O4/TaO x (core/shell) nanoparticles, developed for use in contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI), as dose-enhancing radiosensitizers. First, to verify the detectability of Fe3O4/TaO x nanoparticles in imaging, in vivo tests were conducted. Approximately 600 mg kg‑1 of 19 nm-diameter Fe3O4/TaO x nanoparticles dispersed in phosphate-buffered saline was injected into the tail vein of six Balb/c mice used as tumour (4T1 mammary carcinoma cell) models. Three mice underwent MRI (BioSpec 70/20 USR, Bruker, Billerica, MA, USA) and micro-CT (Inveon, Siemens Preclinical, Knoxville, TN, USA) before and after the injection. The difference between the pre- and post-injection images was quantified by finding the correlation coefficient. The aorta, blood vessel, and liver were clearly seen in the MRI and micro-CT images 60 min after intravenous injection of Fe3O4/TaO x nanoparticles, but the tumour region was not visible in the CT images until after 24 h. There were large differences between the pre- and post-injection images. Second, the therapeutic enhancement dose of nanomaterials was computed via Monte Carlo simulation. Monoenergetic 70- and 150 MeV proton beams irradiated x-ray contrast agent (iodine, BaSO4), MRI contrast agent (gadolinium, Fe3O4), Au, Fe3O4/TaO x (core/shell) nanoparticles and water located at the centre of a 4  ×  4  ×  4 µm3 water phantom, upon which the dose enhancement ratio (DER) (dose with/without nanoparticles) was computed. When 70 MeV protons irradiated the Au, gadolinium, Fe3O4/TaO x , Fe3O4, iodine, and BaSO4 nanoparticles, the DERs at 1 nm were 15.76, 7.68, 7.82, 6.17, 4.85, and 5.51, respectively. Fe3O4/TaO x nanoparticles have the potential to be used as a multifunctional agent that enhances tumour detection and increases the dose. Dose enhancement with Fe3O4/TaO x was half that with Au. However, Fe3O4/TaO x is much cheaper than Au, and it is expected that tumour targeting combined with magnetic field could overcome the low DER.

Feasibility study of Fe₃O₄/TaO_x nanoparticles as a radiosensitizer for proton therapy.

PubMed

Ahn, Sang Hee; Lee, Nohyun; Choi, Changhoon; Shin, Sung Won; Han, Youngyih; Park, Hee Chul

2018-05-04

We investigated the feasibility of using multifunctional Fe3O4/TaOx (core/shell) nanoparticles, developed for use in contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI), as dose-enhancing radiosensitizers. First, to verify the detectability of Fe3O4/TaOx nanoparticles in imaging, in vivo tests were conducted. Approximately 600 mg/kg of 19-nm-diameter Fe3O4/TaOx nanoparticles dispersed in phosphate-buffered saline was injected into the tail vein of six Balb/c mice used as tumour (4T1 mammary carcinoma cell) models. Three mice underwent MRI (BioSpec 70/20 USR, Bruker, Billerica, MA, USA) and micro-CT (Inveon, Siemens Preclinical, Knoxville, TN, USA) before and after the injection. The difference between the pre- and post-injection images was quantified by finding the correlation coefficient. The aorta, blood vessel, and liver were clearly seen in the MRI and micro-CT images 60 min after intravenous injection of Fe3O4/TaOx nanoparticles, but the tumour region was not visible in the CT images until after 24 h. There were large differences between the pre- and post-injection images. Second, the therapeutic enhancement dose of nanomaterials was computed via Monte Carlo simulation. Monoenergetic 70- and 150-MeV proton beams irradiated X-ray contrast agent (iodine, BaSO4) , MRI contrast agent (gadolinium, Fe3O4), Au, Fe3O4/TaOx (core/shell) nanoparticles and water located at the centre of a 4  4  4-μm3 water phantom, upon which the dose enhancement ratio (DER) (dose with/without nanoparticles) was computed. When 70-MeV protons irradiated the Au, gadolinium, Fe3O4/TaOx, Fe3O4, iodine, and BaSO4 nanoparticles, the DERs at 1 nm were 15.76, 7.68, 7.82, 6.17, 4.85, and 5.51, respectively. Fe3O4/TaOx nanoparticles have the potential to be used a multifunctional agent that enhances tumour detection and increases the dose. Dose enhancement with Fe3O4/TaOx was half that with Au. However, Fe3O4/TaOx is much cheaper than Au, and it is expected that tumour targeting combined with magnetic field could overcome the low DER. © 2018 Institute of Physics and Engineering in Medicine.

Differential effects of two MRI contrast agents on the integrity and distribution of rAAV2 and rAAV5 in the rat striatum

PubMed Central

Osting, Sue; Bennett, Antonette; Power, Shelby; Wackett, Jordan; Hurley, Samuel A; Alexander, Andrew L; Agbandje-Mckena, Mavis; Burger, Corinna

2014-01-01

Intraoperative magnetic resonance imaging (MRI) has been proposed as a method to optimize intracerebral targeting and for tracking infusate distribution in gene therapy trials for nervous system disorders. We thus investigated possible effects of two MRI contrast agents, gadoteridol (Gd) and galbumin (Gab), on the distribution and levels of transgene expression in the rat striatum and their effect on integrity and stability of recombinant adeno-associated virus (rAAV) particles. MRI studies showed that contrast agent distribution did not predict rAAV distribution. However, green fluorescent protein (GFP) immunoreactivity revealed an increase in distribution of rAAV5-GFP, but not rAAV2-GFP, in the presence of Gd when compared with viral vector injected alone. In contrast, Gab increased the distribution of rAAV2-GFP not rAAV5-GFP. These observations pointed to a direct effect of infused contrast agent on the rAAV particles. Negative-stain electron microscopy (EM), DNAase treatment, and differential scanning calorimetry (DSC) were used to monitor rAAV2 and rAAV5 particle integrity and stability following contrast agent incubation. EMs of rAAV2-GFP and rAAV5-GFP particles pretreated with Gd appear morphologically similar to the untreated sample; however, Gab treatment resulted in surface morphology changes and aggregation. A compromise of particle integrity was suggested by sensitivity of the packaged genome to DNAase treatment following Gab incubation but not Gd for both vectors. However, neither agent significantly affected particle stability when analyzed by DSC. An increase in Tm was observed for AAV2 in lactated Ringer’s buffer. These results thus highlight potential interactions between MRI contrast agents and AAV that might affect vector distribution and stability, as well as the stabilizing effect of lactated Ringer’s solution on AAV2. PMID:26015943

Macrophages mediated diagnosis of rheumatoid arthritis using fibrin based magnetic nanoparticles as MRI contrast agents.

PubMed

Periyathambi, Prabu; Sastry, Thotapalli Parvathaleswara; Anandasadagopan, Suresh Kumar; Manickavasagam, Kanagavel

2017-01-01

A variety of bioimaging tools assists in the diagnosis and evaluation of rheumatoid arthritis (RA) and other osteoarthritis. However, detection of RA in the early stages by targeting its macrophages with suitable contrast agents will help in arresting the progression of the disease. In the present study, we investigated the effectiveness of using magnetic fibrin nanoparticles (MFNPs) conjugated with folic acid (FA-MFNPs) as a specific contrast agent to target the activated macrophages, which overexpress the folate receptors (FR) in the knee joints of rats with antigen-induced arthritis (AIA). FA-MFNPs were spherical with an average size of 18.3±1.6nm. In vitro studies have shown effective internalization of FA-MFNPs into the Raw264.7 macrophage cells. In vivo studies were carried out by injecting FA-MFNPs intravenously into the arthritic rats. The results showed enhanced MR imaging in the synovium of arthritic joints. Prussian blue histological staining confirmed uptake of FA-MFNPs by macrophages in the synovial tissue. The animal experiment results indicate that FA-MFNPs can be used as a specific MRI contrast agent in identifying phagocytic active macrophages in the synovial joints. Blood is the precursor source for synthesising the fibrin-based iron oxide (magnetic) nanoparticles (MFNPs) with diameters between 12 and 15nm. It has excellent superparamagnetic behaviour, biocompatibility, osteogenic potency, hemocompatibility, and biodegradable properties. MFNPs-based nanocomposites might be a promising contrast agent for bioimaging. Copyright © 2016 Elsevier B.V. All rights reserved.

Grating-Based Phase-Contrast Imaging of Tumor Angiogenesis in Lung Metastases

PubMed Central

Li, Xiangting; Wang, Yujie; Ding, Bei; Shi, Chen; Liu, Huanhuan; Tang, Rongbiao; Sun, Jianqi; Yan, Fuhua; Zhang, Huan

2015-01-01

Purpose To assess the feasibility of the grating-based phase-contrast imaging (GPI) technique for studying tumor angiogenesis in nude BALB/c mice, without contrast agents. Methods We established lung metastatic models of human gastric cancer by injecting the moderately differentiated SGC-7901 gastric cancer cell line into the tail vein of nude mice. Samples were embedded in a 10% formalin suspension and dried before imaging. Grating-based X-ray phase-contrast images were obtained at the BL13W beamline of the Shanghai Synchrotron Radiation Facility (SSRF) and compared with histological sections. Results Without contrast agents, grating-based X-ray phase-contrast imaging still differentiated angiogenesis within metastatic tumors with high spatial resolution. Vessels, down to tens of microns, showed gray values that were distinctive from those of the surrounding tumors, which made them easily identifiable. The vessels depicted in the imaging study were similar to those identified on histopathology, both in size and shape. Conclusions Our preliminary study demonstrates that grating-based X-ray phase-contrast imaging has the potential to depict angiogenesis in lung metastases. PMID:25811626

Fluorine (19F) MRS and MRI in biomedicine

PubMed Central

Ruiz-Cabello, Jesús; Barnett, Brad P.; Bottomley, Paul A.; Bulte, Jeff W.M.

2011-01-01

Shortly after the introduction of 1H MRI, fluorinated molecules were tested as MR-detectable tracers or contrast agents. Many fluorinated compounds, which are nontoxic and chemically inert, are now being used in a broad range of biomedical applications, including anesthetics, chemotherapeutic agents, and molecules with high oxygen solubility for respiration and blood substitution. These compounds can be monitored by fluorine (19F) MRI and/or MRS, providing a noninvasive means to interrogate associated functions in biological systems. As a result of the lack of endogenous fluorine in living organisms, 19F MRI of ‘hotspots’ of targeted fluorinated contrast agents has recently opened up new research avenues in molecular and cellular imaging. This includes the specific targeting and imaging of cellular surface epitopes, as well as MRI cell tracking of endogenous macrophages, injected immune cells and stem cell transplants. PMID:20842758

Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PubMed

Radbruch, Alexander; Weberling, Lukas D; Kieslich, Pascal J; Hepp, Johanna; Kickingereder, Philipp; Wick, Wolfgang; Schlemmer, Heinz-Peter; Bendszus, Martin

2016-11-01

Recent studies reported an increase in the dentate nucleus (DN)-to-pons signal intensity (SI) ratio (DN-pons SI ratio) on unenhanced T1-weighted images in patients who received consecutive serial injections of linear gadolinium-based contrast agents (GBCAs). In contrast, most studies found no increase in the DN-pons SI ratio when patients were treated with consecutive serial injections of macrocyclic GBCAs. However, the potential difference between macrocyclic and linear GBCAs has never been assessed in individuals who received subsequent applications of both contrast agents. In this retrospective study, we assessed the evolution of the DN-pons SI ratio change in patients that were treated with a comparable number of serial consecutive injections of the linear GBCA gadopentetate dimeglumine and subsequent serial injections of the macrocyclic GBCAs gadobutrol and gadoterate meglumine. Data of 36 patients was analyzed. All patients underwent at least 5 consecutive administrations of the linear GBCA gadopentetate dimeglumine followed by an equal number of consecutive administrations of the macrocyclic GBCA gadobutrol. In 12 of the 36 patients, 5 or more final consecutive injections of the macrocyclic GBCA gadoterate meglumine were analyzed additionally. The difference of DN-pons SI ratios on unenhanced T1-weighted images was calculated by subtracting the ratio at the first examination from the ratio at the last examination in each of the 3 periods. The mean DN-pons SI ratio difference in the gadopentetate dimeglumine period was significantly greater than 0 (mean ± SD, 0.0448 ± 0.0345; P < 0.001), whereas the mean DN-pons SI ratio difference in the subsequent gadobutrol and gadoterate meglumine period was significantly smaller than 0 (gadobutrol: -0.0178 ± 0.0459, P = 0.026; gadoterate meglumine: -0.0250 ± 0.0284, P = 0.011). In this observational study, the application of the linear GBCA gadopentetate dimeglumine was associated with a DN-pons SI ratio increase, whereas subsequent applications of the macrocyclic GBCAs gadobutrol or gadoterate meglumine in the same patients were not. Rather, the current data tentatively suggest a decrease in preexisting hyperintensities over time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a washout effect or precipitation of gadolinium. Future patient studies need to include control groups to replicate the present results, and additional animal studies should be conducted to clarify the underlying mechanism of the proposed SI decrease.

Computational Fluid Dynamics modeling of contrast transport in basilar aneurysms following flow-altering surgeries.

PubMed

Vali, Alireza; Abla, Adib A; Lawton, Michael T; Saloner, David; Rayz, Vitaliy L

2017-01-04

In vivo measurement of blood velocity fields and flow descriptors remains challenging due to image artifacts and limited resolution of current imaging methods; however, in vivo imaging data can be used to inform and validate patient-specific computational fluid dynamics (CFD) models. Image-based CFD can be particularly useful for planning surgical interventions in complicated cases such as fusiform aneurysms of the basilar artery, where it is crucial to alter pathological hemodynamics while preserving flow to the distal vasculature. In this study, patient-specific CFD modeling was conducted for two basilar aneurysm patients considered for surgical treatment. In addition to velocity fields, transport of contrast agent was simulated for the preoperative and postoperative conditions using two approaches. The transport of a virtual contrast passively following the flow streamlines was simulated to predict post-surgical flow regions prone to thrombus deposition. In addition, the transport of a mixture of blood with an iodine-based contrast agent was modeled to compare and verify the CFD results with X-ray angiograms. The CFD-predicted patterns of contrast flow were qualitatively compared to in vivo X-ray angiograms acquired before and after the intervention. The results suggest that the mixture modeling approach, accounting for the flow rates and properties of the contrast injection, is in better agreement with the X-ray angiography data. The virtual contrast modeling assessed the residence time based on flow patterns unaffected by the injection procedure, which makes the virtual contrast modeling approach better suited for prediction of thrombus deposition, which is not limited to the peri-procedural state. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of obstructive jaundice on hepatic hemodynamics: use of Sonazoid-enhanced ultrasonography in a prospective study of the blood flow balance between the hepatic portal vein and hepatic artery.

PubMed

Wakui, Noritaka; Takeda, Yuki; Nishinakagawa, Shuta; Ueki, Nobuo; Otsuka, Takafumi; Oba, Nobuyuki; Hashimoto, Hiroshi; Kamiyama, Naohisa; Sumino, Yasukiyo; Kojima, Tatsuya

2015-10-01

To prospectively clarify the effects of obstructive jaundice (OJ) on hepatic hemodynamics using contrast-enhanced ultrasonography (US). Subjects comprised 14 patients admitted to our hospital for OJ between April 2013 and March 2014. Contrast-enhanced US was performed using the LOGIQ E9 ultrasound device during the jaundice phase, before biliary drainage, and again after improvement of jaundice. After injecting the Sonazoid contrast agent, contrast dynamics were recorded in the right kidney and liver segments 5 or 6. Prototype software was used to calculate mean arrival time (AT) of the contrast agent in the liver parenchyma. Statistical analysis was performed to compare the mean AT in the jaundice and improved jaundice phases. We were unable to follow up three of the 14 patients after biliary drainage; thus, we included 11 patients for further analysis. The mean AT of the contrast agent was 2.0 ± 1.8 and 6.1 ± 2.3 s in the jaundice and improved jaundice phases, respectively, showing significantly shorter AT in the jaundice phase (p = 0.0033). Our findings indicate that OJ may influence the blood flow balance between the hepatic portal vein and hepatic artery.

Fluorescence labeled microbubbles for multimodal imaging.

PubMed

Barrefelt, Åsa; Zhao, Ying; Larsson, Malin K; Egri, Gabriella; Kuiper, Raoul V; Hamm, Jörg; Saghafian, Maryam; Caidahl, Kenneth; Brismar, Torkel B; Aspelin, Peter; Heuchel, Rainer; Muhammed, Mamoun; Dähne, Lars; Hassan, Moustapha

2015-08-28

Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-μCT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer.

PubMed

Liu, Yongjun; Chen, Zhijin; Liu, Chunxi; Yu, Dexin; Lu, Zaijun; Zhang, Na

2011-08-01

Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially in the early stage of tumor. Here, we designed a novel multifunctional polymeric nanoparticle contrast agent (Anti-VEGF PLA-PEG-PLL-Gd NP) simultaneously modified with Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and anti-vascular endothelial growth factor (VEGF) antibody to deliver Gd-DTPA to the tumor area and achieve the early diagnosis of hepatocellular carcinoma (HCC). The Anti-VEGF PLA-PEG-PLL-Gd NPs exhibited high T(1) relaxivity and no obvious cytotoxicity under the experimental concentrations in human hepatocellular carcinoma (HepG2) cells. The results of in vitro cell uptake experiments demonstrated that the uptake process of NPs was both concentration and time depended. Compared with non-targeted NPs, the Anti-VEGF antibody modified NPs showed much higher cell uptake in the HepG2 cells. During in vivo studies, the targeted NPs showed significantly signal intensity enhancement at the tumor site (mouse hepatocarcinoma tumor, H22) compared with non-targeted NPs and Gd-DTPA injection in tumor-bearing mice and the imaging time was significantly prolonged from less than an hour (Gd-DTPA injection group) to 12 h. These results demonstrated that this novel MRI contrast agent Anti-VEGF PLA-PEG-PLL-Gd NPs showed great potential in the early diagnosis of liver tumors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Feasibility of contrast-enhanced ultrasound-guided biopsy of sentinel lymph nodes in dogs.

PubMed

Gelb, Hylton R; Freeman, Lynetta J; Rohleder, Jacob J; Snyder, Paul W

2010-01-01

Our goal was to develop and validate a technique to identify the sentinel lymph nodes of the mammary glands of healthy dogs with contrast-enhanced ultrasound, and evaluate the feasibility of obtaining representative samples of a sentinel lymph node under ultrasound guidance using a new biopsy device. Three healthy intact female adult hounds were anesthetized and each received an injection of octafluoropropane-filled lipid microspheres and a separate subcutaneous injection of methylene blue dye around a mammary gland. Ultrasound was then used to follow the contrast agent through the lymphatic channel to the sentinel lymph node. Lymph node biopsy was performed under ultrasound guidance, followed by an excisional biopsy of the lymph nodes and a regional mastectomy procedure. Excised tissues were submitted for histopathologic examination and evaluated as to whether they were representative of the node. The ultrasound contrast agent was easily visualized with ultrasound leading up to the sentinel lymph nodes. Eight normal lymph nodes (two inguinal, one axillary in two dogs; two inguinal in one dog) were identified and biopsied. Lymphoid tissue was obtained from all biopsy specimens. Samples from four of eight lymph nodes contained both cortical and medullary lymphoid tissue. Contrast-enhanced ultrasound can be successfully used to image and guide minimally invasive biopsy of the normal sentinel lymph nodes draining the mammary glands in healthy dogs. Further work is needed to evaluate whether this technique may be applicable in patients with breast cancer or other conditions warranting evaluation of sentinel lymph nodes in animals.

Contrast imaging in mouse embryos using high-frequency ultrasound.

PubMed

Denbeigh, Janet M; Nixon, Brian A; Puri, Mira C; Foster, F Stuart

2015-03-04

Ultrasound contrast-enhanced imaging can convey essential quantitative information regarding tissue vascularity and perfusion and, in targeted applications, facilitate the detection and measure of vascular biomarkers at the molecular level. Within the mouse embryo, this noninvasive technique may be used to uncover basic mechanisms underlying vascular development in the early mouse circulatory system and in genetic models of cardiovascular disease. The mouse embryo also presents as an excellent model for studying the adhesion of microbubbles to angiogenic targets (including vascular endothelial growth factor receptor 2 (VEGFR2) or αvβ3) and for assessing the quantitative nature of molecular ultrasound. We therefore developed a method to introduce ultrasound contrast agents into the vasculature of living, isolated embryos. This allows freedom in terms of injection control and positioning, reproducibility of the imaging plane without obstruction and motion, and simplified image analysis and quantification. Late gestational stage (embryonic day (E)16.6 and E17.5) murine embryos were isolated from the uterus, gently exteriorized from the yolk sac and microbubble contrast agents were injected into veins accessible on the chorionic surface of the placental disc. Nonlinear contrast ultrasound imaging was then employed to collect a number of basic perfusion parameters (peak enhancement, wash-in rate and time to peak) and quantify targeted microbubble binding in an endoglin mouse model. We show the successful circulation of microbubbles within living embryos and the utility of this approach in characterizing embryonic vasculature and microbubble behavior.

The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging

NASA Astrophysics Data System (ADS)

Xing, Zhanwen; Wang, Jinrui; Ke, Hengte; Zhao, Bo; Yue, Xiuli; Dai, Zhifei; Liu, Jibin

2010-04-01

Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

High-resolution motion compensated MRA in patients with congenital heart disease using extracellular contrast agent at 3 Tesla

PubMed Central

2012-01-01

Background Using first-pass MRA (FP-MRA) spatial resolution is limited by breath-hold duration. In addition, image quality may be hampered by respiratory and cardiac motion artefacts. In order to overcome these limitations an ECG- and navigator-gated high-resolution-MRA sequence (HR-MRA) with slow infusion of extracellular contrast agent was implemented at 3 Tesla for the assessment of congenital heart disease and compared to standard first-pass-MRA (FP-MRA). Methods 34 patients (median age: 13 years) with congenital heart disease (CHD) were prospectively examined on a 3 Tesla system. The CMR-protocol comprised functional imaging, FP- and HR-MRA, and viability imaging. After the acquisition of the FP-MRA sequence using a single dose of extracellular contrast agent the motion compensated HR-MRA sequence with isotropic resolution was acquired while injecting the second single dose, utilizing the timeframe before viability imaging. Qualitative scores for image quality (two independent reviewers) as well as quantitative measurements of vessel sharpness and relative contrast were compared using the Wilcoxon signed-rank test. Quantitative measurements of vessel diameters were compared using the Bland-Altman test. Results The mean image quality score revealed significantly better image quality of the HR-MRA sequence compared to the FP-MRA sequence in all vessels of interest (ascending aorta (AA), left pulmonary artery (LPA), left superior pulmonary vein (LSPV), coronary sinus (CS), and coronary ostia (CO); all p < 0.0001). In comparison to FP-MRA, HR-MRA revealed significantly better vessel sharpness for all considered vessels (AA, LSPV and LPA; all p < 0.0001). The relative contrast of the HR-MRA sequence was less compared to the FP-MRA sequence (AA: p <0.028, main pulmonary artery: p <0.004, LSPV: p <0.005). Both, the results of the intra- and interobserver measurements of the vessel diameters revealed closer correlation and closer 95 % limits of agreement for the HR-MRA. HR-MRA revealed one additional clinical finding, missed by FP-MRA. Conclusions An ECG- and navigator-gated HR-MRA-protocol with infusion of extracellular contrast agent at 3 Tesla is feasible. HR-MRA delivers significantly better image quality and vessel sharpness compared to FP-MRA. It may be integrated into a standard CMR-protocol for patients with CHD without the need for additional contrast agent injection and without any additional examination time. PMID:23107424

Transcranial functional ultrasound imaging of the brain using microbubble-enhanced ultrasensitive Doppler

PubMed Central

Errico, Claudia; Osmanski, Bruno-Félix; Pezet, Sophie; Couture, Olivier; Lenkei, Zsolt; Tanter, Mickael

2016-01-01

Functional ultrasound (fUS) is a novel neuroimaging technique, based on high-sensitivity ultrafast Doppler imaging of cerebral blood volume, capable of measuring brain activation and connectivity in rodents with high spatiotemporal resolution (100 μm, 1 ms). However, the skull attenuates acoustic waves, so fUS in rats currently requires craniotomy or a thinned-skull window. Here we propose a non-invasive approach by enhancing the fUS signal with a contrast agent, inert gas microbubbles. Plane-wave illumination of the brain at high frame rate (500 Hz compounded sequence with three tilted plane waves, PRF = 1500Hz with a 128 element 15 MHz linear transducer), yields highly-resolved neurovascular maps. We compared fUS imaging performance through the intact skull bone (transcranial fUS) versus a thinned-skull window in the same animal. First, we show that the vascular network of the adult rat brain can be imaged transcranially only after a bolus intravenous injection of microbubbles, which leads to a 9 dB gain in the contrast-to-tissue ratio. Next, we demonstrate that functional increase in the blood volume of the primary sensory cortex after targeted electrical-evoked stimulations of the sciatic nerve is observable transcranially in presence of contrast agents, with high reproducibility (Pearson's coefficient ρ = 0.7 ± 0.1, p = 0.85). Our work demonstrates that the combination of ultrafast Doppler imaging and injection of contrast agent allows non-invasive functional brain imaging through the intact skull bone in rats. These results should ease non-invasive longitudinal studies in rodents and open a promising perspective for the adoption of highly resolved fUS approaches for the adult human brain. PMID:26416649

Liposomes loaded with hydrophilic magnetite nanoparticles: Preparation and application as contrast agents for magnetic resonance imaging.

PubMed

German, S V; Navolokin, N A; Kuznetsova, N R; Zuev, V V; Inozemtseva, O A; Anis'kov, A A; Volkova, E K; Bucharskaya, A B; Maslyakova, G N; Fakhrullin, R F; Terentyuk, G S; Vodovozova, E L; Gorin, D A

2015-11-01

Magnetic fluid-loaded liposomes (MFLs) were fabricated using magnetite nanoparticles (MNPs) and natural phospholipids via the thin film hydration method followed by extrusion. The size distribution and composition of MFLs were studied using dynamic light scattering and spectrophotometry. The effective ranges of magnetite concentration in MNPs hydrosol and MFLs for contrasting at both T2 and T1 relaxation were determined. On T2 weighted images, the MFLs effectively increased the contrast if compared with MNPs hydrosol, while on T1 weighted images, MNPs hydrosol contrasting was more efficient than that of MFLs. In vivo magnetic resonance imaging (MRI) contrasting properties of MFLs and their effects on tumor and normal tissues morphology, were investigated in rats with transplanted renal cell carcinoma upon intratumoral administration of MFLs. No significant morphological changes in rat internal organs upon intratumoral injection of MFLs were detected, suggesting that the liposomes are relatively safe and can be used as the potential contrasting agents for MRI. Copyright © 2015 Elsevier B.V. All rights reserved.

Successful transfemoral aortic Edwards(®) SAPIEN(®) bioprosthesis implantation without using iodinated contrast media in a woman with severe allergy to contrast agent.

PubMed

Leroux, Lionel; Dijos, Marina; Dos Santos, Pierre

2013-12-01

Severe anaphylactoid reaction after the use of iodinated contrast media are rare but can contraindicate the use of contrast agent. It was the case of a 53-year-old woman suffering from symptomatic severe aortic stenosis, recused for cardiac surgery because of deleterious effects of chest-wall irradiation, with porcelain aorta. We decided to implant a 23-mm Edwards(®) SAPIEN(®) transcatheter aortic valve via a femoral route without using any contrast media. The implantation was successful after surgical approach of the femoral artery, transesophageal echocardiography guiding, and localization of native leaflets and coronary trunk with catheters. Immediate and one month post-interventional follow-up was favorable and echocardiography showed a good functioning of the aortic bioprosthesis. Although conventional angiography is the best way to visualize the good positioning of the valve before deployment, our case suggests that, in special situations, transfemoral implantation of an Edwards(®) SAPIEN(®) aortic bioprosthesis is feasible without any contrast injection. Copyright © 2012 Wiley Periodicals, Inc.

Multispectral photoacoustic decomposition with localized regularization for detecting targeted contrast agent

NASA Astrophysics Data System (ADS)

Tavakoli, Behnoosh; Chen, Ying; Guo, Xiaoyu; Kang, Hyun Jae; Pomper, Martin; Boctor, Emad M.

2015-03-01

Targeted contrast agents can improve the sensitivity of imaging systems for cancer detection and monitoring the treatment. In order to accurately detect contrast agent concentration from photoacoustic images, we developed a decomposition algorithm to separate photoacoustic absorption spectrum into components from individual absorbers. In this study, we evaluated novel prostate-specific membrane antigen (PSMA) targeted agents for imaging prostate cancer. Three agents were synthesized through conjugating PSMA-targeting urea with optical dyes ICG, IRDye800CW and ATTO740 respectively. In our preliminary PA study, dyes were injected in a thin wall plastic tube embedded in water tank. The tube was illuminated with pulsed laser light using a tunable Q-switch ND-YAG laser. PA signal along with the B-mode ultrasound images were detected with a diagnostic ultrasound probe in orthogonal mode. PA spectrums of each dye at 0.5 to 20 μM concentrations were estimated using the maximum PA signal extracted from images which are obtained at illumination wavelengths of 700nm-850nm. Subsequently, we developed nonnegative linear least square optimization method along with localized regularization to solve the spectral unmixing. The algorithm was tested by imaging mixture of those dyes. The concentration of each dye was estimated with about 20% error on average from almost all mixtures albeit the small separation between dyes spectrums.

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 tumor parenchyma. PMID:23932272

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 the tumor parenchyma. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Fluorine (19F) MRS and MRI in biomedicine.

PubMed

Ruiz-Cabello, Jesús; Barnett, Brad P; Bottomley, Paul A; Bulte, Jeff W M

2011-02-01

Shortly after the introduction of (1)H MRI, fluorinated molecules were tested as MR-detectable tracers or contrast agents. Many fluorinated compounds, which are nontoxic and chemically inert, are now being used in a broad range of biomedical applications, including anesthetics, chemotherapeutic agents, and molecules with high oxygen solubility for respiration and blood substitution. These compounds can be monitored by fluorine ((19)F) MRI and/or MRS, providing a noninvasive means to interrogate associated functions in biological systems. As a result of the lack of endogenous fluorine in living organisms, (19)F MRI of 'hotspots' of targeted fluorinated contrast agents has recently opened up new research avenues in molecular and cellular imaging. This includes the specific targeting and imaging of cellular surface epitopes, as well as MRI cell tracking of endogenous macrophages, injected immune cells and stem cell transplants. Copyright © 2010 John Wiley & Sons, Ltd.

T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues

NASA Astrophysics Data System (ADS)

Na, Jin Hee; Lee, Sangmin; Koo, Heebeom; Han, Hyounkoo; Lee, Kyung Eun; Han, Seung Jin; Choi, Seung Hong; Kim, Hyuncheol; Lee, Seulki; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung

2016-05-01

Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent.Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06673e

Dynamic contrast-enhanced diffuse optical tomography (DCE-DOT): experimental validation with a dynamic phantom

NASA Astrophysics Data System (ADS)

Burcin Unlu, Mehmet; Lin, Yuting; Gulsen, Gultekin

2009-11-01

Dynamic contrast-enhanced diffuse optical tomography (DCE-DOT) can provide spatially resolved enhancement kinetics of an optical contrast agent. We undertook a systematic phantom study to evaluate the effects of the geometrical parameters such as the depth and size of the inclusion as well as the optical parameters of the background on the recovered enhancement kinetics of the most commonly used optical contrast agent, indocyanine green (ICG). For this purpose a computer-controlled dynamic phantom was constructed. An ICG-intralipid-water mixture was circulated through the inclusions while the DCE-DOT measurements were acquired with a temporal resolution of 16 s. The same dynamic study was repeated using inclusions of different sizes located at different depths. In addition to this, the effect of non-scattering regions was investigated by placing a second inclusion filled with water in the background. The phantom studies confirmed that although the peak enhancement varied substantially for each case, the recovered injection and dilution rates obtained from the percentage enhancement maps agreed within 15% independent of not only the depth and the size of the inclusion but also the presence of a non-scattering region in the background. Although no internal structural information was used in these phantom studies, it may be necessary to use it for small objects buried deep in tissue. However, the different contrast mechanisms of optical and other imaging modalities as well as imperfect co-registration between both modalities may lead to potential errors in the structural a priori. Therefore, the effect of erroneous selection of structural priors was investigated as the final step. Again, the injection and dilution rates obtained from the percentage enhancement maps were also immune to the systematic errors introduced by erroneous selection of the structural priors, e.g. choosing the diameter of the inclusion 20% smaller increased the peak enhancement 60% but changed the injection and dilution rates only less than 10%.

Fibrin-Targeted Magnetic Resonance Imaging Allows In Vivo Quantification of Thrombus Fibrin Content and Identifies Thrombi Amenable for Thrombolysis

PubMed Central

Jenkins, Julia; Modarai, Bijan; Wiethoff, Andrea J.; Phinikaridou, Alkystis; Grover, Steven P.; Patel, Ashish S.; Schaeffter, Tobias; Smith, Alberto; Botnar, Rene M.

2014-01-01

Objective Deep venous thrombosis is a major health problem. Thrombolytic therapies are effective in recanalizing the veins and preventing post-thrombotic complications, but there is no consensus on selection criteria. The aim of this study was to investigate a fibrin-specific MRI contrast agent (EP-2104R) for the accurate quantification of thrombus’ fibrin content in vivo and for the identification of thrombus suitable for thrombolysis. Approach and Results Venous thrombosis was induced in the inferior vena cava of 8- to 10-week-old male BALB/C mice and MRI performed 2, 4, 7, 10, 14, and 21 days later. Eighteen mice were scanned at each time point pre and 2 hours post injection of EP-2104R (8.0 μmol/kg) with 12 mice at each time point used to correlate fibrin contrast uptake with thrombus’ histological stage and fibrin content. Six mice at each time point were immediately subjected to intravascular thrombolytic therapy (10 mg/kg of tissue-type plasminogen activator). Mice were imaged to assess response to lytic therapy 24 hours after thrombolytic treatment. Two mice at each time point were scanned post injection of 0.2 mmol/kg of Gd-DTPA (gadolinium with diethylenetriaminepentacetate, Magnevist, Schering AG, Berlin, Germany) for control purpose. Contrast uptake was correlated positively with the fibrin content of the thrombus measured by Western blotting (R2=0.889; P<0.001). Thrombus relaxation rate (R1) post contrast and the change in visualized thrombus size on late gadolinium enhancement inversion recovery MRI pre–EP-2104R and post–EP-2104R injection were the best predictors for successful thrombolysis (area under the curve, 0.989 [95% confidence interval, 0.97–1.00] and 0.994 [95% confidence interval, 0.98–1.00] respectively). Conclusions MRI with a fibrin-specific contrast agent accurately estimates thrombus fibrin content in vivo and identifies thrombi that are amenable for thrombolysis. PMID:24723557

Coronary Computed Tomographic Angiography at Low Concentration of Contrast Agent and Low Tube Voltage in Patients with Obesity:: A Feasibility Study.

PubMed

Pan, Yu-Ning; Li, Ai-Jing; Chen, Xiao-Min; Wang, Jian; Ren, Da-Wei; Huang, Qiu-Li

2016-04-01

Using lower tube voltage can reduce the exposure to radiation and the dose of contrast agent. However, lower tube voltage is often linked to more noise and poor image quality, which create a need for more effective technology to resolve this problem. To explore the feasibility of coronary computed tomographic angiography (CCTA) in patients with obesity at low tube voltage (100 kV) and low contrast agent concentration (270 mg/mL) using iterative reconstruction. A total of 48 patients with body mass index greater than 30 kg/m(2) were included and randomly divided into two groups. Group A received a traditional protocol (iopromide 370 mg/mL + 120 kV); group B received a protocol with low tube voltage (100 kV), low contrast agent concentration (270 mg/mL), and iterative reconstruction. The effective dose (ED), average attenuation values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), the figure of merit (FOM), image quality scores, and the total iodine intake were compared. No significant differences in average CT attenuations, SNR, CNR, and subjective scores were noticed between the two groups (P > 0.05), whereas the FOM of group B was significantly higher than that of group A. Effective radiation dose, total iodine, and iodine injection rate in group B were lower than those of group A (P <0.01). In patients with obesity, isotonic contrast agent with low iodine concentration and low-dose CCTA were feasible. Substantial reduction in radiation dose and the iodine intake could be achieved without compromising the image quality. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Impact of Impaired Renal Function on Gadolinium Retention After Administration of Gadolinium-Based Contrast Agents in a Mouse Model.

PubMed

Kartamihardja, A Adhipatria P; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito

2016-10-01

The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.

Fluorescent Heterodoped Nanotetrapods as Synergistically Enhancing Positive and Negative Magnetic Resonance Imaging Contrast Agents.

PubMed

Sharma, V K; Alipour, A; Soran-Erdem, Z; Kelestemur, Y; Aykut, Z G; Demir, H V

2016-05-18

In this work, we report Mn-Fe heterodoped ZnSe tetrapod nanocrystals (NCs) synthesized to synergistically enhance contrast in both T1- and T2-weighted magnetic resonance imaging (MRI). The proposed NCs were prepared using a customized heteroarchitecture such that the manganese (Mn) is confined in the core and iron (Fe) in the branches of the tetrapods. The elemental composition and profile of these NCs were studied using X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, and inductively coupled plasma mass spectroscopy. Photoluminescence quantum yield of these heterodoped NCs in water is ∼30%. Magnetic measurements reveal the simultaneous presence of superparamagnetic and paramagnetic behavior in these NCs because of the coexistence of Mn(2+) and Fe(2+) dopants. Their potential as simultaneous positive and negative MRI contrast agents was demonstrated by relaxivity measurements and in vivo MRI. From the in vivo studies, we also found that these NCs (with a hydrodynamic diameter of 20 nm) are excreted from the body within 24 h after the injection. Therefore, these heterodoped tetrapods NCs, while being fluorescent and safe, hold great future as a synergistically enhancing dual-modal MRI contrast agent.

IV Administered Gadodiamide Enters the Lumen of the Prostatic Glands: X-Ray Fluorescence Microscopy Examination of a Mouse Model

DOE PAGES

Mustafi, Devkumar; Gleber, Sophie-Charlotte; Ward, Jesse; ...

2015-09-01

In our objective, we descibe how dynamic contrast-enhanced MRI (DCE-MRI) has become a standard component of multiparametric protocols for MRI examination of the prostate, and its use is incorporated into current guidelines for prostate MRI examination. Analysis of DCE-MRI data for the prostate is usually based on the distribution of gadolinium-based agents, such as gadodiamide, into two well-mixed compartments, and it assumes that gadodiamide does not enter into the glandular lumen. However, this assumption has not been directly tested. The purpose of this study was to use x-ray fluorescence microscopy (XFM) imaging in situ to measure the concentration of gadodiamidemore » in the epithelia and lumens of the prostate of healthy mice after IV injection of the contrast agent. For our materials and methods, six C57Bl6 male mice (age, 28 weeks) were sacrificed 10 minutes after IV injection of gadodiamide (0.13 mmol/kg), and three mice were sacrificed after saline injection. Prostate tissue samples obtained from each mouse were harvested and frozen; 7-μm-thick slices were sectioned for XFM imaging, and adjacent 5-μm-thick slices were sectioned for H and E staining. Elemental concentrations were determined from XFM images. Our results show mean (± SD) baseline concentration of gadolinium of 0.01 ± 0.01 mM was determined from XFM measurements of prostatic tissue samples when no gadodiamide was administered, and it was used to determine the measurement error. When gadodiamide was added, the mean concentrations of gadolinium in the epithelia and lumens in 32 prostatic glands from six mice were 1.00 ± 0.13 and 0.36 ± 0.09 mM, respectively. In conclusion, our data suggest that IV administration of gadodiamide results in uptake of contrast agent by the glandular lumens of the mouse prostate. We were able to quantitatively determine gadodiamide distributions in mouse prostatic epithelia and lumens.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mustafi, Devkumar; Gleber, Sophie-Charlotte; Ward, Jesse

In our objective, we descibe how dynamic contrast-enhanced MRI (DCE-MRI) has become a standard component of multiparametric protocols for MRI examination of the prostate, and its use is incorporated into current guidelines for prostate MRI examination. Analysis of DCE-MRI data for the prostate is usually based on the distribution of gadolinium-based agents, such as gadodiamide, into two well-mixed compartments, and it assumes that gadodiamide does not enter into the glandular lumen. However, this assumption has not been directly tested. The purpose of this study was to use x-ray fluorescence microscopy (XFM) imaging in situ to measure the concentration of gadodiamidemore » in the epithelia and lumens of the prostate of healthy mice after IV injection of the contrast agent. For our materials and methods, six C57Bl6 male mice (age, 28 weeks) were sacrificed 10 minutes after IV injection of gadodiamide (0.13 mmol/kg), and three mice were sacrificed after saline injection. Prostate tissue samples obtained from each mouse were harvested and frozen; 7-μm-thick slices were sectioned for XFM imaging, and adjacent 5-μm-thick slices were sectioned for H and E staining. Elemental concentrations were determined from XFM images. Our results show mean (± SD) baseline concentration of gadolinium of 0.01 ± 0.01 mM was determined from XFM measurements of prostatic tissue samples when no gadodiamide was administered, and it was used to determine the measurement error. When gadodiamide was added, the mean concentrations of gadolinium in the epithelia and lumens in 32 prostatic glands from six mice were 1.00 ± 0.13 and 0.36 ± 0.09 mM, respectively. In conclusion, our data suggest that IV administration of gadodiamide results in uptake of contrast agent by the glandular lumens of the mouse prostate. We were able to quantitatively determine gadodiamide distributions in mouse prostatic epithelia and lumens.« less

Cardiac Arrhythmia and Injury Induced in Rats by Burst and Pulsed Mode Ultrasound with Gas Body Contrast Agent

PubMed Central

Miller, Douglas L.; Dou, Chunyan; Lucchesi, Benedict R.

2009-01-01

Objective Premature complexes (PCs) in the electrocardiogram (ECG) signal have been reported for myocardial contrast echocardiography and also for burst mode (physical therapy) ultrasound with gas body contrast agent at lower peak rarefactional pressure amplitudes (PRPAs). For contrast echocardiography, irreversibly injured cardiomyocytes have been associated with the arrhythmia. The objective was to determine if cardiomyocyte injury is associated with the PCs induced by the burst mode at lower PRPAs. Methods Anesthetized rats were exposed to focused 1.5 MHz ultrasound in a water bath. Evans blue dye was injected IP to stain injured cardiomyocytes and Definity ultrasound contrast agent was infused IV. Continuous burst mode simulated physical therapy ultrasound. Intermittent 2 ms bursts, or envelopes of pulses simulating diagnostic ultrasound, were triggered 1:4 at end systole. PCs were observed on ECG recordings and stained cardiomyocytes were counted in frozen sections. Results The continuous burst mode produced variable PCs and stained cells above 0.3 MPa PRPA. The triggered bursts above 0.3 MPa and pulse envelopes above 1.2 MPa produced statistically significant (P<0.01) PCs and stained cardiomyocytes. Conclusion Irreversible cardiomyocyte injury was associated with the development of PCs for burst mode and occurred at substantially lower PRPAs than for pulsed ultrasound. PMID:19854967

Intratympanic Iodine Contrast Injection Diffuses Across the Round Window Membrane Allowing for Perilymphatic CT Volume Acquisition Imaging.

PubMed

Abt, Nicholas B; Lehar, Mohamed; Guajardo, Carolina Trevino; Penninger, Richard T; Ward, Bryan K; Pearl, Monica S; Carey, John P

2016-04-01

Whether the round window membrane (RWM) is permeable to iodine-based contrast agents (IBCA) is unknown; therefore, our goal was to determine if IBCAs could diffuse through the RWM using CT volume acquisition imaging. Imaging of hydrops in the living human ear has attracted recent interest. Intratympanic (IT) injection has shown gadolinium's ability to diffuse through the RWM, enhancing the perilymphatic space. Four unfixed human cadaver temporal bones underwent intratympanic IBCA injection using three sequentially studied methods. The first method was direct IT injection. The second method used direct RWM visualization via tympanomeatal flap for IBCA-soaked absorbable gelatin pledget placement. In the third method, the middle ear was filled with contrast after flap elevation. Volume acquisition CT images were obtained immediately postexposure, and at 1-, 6-, and 24-hour intervals. Postprocessing was accomplished using color ramping and subtraction imaging. After the third method, positive RWM and perilymphatic enhancement were observed with endolymph sparing. Gray scale and color ramp multiplanar reconstructions displayed increased signal within the cochlea compared with precontrast imaging. The cochlea was measured for attenuation differences compared with pure water, revealing a preinjection average of -1,103 HU and a postinjection average of 338 HU. Subtraction imaging shows enhancement remaining within the cochlear space, Eustachian tube, middle ear epithelial lining, and mastoid. Iohexol iodine contrast is able to diffuse across the RWM. Volume acquisition CT imaging was able to detect perilymphatic enhancement at 0.5-mm slice thickness. The clinical application of IBCA IT injection seems promising but requires further safety studies.

Dynamics of encapsulated microbubbles for contrast ultrasound imaging and drug delivery: from pressure dependent subharmonic to collapsing jet and acoustic streaming

NASA Astrophysics Data System (ADS)

Sarkar, Kausik

2016-11-01

Intravenously injected microbubbles used as ultrasound contrast enhancing agents are encapsulated by a nanometer-thick layer of lipids, proteins or polymers to stabilize them against premature dissolution. Over the years, we have developed interfacial rheological models for the encapsulation and used them to characterize several contrast agents by acoustic means. We will present an overview of our research emphasizing recent efforts in two directions. The first is on using subharmonic signals from the contrast microbubbles for non-invasive pressure estimation. Experimental measurement and modeling show that the subharmonic signal can both increase or decrease with pressure depending on frequency. Secondly, we will discuss boundary element (BEM) simulation of the collapse of an encapsulated microbubbles forming a jet near a blood vessel wall. Different rheology models of the encapsulation have been rigorously implemented in the BEM formulation. We will discuss the resulting stresses and the acoustic streaming near the wall leading to sonoporation and other bioeffects. Partially supported by Natinal Science Foundation.

DCE-MRI using small-molecular and albumin-binding contrast agents in experimental carcinomas with different stromal content.

PubMed

Farace, Paolo; Merigo, Flavia; Fiorini, Silvia; Nicolato, Elena; Tambalo, Stefano; Daducci, Alessandro; Degrassi, Anna; Sbarbati, Andrea; Rubello, Domenico; Marzola, Pasquina

2011-04-01

To compare DCE-MRI experiments performed using a standard small-molecular (Gd-DTPA) and an albumin-binding (MS-325) contrast agent in two carcinoma models with different stromal content. DU-145 or BXPC-3 cancer cells were subcutaneously injected into nude mice. DCE-MRI was performed by a bolus injection of Gd-DTPA or MS-325 about 2 weeks after inoculation. For quantitative analysis a volume of interest was manually drawn over each tumor. To address the heterogeneous enhancement, each tumor volume was then divided into the 20% most-enhancing and the remaining 80% least-enhancing fractions. Mean tumor enhancement was calculated over these selected tumor volumes and compared between tumor groups and contrast agents. Maps of differential enhancement, peak enhancement and time-to-peak were used for visual evaluation. CD31 and VEGF immunohistochemistry were performed in excised tumors. In the 80% least-enhancing volume, at late time points of the dynamic scan, the mean enhancement elicited by MS-325 was higher in BXPC-3 than in DU-145 tumors. In the 20% most-enhancing volume, using either contrast agents, significant difference between the two tumors types were observed only early, while at later time points of the dynamic scan the difference were obscured by the faster washout observed in the BXPC-3 tumors. Enhancement maps confirmed that BXPC-3 tumors were characterized by marked washout rate using either contrast agent, particularly in the higher enhancing peripheral rim. With MS-325 this washout pattern appeared to be specific to the BXPC-3 carcinomas, since it was not observed in the DU-145 tumors. Finally, in both tumor types, MS-325 produced significantly higher enhancement than Gd-DTPA in the late phase of the dynamic scan. Ex vivo analysis confirmed the marked presence of aberrant infiltrative stroma in BXPC-3 tumors, in which tumor vessels were embedded. In all tumors the central portion was less viable and less infiltrated by stromal tissue then the peripheral areas. Contrast distribution proved to be related to stromal content, which presumably produced the higher enhancement and faster washout observed in the BXPC-3 tumors. In particular, 'early' contrast-enhanced MRI, appeared as the most sensitive technique to detect the tumor portions characterized by a high stromal content, i.e. the peripheral rim of the BXPC-3 tumors. Since the same tumor models were recently investigated using FDG-PET imaging, showing inverse relationship between FDG uptake and stromal content, contrast-enhanced MRI and FDG-PET could provide complementary and comprehensive sensitivity in the assessment of carcinomas. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

PEGylated hybrid ytterbia nanoparticles as high-performance diagnostic probes for in vivo magnetic resonance and X-ray computed tomography imaging with low systemic toxicity

NASA Astrophysics Data System (ADS)

Liu, Zhen; Pu, Fang; Liu, Jianhua; Jiang, Liyan; Yuan, Qinghai; Li, Zhengqiang; Ren, Jinsong; Qu, Xiaogang

2013-05-01

Novel nanoparticulate contrast agents with low systemic toxicity and inexpensive character have exhibited more advantages over routinely used small molecular contrast agents for the diagnosis and prognosis of disease. Herein, we designed and synthesized PEGylated hybrid ytterbia nanoparticles as high-performance nanoprobes for X-ray computed tomography (CT) imaging and magnetic resonance (MR) imaging both in vitro and in vivo. These well-defined nanoparticles were facile to prepare and cost-effective, meeting the criteria as a biomedical material. Compared with routinely used Iobitridol in clinic, our PEG-Yb2O3:Gd nanoparticles could provide much significantly enhanced contrast upon various clinical voltages ranging from 80 kVp to 140 kVp owing to the high atomic number and well-positioned K-edge energy of ytterbium. By the doping of gadolinium, our nanoparticulate contrast agent could perform perfect MR imaging simultaneously, revealing similar organ enrichment and bio-distribution with the CT imaging results. The super improvement in imaging efficiency was mainly attributed to the high content of Yb and Gd in a single nanoparticle, thus making these nanoparticles suitable for dual-modal diagnostic imaging with a low single-injection dose. In addition, detailed toxicological study in vitro and in vivo indicated that uniformly sized PEG-Yb2O3:Gd nanoparticles possessed excellent biocompatibility and revealed overall safety.Novel nanoparticulate contrast agents with low systemic toxicity and inexpensive character have exhibited more advantages over routinely used small molecular contrast agents for the diagnosis and prognosis of disease. Herein, we designed and synthesized PEGylated hybrid ytterbia nanoparticles as high-performance nanoprobes for X-ray computed tomography (CT) imaging and magnetic resonance (MR) imaging both in vitro and in vivo. These well-defined nanoparticles were facile to prepare and cost-effective, meeting the criteria as a biomedical material. Compared with routinely used Iobitridol in clinic, our PEG-Yb2O3:Gd nanoparticles could provide much significantly enhanced contrast upon various clinical voltages ranging from 80 kVp to 140 kVp owing to the high atomic number and well-positioned K-edge energy of ytterbium. By the doping of gadolinium, our nanoparticulate contrast agent could perform perfect MR imaging simultaneously, revealing similar organ enrichment and bio-distribution with the CT imaging results. The super improvement in imaging efficiency was mainly attributed to the high content of Yb and Gd in a single nanoparticle, thus making these nanoparticles suitable for dual-modal diagnostic imaging with a low single-injection dose. In addition, detailed toxicological study in vitro and in vivo indicated that uniformly sized PEG-Yb2O3:Gd nanoparticles possessed excellent biocompatibility and revealed overall safety. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr00491k

Gadolinium heteropoly complex K 17[Gd(P 2W 17O 61) 2] as a potential MRI contrast agent

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Wu, Huifeng; Pei, Fengkui; Fang, Ke; Lei, Hao

2004-10-01

Gadolinium heteropoly complex K17[Gd(P2W17O61)2] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T1 relaxivity is 7.59 mM-1 s-1 in aqueous solution and 7.97 mM-1 s-1 in 0.725 mmol l-1 bovine serum albumin (BSA) solution at 25 °C and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1±16.9% during the whole imaging period at 0.082 mmol kg-1dose. Our preliminary in vitro and in vivo studies indicate that K17[Gd(P2W17O61)2] is a potential liver-specific MRI contrast agent.

Quantitative evaluation of microvascular blood flow by contrast-enhanced ultrasound (CEUS).

PubMed

Greis, Christian

2011-01-01

Ultrasound contrast agents consist of tiny gas-filled microbubbles the size of red blood cells. Due to their size distribution, they are purely intravascular tracers which do not extravasate into the interstitial fluid, and thus they are perfect agents for imaging blood distribution and flow. Using ultrasound scanners with contrast-specific software, the specific microbubble-derived echo signals can be separated from tissue signals in realtime, allowing selective imaging of the contrast agent. The signal intensity obtained lies in a linear relationship to the amount of microbubbles in the target organ, which allows easy and reliable assessment of relative blood volume. Imaging of the contrast wash-in and wash-out after bolus injection, or more precisely using the flash-replenishment technique, allows assessment of regional blood flow velocity. Commercially available quantification software packages can calculate time-related intensity values from the contrast wash-in and wash-out phase for each image pixel from stored video clips. After fitting of a mathematical model curve according to the respective kinetic model (bolus or flash-replenishment kinetics), time/intensity curves (TIC) can be calculated from single pixels or user-defined regions of interest (ROI). Characteristic parameters of these TICs (e.g. peak intensity, area under the curve, wash-in rate, etc.) can be displayed as color-coded parametric maps on top of the anatomical image, to identify cold and hot spots with abnormal perfusion.

A polymeric micelle magnetic resonance imaging (MRI) contrast agent reveals blood-brain barrier (BBB) permeability for macromolecules in cerebral ischemia-reperfusion injury.

PubMed

Shiraishi, Kouichi; Wang, Zuojun; Kokuryo, Daisuke; Aoki, Ichio; Yokoyama, Masayuki

2017-05-10

Blood-brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-"rtPA treatment" stage is the task of developing a rigorous method for hemorrhage-risk assessments. Therefore, we examined a novel method for assessment of rtPA-extravasation through a hyper-permeable BBB. To examine the image diagnosis of rtPA-extravasation for a rat transient occlusion-reperfusion model, in this study we used a polymeric micelle MRI contrast-agent (Gd-micelles). Specifically, we used two MRI contrast agents at 1h after reperfusion. Gd-micelles provided very clear contrast images in 15.5±10.3% of the ischemic hemisphere at 30min after i.v. injection, whereas a classic gadolinium chelate MRI contrast agent provided no satisfactorily clear images. The obtained images indicate both the hyper-permeable BBB area for macromolecules and the distribution area of macromolecules in the ischemic hemisphere. Owing to their large molecular weight, Gd-micelles remained in the ischemic hemisphere through the hyper-permeable BBB. Our results indicate the feasibility of a novel clinical diagnosis for evaluating rtPA-related hemorrhage risks. Copyright © 2017 Elsevier B.V. All rights reserved.

Cyanine 5.5 Conjugated Nanobubbles as a Tumor Selective Contrast Agent for Dual Ultrasound-Fluorescence Imaging in a Mouse Model

PubMed Central

Li, Jing; Wei, Qiong; Yuchi, Ming; He, Xiaoling; Ding, Mingyue; Zhou, Qibing

2013-01-01

Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan–vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400–800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan–vitamin C lipid system have achieved tumor-selective imaging in vivo. PMID:23637799

Cyanine 5.5 conjugated nanobubbles as a tumor selective contrast agent for dual ultrasound-fluorescence imaging in a mouse model.

PubMed

Mai, Liyi; Yao, Anna; Li, Jing; Wei, Qiong; Yuchi, Ming; He, Xiaoling; Ding, Mingyue; Zhou, Qibing

2013-01-01

Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan-vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400-800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan-vitamin C lipid system have achieved tumor-selective imaging in vivo.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jens, Sjoerd, E-mail: s.jens@amc.uva.nl; Marquering, Henk A., E-mail: h.a.marquering@amc.uva.nl; Koelemay, Mark J. W., E-mail: m.j.koelemaij@amc.uva.nl

ObjectiveTo study the feasibility of 2D perfusion imaging in critical limb ischemia (CLI).Methods/ResultsPerfusion angiography is a new technology which was tested in 18 patients with CLI of the foot. A standardized protocol was used with a catheter placed at the mid-part of the popliteal artery, and a total of 9 cc of non-ionic iodinated contrast material was injected at a rate of 3 cc/sec. The technology is based on early cardiology research where iodinated contrast agents were used for imaging of cardiac perfusion. During the first pass of the contrast, there is a significant diffusion of the contrast agents into the interstitialmore » space, particularly for non-ionic and low-molecular-weight compounds.DiscussionThe original angiography data can be used to make a time–density curve, which represents the actual perfusion of the foot in time. Angiographic perfusion imaging is a post-processing modality for which no extra contrast or radiation is needed. With this technique, it is possible to get more information about the perfusion status and microcirculation of the foot. This is a step toward functional imaging in CLI patients.« less

Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling.

PubMed

Taverna, Gianluigi; Morandi, Giovanni; Seveso, Mauro; Giusti, Guido; Benetti, Alessio; Colombo, Piergiuseppe; Minuti, Francesco; Grizzi, Fabio; Graziotti, Pierpaolo

2011-12-01

What's known on the subject? and What does the study add? Transrectal gray-scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10-30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue™ microbubble contrast agent, versus the transrectal ultrasongraphy-guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection. • To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue™ contrast agent with transrectal ultrasonography-guided systematic biopsy sampling. • A total of 300 patients with negative digital rectal examination and transrectal grey-scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography-guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue™. • Contrast-enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. • All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group. • In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. • No significant differences were found among the three groups for cancer detection rate (P= 0.329). • Additionally, low sensitivity, specificity and accuracy of colour Doppler with or without SonoVue™ contrast agent were found. • Prostate cancer detection rate does not significantly improve with the use of colour Doppler ultrasonography with or without SonoVue™. • Although no collateral effects have been highlighted, the combined use of colour Doppler ultrasonography and SonoVue™ determines adjunctive costs and increases the mean time for taking a single prostate biopsy. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.

PubMed

Chen, Zhijin; Yu, Dexin; Liu, Chunxi; Yang, Xiaoyan; Zhang, Na; Ma, Chunhong; Song, Jibin; Lu, Zaijun

2011-09-01

A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.

Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy.

PubMed

Ribot, E; Bouzier-Sore, A-K; Bouchaud, V; Miraux, S; Delville, M-H; Franconi, J-M; Voisin, P

2007-08-01

Microglia are phagocytic cells that are chemoattracted by brain tumors and can represent up to 70% of the tumor cell population. To get insight into gene therapy against glioma, we decided to take advantage of those microglia properties and to use those cells as vehicles to transport simultaneously a suicide gene (under the control of a heat-sensitive promoter) and contrast agents to localize them by magnetic resonance imaging before applying any therapeutic treatment. Thymidine kinase (TK) expression and its functionality after gancyclovir administration were investigated. After the heat shock (44 degrees C and 20 min), TK was expressed in 50% of the cells. However, after gancyclovir treatment, 90% of the cells died by apoptosis, showing an important bystander effect. Then, the cells were incubated with new lanthanide contrast agents to check both their potential toxicity and their MR properties. Results indicate that the nanoparticles did not induce any cell toxicity and yield a hypersignal on MR images at 4.7 T. These in vitro experiments indicate that microglia are good candidates as vectors in gene therapy against brain tumors. Finally, microglia containing gadolinium-grafted nanoparticles were injected in the close vicinity of C6 tumor, in a mouse. The hyperintensive signal obtained on in vivo images as well as its retention time show the potential of the novel contrast agents for cellular imaging.

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

PubMed Central

Uchiyama, Mayara Klimuk; Toma, Sergio Hiroshi; Rodrigues, Stephen Fernandes; Shimada, Ana Lucia Borges; Loiola, Rodrigo Azevedo; Cervantes Rodríguez, Hernán Joel; Oliveira, Pedro Vitoriano; Luz, Maciel Santos; Rabbani, Said Rahnamaye; Toma, Henrique Eisi; Poliselli Farsky, Sandra Helena; Araki, Koiti

2015-01-01

Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM−1s−1 in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics. PMID:26251595

Phosphatidylserine-targeted liposome for enhanced glioma-selective imaging.

PubMed

Zhang, Liang; Habib, Amyn A; Zhao, Dawen

2016-06-21

Phosphatidylserine (PS), which is normally intracellular, becomes exposed on the outer surface of viable endothelial cells (ECs) of tumor vasculature. Utilizing a PS-targeting antibody, we have recently established a PS-targeted liposomal (PS-L) nanoplatform that has demonstrated to be highly tumor-selective. Because of the vascular lumen-exposed PS that is immediately accessible without a need to penetrate the intact blood brain barrier (BBB), we hypothesize that the systemically administered PS-L binds specifically to tumor vascular ECs, becomes subsequently internalized into the cells and then enables its cargos to be efficiently delivered to glioma parenchyma. To test this, we exploited the dual MRI/optical imaging contrast agents-loaded PS-L and injected it intravenously into mice bearing intracranial U87 glioma. At 24 h, both in vivo optical imaging and MRI depicted enhanced tumor contrast, distinct from the surrounding normal brain. Intriguingly, longitudinal MRI revealed temporal and spatial intratumoral distribution of the PS-L by following MRI contrast changes, which appeared punctate in tumor periphery at an earlier time point (4 h), but became clustering and disseminated throughout the tumor at 24 h post injection. Importantly, glioma-targeting specificity of the PS-L was antigen specific, since a control probe of irrelevant specificity showed minimal accumulation in the glioma. Together, these results indicate that the PS-L nanoplatform enables the enhanced, glioma-targeted delivery of imaging contrast agents by crossing the tumor BBB efficiently, which may also serve as a useful nanoplatform for anti-glioma drugs.

Magnetic Resonance Imaging of Acute Reperfused Myocardial Infarction: Intraindividual Comparison of ECIII-60 and Gd-DTPA in a Swine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin Jiyang; Teng Gaojun; Feng Yi

2007-04-15

Purpose. To compare a necrosis-avid contrast agent (NACA) bis-Gd-DTPA-pamoic acid derivative (ECIII-60) after intracoronary delivery with an extracellular agent Gd-DTPA after intravenous injection on magnetic resonance imaging (MRI) in a swine model of acute reperfused myocardial infarction (MI). Methods. Eight pigs underwent 90 min of transcatheter coronary balloon occlusion and 60 min of reperfusion. After intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg, all pigs were scanned with T1-weighted MRI until the delayed enhancement of MI disappeared. Then they were intracoronarily infused with ECIII-60 at 0.0025 mmol/kg and imaged for 5 hr. Signal intensity, infarct-over-normal contrast ratio andmore » relative infarct size were quantified, compared, and correlated with the results of postmortem MRI and triphenyltetrazolium chloride (TTC) histochemical staining. Results. A contrast ratio over 3.0 was induced by both Gd-DTPA and ECIII-60. However, while the delayed enhancement with Gd-DTPA virtually vanished in 1 hr, ECIII-60 at an 80x smaller dose depicted the MI accurately over 5 hr as proven by ex vivo MRI and TTC staining. Conclusion. Both Gd-DTPA and ECIII-60 strongly enhanced acute MI. Comparing with fading contrast in a narrow time window with intravenous Gd-DTPA, intracoronary ECIII-60 persistently demarcated the acute MI, indicating a potential method for postprocedural assessment of myocardial viability after coronary interventions.« less

Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals.

PubMed

Jarockyte, Greta; Daugelaite, Egle; Stasys, Marius; Statkute, Urte; Poderys, Vilius; Tseng, Ting-Chen; Hsu, Shan-Hui; Karabanovas, Vitalijus; Rotomskis, Ricardas

2016-08-19

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3-24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.

Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals

PubMed Central

Jarockyte, Greta; Daugelaite, Egle; Stasys, Marius; Statkute, Urte; Poderys, Vilius; Tseng, Ting-Chen; Hsu, Shan-Hui; Karabanovas, Vitalijus; Rotomskis, Ricardas

2016-01-01

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3–24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining. PMID:27548152

Intraarticular local anesthesia: can it reduce pain related to MR or CT arthrography of the shoulder?

PubMed

Choo, Hye Jung; Lee, Sun Joo; Kim, Dong Wook; Choi, Seok Jin; Lee, In Sook

2013-04-01

The objective of this study was to prospectively evaluate whether intraarticular anesthesia can reduce pain after MR or CT arthrography of the shoulder. This study included 120 patients who underwent CT or MR arthrography of the shoulder. The patients were randomized into two groups: the study group (n = 60), each administered an intraarticular injection of the contrast agent mixed with a local anesthetic (2% mepivacaine); and the control group (n = 60), each injected with the contrast agent only. Each patient's pain level was assessed at five phases-baseline and immediately, 2 hours, 1 day, and 2 days after injection-by using a visual analog scale or a verbal rating scale. The net pain score at each phase was also calculated. The pain course and net pain score were compared between study and control groups by repeated-measures analysis of variance. After the patients were divided into subgroups according to patient- or procedure-related factors, the efficacy of the intraarticular local anesthetic in each subgroup was evaluated. The pain course showed a quadratic trend and was not significantly different between study and control groups. The net pain score also was not significantly different between the two groups. No subgroup showed a significantly different efficacy of the intraarticular local anesthetic between the two groups. Intraarticular local anesthesia did not reduce arthrography-related pain.

Using flow information to support 3D vessel reconstruction from rotational angiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waechter, Irina; Bredno, Joerg; Weese, Juergen

2008-07-15

For the assessment of cerebrovascular diseases, it is beneficial to obtain three-dimensional (3D) morphologic and hemodynamic information about the vessel system. Rotational angiography is routinely used to image the 3D vascular geometry and we have shown previously that rotational subtraction angiography has the potential to also give quantitative information about blood flow. Flow information can be determined when the angiographic sequence shows inflow and possibly outflow of contrast agent. However, a standard volume reconstruction assumes that the vessel tree is uniformly filled with contrast agent during the whole acquisition. If this is not the case, the reconstruction exhibits artifacts. Here,more » we show how flow information can be used to support the reconstruction of the 3D vessel centerline and radii in this case. Our method uses the fast marching algorithm to determine the order in which voxels are analyzed. For every voxel, the rotational time intensity curve (R-TIC) is determined from the image intensities at the projection points of the current voxel. Next, the bolus arrival time of the contrast agent at the voxel is estimated from the R-TIC. Then, a measure of the intensity and duration of the enhancement is determined, from which a speed value is calculated that steers the propagation of the fast marching algorithm. The results of the fast marching algorithm are used to determine the 3D centerline by backtracking. The 3D radius is reconstructed from 2D radius estimates on the projection images. The proposed method was tested on computer simulated rotational angiography sequences with systematically varied x-ray acquisition, blood flow, and contrast agent injection parameters and on datasets from an experimental setup using an anthropomorphic cerebrovascular phantom. For the computer simulation, the mean absolute error of the 3D centerline and 3D radius estimation was 0.42 and 0.25 mm, respectively. For the experimental datasets, the mean absolute error of the 3D centerline was 0.45 mm. Under pulsatile and nonpulsatile conditions, flow information can be used to enable a 3D vessel reconstruction from rotational angiography with inflow and possibly outflow of contrast agent. We found that the most important parameter for the quality of the reconstruction of centerline and radii is the range through which the x-ray system rotates in the time span of the injection. Good results were obtained if this range was at least 135 deg. . As a standard c-arm can rotate 205 deg., typically one third of the acquisition can show inflow or outflow of contrast agent, which is required for the quantification of blood flow from rotational angiography.« less

Arterial wall perfusion measured with photon counting spectral x-ray CT

NASA Astrophysics Data System (ADS)

Jorgensen, Steven M.; Korinek, Mark J.; Vercnocke, Andrew J.; Anderson, Jill L.; Halaweish, Ahmed; Leng, Shuai; McCollough, Cynthia H.; Ritman, Erik L.

2016-10-01

Early atherosclerosis changes perfusion of the arterial wall due to localized proliferation of the vasa vasorum. When contrast agent passes through the artery, some enters the vasa vasorum and increases radiopacity of the arterial wall. Technical challenges to detecting changes in vasa vasorum density include the thin arterial wall, partial volume averaging at the arterial lumen/wall interface and calcification within the wall. We used a photon-counting spectral CT scanner to study carotid arteries of anesthetized pigs and micro-CT of these arteries to quantify vasa vasorum density. The left carotid artery wall was injected with autologous blood to stimulate vasa vasorum angiogenesis. The scans were performed at 25-120 keV; the tube-current-time product was 550 mAs. A 60 mL bolus of iodine contrast agent was injected into the femoral vein at 5mL/s. Two seconds post injection, an axial scan was acquired at every 3 s over 60 s (i.e., 20 time points). Each time point acquired 28 contiguous transaxial slices with reconstructed voxels 0.16 x 0.16 x 1 mm3. Regions-of-interest in the outer 2/3 of the arterial wall and in the middle 2/3 of the lumen were drawn and their enhancements plotted versus time. Lumenal CT values peaked several seconds after injection and then returned towards baseline. Arterial wall CT values peaked concurrent to the lumen. The peak arterial wall enhancement in the left carotid arterial wall correlated with increased vasa vasorum density observed in micro-CT images of the isolated arteries.

Arterial Wall Perfusion Measured with Photon Counting Spectral X-ray CT.

PubMed

Jorgensen, Steven M; Korinek, Mark J; Vercnocke, Andrew J; Anderson, Jill L; Halaweish, Ahmed; Leng, Shuai; McCollough, Cynthia H; Ritman, Erik L

2016-08-28

Early atherosclerosis changes perfusion of the arterial wall due to localized proliferation of the vasa vasorum. When contrast agent passes through the artery, some enters the vasa vasorum and increases radiopacity of the arterial wall. Technical challenges to detecting changes in vasa vasorum density include the thin arterial wall, partial volume averaging at the arterial lumen/wall interface and calcification within the wall. We used a photon-counting spectral CT scanner to study carotid arteries of anesthetized pigs and micro-CT of these arteries to quantify vasa vasorum density. The left carotid artery wall was injected with autologous blood to stimulate vasa vasorum angiogenesis. The scans were performed at 25-120 keV; the tube-current-time product was 550 mAs. A 60 mL bolus of iodine contrast agent was injected into the femoral vein at 5mL/s. Two seconds post injection, an axial scan was acquired at every 3 s over 60 s (i.e., 20 time points). Each time point acquired 28 contiguous transaxial slices with reconstructed voxels 0.16 × 0.16 × 1 mm 3 . Regions-of-interest in the outer 2/3 of the arterial wall and in the middle 2/3 of the lumen were drawn and their enhancements plotted versus time. Lumenal CT values peaked several seconds after injection and then returned towards baseline. Arterial wall CT values peaked concurrent to the lumen. The peak arterial wall enhancement in the left carotid arterial wall correlated with increased vasa vasorum density observed in micro-CT images of the isolated arteries.

Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

NASA Astrophysics Data System (ADS)

Wang, Jianxin Steven

The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in vivo.

Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations.

PubMed

Granata, Vincenza; Cascella, Marco; Fusco, Roberta; dell'Aprovitola, Nicoletta; Catalano, Orlando; Filice, Salvatore; Schiavone, Vincenzo; Izzo, Francesco; Cuomo, Arturo; Petrillo, Antonella

2016-01-01

Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives.

Comparison of Gadofluorine-M and Gd-DTPA for Non-Invasive Staging of Atherosclerotic Plaque Stability Using MRI

PubMed Central

Ronald, John A.; Chen, Yuanxin; Belisle, Andre J.-L.; Hamilton, Amanda M.; Rogers, Kem A.; Hegele, Robert A.; Misselwitz, Bernd; Rutt, Brian K.

2009-01-01

Background Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. Here we determined the utility of the MR contrast agent Gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA. Methods and Results 5 control and 7 atherosclerotic rabbits were sequentially imaged following administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T1-weighted pulse sequence on a 3T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values following GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours post-injection, but not Gd-DTPA at peak enhancement, was shown to correlate with a quantitative histological morphology index related to these two plaque features. Conclusions GdF-enhanced MRI of atherosclerotic plaques allows non-invasive quantitative information about plaque composition to be acquired at multiple time points post-injection (within 1 and up to 24 hours post-injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events. PMID:19808597

Early diagnosis of Budd-Chiari syndrome by computed tomography and ultrasonography: report of five cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baert, A.L.; Fevery, J.; Marchal, G.

1983-03-01

In 5 patients with Budd-Chiari syndrome, computed tomography after intravenous bolus injection of iodinated contrast agents demonstrated images not previously seen in other diseases. The images are compatible with stagnation of contrast material at the periphery of the liver. In 3 of the 5 cases, grey-scale ultrasonography failed to document the normal hepatic veins draining into the inferior caval vein, but showed an intrahepatic network of comma-shaped venous structures. It is proposed that these two noninvasive approaches can help in establishing an early diagnosis.

Nanobubbles as ultrasound contrast agent for facilitating small cell lung cancer imaging

PubMed Central

Wang, Jin-Ping; Zhou, Xiao-Lin; Yan, Ji-Ping; Zheng, Rong-Qin; Wang, Wei

2017-01-01

Background This study is to investigate whether liposome-loaded nanobubbles (NBs) have the potentials to carry anti-pro-gastrin releasing peptide (proGRP) antibody and enhance ultrasound imaging of small cell lung cancer (SCLC). Methods NBs were loaded with an antibody against SCLC (H446 cell line). A nude mouse model of SCLC tumor was established by a subcutaneous injection of tumor cell suspension in the dorsal skin. Images for contrast-enhanced ultrasound (CEUS) of xenograft tumors in the model were obtained through an intravenous injection of blank and targeting NBs. Results The targeted NBs showed a high binding affinity (90.2 ± 3.24%) of the H446 cells in vitro as compared to the blank NBs that have no affinity of the cells. In process of tumor imaging, no mice died of the NB application. CEUS imaging of the targeted NBs manifested significant increases in half-peak time, area under the curve and peak intensity as compared to the blank NBs. In the model of SCLC, treatment with targeting NBs resulted in a large amount of fluorescent dye accumulated in the tumor tissue but not the liver tissue. Conclusion Our results indicate that NBs can carry antibody traveling to the SCLC cells, whereas application of NBs is safe and reliable in serving as ultrasound contrast agents for improving SCLC imaging. PMID:29100457

A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity**

PubMed Central

Chen, Kuan-Ju; Wolahan, Stephanie M.; Wang, Hao; Hsu, Chao-Hsiung; Chang, Hsing-Wei; Durazo, Armando; Hwang, Lian-Pin; Garcia, Mitch A.; Jiang, Ziyue Karen; Wu, Lily

2010-01-01

We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd3+·DOTA-encapsulated supramolecular nanoparticles (Gd3+·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd3+·DOTA⊂SNPs with an r1 of 17.3 s−1mM−1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1-weighted imaging of Gd3+·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd3+·DTPA. A Gd3+·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1-weighted imaging after injecting Gd3+·DOTA⊂SNPs but not after injecting Gd3+·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd3+·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis. PMID:21167594

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging.

PubMed

Unterweger, Harald; Janko, Christina; Schwarz, Marc; Dézsi, László; Urbanics, Rudolf; Matuszak, Jasmin; Őrfi, Erik; Fülöp, Tamás; Bäuerle, Tobias; Szebeni, János; Journé, Clément; Boccaccini, Aldo R; Alexiou, Christoph; Lyer, Stefan; Cicha, Iwona

2017-01-01

Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial-monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size <30 nm was achieved, without affecting their hemo- and biocompatibility. Our findings suggest that due to their excellent biocompatibility, safety upon intravenous administration and size-tunability, SPIONdex particles may represent a suitable candidate for a new-generation MRI contrast agent.

Evaluation of contrast-enhanced power Doppler imaging for measuring blood flow

NASA Astrophysics Data System (ADS)

Ansaloni, Sara; Arger, Peter H.; Cary, Ted W.; Sehgal, Chandra M.

2005-04-01

Power Doppler ultrasound enhanced by microbubble contrast agent has been used to image tissue vascularity and blood flow for the assessment of antivascular therapies. We have proposed a multigating technique that measures bubble concentration as a function of ultrasound exposure for deriving tumor blood flow and vascularity.1 Techniques using ultrasound contrast agent are known to be sensitive to the choice of imaging parameters like mechanical index and tissue attenuation. In this paper, the roles of mechanical index (MI) and tissue attenuation were evaluated experimentally in a rubber tubing flow phantom connected to a mixing chamber and a variable speed pump. The contrast was injected in the mixing chamber and the flow rate was measured using power Doppler imaging. The measurements were repeated at different MIs (0.1 to 1.3), and at different levels of attenuation, obtained with solutions of glycerol-water (10-20%). True flow was measured by collecting liquid flowing out of the phantom over a fixed duration. At low MI (<0.5), the grayscale and Doppler signal were weak, making these images unsuitable for analysis. At higher MI (> 0.8), there was a well-defined enhancement by contrast agent resulting in reproducible flow measurements at variable MIs. A balance between the number of bubbles destroyed and the echo they generate must be achieved for optimal imaging. The increased attenuation of ultrasound by the overlying medium did not influence the flow measurements.

Cerebral perfusion imaging with bolus harmonic imaging (Honorable Mention Poster Award)

NASA Astrophysics Data System (ADS)

Kier, Christian; Toth, Daniel; Meyer-Wiethe, Karsten; Schindler, Angela; Cangur, Hakan; Seidel, Gunter; Aach, Til

2005-04-01

Fast visualisation of cerebral microcirculation supports diagnosis of acute stroke. However, the commonly used CT/MRI-based methods are time consuming, costly and not applicable to every patient. The bolus perfusion harmonic imaging (BHI) method is an ultrasound imaging technique which makes use of the fact, that ultrasound contrast agents unlike biological tissues resonate at harmonic frequencies. Exploiting this effect, the contrast between perfused and non-perfused areas can be improved. Thus, BHI overcomes the low signal-to-noise ratio of transcranial ultrasound and the high impedance of the skull. By analysing image sequences, visualising the qualitative characteristics of an US contrast agent bolus injection becomes possible. The analysis consists of calculating four perfusion-related parameters, Local Peak Intensity, Time To Peak, Area Under Curve, and Average Rising, from the time/intensity curve and providing them as colour-coded images. For calculating these parameters the fundamental assumption is that image intensity corresponds to contrast agent concentration which in turn shows the perfusion of the corresponding brain region. In a clinical study on patients suffering from acute ischemic stroke it is shown that some of the parameters correlate significantly to the infarction area. Thus, BHI becomes a less time-consuming and inexpensive bedside method for diagnosis of cerebral perfusion deficits.

Photoacoustic imaging of tumor targeting with biotin conjugated nanostructured phthalocyanine assemblies

NASA Astrophysics Data System (ADS)

Lee, Seunghyun; Li, Xingshu; Lee, Dayoung; Yoon, Juyoung; Kim, Chulhong

2018-02-01

Visualizing biological markers and delivering bioactive agents to living organisms are important to biological research. In recent decades, photoacoustic imaging (PAI) has been significantly improved in the area of molecular imaging, which provides high-resolution volume imaging with high optical absorption contrast. To demonstrate the ability of nanoprobes to target tumors using PAI, we synthesize convertible nanostructured agents with strong photothermal and photoacoustic properties and linked the nanoprobe with biotin to target tumors in small animal model. Interestingly, these nanoprobes allow partial to disassemble in the presence of targeted proteins that switchable photoactivity, thus the nanoprobes provides a fluorescent-cancer imaging with high signal-to-background ratios. The proposed nanoprobe produce a much stronger PA signal compared to the same concentration of methylene blue (MB), which is widely used in clinical study and contrast agent for PAI. The biotin conjugated nanoprobe has high selectivity for biotin receptor positive cancer cells such as A549 (human lung cancer). Then we subsequently examined the PA properties of the nanoprobe that are inherently suitable for in vivo PAI. After injecting of the nanoprobe via intravenous method, we observed the mice's whole body by PA imaging and acquired the PA signal near the cancer. The PA signal increased linearly with time after injection and the fluorescence signal near the cancer was confirmed by fluorescence imaging. The ability to target a specific cancer of the nanoprobe was well verified by PA imaging. This study provides valuable perspective on the advancement of clinical translations and in the design of tumor-targeting phototheranostic agents that could act as new nanomedicines.

Contrast enhancement of central nervous system lesions: multicenter intraindividual crossover comparative study of two MR contrast agents.

PubMed

Maravilla, Kenneth R; Maldjian, Joseph A; Schmalfuss, Ilona M; Kuhn, Matthew J; Bowen, Brian C; Wippold, Franz J; Runge, Val M; Knopp, Michael V; Kremer, Stephane; Wolansky, Leo J; Anzalone, Nicoletta; Essig, Marco; Gustafsson, Lars

2006-08-01

To prospectively compare gadobenate dimeglumine with gadopentetate dimeglumine (0.1 mmol per kilogram body weight) for enhanced magnetic resonance (MR) imaging of central nervous system (CNS) lesions. This study was HIPAA-compliant at U.S. centers and was conducted at all centers according to the Good Clinical Practice standard. Institutional review board and regulatory approval were granted; written informed consent was obtained. Seventy-nine men and 78 women (mean age, 50.5 years +/- 14.4 [standard deviation]) were randomized to group A (n = 78) or B (n = 79). Patients underwent two temporally separated 1.5-T MR imaging examinations. In randomized order, gadobenate followed by gadopentetate was administered in group A; order of administration was reversed in group B. Contrast agent administration (volume, speed of injection), imaging parameters before and after injection, and time between injections and postinjection acquisitions were identical for both examinations. Three blinded neuroradiologists evaluated images by using objective image interpretation criteria for diagnostic information end points (lesion border delineation, definition of disease extent, visualization of internal morphologic features of the lesion, enhancement of the lesion) and quantitative parameters (percentage of lesion enhancement, contrast-to-noise ratio [CNR]). Overall diagnostic preference in terms of lesion conspicuity, detectability, and diagnostic confidence was assessed. Between-group comparisons were performed with Wilcoxon signed rank test. Readers 1, 2, and 3 demonstrated overall preference for gadobenate in 75, 89, and 103 patients, compared with that for gadopentetate in seven, 10, and six patients, respectively (P < .0001). Significant (P < .0001) preference for gadobenate was demonstrated for diagnostic information end points, percentage of lesion enhancement, and CNR. Superiority of gadobenate was significant (P < .001) in patients with intraaxial and extraaxial lesions. Gadobenate compared with gadopentetate at an equivalent dose provides significantly better enhancement and diagnostic information for CNS MR imaging. RSNA, 2006

Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

PubMed

Kaneshiro, Todd L; Ke, Tianyi; Jeong, Eun-Kee; Parker, Dennis L; Lu, Zheng-Rong

2006-06-01

The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. These novel GCAC are promising contrast agents for cardiovascular and tumor MRI, which are later cleaved into low molecular weight Gd(III) chelates and rapidly cleared from the body.

MO-F-CAMPUS-J-01: Effect of Iodine Contrast Agent Concentration On Cerebrovascular Dose for Synchrotron Radiation Microangiography Based On a Simple Mouse Head Model and a Voxel Mouse Head Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, H; Jing, J; Xie, C

Purpose: To find effective setting methods to mitigate the irradiation injure in synchrotron radiation microangiography(SRA) by Monte Carlo simulation. Methods: A mouse 1-D head model and a segmented voxel mouse head phantom were simulated by EGSnrc/Dosxyznrc code to investigate the dose enhancement effect of the iodine contrast agent irradiated by a monochromatic synchrotron radiation(SR) source. The influence of, like iodine concentration (IC), vessel width and depth, with and without skull layer protection and the various incident X ray energies, were simulated. The dose enhancement effect and the absolute dose based on the segmented voxel mouse head phantom were evaluated. Results:more » The dose enhancement ratio depends little on the irradiation depth, but strongly on the IC, which is linearly increases with IC. The skull layer protection cannot be ignored in SRA, the 700µm thick skull could decrease 10% of the dose. The incident X-ray energy can significantly affact the dose. E.g. compared to the dose of 33.2keV for 50mgI/ml, the 32.7keV dose decreases 38%, whereas the dose of 33.7 keV increases 69.2%, and the variation will strengthen more with enhanced IC. The segmented voxel mouse head phantom also showed that the average dose enhancement effect and the maximal voxel dose per photon depends little on the iodine voxel volume ratio, but strongly on IC. Conclusion: To decrease dose damage in SRA, the high-Z contrast agent should be used as little as possible, and try to avoid radiating locally the injected position immediately after the contrast agent injection. The fragile vessel containing iodine should avoid closely irradiating. Avoiding irradiating through the no or thin skull region, or appending thin equivalent material from outside to protect is also a better method. As long as SRA image quality is ensured, using incident X-ray energy as low as possible.« less

Is bacteriostatic saline superior to normal saline as an echocardiographic contrast agent?

PubMed

Cardozo, Shaun; Gunasekaran, Prasad; Patel, Hena; McGorisk, Timothy; Toosi, Mehrdad; Faraz, Haroon; Zalawadiya, Sandip; Alesh, Issa; Kottam, Anupama; Afonso, Luis

2014-12-01

Objective data on the performance characteristics and physical properties of commercially available saline formulations [normal saline (NS) vs. bacteriostatic normal saline (bNS)] are sparse. This study sought to compare the in vitro physical properties and in vivo characteristics of two commonly employed echocardiographic saline contrast agents in an attempt to assess superiority. Nineteen patients undergoing transesophageal echocardiograms were each administered agitated regular NS and bNS injections in random order and in a blinded manner according to a standardized protocol. Video time-intensity (TI) curves were constructed from a representative region of interest, placed paraseptally within the right atrium, in the bicaval view. TI curves were analyzed for maximal plateau acoustic intensity (Vmax, dB) and dwell time (DT, s), defined as time duration between onset of Vmax and decay of video intensity below clinically useful levels, reflecting the duration of homogenous opacification of the right atrium. To further characterize the physical properties of the bubbles in vitro, fixed aliquots of similarly agitated saline were injected into a glass well slide-cover slip assembly and examined using an optical microscope to determine bubble diameter in microns (µm) and concentration [bubble count/high power field (hpf)]. A higher acoustic intensity (a less negative dB level), higher bubble concentration and longer DT were considered properties of a superior contrast agent. For statistical analysis, a paired t test was conducted to evaluate the differences in means of Vmax and DT. Compared to NS, bNS administration was associated with superior opacification (video intensity -8.69 ± 4.7 vs. -10.46 ± 4.1 dB, P = 0.002), longer DT (17.3 ± 6.1 vs. 10.2 ± 3.7 s) in vivo and smaller mean bubble size (43.4 vs. 58.6 μm) and higher bubble concentration (1,002 vs. 298 bubble/hpf) in vitro. bNS provides higher intensity and more sustained opacification of the right atrium compared to NS. Higher bubble concentration and stability appear to be additional desirable rheological characteristics favoring bNS as a contrast agent.

Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent.

PubMed

Ge, Pingju; Sheng, Fugeng; Jin, Yiguang; Tong, Li; Du, Lina; Zhang, Lei; Tian, Ning; Li, Gongjie

2016-12-01

Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd 2 -diethylenetriaminepentaacetate-bis(alendronate) (Gd 2 -DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pK a , complex constant, and T 1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd 2 -DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd 2 -DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r 1 ) of 7.613mM -1 s -1 (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd 2 -DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd 2 -DTPA-BA. The signal intensity of Gd 2 -DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd 2 -DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd 2 -DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Dual-Energy Micro-CT Functional Imaging of Primary Lung Cancer in Mice Using Gold and Iodine Nanoparticle Contrast Agents: A Validation Study

PubMed Central

Ashton, Jeffrey R.; Clark, Darin P.; Moding, Everett J.; Ghaghada, Ketan; Kirsch, David G.; West, Jennifer L.; Badea, Cristian T.

2014-01-01

Purpose To provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT. Methods Primary lung tumors were generated in LSL-KrasG12D; p53FL/FL mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed–two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues. Results Dual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R2 = 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements. Conclusions Dual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex vivo methods, CT-derived nanoparticle concentrations are accurate. This method could play an important role in lung tumor characterization by CT. PMID:24520351

Single-layer and dual-layer contrast-enhanced mammography using amorphous selenium flat panel detectors

NASA Astrophysics Data System (ADS)

Allec, N.; Abbaszadeh, S.; Karim, K. S.

2011-09-01

The accumulation of injected contrast agents allows the image enhancement of lesions through the use of contrast-enhanced mammography. In this technique, the combination of two acquired images is used to create an enhanced image. There exist several methods to acquire the images to be combined, which include dual energy subtraction using a single detection layer that suffers from motion artifacts due to patient motion between image acquisition. To mitigate motion artifacts, a detector composed of two layers may be used to simultaneously acquire the low and high energy images. In this work, we evaluate both of these methods using amorphous selenium as the detection material to find the system parameters (tube voltage, filtration, photoconductor thickness and relative intensity ratio) leading to the optimal performance. We then compare the performance of the two detectors under the variation of contrast agent concentration, tumor size and dose. The detectability was found to be most comparable at the lower end of the evaluated factors. The single-layer detector not only led to better contrast, due to its greater spectral separation capabilities, but also had lower quantum noise. The single-layer detector was found to have a greater detectability by a factor of 2.4 for a 2.5 mm radius tumor having a contrast agent concentration of 1.5 mg ml-1 in a 4.5 cm thick 50% glandular breast. The inclusion of motion artifacts in the comparison is part of ongoing research efforts.

Single-layer and dual-layer contrast-enhanced mammography using amorphous selenium flat panel detectors.

PubMed

Allec, N; Abbaszadeh, S; Karim, K S

2011-09-21

The accumulation of injected contrast agents allows the image enhancement of lesions through the use of contrast-enhanced mammography. In this technique, the combination of two acquired images is used to create an enhanced image. There exist several methods to acquire the images to be combined, which include dual energy subtraction using a single detection layer that suffers from motion artifacts due to patient motion between image acquisition. To mitigate motion artifacts, a detector composed of two layers may be used to simultaneously acquire the low and high energy images. In this work, we evaluate both of these methods using amorphous selenium as the detection material to find the system parameters (tube voltage, filtration, photoconductor thickness and relative intensity ratio) leading to the optimal performance. We then compare the performance of the two detectors under the variation of contrast agent concentration, tumor size and dose. The detectability was found to be most comparable at the lower end of the evaluated factors. The single-layer detector not only led to better contrast, due to its greater spectral separation capabilities, but also had lower quantum noise. The single-layer detector was found to have a greater detectability by a factor of 2.4 for a 2.5 mm radius tumor having a contrast agent concentration of 1.5 mg ml(-1) in a 4.5 cm thick 50% glandular breast. The inclusion of motion artifacts in the comparison is part of ongoing research efforts.

Effect of intravascular contrast agent on diffusion and perfusion fraction coefficients in the peripheral zone and prostate cancer.

PubMed

Mazaheri, Yousef; Hötker, Andreas M; Shukla-Dave, Amita; Akin, Oguz; Hricak, Hedvig

2018-09-01

To determine whether water diffusion and the perfusion fraction coefficients in prostate peripheral zone (PZ) and prostate cancer (PCa) are affected by intravenous contrast injection and explore the potential mechanism behind previously reported differences between pre- and post-contrast ADC values. Our institutional review board waived informed consent for this HIPAA-compliant, retrospective study, which included 32 patients (median age, 63 years; range, 47-77 years) with biopsy-proven, untreated PCa who underwent 3-Tesla MRI, including DW-MRI at b-values 0, 400, 700, 1000 s/mm 2 before and after gadolinium injection. For regions of interest (ROIs) in presumed benign PZ and PZ PCa, apparent diffusion coefficient (ADC), perfusion fraction f, and diffusion coefficient D were estimated voxel-wise, and signal-to-noise ratio (SNR) and contrast-to-noise (CNR) were estimated. Pre- and post-contrast measurements were compared by Wilcoxon signed-rank test; P < 0.05 was considered significant. In PZ, f (P = 0.002) was significantly higher on post-contrast imaging than on pre-contrast imaging, but ADC and D values did not change significantly (P = 0.562 and 0.295 respectively). In PCa, all parameters differed significantly between post-contrast and pre-contrast imaging (P < 0.0001 for ADC, P = 0.0084 for D, and P = 0.029 for f). On post-contrast imaging, SNR was not significantly different in PZ (P = 0.260) but was significantly lower in PCa (P < 0.0001); CNR did not change significantly (P = 0.059). After contrast injection, ADC and D declined significantly in PCa only, while f increased significantly in both PCa and PZ. Pre- and post-contrast diffusion parameters cannot be used interchangeably for diagnostic purposes that require quantitative diffusion estimates. Copyright © 2018. Published by Elsevier Inc.

SU-E-QI-21: Iodinated Contrast Agent Time Course In Human Brain Metastasis: A Study For Stereotactic Synchrotron Radiotherapy Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obeid, L; Esteve, F; Adam, J

2014-06-15

Purpose: Synchrotron stereotactic radiotherapy (SSRT) is an innovative treatment combining the selective accumulation of heavy elements in tumors with stereotactic irradiations using monochromatic medium energy x-rays from a synchrotron source. Phase I/II clinical trials on brain metastasis are underway using venous infusion of iodinated contrast agents. The radiation dose enhancement depends on the amount of iodine in the tumor and its time course. In the present study, the reproducibility of iodine concentrations between the CT planning scan day (Day 0) and the treatment day (Day 10) was assessed in order to predict dose errors. Methods: For each of days 0more » and 10, three patients received a biphasic intravenous injection of iodinated contrast agent (40 ml, 4 ml/s, followed by 160 ml, 0.5 ml/s) in order to ensure stable intra-tumoral amounts of iodine during the treatment. Two volumetric CT scans (before and after iodine injection) and a multi-slice dynamic CT of the brain were performed using conventional radiotherapy CT (Day 0) or quantitative synchrotron radiation CT (Day 10). A 3D rigid registration was processed between images. The absolute and relative differences of absolute iodine concentrations and their corresponding dose errors were evaluated in the GTV and PTV used for treatment planning. Results: The differences in iodine concentrations remained within the standard deviation limits. The 3D absolute differences followed a normal distribution centered at zero mg/ml with a variance (∼1 mg/ml) which is related to the image noise. Conclusion: The results suggest that dose errors depend only on the image noise. This study shows that stable amounts of iodine are achievable in brain metastasis for SSRT treatment in a 10 days interval.« less

Ultrasound-guided photoacoustic imaging of lymph nodes with biocompatible gold nanoparticles as a novel contrast agent (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, In-Cheol; Dumani, Diego; Emelianov, Stanislav Y.

2017-02-01

A key step in staging cancer is the diagnosis of metastasis that spreads through lymphatic system. For this reason, researchers develop various methods of sentinel lymph node mapping that often use a radioactive tracer. This study introduces a safe, cost-effective, high-resolution, high-sensitivity, and real-time method of visualizing the sentinel lymph node: ultrasound-guided photoacoustic (US/PA) imaging augmented by a contrast agent. In this work, we use clearable gold nanoparticles covered by a biocompatible polymer (glycol chitosan) to enhance cellular uptake by macrophages abundant in lymph nodes. We incubate macrophages with glycol-chitosan-coated gold nanoparticles (0.05 mg Au/ml), and then fix them with paraformaldehyde solution for an analysis of in vitro dark-field microscopy and cell phantom. The analysis shows enhanced cellular uptake of nanoparticles by macrophages and strong photoacoustic signal from labeled cells in tissue-mimicking cell phantoms consisting gelatin solution (6 %) with silica gel (25 μm, 0.3%) and fixed macrophages (13 X 105 cells). The in-vivo US/PA imaging of cervical lymph nodes in healthy mice (nu/nu, female, 5 weeks) indicates a strong photoacoustic signal from a lymph node 10 minutes post-injection (2.5 mg Au/ml, 80 μl). The signal intensity and the nanoparticle-labeled volume of tissue within the lymph node continues to increase until 4 h post-injection. Histological analysis further confirms the accumulation of gold nanoparticles within the lymph nodes. This work suggests the feasibility of molecular/cellular US/PA imaging with biocompatible gold nanoparticles as a photoacoustic contrast agent in the diagnosis of lymph-node-related diseases.

Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

PubMed

Menendez-Castro, Carlos; Zapke, Maren; Fahlbusch, Fabian; von Goessel, Heiko; Rascher, Wolfgang; Jüngert, Jörg

2017-07-06

Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

Arterial spin labeling blood flow magnetic resonance imaging for evaluation of renal injury.

PubMed

Liu, Yupin P; Song, Rui; Liang, Chang hong; Chen, Xin; Liu, Bo

2012-08-15

A multitude of evidence suggests that iodinated contrast material causes nephrotoxicity; however, there have been no previous studies that use arterial spin labeling (ASL) blood flow functional magnetic resonance imaging (fMRI) to investigate the alterations in effective renal plasma flow between normointensive and hypertensive rats following injection of contrast media. We hypothesized that FAIR-SSFSE arterial spin labeling MRI may enable noninvasive and quantitative assessment of regional renal blood flow abnormalities and correlate with disease severity as assessed by histological methods. Renal blood flow (RBF) values of the cortex and medulla of rat kidneys were obtained from ASL images postprocessed at ADW4.3 workstation 0.3, 24, 48, and 72 h before and after injection of iodinated contrast media (6 ml/kg). The H&E method for morphometric measurements was used to confirm the MRI findings. The RBF values of the outer medulla were lower than those of the cortex and the inner medulla as reported previously. Iodinated contrast media treatment resulted in decreases in RBF in the outer medulla and cortex in spontaneously hypertensive rats (SHR), but only in the outer medulla in normotensive rats. The iodinated contrast agent significantly decreased the RBF value in the outer medulla and the cortex in SHR compared with normotensive rats after injection of the iodinated contrast media. Histological observations of kidney morphology were also consistent with ASL perfusion changes. These results demonstrate that the RBF value can reflect changes of renal perfusion in the cortex and medulla. ASL-MRI is a feasible and accurate method for evaluating nephrotoxic drugs-induced kidney damage.

Novel receptor-targeted contrast agents for optical imaging of tumors

NASA Astrophysics Data System (ADS)

Becker, Andreas; Hessenius, Carsten; Bhargava, Sarah; Ebert, Bernd; Sukowski, Uwe; Rinneberg, Herbert H.; Wiedenmann, Bertram; Semmler, Wolfhard; Licha, Kai

2000-04-01

Many gastroenteropancreatic tumors express receptors for somatostatin (SST) and/or vasoactive intestinal peptide (VIP). These receptors can be used as molecular targets for the delivery of contrast agents for tumor diagnostics. We have synthesized conjugates consisting of a cyanine dye and an SST analogue or VIP for use as contrast agents in optical imaging. Receptor binding and internalization of these compounds were examined with optical methods in transfected RIN38 tumor cells expressing the SST2 receptor or a GFP- labeled VIP (VPAC1) receptor. Furthermore, biodistribution of the conjugates was examined by laser-induced fluorescence imaging in nude mice bearing SST2 or VPAC1 receptor- expressing tumors. After incubation of RIN38 SSTR2 cells in the presence of 100 nM indotricarbocyanine-SST analogue, cell-associated fluorescence increased, whereas no increase was observed when receptor-medicated endocytosis was inhibited. Indodicarbocyanine-VIP accumulated in RIN38 VPAC1 cells and co-localization with the GFP-labeled VPAC1 receptor was observed. After injection of indotricarbocyanine-SST analogue into tumor-bearing nude mice, SST2 receptor-positive tumors could be visualized for a time period from 10 min to at least 48 h. After application of indodicarbocyanine-VIP, a fluorescence signal in VIP1 receptor-expressing tumors was only detected during the first hour. We conclude that cyanine dye-labeled VIP and SST analogue are novel, targeted contrast agents for the optical imaging of tumors expressing the relevant receptor.

Influence of temperature, needle gauge and injection rate on the size distribution, concentration and acoustic responses of ultrasound contrast agents at high frequency.

PubMed

Sun, Chao; Panagakou, Ioanna; Sboros, Vassilis; Butler, Mairead B; Kenwright, David; Thomson, Adrian J W; Moran, Carmel M

2016-08-01

This paper investigated the influence of needle gauge (19G and 27G), injection rate (0.85ml·min(-1), 3ml·min(-1)) and temperature (room temperature (RT) and body temperature (BT)) on the mean diameter, concentration, acoustic attenuation, contrast to tissue ratio (CTR) and normalised subharmonic intensity (NSI) of three ultrasound contrast agents (UCAs): Definity, SonoVue and MicroMarker (untargeted). A broadband substitution technique was used to acquire the acoustic properties over the frequency range 17-31MHz with a preclinical ultrasound scanner Vevo770 (Visualsonics, Canada). Significant differences (P<0.001-P<0.05) between typical in vitro setting (19G needle, 3ml·min(-1) at RT) and typical in vivo setting (27G needle, 0.85ml·min(-1) at BT) were found for SonoVue and MicroMarker. Moreover we found that the mean volume-based diameter and concentration of both SonoVue and Definity reduced significantly when changing from typical in vitro to in vivo experimental set-ups, while those for MicroMarker did not significantly change. From our limited measurements of Definity, we found no significant change in attenuation, CTR and NSI with needle gauge. For SonoVue, all the measured acoustic properties (attenuation, CTR and NSI) reduced significantly when changing from typical in vitro to in vivo experimental conditions, while for MicroMarker, only the NSI reduced, with attenuation and CTR increasing significantly. These differences suggest that changes in physical compression and temperature are likely to alter the shell structure of the UCAs resulting in measureable and significant changes in the physical and high frequency acoustical properties of the contrast agents under typical in vitro and preclinical in vivo experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

High-resolution contrast-enhanced optical coherence tomography in mice retinae

NASA Astrophysics Data System (ADS)

Sen, Debasish; SoRelle, Elliott D.; Liba, Orly; Dalal, Roopa; Paulus, Yannis M.; Kim, Tae-Wan; Moshfeghi, Darius M.; de la Zerda, Adam

2016-06-01

Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo inside mice retinae. We corroborated OCT observations with hyperspectral dark-field microscopy of formalin-fixed histological sections. Our results show that mouse leukocytes that otherwise do not produce OCT contrast can be labeled with GNRs leading to significant OCT intensity equivalent to a 0.5 nM GNR solution. Furthermore, GNRs injected intravenously can be detected inside retinal blood vessels at a sensitivity of ˜0.5 nM, and GNR-labeled cells injected intravenously can be detected inside retinal capillaries by enhanced OCT contrast. We envision the unprecedented resolution and sensitivity of functionalized GNRs coupled with OCT to be adopted for longitudinal studies of retinal disorders.

Small animal optoacoustic tomography system for molecular imaging of contrast agents

NASA Astrophysics Data System (ADS)

Su, Richard; Liopo, Anton; Ermilov, Sergey A.; Oraevsky, Alexander A.

2016-03-01

We developed a new and improved Laser Optoacoustic Imaging System, LOIS-3D for preclinical research applications in small animal models. The advancements include (i) a new stabilized imaging module with a more homogeneous illumination of the mouse yielding a better spatial resolution (<0.2 mm) and (ii) a new low noise amplifier incorporated into the ultrasonic probe and providing the noise equivalent pressure around 2 Pa resulting in increased signal-to-noise ratio and the optical absorption sensitivity of about 0.15 cm-1. We also improved scan time and the image reconstruction times. This prototype has been commercialized for a number of biomedical research applications, such as imaging vascularization and measuring hemoglobin / oxyhemoglobin distribution in the organs as well as imaging exogenous or endogenous optoacoustic contrast agents. As examples, we present in vivo experiments using phantoms and mice with and without tumor injected with contrast agents with indocyanine green (ICG). LOIS-3D was capable of detecting ~1-2 pmole of the ICG, in tissues with relatively low blood content. With its high sensitivity and excellent spatial resolution LOIS-3D is an advanced alternative to fluorescence and bioluminescence based modalities for molecular imaging in live mice.

Assessment of tumor angiogenesis using fluorescence contrast agents

NASA Astrophysics Data System (ADS)

Chen, Yu; Liu, Qian; Huang, Ping; Hyman, Shay; Intes, Xavier; Lee, William; Chance, Britton

2003-12-01

Angiogenesis is an important factor for further tumor growth and thus could be an attractive therapeutic target. Optical imaging can provide a non-invasive way to measure the permeability of tumor blood vessels and assess the tumor vasculature. We have developed a dual-channel near-infrared fluorescence system for simultaneous measurement of the pharmacokinetics of tumorous and normal tissues with exogenous contrast agents. This frequency-domain system consists of the light source (780 nm laser diode), fiber optics, interference filter (830 nm) and the detector (PMT). The fluorescent contrast agent used in this study is Indocyanine Green (ICG), and the normal dosage is 100 μl at a concentration of 5 μM. In vivo animal study is performed on the K1735 melanoma-bearing mouse. The fluorescence signals both tumorous and normal tissues after the bolus injection of ICG through the tail vein are continuously recorded as a function of time. The data is fitted by a double-exponential model to reveal the wash-in and wash-out parameters of different tissues. We observed an elongated wash-out from the tumor compared with normal tissue (leg). The effect of radiation therapy on the tumor vasculature is also discussed.

X-ray Scatter Imaging of Hepatocellular Carcinoma in a Mouse Model Using Nanoparticle Contrast Agents

NASA Astrophysics Data System (ADS)

Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R.; Rose-Petruck, Christoph

2015-10-01

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T.

PubMed

Longo, Dario Livio; Dastrù, Walter; Digilio, Giuseppe; Keupp, Jochen; Langereis, Sander; Lanzardo, Stefania; Prestigio, Simone; Steinbach, Oliver; Terreno, Enzo; Uggeri, Fulvio; Aime, Silvio

2011-01-01

Iopamidol (Isovue®-Bracco Diagnostic Inc.) is a clinically approved X-Ray contrast agent used in the last 30 years for a wide variety of diagnostic applications with a very good clinical acceptance. Iopamidol contains two types of amide functionalities that can be exploited for the generation of chemical exchange saturation transfer effect. The exchange rate of the two amide proton pools is markedly pH-dependent. Thus, a ratiometric method for pH assessment has been set-up based on the comparison of the saturation transfer effects induced by selective irradiation of the two resonances. This ratiometric approach allows to rule out the concentration effect of the contrast agent and provides accurate pH measurements in the 5.5-7.4 range. Upon injection of Iopamidol into healthy mice, it has been possible to acquire pH maps of kidney regions. Furthermore, it has been also shown that the proposed method is able to report about pH-changes induced in control mice fed with acidified or basified water for a period of a week before image acquisition. © 2010 Wiley-Liss, Inc.

An analysis of the uncertainty and bias in DCE-MRI measurements using the spoiled gradient-recalled echo pulse sequence.

PubMed

Subashi, Ergys; Choudhury, Kingshuk R; Johnson, G Allan

2014-03-01

The pharmacokinetic parameters derived from dynamic contrast-enhanced (DCE) MRI have been used in more than 100 phase I trials and investigator led studies. A comparison of the absolute values of these quantities requires an estimation of their respective probability distribution function (PDF). The statistical variation of the DCE-MRI measurement is analyzed by considering the fundamental sources of error in the MR signal intensity acquired with the spoiled gradient-echo (SPGR) pulse sequence. The variance in the SPGR signal intensity arises from quadrature detection and excitation flip angle inconsistency. The noise power was measured in 11 phantoms of contrast agent concentration in the range [0-1] mM (in steps of 0.1 mM) and in onein vivo acquisition of a tumor-bearing mouse. The distribution of the flip angle was determined in a uniform 10 mM CuSO4 phantom using the spin echo double angle method. The PDF of a wide range of T1 values measured with the varying flip angle (VFA) technique was estimated through numerical simulations of the SPGR equation. The resultant uncertainty in contrast agent concentration was incorporated in the most common model of tracer exchange kinetics and the PDF of the derived pharmacokinetic parameters was studied numerically. The VFA method is an unbiased technique for measuringT1 only in the absence of bias in excitation flip angle. The time-dependent concentration of the contrast agent measured in vivo is within the theoretically predicted uncertainty. The uncertainty in measuring K(trans) with SPGR pulse sequences is of the same order, but always higher than, the uncertainty in measuring the pre-injection longitudinal relaxation time (T10). The lowest achievable bias/uncertainty in estimating this parameter is approximately 20%-70% higher than the bias/uncertainty in the measurement of the pre-injection T1 map. The fractional volume parameters derived from the extended Tofts model were found to be extremely sensitive to the variance in signal intensity. The SNR of the pre-injection T1 map indicates the limiting precision with which K(trans) can be calculated. Current small-animal imaging systems and pulse sequences robust to motion artifacts have the capacity for reproducible quantitative acquisitions with DCE-MRI. In these circumstances, it is feasible to achieve a level of precision limited only by physiologic variability.

Development and evaluation of a novel VEGFR2-targeted nanoscale ultrasound contrast agents

NASA Astrophysics Data System (ADS)

Yu, Houqiang; Li, Chunfang; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

2016-04-01

Recent literatures have reported that the targeted nanoscale ultrasound contrast agents are becoming more and more important in medical application, like ultrasound imaging, detection of perfusion, drug delivery and molecular imaging and so on. In this study, we fabricated an uniform nanoscale bubbles (257 nm with the polydispersity index of 0.458) by incorporation of antibody targeted to vascular endothelial growth factor receptor 2 (VEGFR2) into the nanobubbles membrane by using avidin-biotin interaction. Some fundamental characterizations such as nanobubble suspension, surface morphology, particle size distribution and zeta potential were investigated. The concentration and time-intensity curves (TICs) were obtained with a self-made ultrasound experimental setup in vitro evaluation. In addition, in order to evaluate the contrast enhancement ability and the potential tumor-targeted ability in vivo, normal Wistar rats and nude female BALB/c mice were intravascular administration of the nanobubbles via tail vein injection, respectively. Significant contrast enhancement of ultrasound imaging within liver and tumor were visualized. These experiments demonstrated that the targeted nanobubbles is efficient in ultrasound molecular imaging by enhancement of the contrast effect and have potential capacity for targeted tumor diagnosis and therapy in the future.

Coronary angiography using synchrotron radiation (invited)

NASA Astrophysics Data System (ADS)

Thompson, A. C.; Rubenstein, E.; Zeman, H. D.; Hofstadter, R.; Otis, J. N.; Giacomini, J. C.; Gordon, H. J.; Brown, G. S.; Thomlinson, W.; Kernoff, R. S.

1989-07-01

Imaging of coronary arteries using a venous instead of an arterial injection of contrast agent could provide a much safer method to diagnose heart disease. The tunability, intensity, and collimation of synchrotron radiation x-ray beams makes possible imaging systems with greatly improved imaging sensitivity. A pair of fan x-ray beams, a movable patient chair, and a multielement x-ray detector are used to acquire a pair of x-ray images above and below the iodine K edge. The logarithmic subtraction of these two images produces an image with excellent sensitivity to contrast agent and minimal sensitivity to bone and tissue. High-quality images from a dog and preliminary images from five humans have been obtained. Improvements are being made to the system to increase the effective radiation flux and to measure the position of both x-ray beams.

TOPICAL REVIEW: Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

NASA Astrophysics Data System (ADS)

Qin, Shengping; Caskey, Charles F.; Ferrara, Katherine W.

2009-03-01

Microbubble contrast agents and the associated imaging systems have developed over the past 25 years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium.

Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

PubMed Central

Qin, Shengping; Caskey, Charles F; Ferrara, Katherine W

2010-01-01

Microbubble contrast agents and the associated imaging systems have developed over the past twenty-five years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium. PMID:19229096

Computed tomography and magnetic resonance imaging in diagnosing hepatocellular carcinoma.

PubMed

Dalla Palma, L; Pozzi-Mucelli, R S

1992-02-01

The evaluation of hepatocellular carcinoma (HCC) is based upon ultrasonography (US) which has proved to have a high sensitivity and is also extremely useful in guiding the percutaneous needle biopsy. The main role of computed tomography (CT) and magnetic resonance imaging (MRI) is to supplement US in evaluating the extent of HCC. The Authors discuss the different techniques of examinations of the liver both for CT and MRI as far as the modalities of contrast enhancement, site of injection, and type of contrast agents are concerned. The differences between low field and high field magnets are also discussed. The main CT and MRI findings are illustrated, depending upon the technique of examination. Finally the role of these techniques is discussed. Based upon personal experience and the data in CT literature, and if performed with updated technology and intraarterial injection (lipiodol), CT is the method of choice in order to supplement US in the evaluation of HCC.

Differences in perilymphatic space enhancement and adverse inflammatory reaction after intratympanic injection of two different gadolinium agents: A 9.4-T magnetic resonance imaging study.

PubMed

Park, Mina; Lee, Ho Sun; Kim, Hyeonjin; Oh, Seung Ha; Lee, Jun Ho; Suh, Myung-Whan

2016-03-01

To compare the inner ear enhancement after intratympanic injection of two widely used gadolinium (Gd) agents by 9.4 T micro-magnetic resonance imaging (MRI) and to investigate the effects of Gd on the inner ear. Twelve ears of six rats received intratympanic administration of 1/5 diluted Gd agents: gadoterate meglumine (Gd-DTPA) for the left ear and gadodiamide (Gd-DTPA-BMA) for the right ear. MRI was performed every 30 min from 1 to 4 h after administration. The normalized signal intensity was evaluated by quantitative analysis at each cochlear fluid compartment. Eight, six, and seven ears treated with Gd-DTPA, Gd-DPTA-BMA, and nothing as controls, respectively, were processed for histological evaluation after MRI. After hematoxylin & eosin staining, adverse inflammatory reactions were evaluated for turbid aggregation and lymphocytes. The perilymphatic enhancement of Gd-DTPA was superior to that of Gd-DTPA-BMA regardless of cochlear turn, compartment, and time point. Inflammatory reactions were found in 4/8 (50.0%) and 4/6 (66.6%) ears administered Gd-DTPA and Gd-DTPA-BMA, respectively. Regardless of the contrast agent used, inflammatory reactions were most definite in the scala tympani of the basal turn, i.e., near the round window. Slightly greater inflammatory reactions were observed in ears injected with Gd-DTPA-BMA compared to Gd-DTPA although the difference was not statistically significant. No inflammatory reaction was observed in any of the seven controls. The auditory brainstem response threshold was 11.8 ± 2.5 dB SPL before IT Gd injection and it did not change for up to 5 days (15.4 ± 6.6 dB SPL) post-injection. Gd-DTPA was superior to Gd-DTPA-BMA for visualization of the inner ear. Administration of diluted Gd agents intratympanically may induce considerable inflammatory reactions in the inner ear. Copyright © 2015 Elsevier B.V. All rights reserved.

Contrast-enhanced photoacoustic imaging with an optical wavelength of 1064 nm

NASA Astrophysics Data System (ADS)

Kim, Jeesu; Park, Sara; Park, Gyeong Bae; Choi, Wonseok; Jeong, Unyong; Kim, Chulhong

2018-02-01

Photoacoustic (PA) imaging is a biomedical imaging method that can provide both structural and functional information of living tissues beyond the optical diffusion limit by combining the concepts of conventional optical and ultrasound imaging methods. Although endogenous chromophores can be utilized to acquire PA images of biological tissues, exogenous contrast agents that absorb near-infrared (NIR) lights have been extensively explored to improve the contrast and penetration depth of PA images. Here, we demonstrate Bi2Se3 nanoplates, that strongly absorbs NIR lights, as a contrast agent for PA imaging. In particularly, the Bi2Se3 nanoplates produce relatively strong PA signals with an optical wavelength of 1064 nm, which has several advantages for deep tissue imaging including: (1) relatively low absorption by other intrinsic chromophores, (2) cost-effective light source using Nd:YAG laser, and (3) higher available energy than other NIR lights according to American National Standards Institute (ANSI) safety limit. We have investigated deep tissue imaging capability of the Bi2Se3 nanoplates by acquiring in vitro PA images of microtubes under chicken breast tissues. We have also acquired in vivo PA images of bladders, gastrointestinal tracts, and sentinel lymph nodes in mice after injection of the Bi2Se3 nanoplates to verify their applicability to a variety of biomedical research. The results show the promising potential of the Bi2Se3 nanoplates as a PA contrast agent for deep tissue imaging with an optical wavelength of 1064 nm.

Measurement of pulmonary transit time in healthy cats by use of ultrasound contrast media "Sonovue®": feasibility, reproducibility, and values in 42 cats.

PubMed

Streitberger, Andrea; Hocke, Verena; Modler, Peter

2013-09-01

To evaluate the feasibility of measuring pulmonary transit time (PTT) in healthy cats by transthoracic echocardiography using the ultrasound contrast agent Sonovue(®). To determine normalized PTT (nPTT) values in 42 healthy cats and to estimate the interobserver variability and the within-day repeatability of nPTT measurements. Forty-two privately owned healthy cats of different breeds, gender and age presented for cardiac examination. A bolus injection of contrast agent (Sonovue(®)) was administered intravenously. The right parasternal short axis echocardiographic view was used to record the contrast agent's transit time from the pulmonary artery to the left atrium. Pulmonary transit time and nPTT were determined independently by three examiners with different levels of experience. Normalized PTT was 4.12 ± 1.0 (mean ± SD) in our population. The median interobserver variability across our population was 6.8%, the median within-day variability for the three observers were 13.1%, 12.7% and 13%. No effect of the observer's experience on nPTT measurement was identified. Age, sex and body weight did not significantly influence nPTT. This study demonstrates that nPTT measurement is feasible in cats using ultrasound and the blood pool contrast media Sonovue(®). Measurements of nPTT can be performed in a clinical setting. Normalized PTT values in healthy cats are comparable with those reported in healthy dogs. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of acetylcysteine and probucol on contrast medium-induced depression of intrinsic renal glutathione peroxidase activity in diabetic rats.

PubMed

Yen, Hsueh-Wei; Lee, Hsiang-Chun; Lai, Wen-Te; Sheu, Sheng-Hsiung

2007-04-01

Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity. Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ). We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD. These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity.

3D map of theranostic nanoparticles distribution in mice brain and liver by means of X-ray Phase Contrast Tomography

NASA Astrophysics Data System (ADS)

Longo, E.; Bravin, A.; Brun, F.; Bukreeva, I.; Cedola, A.; Fratini, M.; Le Guevel, X.; Massimi, L.; Sancey, L.; Tillement, O.; Zeitoun, P.; de La Rochefoucauld, O.

2018-01-01

The word "theranostic" derives from the fusion of two terms: therapeutic and diagnostic. It is a promising research field that aims to develop innovative therapies with high target specificity by exploiting the therapeutic and diagnostic properties, in particular for metal-based nanoparticles (NPs) developed to erase cancer. In the framework of a combined research program on low dose X-ray imaging and theranostic nanoparticles (NPs), high resolution Phase-Contrast Tomography images of mice organs injected with gadolinium and gold-NPs were acquired at the European Synchrotron Radiation Facility (ESRF). Both compounds are good X-ray contrast agents due to their high attenuation coefficient with respect to biological tissues, especially immediately above K-edge energy. X-ray tomography is a powerful non-invasive technique to image the 3D vasculature network in order to detect abnormalities. Phase contrast methods provide more detailed anatomical information with higher discrimination among soft tissues. We present the images of mice liver and brain injected with gold and gadolinium NPs, respectively. We discuss different image processing methods used aiming at enhancing the accuracy on localizing nanoparticles.

Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model.

PubMed

Scheller, Bruno; Speck, Ulrich; Romeike, Bernd; Schmitt, Alexander; Sovak, Milos; Böhm, Michael; Stoll, Hans Peter

2003-08-01

Lipophilic taxanes can be dissolved in contrast media at significantly higher concentration than in saline. As contrast media have occasionally been observed to delineate the contour of coronary arteries for some seconds they may serve as a matrix for an antiproliferative drug aimed at preventing restenosis. The aim of this study was to test a novel taxane-contrast agent formulation for this new approach in the setting of coronary stenting. In cell culture experiments (bovine vascular smooth muscle cells), 60-min incubation with contrast agent-taxane formulations (iopromide-paclitaxel, iopromide-protaxel) induced a significant, concentration-dependent inhibition of vascular smooth muscle cell (VSMC) proliferation over 12 days. Shorter incubation times of 10 and 3 min showed the same efficacy. For in vivo investigation, 16 stents were implanted into the coronary arteries of eight pigs using a 1.3 to 1 overstretch ratio. A control group received iopromide 370 alone while the treatment group was injected with a iopromide-protaxel formulation at a dose of 74 micromol/l, which is far below protaxel levels inducing systemic toxicity. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment groups. After 28 days, the treatment group showed a marked reduction of the parameters characterizing in-stent restenosis, especially a 34% reduction of the neointimal area. First evidence is provided that using a contrast agent as solvent for a taxane constitutes a new drug delivery mechanism able to inhibit in-stent restenosis in the porcine restenosis model.

Contrast-enhanced computed tomography of the gastrointestinal tract in clinically normal alpacas and llamas.

PubMed

Stieger-Vanegas, Susanne M; Cebra, Christopher K

2013-01-15

To assess the feasibility and usefulness of CT enterography to evaluate the gastrointestinal tract in clinically normal llamas and alpacas. Prospective observational study. 7 clinically normal alpacas and 8 clinically normal llamas. The imaging protocol included orogastric administration of iodinated contrast material mixed with water. Three hours later, helical CT scanning was performed of the entire abdomen with transverse and multiplanar sagittal and dorsal projections before and after IV iodinated contrast agent injection. Both oral and IV contrast agents were well tolerated, and no adverse reactions were observed. Transverse images depicted the gastrointestinal tract and pancreas in the short axis; however, dorsal and sagittal projections aided in localizing and differentiating the various gastrointestinal segments, including the pancreas. In all camelids, the wall of the gastrointestinal tract was well differentiated. In all but 2 camelids, all gastrointestinal segments were well visualized and differentiated. In those 2 animals, the cecum was difficult to identify. Good distention of the small intestine was achieved by use of the oral contrast agent. The dorsal projections were useful to identify the pancreas in its entire length. The present study supplied new information about gastrointestinal wall thickness, intestinal diameter, and location of the pancreas and ileocecocolic junction in alpacas and llamas. Multiplanar contrast-enhanced CT was useful to reveal the various segments of the gastrointestinal tract, pancreas, and abdominal lymph nodes. The shorter time delay before imaging, compared with the delay with conventional barium studies, makes this technique complementary or superior to conventional radiographic or ultrasonographic studies for evaluation of the gastrointestinal tract.

Cellular internalization and morphological analysis after intravenous injection of a highly hydrophilic octahedral rhenium cluster complex - a new promising X-ray contrast agent.

PubMed

Krasilnikova, Anna A; Solovieva, Anastasiya O; Trifonova, Kristina E; Brylev, Konstantin A; Ivanov, Anton A; Kim, Sung-Jin; Shestopalov, Michael A; Fufaeva, Maria S; Shestopalov, Alexander M; Mironov, Yuri V; Poveshchenko, Alexander F; Shestopalova, Lidia V

2016-11-01

The octahedral cluster compound Na 2 H 8 [{Re 6 Se 8 }(P(C 2 H 4 CONH 2 )(C 2 H 4 COO) 2 ) 6 ] has been shown to be highly radio dense, thus becoming a promising X-ray contrast agent. It was also shown that this compound had low cytotoxic effect in vitro, low acute toxicity in vivo and was eliminated rapidly from the body through the urinary tract. The present contribution describes a more detailed cellular internalization assay and morphological analysis after intravenous injection of this hexarhenium cluster compound at different doses. The median lethal dose (LD 50 ) of intravenously administrated compound was calculated (4.67 ± 0.69 g/kg). Results of the study clearly indicated that the cluster complex H n [{Re 6 Se 8 }(P(C 2 H 4 CONH 2 )(C 2 H 4 COO) 2 ) 6 ] n-10 was not internalized into cells in vitro and induced only moderate morphological alterations of kidneys at high doses without any changes in morphology of liver, spleen, duodenum, or heart of mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Visualization of subcutaneous insulin injections by x-ray computed tomography

NASA Astrophysics Data System (ADS)

Thomsen, M.; Poulsen, M.; Bech, M.; Velroyen, A.; Herzen, J.; Beckmann, F.; Feidenhans'l, R.; Pfeiffer, F.

2012-11-01

We report how the three-dimensional structure of subcutaneous injections of soluble insulin can be visualized by x-ray computed tomography using an iodine based contrast agent. The injections investigated are performed ex vivo in porcine adipose tissue. Full tomography scans carried out at a laboratory x-ray source with a total acquisition time of about 1 min yield CT-images with an effective pixel size of 109 × 109 μm2. The depots are segmented using a modified Chan-Vese algorithm and we are able to observe differences in the shape of the injection depot and the position of the depot in the skin among equally performed injections. To overcome the beam hardening artefacts, which affect the quantitative prediction of the volume injected, we additionally present results concerning the visualization of two injections using synchrotron radiation. The spatial concentration distribution of iodine is calculated to show the dilution of the insulin drug inside the depot. Characterisation of the shape of the depot and the spatial concentration profile of the injected fluid is important knowledge when improving the clinical formulation of an insulin drug, the performance of injection devices and when predicting the effect of the drug through biomedical simulations.

A novel bubble-forming material for preparing hydrophobic-agent-loaded bubbles with theranostic functionality.

PubMed

Yang, Pei-Sin; Tung, Fu-I; Chen, Hsiao-Ping; Liu, Tse-Ying; Lin, Yi-Ying

2014-08-01

In the present study, a new bubble-forming material (carboxymethyl hexanoyl chitosan, CHC), together with superparamagnetic iron oxide (SPIO) nanoparticles, was employed to prepare image-guided bubbles for efficiently encapsulating and delivering hydrophobic agents to kill tumor cells. The results showed that CHC could be used for preparing not only micronized bubbles (CHC/SPIO MBs) to exhibit ultrasound imaging functionality but also nanosized bubbles (CHC/SPIO NBs) to exhibit magnetic resonance T2 image contrast. It was found that the amounts of SPIO nanoparticles and hexane during preparation process were the key factors to obtaining CHC/SPIO NBs. Most importantly, under in vitro cell culture conditions with the same amount of camptothecin (CPT) and therapeutic sonication, CPT-loaded CHC/SPIO NBs demonstrated more significant transcellular delivery and cytotoxicity than free CPT. Subsequently, an intratumoral injection was proposed for the in vivo administration of hydrophobic-agent-loaded CHC/SPIO NBs. After injection, the distribution of a hydrophobic dye (DiR, an agent with near-infrared (NIR) fluorescence used as a model drug) released from the CHC/SPIO NBs was tracked by an NIR imaging technique. A significant tumor-specific accumulation was observed in the mouse that received the DiR-loaded CHC/SPIO NBs; the same was not observed in the mouse that received the free dye (without incorporating with CHC/SPIO NBs). It is expected, in the future, both the dose of the therapeutic agent administered and its side effects can be significantly lowered by using novel CHC/SPIO NBs together with local delivery (intratumoral injection), targeted imaging and enhanced cellular uptake of the drug. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Magnetic resonance imaging of post-ischemic blood-brain barrier damage with PEGylated iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Liu, Dong-Fang; Qian, Cheng; An, Yan-Li; Chang, Di; Ju, Sheng-Hong; Teng, Gao-Jun

2014-11-01

Blood-brain barrier (BBB) damage during ischemia may induce devastating consequences like cerebral edema and hemorrhagic transformation. This study presents a novel strategy for dynamically imaging of BBB damage with PEGylated supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The employment of SPIONs as contrast agents made it possible to dynamically image the BBB permeability alterations and ischemic lesions simultaneously with T2-weighted MRI, and the monitoring could last up to 24 h with a single administration of PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd-DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The immunohistochemical staining also confirmed the leakage of SPION-PEG from cerebral vessels into parenchyma. This study provides a novel and convenient route for imaging BBB alteration in the experimental ischemic stroke model.

Videodensitometric Methods for Cardiac Output Measurements

NASA Astrophysics Data System (ADS)

Mischi, Massimo; Kalker, Ton; Korsten, Erik

2003-12-01

Cardiac output is often measured by indicator dilution techniques, usually based on dye or cold saline injections. Developments of more stable ultrasound contrast agents (UCA) are leading to new noninvasive indicator dilution methods. However, several problems concerning the interpretation of dilution curves as detected by ultrasound transducers have arisen. This paper presents a method for blood flow measurements based on UCA dilution. Dilution curves are determined by real-time densitometric analysis of the video output of an ultrasound scanner and are automatically fitted by the Local Density Random Walk model. A new fitting algorithm based on multiple linear regression is developed. Calibration, that is, the relation between videodensity and UCA concentration, is modelled by in vitro experimentation. The flow measurement system is validated by in vitro perfusion of SonoVue contrast agent. The results show an accurate dilution curve fit and flow estimation with determination coefficient larger than 0.95 and 0.99, respectively.

Contrast agent comparison for three-dimensional micro-CT angiography: A cadaveric study.

PubMed

Kingston, Mitchell J; Perriman, Diana M; Neeman, Teresa; Smith, Paul N; Webb, Alexandra L

2016-07-01

Barium sulfate and lead oxide contrast media are frequently used for cadaver-based angiography studies. These contrast media have not previously been compared to determine which is optimal for the visualisation and measurement of blood vessels. In this study, the lower limb vessels of 16 embalmed Wistar rats, and four sets of cannulae of known diameter, were injected with one of three different contrast agents (barium sulfate and resin, barium sulfate and gelatin, and lead oxide combined with milk powder). All were then scanned using micro-computed tomography (CT) angiography and 3-D reconstructions generated. The number of branching generations of the rat lower limb vessels were counted and compared between the contrast agents using ANOVA. The diameter of the contrast-filled cannulae, were measured and used to calculate the accuracy of the measurements by comparing the bias and variance of the estimates. Intra- and inter-observer reliability were calculated using intra-class correlation coefficients. There was no significant difference (mean difference [MD] 0.05; MD 95% confidence interval [CI] -0.83 to 0.93) between the number of branching generations for barium sulfate-resin and lead oxide-milk powder. Barium sulfate-resin demonstrated less bias and less variance of the estimates (MD 0.03; standard deviation [SD] 1.96 mm) compared to lead oxide-milk powder (MD 0.11; SD 1.96 mm) for measurements of contrast-filled cannulae scanned at high resolution. Barium sulfate-resin proved to be more accurate than lead oxide-milk powder for high resolution micro-CT scans and is preferred due to its non-toxicity. This technique could be applied to any embalmed specimen model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Comparative analysis of renal flow using contrast power Doppler and gray-scale ultrasound

NASA Astrophysics Data System (ADS)

Sehgal, Chandra M.; Arger, Peter H.; Bovee, Kenneth C.; Pugh, Charles; Kirchhofer, Justin I.

1997-05-01

Our previous studies have shown that renal perfusion can be visualized by imaging the transit of a contrast agent through the parenchyma of the organ using gray scale (GS) and power Doppler (PD) ultrasound.However, the relative merits and the sensitivities of the two imaging methods are not known. This study compares the effectiveness of the two modes in visualizing kidney perfusion at the clinical dose of contrast agents. GS and PD images of the dog kidneys were recorded using a clinical ultrasound scanner at 4-7 MHz. A fixed longitudinal plane of the kidney was imaged by mounting the transducer on the animal with a specially designed holder. A dose of 0.1 m1/kg of Echogen was injected intravenously and GS and PD images were recorded simultaneously on two separate time-encoded video tapes during the passage of the contrast agent through the kidneys. The enhancement of GS and PD images was assessed qualitatively by three radiologists. The quantitative assessment was made by measuring the regional and global enhancements of digitized B-scan and PS images. Regional measurements were made by comparing brightness of the post contrast images with that of a pre-contrast reference image pixel by pixel. Student t-test was used to determine the statistical significance of the change. The regions representing statistically significant differences were encoded on the image in color with brightness proportional to the magnitude of change. The regions with no significant change were represented in GS. This generated a series of new images, referred to as StatMap, with color representing regions of perfusion. Changes in power Doppler images were visually detectable with high confidence in all five dogs by al three radiologists. There was no perceptible changes in B-scans. Computer analysis of PD images yielded characteristic indicator dilution curves in all five dogs with an initial rise time of 2-5 sec and a peak at 7-20 sec. The enhancement in PD lasted for 97-400 seconds. The peak to pre-injection Doppler power ratio was 2.41 +/- 0.85. There were not detectable changes in gray scale images except in one dog which exhibited a small change. The StatMap images of PD exhibited perfusion over the entire kidney, whereas the GS images showed perfusion to be sparsely distributed.

Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.

PubMed

Li, Guolin; Slansky, Adam; Dobhal, Mahabeer P; Goswami, Lalit N; Graham, Andrew; Chen, Yihui; Kanter, Peter; Alberico, Ronald A; Spernyak, Joseph; Morgan, Janet; Mazurchuk, Richard; Oseroff, Allan; Grossman, Zachary; Pandey, Ravindra K

2005-01-01

A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important milestone toward improving cancer diagnosis and tumor characterization. More importantly, this paper describes a new family of bifunctional agents that combine two modalities into a single cost-effective "see and treat" approach, namely, a single agent that can be used for contrast agent-enhanced MR imaging followed by targeted photodynamic therapy.

Influence of CT contrast agent on dose calculation of intensity modulated radiation therapy plan for nasopharyngeal carcinoma.

PubMed

Lee, F K-H; Chan, C C-L; Law, C-K

2009-02-01

Contrast enhanced computed tomography (CECT) has been used for delineation of treatment target in radiotherapy. The different Hounsfield unit due to the injected contrast agent may affect radiation dose calculation. We investigated this effect on intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC). Dose distributions of 15 IMRT plans were recalculated on CECT. Dose statistics for organs at risk (OAR) and treatment targets were recorded for the plain CT-calculated and CECT-calculated plans. Statistical significance of the differences was evaluated. Correlations were also tested, among magnitude of calculated dose difference, tumor size and level of enhancement contrast. Differences in nodal mean/median dose were statistically significant, but small (approximately 0.15 Gy for a 66 Gy prescription). In the vicinity of the carotid arteries, the difference in calculated dose was also statistically significant, but only with a mean of approximately 0.2 Gy. We did not observe any significant correlation between the difference in the calculated dose and the tumor size or level of enhancement. The results implied that the calculated dose difference was clinically insignificant and may be acceptable for IMRT planning.

HIFU Hemostasis of Liver Injuries Enhanced by Ultrasound Contrast Agents

NASA Astrophysics Data System (ADS)

Zderic, Vesna; Vaezy, Shahram; Brayman, Andrew A.; Matula, Thomas J.; O'Keefe, Grant E.; Crum, Lawrence A.

2005-03-01

Our objective was to investigate whether High-Intensity Focused Ultrasound (HIFU) hemostasis can be achieved faster in the presence of ultrasound contrast agents (UCA). Incisions (3 cm long and 0.5 cm deep) were made in surgically exposed rabbit liver. Optison at a concentration of 0.18 ml/kg was injected into the mesenteric vein, immediately before the incision was made. The HIFU applicator (frequency of 5.5 MHz, and intensity of 3,700 W/cm2) was scanned manually over the incision (at an approximate rate of 1 mm/s) until hemostasis was achieved. The times to complete hemostasis were measured and normalized with the initial blood loss. The hemostasis times were 59±23 s in the presence of Optison and 70±23 s without Optison. The presence of Optison produced a 37% reduction in the normalized hemostasis times (p<0.05). Optison also provided faster (by 34%) formation of the coagulum seal over the lesion. Gross observations showed that the lesion size did not change due to the presence of Optison. Histological analysis showed that lesions consisted of an area of coagulation necrosis in vicinity of the incision, occasionally surrounded by a congestion zone filled with blood. Our results suggest the potential utility of microbubble contrast agents for increasing efficiency of HIFU hemostasis of internal organ injuries.

X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

DOE PAGES

Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; ...

2015-10-29

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form anmore » image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. As a result, the enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.« less

Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

PubMed Central

Curtet, C; Tellier, C; Bohy, J; Conti, M L; Saccavini, J C; Thedrez, P; Douillard, J Y; Chatal, J F; Koprowski, H

1986-01-01

Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors. Images PMID:3459174

Contrast-enhanced magnetic resonance angiography: first-pass arterial enhancement as a function of gadolinium-chelate concentration, and the saline chaser volume and injection rate.

PubMed

Husarik, Daniela B; Bashir, Mustafa R; Weber, Paul W; Nichols, Eli B; Howle, Laurens E; Merkle, Elmar M; Nelson, Rendon C

2012-02-01

To evaluate the effect of the contrast medium (CM) concentration and the saline chaser volume and injection rate on first-pass aortic enhancement characteristics in contrast-enhanced magnetic resonance angiography using a physiologic flow phantom. Imaging was performed on a 3.0-T magnetic resonance system (MAGNETOM Trio, Siemens Healthcare Solutions, Inc, Erlangen, Germany) using a 2-dimensional fast low angle shot T1-weighted sequence (repetition time, 500 milliseconds; echo time, 1.23 milliseconds; flip angle, 8 degrees; 1 frame/s × 60 seconds). The following CM concentrations injected at 2 mL/s were used with 3 different contrast agents (gadolinium [Gd]-BOPTA, Gd-HP-DO3A, Gd-DTPA): 20 mL of undiluted CM (100%) and 80%, 40%, 20%, 10%, 5%, and 2.5% of the full amount, all diluted in saline to a volume of 20 mL to ensure equal bolus volume. The CM was followed by saline chasers of 20 to 60 mL injected at 2 mL/s and 6 mL/s. Aortic signal intensity (SI) was measured, and normalized SI versus time (SI/Tn) curves were generated. The maximal SI (SI(max)), bolus length, and areas under the SI/Tn curve were calculated. Decreasing the CM concentration from 100% to 40% resulted in a decrease of SI(max) to 86.1% (mean). Further decreasing the CM concentration to 2.5% decreased SI(max) to 5.1% (mean). Altering the saline chaser volume had no significant effect on SI(max). Increasing the saline chaser injection rate had little effect (mean increase, 2.2%) on SI(max) when using ≥40% of CM. There was a larger effect (mean increase, 19.6%) when ≤20% of CM were used. Bolus time length was significantly shorter (P < 0.001), and area under the SI/T(n) curve was significantly smaller (P < 0.01) for the CM protocols followed by a saline chaser injected at 6 mL/s compared with a saline chaser injected at 2 mL/s. With 40% of CM and a fast saline chaser, SImax close to that with undiluted CM can be achieved. An increased saline chaser injection rate has a more pronounced effect on aortic enhancement characteristics at lower CM concentrations than at higher CM concentrations.

Evaluation of pharmacokinetic models for perfusion imaging with dynamic contrast-enhanced magnetic resonance imaging in porcine skeletal muscle using low-molecular-weight contrast agents.

PubMed

Hindel, Stefan; Papanastasiou, Giorgos; Wust, Peter; Maaß, Marc; Söhner, Anika; Lüdemann, Lutz

2018-06-01

Pharmacokinetic models for perfusion quantification with a low-molecular-weight contrast agent (LMCA) in skeletal muscle using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were evaluated. Tissue perfusion was measured in seven regions of interest (ROIs) placed in the total hind leg supplied by the femoral artery in seven female pigs. DCE-MRI was performed using a 3D gradient echo sequence with k-space sharing. The sequence was acquired twice, first after LMCA and then after blood pool contrast agent injection. Blood flow was augmented by continuous infusion of the vasodilator adenosine into the femoral artery, resulting in up to four times increased blood flow. The results obtained with several LMCA models were compared with those of a two-compartment blood pool model (2CBPM) consisting of a capillary and an arteriolar compartment. Measurements performed with a Doppler flow probe placed at the femoral artery served as ground truth. The two-compartment exchange model extended by an arteriolar compartment (E2CXM) showed the highest fit quality of all LMCA models and the most significant correlation with the Doppler measurements, r = 0.78 (P < 0.001). The best correspondence between the capillary perfusion measurements of the LMCA models and those of the 2CBPM was found with the E2CXM (slope of the regression line equal to 1, r = 0.85, P < 0.001). The results for the clinical patient data corresponded very well with the results obtained in the animal experiments. Double-contrast agent DCE-MRI in combination with the E2CXM yields the most reliable results and can be used in clinical routine. Magn Reson Med 79:3154-3162, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Tumor Xenograft Response to Redox-Active Therapies Assessed by Magnetic Resonance Imaging Using a Thiol-Bearing DOTA Complex of Gadolinium1

PubMed Central

Guntle, Gerald P; Jagadish, Bhumasamudram; Mash, Eugene A; Powis, Garth; Dorr, Robert T; Raghunand, Natarajan

2012-01-01

Gd-LC6-SH is a thiol-bearing DOTA complex of gadolinium designed to bind plasma albumin at the conserved Cys34 site. The binding of Gd-LC6-SH shows sensitivity to the presence of competing thiols. We hypothesized that Gd-LC6-SH could provide magnetic resonance imaging (MRI) enhancement that is sensitive to tumor redox state and that the prolonged retention of albumin-bound Gd-LC6-SH in vivo can be exploited to identify a saturating dose above which the shortening of MRI longitudinal relaxation time (T1) of tissue is insensitive to the injected gadolinium dose. In the Mia-PaCa-2 pancreatic tumor xenograft model in SCID mice, both the small-molecule Gd-DTPA-BMA and the macromolecule Galbumin MRI contrast agents produced dose-dependent decreases in tumor T1. By contrast, the decreases in tumor T1 provided by Gd-LC6-SH at 0.05 and 0.1 mmol/kg were not significantly different at longer times after injection. SCID mice bearing Mia-PaCa-2 or NCI-N87 tumor xenografts were treated with either the glutathione synthesis inhibitor buthionine sulfoximine or the thiol-oxidizing anticancer drug Imexon, respectively. In both models, there was a significantly greater increase in tumor R1 (=1/T1) 60 minutes after injection of Gd-LC6-SH in drug-treated animals relative to saline-treated controls. In addition, Mercury Orange staining for nonprotein sulfhydryls was significantly decreased by drug treatment relative to controls in both tumor models. In summary, these studies show that thiol-bearing complexes of gadolinium such as Gd-LC6-SH can serve as redox-sensitive MRI contrast agents for detecting differences in tumor redox status and can be used to evaluate the effects of redox-active drugs. PMID:22741038

In vitro and in vivo magnetic resonance imaging with chlorotoxin-conjugated superparamagnetic nanoprobes for targeting hepatocarcinoma.

PubMed

Chen, Zhu; Xiao, En-Hua; Kang, Zhen; Zeng, Wen-Bin; Tan, Hui-Long; Li, Hua-Bing; Bian, Du-Jun; Shang, Quan-Liang

2016-05-01

The present study aimed to assess the in vitro and in vivo magnetic resonance imaging (MRI) features of chlorotoxin (CTX)-conjugated superparamagnetic iron oxide (SPIO) nanoprobes. CTX-conjugated nanoprobes were composed of SPIO coated with polyethylene glycol (PEG) and conjugated with CTX. The nanoprobes were termed SPIO-PEG-CTX. MRI of the SPIO and SPIO-PEG-CTX solutions at a different concentration was performed with a 3.0-T MRI scanner (Philips Achieva 3.0T X Series; Phillips Healthcare, The Netherlands). Rabbit VX2 hepatocarcinoma was established by a traditional laparotomy method (injection of the tumor particles into the liver using a 15G syringe needle) following approval by the institutional animal care and use committee. Contrast-enhanced MRI of VX2 rabbits (n=8) was performed using the same MRI scanner with SPIO‑PEG-CTX solutions as the contrast agent. Data were analyzed with calibration curve and a paired t-test. The SPIO-PEG-CTX nanoparticles were successfully prepared. With increasing concentrations of the solutions, the MRI signal intensity was increased at T1WI, but decreased at T2WI, which were the same as that for SPIO. Rabbit VX2 carcinoma appeared as a low MRI signal at T1WI, and high at T2WI. After injection of the contrast agent, the MRI signal of carcinoma was decreased relative to that before injection at T2WI (1,161±331.5 vs. 1,346±300.5; P=0.004<0.05), while the signal of the adjacent normal hepatic tissues was unchanged (480.6±165.1 vs. 563.4±67.8; P=0.202>0.05). The SPIO-PEG-CTX nanoparticles showed MRI negative enhancement at T2WI and a targeting effect in liver cancer, which provides the theoretical basis for further study of the early diagnosis of hepatocellular carcinoma.

Comparison of in vitro and in vivo acoustic response of a novel 50:50 PLGA contrast agent.

PubMed

Wheatley, Margaret A; Forsberg, Flemming; Oum, Kelleny; Ro, Raymond; El-Sherif, Dalia

2006-11-01

A comparison between in vitro and in vivo experiments conducted to investigate the acoustic properties of a novel, 1.2 microm diameter poly(lactic-co-glycolic acid) (50:50) (PLGA) ultrasound contrast agent, the development of which was described previously by us, is presented. A pulse-echo setup was used to determine enhancement in vitro. Additional in vitro studies further characterized the hollow microcapsules, including resonance frequency from attenuation measurements (from 2.25 to 15 MHz) and temperature effects (25 degrees C vs. 37 degrees C). In vivo, four rabbits received intravenous injections of the agent (dose range: 0.005-0.13 ml/kg). Quantitative in vivo dose-responses were calculated off-line using spectral power analysis of audio Doppler signals acquired from a custom-made 10 MHz cuff transducer placed around the surgically exposed distal aorta. This frequency was chosen since the very shallow scanning depths encountered in rabbits, in particular for the cuff transducer placed directly around the vessel, necessitates the use of high frequency imaging devices with sufficient spatial resolution to enable meaningful measurements. For qualitative assessments, two rabbits were imaged pre- and post-contrast administration (dose: 0.1 ml/kg) in power Doppler mode. Significant acoustic enhancements (up to 24 dB) were reported both in vitro and in vivo. Moreover, the rabbits did not show any adverse side effects from multiple injections (>20) of the agent. Measured in vitro resonance frequency between 3.09 and 3.49 MHz was lower than predicted for a similar sized free bubble, potentially due to capsule wall structure. Minimal loss of signal (approximately 4 dB) was observed at 25 degrees C over 20 min of insonation at 5 MHz but at 37 degrees C the signal dropped close to base line within the first 5 min. This temperature sensitivity could be due to loss of capsule integrity (and hence loss of gas). Potential causes include increased hydrolysis or polymer softening and increased water uptake by the shell at temperatures closer to the glass transition temperature (T(g)).

Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection.

PubMed

Bagga, Puneet; Haris, Mohammad; D'Aquilla, Kevin; Wilson, Neil E; Marincola, Francesco M; Schnall, Mitchell D; Hariharan, Hari; Reddy, Ravinder

2017-05-30

Image contrast enhanced by exogenous contrast agents plays a crucial role in the early detection, characterization, and determination of the precise location of cancers. Here, we investigate the feasibility of using a non-nutritive sweetener, sucralose (commercial name, Splenda), as magnetic resonance imaging (MRI) contrast agent for cancer studies. High-resolution nuclear-magnetic-resonance spectroscopy and MR studies on sucralose solution phantom were performed to detect the chemical exchange saturation transfer (CEST) property of sucralose hydroxyl protons with bulk water (sucCEST). For the animal experiments, female Fisher rats (F344/NCR) were used to generate 9L-gliosarcoma model. MRI with CEST experiments were performed on anesthetized rats at 9.4 T MR scanner. Following the baseline CEST scans, sucralose solution was intravenously administered in control and tumor bearing rats. CEST acquisitions were continued during and following the administration of sucralose. Following the sucCEST, Gadolinium-diethylenetriamine pentaacetic acid was injected to perform Gd-enhanced imaging for visualizing the tumor. The sucCEST contrast in vitro was found to correlate positively with the sucralose concentration and negatively with the pH, indicating the potential of this technique in cancer imaging. In a control animal, the CEST contrast from the brain was found to be unaffected following the administration of sucralose, demonstrating its blood-brain barrier impermeability. In a 9L glioma model, enhanced localized sucCEST contrast in the tumor region was detected while the unaffected brain region showed unaltered CEST effect implying the specificity of sucralose toward the tumorous tissue. The CEST asymmetry plots acquired from the tumor region before and after the sucralose infusion showed elevation of asymmetry at 1 ppm, pointing towards the role of sucralose in increased contrast. We show the feasibility of using sucralose and sucCEST in study of preclinical models of cancer. This study paves the way for the potential development of sucralose and other sucrose derivatives as contrast agents for clinical MRI applications.

Synchrotron radiation microimaging in rabbit models of cancer for preclinical testing

NASA Astrophysics Data System (ADS)

Umetani, Keiji; Uesugi, Kentaro; Kobatake, Makito; Yamamoto, Akira; Yamashita, Takenori; Imai, Shigeki

2009-10-01

Preclinical laboratory animal imaging modalities such as microangiography and micro-computed tomography (micro-CT) have been developed at the SPring-8 BL20B2 bending magnet beamline. The objective of this paper is to demonstrate the usefulness of microangiography systems for physiological examinations of live animals and micro-CT systems for postmortem morphological examinations. Synchrotron radiation microangiography and micro-CT with contrast agents present the main advantageous capability of depicting the anatomy of small blood vessels with tens of micrometers' diameter. This paper reports two imaging instrument types and their respective applications to preclinical imaging of tumor angiogenic blood vessels in tumor-bearing rabbits, where tumor angiogenesis is characterized morphologically by an increased number of blood vessels. A microangiography system with spatial resolution around 10 μm has been used for therapeutically evaluating angiogenic vessels in a rabbit model of cancer for evaluating embolization materials in transcatheter arterial embolization and for radiation therapy. After an iodine contrast agent was injected into an artery, in vivo imaging was carried out using a high-resolution real-time detector incorporating an X-ray direct-conversion-type SATICON pickup tube. On the other hand, a micro-CT system capably performed three-dimensional visualization of tumor angiogenic blood vessels using tumor-transplanted rabbit specimens with a barium sulfate contrast agent injected into the blood vessels. For specimen imaging, a large-field high-resolution micro-CT system based on a 10-megapixel CCD camera was developed to study tumor-associated alterations in angioarchitecture. Evidence of increased vascularity by tumor angiogenesis and decreased vascularity by tumor treatments was achieved by physiological evaluation of angiogenic small blood vessels in microangiographic imaging and by morphological assessment in micro-CT imaging. These results demonstrate the accuracy and usefulness of microangiography and micro-CT systems for quantitative examination of animals' angioarchitecture, respectively, during live and postmortem examinations.

X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Umetani, K.; Fukushima, K.

2013-03-15

An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 {mu}m, yielding sharp images of small arteries. The exposure time has been shortened to around 2 msmore » using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 {mu}m diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 {mu}m was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct investigation of mechanisms of vascular dysfunctions.« less

Photoacoustic tomography of joints aided by an Etanercept-conjugated gold nanoparticle contrast agent—an ex vivo preliminary rat study

NASA Astrophysics Data System (ADS)

Chamberland, David L.; Agarwal, Ashish; Kotov, Nicholas; Fowlkes, J. Brian; Carson, Paul L.; Wang, Xueding

2008-03-01

Monitoring of anti-rheumatic drug delivery in experimental models and in human diseases would undoubtedly be very helpful for both basic research and clinical management of inflammatory diseases. In this study, we have investigated the potential of an emerging hybrid imaging technology—photoacoustic tomography—in noninvasive monitoring of anti-TNF drug delivery. After the contrast agent composed of gold nanorods conjugated with Etanercept molecules was produced, ELISA experiments were performed to prove the conjugation and to show that the conjugated anti-TNF-α drug was biologically active. PAT of ex vivo rat tail joints with the joint connective tissue enhanced by intra-articularly injected contrast agent was conducted to examine the performance of PAT in visualizing the distribution of the gold-nanorod-conjugated drug in articular tissues. By using the described system, gold nanorods with a concentration down to 1 pM in phantoms or 10 pM in biological tissues can be imaged with good signal-to-noise ratio and high spatial resolution. This study demonstrates the feasibility of conjugating TNF antagonist pharmaceutical preparations with gold nanorods, preservation of the mechanism of action of TNF antagonist along with preliminary evaluation of novel PAT technology in imaging optical contrast agents conjugated with anti-rheumatic drugs. Further in vivo studies on animals are warranted to test the specific binding between such conjugates and targeted antigen in joint tissues affected by inflammation.

Assessment of Myocardial Remodeling Using an Elastin/Tropoelastin Specific Agent with High Field Magnetic Resonance Imaging (MRI).

PubMed

Protti, Andrea; Lavin, Begoña; Dong, Xuebin; Lorrio, Silvia; Robinson, Simon; Onthank, David; Shah, Ajay M; Botnar, Rene M

2015-08-13

Well-defined inflammation, proliferation, and maturation phases orchestrate the remodeling of the injured myocardium after myocardial infarction (MI) by controlling the formation of new extracellular matrix. The extracellular matrix consists mainly of collagen but also fractions of elastin. It is thought that elastin is responsible for maintaining elastic properties of the myocardium, thus reducing the risk of premature rupture. An elastin/tropoelastin-specific contrast agent (Gd-ESMA) was used to image tropoelastin and mature elastin fibers for in vivo assessment of extracellular matrix remodeling post-MI. Gd-ESMA enhancement was studied in a mouse model of myocardial infarction using a 7 T MRI scanner and results were compared to those achieved after injection of a nonspecific control contrast agent, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). In the infarcted tissue, Gd-ESMA uptake (measured as R1 relaxation rate) steadily increased from day 3 to day 21 as a result of the synthesis of elastin/tropoelastin. R1 values were in good agreement with histological findings. A similar R1 behavior was observed in the remote myocardium. No mature cross-linked elastin was found at any time point. In contrast, Gd-DTPA uptake was only observed in the infarct with no changes in R1 values between 3 and 21 days post-MI. We demonstrate the feasibility of in vivo imaging of extracellular matrix remodeling post-MI using a tropoelastin/elastin binding MR contrast agent, Gd-ESMA. We found that tropoelastin is the main contributor to the increased MRI signal at late stages of MI where its augmentation in areas of infarction was in good agreement with the R1 increase. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Saphenous Venous Ablation with Hot Contrast in a Canine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prasad, Amit; Qian Zhong; Kirsch, David

2008-01-15

Purpose. To determine the feasibility, efficacy, and safety of thermal ablation of the saphenous vein with hot contrast medium. Methods. Twelve saphenous veins of 6 dogs were percutaneously ablated with hot contrast medium. In all animals, ablation was performed in the vein of one leg, followed by ablation in the contralateral side 1 month later. An occlusion balloon catheter was placed in the infragenicular segment of the saphenous vein via a jugular access to prevent unwanted thermal effects on the non-target segment of the saphenous vein. After inflation of the balloon, 10 ml of hot contrast medium was injected undermore » fluoroscopic control through a sheath placed in the saphenous vein above the ankle. A second 10 ml injection of hot contrast medium was made after 5 min in each vessel. Venographic follow-up of the ablated veins was performed at 1 month (n = 12) and 2 months (n = 6). Results. Follow-up venograms showed that all ablated venous segments were occluded at 1 month. In 6 veins which were followed up to 2 months, 4 (66%) remained occluded, 1 (16%) was partially patent, and the remaining vein (16%) was completely patent. In these latter 2 cases, an inadequate amount of hot contrast was delivered to the lumen due to a closed balloon catheter downstream which did not allow contrast to displace blood within the vessel. Discussion. Hot contrast medium thermal ablation of the saphenous vein appears feasible, safe, and effective in the canine model, provided an adequate amount of embolization agent is used.« less

Identification and characterization of gadolinium(III) complexes in biological tissue extracts.

PubMed

Kahakachchi, Chethaka L; Moore, Dennis A

2010-07-01

The gadolinium species present in a rat kidney following intravenous administration of a gadolinium-based magnetic resonance contrast agent (Optimark™, Gadoversetamide injection) to a rat was examined in the present study. The major gadolinium species in the supernatant of the rat kidney tissue extracts was determined by reversed-phase liquid chromatography with online inductively coupled plasma optical emission spectrometry (HPLC-ICP-OES). The identity of the compound was established by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) detection. The principal gadolinium(III) complex in a rat kidney tissue extract was identified as Gd-DTPA-BMEA 24 Hrs and 7 days after a single intravenous injection of Optimark™ (gadoversetamide; Gd-DTPA-BMEA) at a dose of 5 mmol Gd/kg body weight. The study demonstrated for the first time the feasibility of the use of two complementary techniques, HPLC-ICP-OES and HPLC-ESI-MS to study the in vivo behavior of gadolinium-based magnetic resonance contrast media.

Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes.

PubMed

Lunov, Oleg; Syrovets, Tatiana; Röcker, Carlheinz; Tron, Kyrylo; Nienhaus, G Ulrich; Rasche, Volker; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

2010-12-01

Contrast agents based on dextran-coated superparamagnetic iron oxide nanoparticles (SPIO) are internalized by professional phagocytes such as hepatic Kupffer cells, yet their role in phagocyte biology remains largely unknown. Here we investigated the effects of the SPIO ferucarbotran on murine Kupffer cells and human macrophages. Intravenous injection of ferucarbotran into mice led to rapid accumulation of the particles in phagocytes and to long-lasting increased iron deposition in liver and kidneys. Macrophages incorporate ferucarbotran in lysosomal vesicles containing α-glucosidase, which is capable of degrading the carboxydextran shell of the ferucarbotran particles. Intravenous injection of ferucarbotran into mice followed by incorporation of the nanoparticles into Kupffer cells triggered apoptosis and the subsequent depletion of Kupffer cells. In macrophages, the proinflammatory cytokine TNF-α increased the apoptosis rate, the reactive oxygen species production and the activation of c-Jun N-terminal kinase elicited by ferucarbotran, which might be mediated by the induction of cytoplasmic phospholipase A2 by TNF-α. Notably, the nanoparticle-induced apoptosis of murine Kupffer cells could be prevented by treatment of the mice with the radical scavenger edaravone. Thus, nanosized carboxydextran-coated SPIO-based contrast agents are retained for extended time periods by liver macrophages, where they elicit delayed cell death, which can be antagonized by a therapeutic radical scavenger. Copyright © 2010 Elsevier Ltd. All rights reserved.

Severe Ocular Inflammation Following Ranibizumab or Aflibercept Injections for Age-Related Macular Degeneration: A Retrospective Claims Database Analysis

PubMed Central

Souied, Eric H.; Dugel, Pravin U.; Ferreira, Alberto; Hashmonay, Ron; Lu, Jingsong; Kelly, Simon P.

2016-01-01

ABSTRACT Purpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept. Methods: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections. Results: The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91–1.21, vs. 0.64/1000 injections, 95% CI 0.54–0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment. Conclusions: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring of novel medicines, and may aid clinical decision-making, including choice of anti-VEGF agent. PMID:26855278

Fabrication of Gd/Eu-codoped SmPO4 nanorods for dual-modal magnetic resonance and bio-optical imaging.

PubMed

Wu, Zhi; Huang, Zhongbing; Yin, Guangfu; Wang, Lei; Gao, Fabao

2016-03-15

Ln-based complexes can be used as T1-enhanced contrast agents of magnetic resonance (MR) imaging in clinical field. Herein, we present a facile and feasible biomineralization process to fabricate Gd/Eu-codoped SmPO4 nanorods (NRs) with silk fibroin (SF) peptides (codoped SF-NRs) as T1-enhanced contrast agents, which possess paramagnetic property, photoluminescence (PL), better cyto-/tissue-compatibility and longer half-life in blood due to SF coating on their surface. Their bio-distributions in TB-N mice via tail-vein injection indicated that, although SF-NRs could be safely cleared away through renal and fecal excretion, SF-NRs easily permeated and aggregated in tumors. The results of in vitro MR imaging demonstrate that the longitudinal relaxivity r1 value of codoped SF-NRs (0.31 Sm-Gd mM(-1) s(-1)) is not only significantly higher than those of Gd-doped and Eu-doped SmPO4 SF-NRs, but also higher than those of codoped pure NRs. The tests of in vivo T1 weighted MR imaging via intro-tumor injection and tail-vein injection confirm that, compared to the pure NRs, the codoped SF-NRs exhibited higher positive signal-enhancement ability. Furthermore, the better luminescence imaging of living cells under the fluorescence microscope (94% stronger than that of the NRs without SF). A formation mechanism of codoped SF-NRs is proposed, to explain the synergistic effect of Gd/Eu codoping and SF coating on their enhanced bio-compatibility, half-life in blood, T1-weighted MR imaging and PL imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

THE PATHOGENESIS OF HYPERLIPEMIA INDUCED BY MEANS OF SURFACE-ACTIVE AGENTS

PubMed Central

Hirsch, Robert L.; Kellner, Aaron

1956-01-01

Rabbits subjected to subtotal hepatectomy failed to develop increased serum cholesterol levels following parenteral injection of triton WR 1339, the finding indicating that the liver is essential for the establishment of the hypercholesterolemia induced by surface-active agents. The cholesterol content of the livers of rabbits rendered hyperlipemic by means of triton remained unchanged both during the rapid rise of the serum cholesterol levels and during the return to normal values. By contrast, the cholesterol content of the livers of rabbits fed cholesterol rose progressively over a period of 5 weeks, concommittant with the increase in serum cholesterol levels. The findings provide support for the hypothesis that surface-active agents bring about hyperlipemia by altering the circulating lipoproteins in some manner so that they are retained in the circulating body fluids. PMID:13332177

Extravasation from venous catheter: a serious complication potentially missed by lung imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spicer, K.M.; Gordon, L.

Three patients were referred for lung ventiliation and perfusion (V/Q) imaging with symptoms strongly suggestive of pulmonary embolus (PE). Chest roentgenograms and xenon ventilation studies on all three were normal, save for prominent mediastinal silhouettes and effusions. Technetium-99m macroaggregated albumin(Tc-99m MAA), when injected through the central venous catheter (CVP), revealed mediastinal localization, whereas antecubital injections showed normal pulmonary perfusion. Contrast fluoroscopy introduced through the venous catheter in the first patient defined the extravasation. For patients under strong suspicion of PE, with a venous catheter whose distal tip is seen about the level of the heart on chest radiograph, the authorsmore » recommend administering the perfusion agent slowly through the central catheter to exclude catheter-induced complications. When extravasation is detected, injection of Tc-99m MAA by peripheral vein should be used to exclude PE.« less

TH-EF-207A-04: A Dynamic Contrast Enhanced Cone Beam CT Technique for Evaluation of Renal Functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Z; Shi, J; Yang, Y

Purpose: To develop a simple but robust method for the early detection and evaluation of renal functions using dynamic contrast enhanced cone beam CT technique. Methods: Experiments were performed on an integrated imaging and radiation research platform developed by our lab. Animals (n=3) were anesthetized with 20uL Ketamine/Xylazine cocktail, and then received 200uL injection of iodinated contrast agent Iopamidol via tail vein. Cone beam CT was acquired following contrast injection once per minute and up to 25 minutes. The cone beam CT was reconstructed with a dimension of 300×300×800 voxels of 130×130×130um voxel resolution. The middle kidney slices in themore » transvers and coronal planes were selected for image analysis. A double exponential function was used to fit the contrast enhanced signal intensity versus the time after contrast injection. Both pixel-based and region of interest (ROI)-based curve fitting were performed. Four parameters obtained from the curve fitting, namely the amplitude and flow constant for both contrast wash in and wash out phases, were investigated for further analysis. Results: Robust curve fitting was demonstrated for both pixel based (with R{sup 2}>0.8 for >85% pixels within the kidney contour) and ROI based (R{sup 2}>0.9 for all regions) analysis. Three different functional regions: renal pelvis, medulla and cortex, were clearly differentiated in the functional parameter map in the pixel based analysis. ROI based analysis showed the half-life T1/2 for contrast wash in and wash out phases were 0.98±0.15 and 17.04±7.16, 0.63±0.07 and 17.88±4.51, and 1.48±0.40 and 10.79±3.88 minutes for the renal pelvis, medulla and cortex, respectively. Conclusion: A robust method based on dynamic contrast enhanced cone beam CT and double exponential curve fitting has been developed to analyze the renal functions for different functional regions. Future study will be performed to investigate the sensitivity of this technique in the detection of radiation induced kidney dysfunction.« less

Balloon-Occluded Carbon Dioxide Gas Angiography for Internal Iliac Arteriography and Intervention.

PubMed

Kishino, Mitsuhiro; Nakaminato, Shuichiro; Kitazume, Yoshio; Miyasaka, Naoyuki; Kudo, Toshifumi; Saida, Yukihisa; Tateishi, Ukihide

2018-07-01

The usefulness of carbon dioxide (CO 2 ) gas digital subtraction angiography (DSA) has been reported for patients with renal insufficiency and allergy to iodinated contrast agents. However, CO 2 gas cannot replace the iodinated contrast agent in all cases owing to some disadvantages. We describe balloon-occluded CO 2 DSA (B-CO 2 DSA) as an improved CO 2 DSA procedure for interventions in the internal iliac artery (IIA) region and compare the quality of images obtained using conventional CO 2 DSA and B-CO 2 DSA. B-CO 2 DSA-guided embolization was performed for one case of genital bleeding with an acute anaphylactic reaction to the iodinated contrast agent and for three cases of type II endoleaks after endovascular abdominal aortic aneurysm repair with renal dysfunction. A 9-mm occlusion balloon catheter was placed just after the orifice of the IIA. Then, 10-15 ml of CO 2 gas was injected manually via the catheter with and without balloon occlusion. The quality of sequential digital subtraction angiograms was analyzed based on a scoring criterion. In all four cases, image quality was improved with B-CO 2 DSA; the poor quality of images without balloon occlusion was because of reflux of the CO 2 gas. B-CO 2 DSA improves the image quality of CO 2 DSA in the IIA region and is useful for vascular intervention. Level IV.

Extremely Small Pseudoparamagnetic Iron Oxide Nanoparticle as a Novel Blood Pool T1 Magnetic Resonance Contrast Agent for 3 T Whole-Heart Coronary Angiography in Canines: Comparison With Gadoterate Meglumine.

PubMed

Park, Eun-Ah; Lee, Whal; So, Young Ho; Lee, Yun-Sang; Jeon, Bong-Sik; Choi, Kyu Sung; Kim, Eung-Gyu; Myeong, Wan-Jae

2017-02-01

The aim of this study was to evaluate an extremely small pseudoparamagnetic iron oxide nanoparticle (ESPIO), KEG3, as a potential blood pool agent in 3 T coronary magnetic resonance angiography (MRA) in canine models and compare its efficacy to that of a gadolinium-based contrast agent. Nine mongrel dogs were subjected to whole-heart coronary MRA in 2 separate sessions at 7-day intervals with a 3 T scanner using the FLASH sequence with either gadoterate meglumine (Gd-DOTA) or the ESPIO (KEG3). Coronary MRA was performed twice at each MR examination: the first scan during the administration of the contrast agent and the subsequent second scan at 15 minutes after contrast injection. Objective measurements of the Gd-DOTA and ESPIO images, including the signal-to-noise ratios (SNRs) for the coronary arteries and cardiac veins, contrast-to-noise ratios (CNRs) between the vessels and fat (CNRfat) and the vessels and the myocardium (CNRmyocardium), and subjective image quality scores on a 4-point scale were evaluated and compared. The mean SNRs and CNRs of all vascular regions in the ESPIO images were similar to those of the corresponding regions in the Gd-DOTA images in the first scan (98.1 ± 32.5 vs 79.1 ± 38.4 for SNR of coronary arteries, P = 0.3; 74.2 ± 30.1 vs 61.4 ± 38.5 for CNR, P = 0.7) and more than 2 times higher than the latter in the second scan (95.2 ± 31.3 vs 32.1 ± 8.1 for SNR of coronary arteries, P = 0.008; 76.1 ± 35.8 vs 17.6 ± 19.2 for CNR, P 0.008). Similarly, the mean values of the subjective measurements of the ESPIO images were similar to those of the Gd-DOTA images (3.9 ± 0.3 vs 3.3 ± 0.8 for coronary arteries, P = 0.1) in the first scan and significantly better than the latter in the second scan (3.9 ± 0.2 vs 2.1 ± 0.6 for coronary arteries, P = 0.007). The experimental blood pool agent KEG3 offers equivalent image quality for whole-heart coronary MRA at 3 T upon contrast administration and persistent better quality in the subsequent scans, compared with a traditional extracellular gadolinium-based contrast agent.

Optimization of the method for assessment of brain perfusion in humans using contrast-enhanced reflectometry: multidistance time-resolved measurements

NASA Astrophysics Data System (ADS)

Milej, Daniel; Janusek, Dariusz; Gerega, Anna; Wojtkiewicz, Stanislaw; Sawosz, Piotr; Treszczanowicz, Joanna; Weigl, Wojciech; Liebert, Adam

2015-10-01

The aim of the study was to determine optimal measurement conditions for assessment of brain perfusion with the use of optical contrast agent and time-resolved diffuse reflectometry in the near-infrared wavelength range. The source-detector separation at which the distribution of time of flights (DTOF) of photons provided useful information on the inflow of the contrast agent to the intracerebral brain tissue compartments was determined. Series of Monte Carlo simulations was performed in which the inflow and washout of the dye in extra- and intracerebral tissue compartments was modeled and the DTOFs were obtained at different source-detector separations. Furthermore, tests on diffuse phantoms were carried out using a time-resolved setup allowing the measurement of DTOFs at 16 source-detector separations. Finally, the setup was applied in experiments carried out on the heads of adult volunteers during intravenous injection of indocyanine green. Analysis of statistical moments of the measured DTOFs showed that the source-detector separation of 6 cm is recommended for monitoring of inflow of optical contrast to the intracerebral brain tissue compartments with the use of continuous wave reflectometry, whereas the separation of 4 cm is enough when the higher-order moments of DTOFs are available.

Inflammatory activity in Crohn disease: ultrasound findings.

PubMed

Migaleddu, Vincenzo; Quaia, Emilio; Scano, Domenico; Virgilio, Giuseppe

2008-01-01

Improvements in the ultrasound examination of bowel disease have registered in the last years the introduction of new technologies regarding high frequency probes (US), highly sensitive color or power Doppler units (CD-US), and the development of new non-linear technologies that optimize detection of contrast agents. Contrast-enhanced ultrasound (CE-US) most importantly increases the results in sonographic evaluation of Crohn disease inflammatory activity. CE-US has become an imaging modality routinely employed in the clinical practice for the evaluation of parenchymal organs due to the introduction of new generation microbubble contrast agents which persist in the bloodstream for several minutes after intravenous injection. The availability of high frequency dedicated contrast-specific US techniques provide accurate depiction of small bowel wall perfusion due to the extremely high sensitivity of non-linear signals produced by microbubble insonation. In Crohn's disease, CE-US may characterize the bowel wall thickness by differentiating fibrosis from edema and may grade the inflammatory disease activity by assessing the presence and distribution of vascularity within the layers of the bowel wall (submucosa alone or the entire bowel wall). Peri-intestinal inflammatory involvement can be also characterized. CE-US can provide prognostic data concerning clinical recurrence of the inflammatory disease and evaluate the efficacy of drugs treatments.

Dynamic contrast-enhanced optical imaging of in vivo organ function

NASA Astrophysics Data System (ADS)

Amoozegar, Cyrus B.; Wang, Tracy; Bouchard, Matthew B.; McCaslin, Addason F. H.; Blaner, William S.; Levenson, Richard M.; Hillman, Elizabeth M. C.

2012-09-01

Conventional approaches to optical small animal molecular imaging suffer from poor resolution, limited sensitivity, and unreliable quantitation, often reducing their utility in practice. We previously demonstrated that the in vivo dynamics of an injected contrast agent could be exploited to provide high-contrast anatomical registration, owing to the temporal differences in each organ's response to the circulating fluorophore. This study extends this approach to explore whether dynamic contrast-enhanced optical imaging (DyCE) can allow noninvasive, in vivo assessment of organ function by quantifying the differing cellular uptake or wash-out dynamics of an agent in healthy and damaged organs. Specifically, we used DyCE to visualize and measure the organ-specific uptake dynamics of indocyanine green before and after induction of transient liver damage. DyCE imaging was performed longitudinally over nine days, and blood samples collected at each imaging session were analyzed for alanine aminotransferase (ALT), a liver enzyme assessed clinically as a measure of liver damage. We show that changes in DyCE-derived dynamics of liver and kidney dye uptake caused by liver damage correlate linearly with ALT concentrations, with an r2 value of 0.91. Our results demonstrate that DyCE can provide quantitative, in vivo, longitudinal measures of organ function with inexpensive and simple data acquisition.

Magnetic resonance imaging provides evidence of glymphatic drainage from human brain to cervical lymph nodes.

PubMed

Eide, Per Kristian; Vatnehol, Svein Are Sirirud; Emblem, Kyrre Eeg; Ringstad, Geir

2018-05-08

Pre-clinical research in rodents provides evidence that the central nervous system (CNS) has functional lymphatic vessels. In-vivo observations in humans, however, are not demonstrated. We here show data on CNS lymphatic drainage to cervical lymph nodes in-vivo by magnetic resonance imaging (MRI) enhanced with an intrathecal contrast agent as a cerebrospinal fluid (CSF) tracer. Standardized MRI of the intracranial compartment and the neck were acquired before and up to 24-48 hours following intrathecal contrast agent administration in 19 individuals. Contrast enhancement was radiologically confirmed by signal changes in CSF nearby inferior frontal gyrus, brain parenchyma of inferior frontal gyrus, parahippocampal gyrus, thalamus and pons, and parenchyma of cervical lymph node, and with sagittal sinus and neck muscle serving as reference tissue for cranial and neck MRI acquisitions, respectively. Time series of changes in signal intensity shows that contrast enhancement within CSF precedes glymphatic enhancement and peaks at 4-6 hours following intrathecal injection. Cervical lymph node enhancement coincides in time with peak glymphatic enhancement, with peak after 24 hours. Our findings provide in-vivo evidence of CSF tracer drainage to cervical lymph nodes in humans. The time course of lymph node enhancement coincided with brain glymphatic enhancement rather than with CSF enhancement.

Contrast-enhanced ultrasound mapping of sentinel lymph nodes in oral tongue cancer-a pilot study.

PubMed

Gvetadze, Shalva R; Xiong, Ping; Lv, Mingming; Li, Jun; Hu, Jingzhou; Ilkaev, Konstantin D; Yang, Xin; Sun, Jian

2017-03-01

To assess the usefulness of contrast-enhanced ultrasound (CEUS) with peritumoral injection of microbubble contrast agent for detecting the sentinel lymph nodes for oral tongue carcinoma. The study was carried out on 12 patients with T1-2cN0 oral tongue cancer. A radical resection of the primary disease was planned; a modified radical supraomohyoid neck dissection was reserved for patients with larger lesions (T2, n = 8). The treatment plan and execution were not influenced by sentinel node mapping outcome. The Sonovue ™ contrast agent (Bracco Imaging, Milan, Italy) was utilized. After detection, the position and radiologic features of the sentinel nodes were recorded. The identification rate of the sentinel nodes was 91.7%; one patient failed to demonstrate any enhanced areas. A total of 15 sentinel nodes were found in the rest of the 11 cases, with a mean of 1.4 nodes for each patient. The sentinel nodes were localized in: Level IA-1 (6.7%) node; Level IB-11 (73.3%) nodes; Level IIA-3 (20.0%) nodes. No contrast-related adverse effects were observed. For oral tongue tumours, CEUS is a feasible and potentially widely available approach of sentinel node mapping. Further clinical research is required to establish the position of CEUS detection of the sentinel nodes in oral cavity cancers.

An in vitro and in vivo evaluation of the efficacy of recombinant human liver prolidase as a catalytic bioscavenger of chemical warfare nerve agents.

PubMed

Rezk, Peter E; Zdenka, Pierre; Sabnekar, Praveena; Kajih, Takwen; Mata, David G; Wrobel, Chester; Cerasoli, Douglas M; Chilukuri, Nageswararao

2015-01-01

In this study, we determined the ability of recombinant human liver prolidase to hydrolyze nerve agents in vitro and its ability to afford protection in vivo in mice. Using adenovirus containing the human liver prolidase gene, the enzyme was over expressed by 200- to 300-fold in mouse liver and purified to homogeneity by affinity and gel filtration chromatography. The purified enzyme hydrolyzed sarin, cyclosarin and soman with varying rates of hydrolysis. The most efficient hydrolysis was with sarin, followed by soman and by cyclosarin {apparent kcat/Km [(1.9 ± 0.3), (1.7 ± 0.2), and (0.45 ± 0.04)] × 10(5 )M(-1 )min(-1), respectively}; VX and tabun were not hydrolyzed by the recombinant enzyme. The enzyme hydrolyzed P (+) isomers faster than the P (-) isomers. The ability of recombinant human liver prolidase to afford 24 hour survival against a cumulative dose of 2 × LD50 of each nerve agent was investigated in mice. Compared to mice injected with a control virus, mice injected with the prolidase expressing virus contained (29 ± 7)-fold higher levels of the enzyme in their blood on day 5. Challenging these mice with two consecutive 1 × LD50 doses of sarin, cyclosarin, and soman resulted in the death of all animals within 5 to 8 min from nerve agent toxicity. In contrast, mice injected with the adenovirus expressing mouse butyrylcholinesterase, an enzyme which is known to afford protection in vivo, survived multiple 1 × LD50 challenges of these nerve agents and displayed no signs of toxicity. These results suggest that, while prolidase can hydrolyze certain G-type nerve agents in vitro, the enzyme does not offer 24 hour protection against a cumulative dose of 2 × LD50 of G-agents in mice in vivo.

A Metal-Free Method for Producing MRI Contrast at Amyloid-Beta

PubMed Central

Hilt, Silvia; Tang, Tang; Walton, Jeffrey H.; Budamagunta, Madhu; Maezawa, Izumi; Kálai, Tamás; Hideg, Kálmán; Singh, Vikrant; Wulff, Heike; Gong, Qizhi; Jin, Lee-Way; Louie, Angelique; Voss, John C.

2017-01-01

Alzheimer’s disease (AD) is characterized by depositions of the amyloid-β (Aβ) peptide in the brain. The disease process develops over decades, with substantial neurological loss occurring before a clinical diagnosis of dementia can be rendered. It is therefore imperative to develop methods that permit early detection and monitoring of disease progression. In addition, the multifactorial pathogenesis of AD has identified several potential avenues for AD intervention. Thus, evaluation of therapeutic candidates over lengthy trial periods also demands a practical, noninvasive method for measuring Aβ in the brain. Magnetic resonance imaging (MRI) is the obvious choice for such measurements, but contrast enhancement for Aβ has only been achieved using Gd(III)-based agents. There is great interest in gadolinium-free methods to image the brain. In this study, we provide the first demonstration that a nitroxide-based small-molecule produces MRI contrast in brain specimens with elevated levels of Aβ. The molecule is comprised of a fluorene (a molecule with high affinity for Aβ) and a nitroxide spin label (a paramagnetic MRI contrast species). Labeling of brain specimens with the spin-labeled fluorene produces negative contrast in samples from AD model mice whereas no negative contrast is seen in specimens harvested from wild-type mice. Injection of SLF into live mice resulted in good brain penetration, with the compound able to generate contrast 24-hr post injection. These results provide a proof of concept method that can be used for early, noninvasive, gadolinium-free detection of amyloid plaques by magnetic resonance imaging (MRI). PMID:27911291

Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

PubMed

Uthaman, Saji; Bom, Joon-suk; Kim, Hyeon Sik; John, Johnson V; Bom, Hee-Seung; Kim, Seon-Jong; Min, Jung-Joon; Kim, Il; Park, In-Kyu

2016-05-01

Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI. © 2016 Wiley Periodicals, Inc.

Congenital heart disease in adults: Quantitative and qualitative evaluation of IR FLASH and IR SSFP MRA techniques using a blood pool contrast agent in the steady state and comparison to first pass MRA.

PubMed

Febbo, Jennifer A; Galizia, Mauricio S; Murphy, Ian G; Popescu, Andrada; Bi, Xiaoming; Turin, Alexander; Collins, Jeremy; Markl, Michael; Edelman, Robert R; Carr, James C

2015-10-01

To evaluate magnetic resonance angiography sequences during the contrast steady-state (SS-MRA) using inversion recovery (IR) with fast low-angle shot (IR-FLASH) or steady-state free precession (IR-SSFP) read-outs, following the injection of a blood-pool contrast agent, and compare them to first-pass MR angiography (FP-MRA) in adults with congenital heart disease (CHD). Twenty-three adult patients with CHD who underwent both SS-MRA and FP-MRA using a 1.5-T scanner were retrospectively identified. Signal-to-noise and contrast-to-noise ratios were obtained at eight locations within the aorta and pulmonary vessels.. Image quality and the presence of artifacts were subjectively assessed by two radiologists. The presence of pathology was noted and given a confidence score. There was no difference in vessel dimensions among the sequences. IR-SSFP showed better image quality and fewer artifacts than IR-FLASH and FP-MRA. Confidence scores were significantly higher for SS-MRA compared to FP-MRA. Seven cases (30.4%) had findings detected at SS-MRA that were not detected at FP-MRA, and 2 cases (8.7%) had findings detected by IR-SSFP only. SS-MRA of the thoracic vasculature using a blood pool contrast agent offers superior image quality and reveals more abnormalities compared to standard FP-MRA in adults with CHD, and it is best achieved with an IR-SSFP sequence. These sequences could lead to increased detection rates of abnormalities and provide a simpler protocol image acquisition. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration

NASA Technical Reports Server (NTRS)

Mukherjee, D.; Wong, J.; Griffin, B.; Ellis, S. G.; Porter, T.; Sen, S.; Thomas, J. D.

2000-01-01

OBJECTIVES: In this study, the feasibility of delivering and enhancing the uptake of vascular endothelial growth factor (VEGF) into the intact endothelium by using ultrasound (US) facilitation was determined. BACKGROUND: A limitation of tissue-targeted drug delivery is the need for direct arterial cannulation. We postulate a mechanism by which agents injected intravenously may be targeted to a tissue using US and ultrasonic contrast agents. METHODS: We used a rat model to test the ability of US and an ultrasonic contrast agent perflurocarbon exposed sonicated dextrose albumin (PESDA) to increase uptake of VEGF in the myocardium. Continuous wave Doppler US (0.6 W/cm2 at 1 MHz for 15 min) was applied to the chest wall overlying the myocardium during intravenous injection with either VEGF (100 microg/kg) alone or a combination of VEGF and PESDA (0.1%). Control rats had VEGF infused without US or PESDA. The VEGF uptake was measured quantitatively in the heart, lung, liver and kidneys by enzyme-linked immunosorbent assay (ng/g of tissue) and morphologically by fluorescence microscopy. RESULTS: There was an eight-fold increase in VEGF uptake in the heart by US alone (16.86 +/- 1.56 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) and a 13-fold increase with US + PESDA (26.78 +/- 2.88 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) compared with control rats. Fluorescence microscopy revealed deposition of VEGF in the endothelium of small intramyocardial arterioles. CONCLUSIONS: These results show a marked increase in endothelial VEGF uptake with US and US + PESDA. Thus, US may be used to augment endothelial VEGF uptake 10-fold to 13-fold.

Different Efficiency of Liposomal Forms with Hydrophilic and Hydrophobic Antitumor Agents in Relation to Solid Transplants of Mouse Tumor and Its Metastases in the Liver.

PubMed

Popova, N A; Kaledin, V I; Nikolin, V P; Bogdanova, L A; Morozkova, T S; Tornuev, Yu V

2016-10-01

Experiments were performed on the model of transplanted mouse tumor with high incidence of liver metastases. Hydrophilic drug cycloplatam (injected intravenously in liposomes) was more potent than "free cycloplatam" (injected intravenously or intraperitoneally in physiological saline) in inhibiting the growth of natural and experimental metastases in the liver. By contrast, liposomal cycloplatam had lower efficiency than free cycloplatam in suppressing the growth of solid tumor. Liposomal and free cortifen (hydrophobic hormonal cytostatic) produced nearly the same effects on solid tumor growth. Our results suggest that liposomal forms of hydrophobic compounds producing nonselective effect on tumor cells (e.g., actinomycin D or Cosmegen), should not have advantages over free forms.

A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation

NASA Astrophysics Data System (ADS)

Park, William K. C.; Mills, David R.; Lim, Sierin; Sana, Barindra; Frank, Victoria E.; Kenyon, Brendan M.; Primmer, Michael P.; Paul, Jarod B.; Baird, Greyson L.; Walsh, Edward; Dupuy, Damian E.

2017-02-01

Purpose: A ferritin-containing nanoparticle conjugated with a target-specific antibody was investigated as a MRI contrast agent for tumor detection. A genetically modified ferritin to markedly improve Fe (III) payload (up to 7,000 Fe ions), was chemically tethered to a monoclonal antibody against rat Nectin-like molecule 5 (Necl-5). Necl-5 is a cell surface glycoprotein that is highly expressed on the cell surface of many common epithelial cancers, including prostate cancer. It was previously demonstrated that this novel nanoconjugate agent exhibited effective in vitro targeting of Necl- 5 expressing tumor cells and exhibited strong MRI contrast characteristics via shortening of T2. Here, we demonstrate that the nanoconjugate-Necl-5 interaction can be exploited to target and detect tumor in vivo by MRI. Procedure: Using an in vivo tumor model (i.e., tumor size 0.5-1 cm, immunodeficient beige/nude/xid mouse, xenograft injection with transformed rat prostate cells), efficacy of the conjugate targeting the tumor was examined. We used two injection strategies, a direct and a tail vein injection (0.8 mg, 300 μL per subject). Pre-injection baseline and postinjection scans were performed with the following spin-echo sequence parameters: Field of view = 90x53mm, reconstruction matrix size = 192x114, slice thickness = 1mm (10 slices), repetition time (TR) = 2070 ms, echo times (TE) = 11-198 ms in 11ms steps (18 echoes), number of averages = 2, acquisition time per scan = 7min 56s. Results: All T2 data obtained were converted to R2 for demonstration purposes (R2 = 1/T2). The tail vein injected conjugate significantly increased R2 response (22.9 +/- 5.2 s-1) as compared to control (13.5 +/-1.7 s-1) at 4 h. The weaker R2 increase was noted (15.2 +/- 2.0 s-1) at 24 h. No notable changes in R2 were observed in surrounding tissues regardless the stages of the measurement. We also measured the initial conjugate kinetics for both injection methods with respect to the ability of targeting the tumor. Direct injection of the nanoconjugate in to the center of the tumor showed a stronger and more rapid increase in R2 than the tail vein injection. Conclusion: The nanoconjugate interacts strongly and selectively in situ with Necl-5 overexpressing tumor cells. Direct injection of the nanoconjugate into the body of the tumor caused a more significant in situ R2 increase in MRI than the tail vein injection. Varying degrees of R2 increase within the tumor mass is likely to represent different distribution patterns of the conjugate, reflective of tumor heterogeneity.

Gadolinium oxide nanoplates with high longitudinal relaxivity for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Cho, Minjung; Sethi, Richa; Ananta Narayanan, Jeyarama Subramanian; Lee, Seung Soo; Benoit, Denise N.; Taheri, Nasim; Decuzzi, Paolo; Colvin, Vicki L.

2014-10-01

Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values moderately reduce as the size of the Gd2O3 nanoplates increases, and are always larger for the PAA-OA coating. Cytotoxicity studies on human dermal fibroblast cells documented no significant toxicity, with 100% cell viability preserved up to 250 μM for the PAA-OA coated Gd2O3 nanoplates. Given the 10 times increase in longitudinal relaxivity over the commercially available Gd-based molecular agents and the favorable toxicity profile, the 2 nm PAA-OA coated Gd2O3 nanoplates could represent a new class of highly effective T1 MRI contrast agents.Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values moderately reduce as the size of the Gd2O3 nanoplates increases, and are always larger for the PAA-OA coating. Cytotoxicity studies on human dermal fibroblast cells documented no significant toxicity, with 100% cell viability preserved up to 250 μM for the PAA-OA coated Gd2O3 nanoplates. Given the 10 times increase in longitudinal relaxivity over the commercially available Gd-based molecular agents and the favorable toxicity profile, the 2 nm PAA-OA coated Gd2O3 nanoplates could represent a new class of highly effective T1 MRI contrast agents. Electronic supplementary information (ESI) available: The histograms of Gd2O3 nanoparticles ranging from 2 to 22 nm, TEM image of 22 nm gadolinium oxide with GIF mapping, size control by reaction parameter, XPS and XRD of Gd2O3 nanoparticles, phase transfer yields of oleic acid and PAA-OA coated Gd2O3 nanoparticles, hydrodynamic size and zeta potentials with table, long-term stability test at different temperature, buffer, pH, and ionic strength conditions with tables. See DOI: 10.1039/c4nr03505d

Assessing Diffusion in the Extra-Cellular Space of Brain Tissue by Dynamic MRI Mapping of Contrast Agent Concentrations

NASA Astrophysics Data System (ADS)

Mériaux, Sébastien; Conti, Allegra; Larrat, Benoît

2018-05-01

The characterization of extracellular space (ECS) architecture represents valuable information for the understanding of transport mechanisms occurring in brain parenchyma. ECS tortuosity reflects the hindrance imposed by cell membranes to molecular diffusion. Numerous strategies have been proposed to measure the diffusion through ECS and to estimate its tortuosity. The first method implies the perfusion for several hours of a radiotracer which effective diffusion coefficient D* is determined after post mortem processing. The most well-established techniques are real-time iontophoresis that measures the concentration of a specific ion at known distance from its release point, and integrative optical imaging that relies on acquiring microscopy images of macromolecules labelled with fluorophore. After presenting these methods, we focus on a recent Magnetic Resonance Imaging (MRI)-based technique that consists in acquiring concentration maps of a contrast agent diffusing within ECS. Thanks to MRI properties, molecular diffusion and tortuosity can be estimated in 3D for deep brain regions. To further discuss the reliability of this technique, we point out the influence of the delivery method on the estimation of D*. We compare the value of D* for a contrast agent intracerebrally injected, with its value when the agent is delivered to the brain after an ultrasound-induced blood-brain barrier (BBB) permeabilization. Several studies have already shown that tortuosity may be modified in pathological conditions. Therefore, we believe that MRI-based techniques could be useful in a clinical context for characterizing the diffusion properties of pathological ECS and thus predicting the drug biodistribution into the targeted area.

Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

PubMed

Miller, Douglas L; Li, Peng; Dou, Chunyan; Gordon, David; Edwards, Chris A; Armstrong, William F

2005-10-01

To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P < .02) and 2.0 MPa (P < .005) relative to the cell counts at sham myocardial contrast echocardiography. Premature heartbeats had a similar exposure-response relationship; however, number of premature heartbeats and EB-stained cell count did not appear to be directly related (coefficient of determination r2 = 0.03). The EB-stained cell counts at end-diastolic triggering were not significantly different from those at end-systolic triggering (P > .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure. RSNA, 2005

Effect of intracoronary nitroprusside injection on flow recovery during primary PCI in acute STEMI patients.

PubMed

Yang, Lixia; Mu, Lihua; Sun, Linhui; Qi, Feng; Guo, Ruiwei

2017-04-01

The no/slow reflow phenomenon during primary percutaneous coronary intervention (PPCI) causes the destruction of the coronary microcirculation and further myocardial damage. Some studies have shown that intracoronary nitroprusside infusion is a safe and effective method for managing the no/slow reflow phenomenon. However, it is uncertain whether the injection of nitroprusside at a specific time point during PPCI can most effectively prevent no-reflow. In this study, we investigated the effect of the timing of an intracoronary nitroprusside injection on flow recovery during PPCI in patients with ST elevation acute myocardial infarction (STEMI). One hundred twenty consecutive patients with STEMI who underwent PPCI were enrolled in the study. Patients who fulfilled the eligibility criteria were randomly allocated to three groups: control group (N.=40) received no nitroprusside before they completed PCI; the second group (N.=40) received nitroprusside before balloon dilatation; and the third group (N.=40) received nitroprusside after each balloon dilatation and before contrast agent refilling. The baseline clinical variables and the details of the PCI procedure were collected. The thrombolysis in myocardial infarction (TIMI) flow grades and the corrected TIMI frame count (cTFC) were evaluated immediately after stent implantation was completed. There were no significant differences in the baseline characteristics, antithrombotic drugs given before PCI, and details of the PCI procedure among the three groups (P>0.05). The incidence of TIMI grade 3 after PCI was significantly higher in the nitroprusside group than in the control group (P=0.025), whereas cTFC was significantly lower in the nitroprusside group (26.6±15.2) than in the control group (38.1±21.3, P=0.001). The incidence of TIMI grade 3 after PCI was significantly higher in the third group than in the second group (P=0.045), and cTFC was significantly lower in the third group (21.5±9.5) than in the second group (31.2±18.3, P=0.002). Multivariable linear regression analyses showed that the intracoronary nitroprusside injection time was a significant predictor of cTFC after PCI. These data suggest that the intracoronary injection of nitroprusside significantly reduced the incidence of no/slow reflow during PPCI. The intracoronary injection of nitroprusside most effectively prevented the no/slow reflow phenomenon when administered between balloon dilatation and contrast agent refilling during PPCI.

Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents.

PubMed

Yan, Guo-Ping; Li, Zhen; Xu, Wei; Zhou, Cheng-Kai; Yang, Lian; Zhang, Qiao; Li, Liang; Liu, Fan; Han, Lin; Ge, Yuan-Xing; Guo, Jun-Fang

2011-04-04

Porphyrin-containing polyaspartamide ligands (APTSPP-PHEA-DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP-PHEA-DTPA-Gd). Experimental data of (1)H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP-PHEA-DTPA-Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd-DTPA. Moreover, APTSPP-PHEA-DTPA-Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

The effect of nanoparticle size on theranostic systems: the optimal particle size for imaging is not necessarily optimal for drug delivery

NASA Astrophysics Data System (ADS)

Dreifuss, Tamar; Betzer, Oshra; Barnoy, Eran; Motiei, Menachem; Popovtzer, Rachela

2018-02-01

Theranostics is an emerging field, defined as combination of therapeutic and diagnostic capabilities in the same material. Nanoparticles are considered as an efficient platform for theranostics, particularly in cancer treatment, as they offer substantial advantages over both common imaging contrast agents and chemotherapeutic drugs. However, the development of theranostic nanoplatforms raises an important question: Is the optimal particle for imaging also optimal for therapy? Are the specific parameters required for maximal drug delivery, similar to those required for imaging applications? Herein, we examined this issue by investigating the effect of nanoparticle size on tumor uptake and imaging. Anti-epidermal growth factor receptor (EGFR)-conjugated gold nanoparticles (GNPs) in different sizes (diameter range: 20-120 nm) were injected to tumor bearing mice and their uptake by tumors was measured, as well as their tumor visualization capabilities as tumor-targeted CT contrast agent. Interestingly, the results showed that different particles led to highest tumor uptake or highest contrast enhancement, meaning that the optimal particle size for drug delivery is not necessarily optimal for tumor imaging. These results have important implications on the design of theranostic nanoplatforms.

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 92.1 μg/mL in four hours. CNPs in the absence of cellulase did not produce glucose. Small fragments of nanoparticle in the treated cohort were observed with electron microscopy. There are few photoacoustic contrast agents that offer both high signal intensity and obvious clearance/biodegradation profiles. To the best of our knowledge, this is the first example of a sugar-based photoacoustic contrast agent with important implications for clinical translation of this emerging molecular imaging modality.

Impact of gadolinium-based contrast agent in the assessment of Crohn's disease activity: Is contrast agent injection necessary?

PubMed

Quaia, Emilio; Sozzi, Michele; Gennari, Antonio Giulio; Pontello, Michele; Angileri, Roberta; Cova, Maria Assunta

2016-03-01

To determine whether magnetic resonance enterography (MRE) performed without intravenous contrast injection is diagnostically noninferior to conventional contrast-enhanced MRE (CE-MRE) in patients with Crohn's disease (CD). This was an Institutional Review Board (IRB)-approved retrospective study. Ninety-six patients (52 male and 44 female; 47.18 years ± 13.6) with a diagnosis of CD underwent MRE at 1.5T including T2 -weighted single-shot turbo-spin-echo, T2 -weighted spectral fat presaturation with inversion recovery (SPAIR), T1 -weighted balanced fast-field-echo MR sequences, and CE-MRE consisting in T1 -weighted breath-hold THRIVE 3D MRI sequences after administration of gadobenate dimeglumine (0.2 mL/kg of body weight). Unenhanced MRE, CE-MRE, and unenhanced MRE plus CE-MRE were reviewed in separate sessions with blinding by two readers in consensus, and subsequently by two other readers independently considering a subgroup of 20 patients. Crohn's Disease Endoscopic Index of Severity (CDEIS) and/or histologic analysis of the surgical specimen were considered as reference standards for the assessment of inflammatory activity. Patients revealed prevalently active (n = 55 patients) or quiescent CD (n = 41 patients). The agreement between unenhanced MRE vs. CE-MRE in interpreting active bowel inflammation was 96% (123/128 bowel segments; one-sided 95% confidence interval [CI], >94.4%). Unenhanced MRE vs. CE-MRE vs. unenhanced MRE plus CE-MRE revealed a diagnostic accuracy of 93% [90/96] vs. 92% [88/96] vs. 97% [93/96] (P > 0.05) in the diagnosis of active CD. Interreader agreement was very good for all variables (κ value = 0.8-0.9) except for the measurement of the length of disease (κ value = 0.45). Unenhanced MRE was noninferior to CE-MRE in diagnosing active inflammation in patients with CD. © 2015 Wiley Periodicals, Inc.

Overall evaluability of low dose protocol for computed tomography angiography of thoracic aorta using 80 kV and iterative reconstruction algorithm using different concentration contrast media.

PubMed

Annoni, Andrea Daniele; Mancini, Maria E; Andreini, Daniele; Formenti, Alberto; Mushtaq, Saima; Nobili, Enrica; Guglielmo, Marco; Baggiano, Andrea; Conte, Edoardo; Pepi, Mauro

2017-10-01

Multidetector Computed Tomography Angiography (MDCTA) is presently the imaging modality of choice for aortic disease. However, the effective radiation dose and the risk related to the use of contrast agents associated with MDCTA is an issue of concern. Aim of this study was to assess image quality of a low dose ECG-gated MDCTA of thoracic aorta using different concentration contrast media without tailored injection protocol. Two-hundred patients were randomised into four different scan protocols: Group A (Iodixanol 320 and 80 Kvp tube voltage), Group B (Iodixanol 320 and 100 Kvp tube voltage), Group C (Iomeprol 400 and 80 Kvp tube voltage) and Group D (Iomeprol 400 and 100 Kvp tube voltage). Image quality, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and effective dose (ED) were compared among groups. No significant differences in image noise, SNR and CNR between groups with the same tube voltage. Significant differences in SNR and CNR were found among groups with 80 kV versus groups using 100 kV but without differences in terms of image quality. ED was significantly lower in groups with 80 kV. Multidetector Computed Tomography Angiography protocols using 80 kV and low concentration contrast media are feasible without need of tailored injection protocols. © 2017 The Royal Australian and New Zealand College of Radiologists.

Automated carbon dioxide digital angiography for lower-limb arterial disease evaluation: safety assessment and comparison with standard iodinated contrast media angiography.

PubMed

Scalise, Filippo; Novelli, Eugenio; Auguadro, Carla; Casali, Valentina; Manfredi, Mariella; Zannoli, Romano

2015-01-01

Carbon dioxide (CO2) has been validated as a contrast agent in a large series of studies. A particular advantages of CO2 over iodinated contrast medium (ICM) is the absence of nephrotoxicity and allergic reactions. One of the limitations of CO2 angiography is the difficulty of CO2 manual injection due to its compressibility. The manual gas injection does not permit optimal control of the gas output. Development of an automated CO2 injector has overcome these problems. This study compares the feasibility, safety, and diagnostic accuracy of automated CO2 digital subtraction angiography (DSA) in comparison with ICM-DSA in the evaluation of critical limb ischemic (CLI) patients. We performed DSA with both CO2 and ICM on 40 consecutive CLI patients and directly compared the two techniques. Sixteen females and 24 males participated in the study (mean age, 71.7 years). We assessed the diagnostic accuracy of CO2 in identifying arterial stenosis in the lower limb, with ICM-DSA used as the gold standard. The overall diagnostic accuracy of CO2-DSA was 96.9% (sensitivity, 99.0%; specificity, 96.1%; positive predictive value, 91.1%; negative predictive value, 99.6%). Tolerable minor symptoms occurred in 3 patients. No allergic reactions or significant decline in renal function were observed in patients receiving the CO2 injection. Carbon dioxide DSA is a valuable and safe alternative to traditional ICM-DSA for evaluating CLI patients. This modality should be considered as the standard choice for CLI patients undergoing angiographic evaluation who are known to have renal insufficiency or contrast allergy.

Microbubbles in Ultrasound-Triggered Drug and Gene Delivery

PubMed Central

Hernot, Sophie; Klibanov, Alexander L.

2008-01-01

Ultrasound contrast agents, in the form of gas-filled microbubbles, are becoming popular in perfusion monitoring; they are employed as molecular imaging agents. Microbubbles are manufactured from biocompatible materials, they can be injected intravenously, and some are approved for clinical use. Microbubbles can be destroyed by ultrasound irradiation. This destruction phenomenon can be applied to targeted drug delivery and enhancement of drug action. The ultrasonic field can be focused at the target tissues and organs; thus, selectivity of the treatment can be improved, reducing undesirable side effects. Microbubbles enhance ultrasound energy deposition in the tissues and serve as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection is observed in the areas of the body where ultrasound is applied after intravascular administration of microbubbles and plasmid DNA. Accelerated blood clot dissolution in the areas of insonation by cooperative action of thrombolytic agents and microbubbles is demonstrated in several clinical trials. PMID:18486268

Effect of injection rate on contrast-enhanced MR angiography image quality: Modulation transfer function analysis.

PubMed

Clark, Toshimasa J; Wilson, Gregory J; Maki, Jeffrey H

2017-07-01

Contrast-enhanced (CE)-MRA optimization involves interactions of sequence duration, bolus timing, contrast recirculation, and both R 1 relaxivity and R2*-related reduction of signal. Prior data suggest superior image quality with slower gadolinium injection rates than typically used. A computer-based model of CE-MRA was developed, with contrast injection, physiologic, and image acquisition parameters varied over a wide gamut. Gadolinium concentration was derived using Verhoeven's model with recirculation, R 1 and R2* calculated at each time point, and modulation transfer curves used to determine injection rates, resulting in optimal resolution and image contrast for renal and carotid artery CE-MRA. Validation was via a vessel stenosis phantom and example patients who underwent carotid CE-MRA with low effective injection rates. Optimal resolution for renal and carotid CE-MRA is achieved with injection rates between 0.5 to 0.9 mL/s and 0.2 to 0.3 mL/s, respectively, dependent on contrast volume. Optimal image contrast requires slightly faster injection rates. Expected signal-to-noise ratio varies with both contrast volume and cardiac output. Simulated vessel phantom and clinical carotid CE-MRA exams at an effective contrast injection rate of 0.4 to 0.5 mL/s demonstrate increased resolution. Optimal image resolution is achieved at intuitively low, effective injection rates (0.2-0.9 mL/s, dependent on imaging parameters and contrast injection volume). Magn Reson Med 78:357-369, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Cost-effectiveness of a novel blood-pool contrast agent in the setting of chest pain evaluation in an emergency department.

PubMed

Espinosa, Gabriela; Annapragada, Ananth

2013-10-01

We evaluated three diagnostic strategies with the objective of comparing the current standard of care for individuals presenting acute chest pain and no history of coronary artery disease (CAD) with a novel diagnostic strategy using an emerging technology (blood-pool contrast agent [BPCA]) to identify the potential benefits and cost reductions. A decision analytic model of diagnostic strategies and outcomes using a BPCA and a conventional agent for CT angiography (CTA) in patients with acute chest pain was built. The model was used to evaluate three diagnostic strategies: CTA using a BPCA followed by invasive coronary angiography (ICA), CTA using a conventional agent followed by ICA, and ICA alone. The use of the two CTA-based triage tests before ICA in a population with a CAD prevalence of less than 47% was predicted to be more cost-effective than ICA alone. Using the base-case values and a cost premium for BPCA over the conventional CT agent (cost of BPCA ≈ 5× that of a conventional agent) showed that CTA with a BPCA before ICA resulted in the most cost-effective strategy; the other strategies were ruled out by simple dominance. The model strongly depends on the rates of complications from the diagnostic tests included in the model. In a population with an elevated risk of contrast-induced nephropathy (CIN), a significant premium cost per BPCA dose still resulted in the alternative whereby CTA using BPCA was more cost-effective than CTA using a conventional agent. A similar effect was observed for potential complications resulting from the BPCA injection. Conversely, in the presence of a similar complication rate from BPCA, the diagnostic strategy of CTA using a conventional agent would be the optimal alternative. BPCAs could have a significant impact in the diagnosis of acute chest pain, in particular for populations with high incidences of CIN. In addition, a BPCA strategy could garner further savings if currently excluded phenomena including renal disease and incidental findings were included in the decision model.

The second window ICG technique demonstrates a broad plateau period for near infrared fluorescence tumor contrast in glioblastoma

PubMed Central

Sheikh, Saad; Xia, Leilei; Pierce, John; Newton, Andrew; Predina, Jarrod; Cho, Steve; Nasrallah, MacLean; Singhal, Sunil; Dorsey, Jay; Lee, John Y. K.

2017-01-01

Introduction Fluorescence-guided surgery has emerged as a powerful tool to detect, localize and resect tumors in the operative setting. Our laboratory has pioneered a novel way to administer an FDA-approved near-infrared (NIR) contrast agent to help surgeons with this task. This technique, coined Second Window ICG, exploits the natural permeability of tumor vasculature and its poor clearance to deliver high doses of indocyanine green (ICG) to tumors. This technique differs substantially from established ICG video angiography techniques that visualize ICG within minutes of injection. We hypothesized that Second Window ICG can provide NIR optical contrast with good signal characteristics in intracranial brain tumors over a longer period of time than previously appreciated with ICG video angiography alone. We tested this hypothesis in an intracranial mouse glioblastoma model, and corroborated this in a human clinical trial. Methods Intracranial tumors were established in 20 mice using the U251-Luc-GFP cell line. Successful grafts were confirmed with bioluminescence. Intravenous tail vein injections of 5.0 mg/kg (high dose) or 2.5 mg/kg (low dose) ICG were performed. The Perkin Elmer IVIS Spectrum (closed field) was used to visualize NIR fluorescence signal at seven delayed time points following ICG injection. NIR signals were quantified using LivingImage software. Based on the success of our results, human subjects were recruited to a clinical trial and intravenously injected with high dose 5.0 mg/kg. Imaging was performed with the VisionSense Iridium (open field) during surgery one day after ICG injection. Results In the murine model, the NIR signal-to-background ratio (SBR) in gliomas peaks at one hour after infusion, then plateaus and remains strong and stable for at least 48 hours. Higher dose 5.0 mg/kg improves NIR signal as compared to lower dose at 2.5 mg/kg (SBR = 3.5 vs. 2.8; P = 0.0624). Although early (≤ 6 hrs) visualization of the Second Window ICG accumulation in gliomas is stronger than late (≥24 hrs) visualization (SBR = 3.94 vs. 2.32; p<0.05) there appears to be a long plateau period of stable ICG NIR signal accumulation within tumors in the murine model. We call this long plateau period the “Second Window” of ICG. In glioblastoma patients, the delayed visualization of intratumoral NIR signal was strong (SBR 7.50 ± 0.74), without any significant difference within the 19 to 30 hour visualization window (R2 = 0.019). Conclusion The Second Window ICG technique allows neurosurgeons to deliver NIR optical contrast agent to human glioblastoma patients, thus providing real-time tumor identification in the operating room. This nonspecific tumor accumulation of ICG within the tumor provides strong signal to background contrast, and is not significantly time dependent between 6 hours to 48 hours, providing a broad plateau for stable visualization. This finding suggests that optimal imaging of the “Second Window of ICG” may be within this plateau period, thus providing signal uniformity across subjects. PMID:28738091

Use of positive oral contrast agents in abdominopelvic computed tomography for blunt abdominal injury: meta-analysis and systematic review.

PubMed

Lee, Chau Hung; Haaland, Benjamin; Earnest, Arul; Tan, Cher Heng

2013-09-01

To determine whether positive oral contrast agents improve accuracy of abdominopelvic CT compared with no, neutral or negative oral contrast agent. Literature was searched for studies evaluating the diagnostic performance of abdominopelvic CT with positive oral contrast agents against imaging with no, neutral or negative oral contrast agent. Meta-analysis reviewed studies correlating CT findings of blunt abdominal injury with positive and without oral contrast agents against surgical, autopsy or clinical outcome allowing derivation of pooled sensitivity and specificity. Systematic review was performed on studies with common design and reference standard. Thirty-two studies were divided into two groups. Group 1 comprised 15 studies comparing CT with positive and without oral contrast agents. Meta-analysis of five studies from group 1 provided no difference in sensitivity or specificity between CT with positive or without oral contrast agents. Group 2 comprised 17 studies comparing CT with positive and neutral or negative oral contrast agents. Systematic review of 12 studies from group 2 indicated that neutral or negative oral contrasts were as effective as positive oral contrast agents for bowel visualisation. There is no difference in accuracy between CT performed with positive oral contrast agents or with no, neutral or negative oral contrast agent. • There is no difference in the accuracy of CT with or without oral contrast agent. • There is no difference in the accuracy of CT with Gastrografin or water. • Omission of oral contrast, utilising neutral or negative oral contrast agent saves time, costs and decreases risk of aspiration.

Evaluation of right ventricular function by coronary computed tomography angiography using a novel automated 3D right ventricle volume segmentation approach: a validation study.

PubMed

Burghard, Philipp; Plank, Fabian; Beyer, Christoph; Müller, Silvana; Dörler, Jakob; Zaruba, Marc-Michael; Pölzl, Leo; Pölzl, Gerhard; Klauser, Andrea; Rauch, Stefan; Barbieri, Fabian; Langer, Christian-Ekkehardt; Schgoer, Wilfried; Williamson, Eric E; Feuchtner, Gudrun

2018-06-04

To evaluate right ventricle (RV) function by coronary computed tomography angiography (CTA) using a novel automated three-dimensional (3D) RV volume segmentation tool in comparison with clinical reference modalities. Twenty-six patients with severe end-stage heart failure [left ventricle (LV) ejection fraction (EF) <35%] referred to CTA were enrolled. A specific individually tailored biphasic contrast agent injection protocol was designed (80%/20% high/low flow) was designed. Measurement of RV function [EF, end-diastolic volume (EDV), end-systolic volume (ESV)] by CTA was compared with tricuspid annular plane systolic excursion (TAPSE) by transthoracic echocardiography (TTE) and right heart invasive catheterisation (IC). Automated 3D RV volume segmentation was successful in 26 (100%) patients. Read-out time was 3 min 33 s (range, 1 min 50s-4 min 33s). RV EF by CTA was stronger correlated with right atrial pressure (RAP) by IC (r = -0.595; p = 0.006) but weaker with TAPSE (r = 0.366, p = 0.94). When comparing TAPSE with RAP by IC (r = -0.317, p = 0.231), a weak-to-moderate non-significant inverse correlation was found. Interobserver correlation was high with r = 0.96 (p < 0.001), r = 0.86 (p < 0.001) and r = 0.72 (p = 0.001) for RV EDV, ESV and EF, respectively. CT attenuation of the right atrium (RA) and right ventricle (RV) was 196.9 ± 75.3 and 217.5 ± 76.1 HU, respectively. Measurement of RV function by CTA using a novel 3D volumetric segmentation tool is fast and reliable by applying a dedicated biphasic injection protocol. The RV EF from CTA is a closer surrogate of RAP than TAPSE by TTE. • Evaluation of RV function by cardiac CTA by using a novel 3D volume segmentation tool is fast and reliable. • A biphasic contrast agent injection protocol ensures homogenous RV contrast attenuation. • Cardiac CT is a valuable alternative modality to CMR for the evaluation of RV function.

Synthetic lipid nanoparticles targeting steroid organs.

PubMed

Mérian, Juliette; Boisgard, Raphaël; Decleves, Xavier; Thezé, Benoît; Texier, Isabelle; Tavitian, Bertrand

2013-11-01

Lipidots are original nanoparticulate lipid delivery vectors for drugs and contrast agents made from materials generally regarded as safe. Here, we characterized the in vivo stability, biodistribution, and pharmacokinetics of lipidots. Lipidots 55 nm in diameter and coated with a phospholipid/poly(ethyleneglycol) surfactant shell were triply labeled with (3)H-cholesteryl-hexadecyl-ether, cholesteryl-(14)C-oleate, and the 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine infrared fluorescent dye and injected intravenously into immunocompetent Friend virus B-type mice. The pharmacokinetics and biodistribution of lipidots were analyzed quantitatively in serial samples of blood and tissue and with in vivo optical imaging and were refined by microscopic examination of selected target tissues. The plasmatic half-life of lipidots was approximately 30 min. Radioactive and fluorescent tracers displayed a similar nanoparticle-driven biodistribution, indicative of the lipidots' integrity during the first hours after injection. Lipidots distributed in the liver and, surprisingly, in the steroid-rich organs adrenals and ovaries, but not in the spleen. This tropism was confirmed at the microscopic level by histologic detection of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine. Nanoparticle loading with cholesterol derivatives increased accumulation in ovaries in a dose-dependent manner. This previously unreported distribution pattern is specific to lipidots and attributed to their nanometric size and composition, conferring on them a lipoproteinlike behavior. The affinity of lipidots for steroid hormone-rich areas is of interest to address drugs and contrast agents to lipoprotein-receptor-overexpressing cancer cells found in hormone-dependent tumors.

Paclitaxel-loaded KMnF3 nanoparticles for cancer imaging and therapy in vivo

NASA Astrophysics Data System (ADS)

Song, Xiao-xia; Wan, Hong-ping; Zhang, Jin-sheng; Tang, Qun

2014-11-01

Biocompatible nanoparticles (NPs) responding to the light, thermal, or magnetic excitation are attracting more attention for diagnosis and therapy of cancer. Design of an effective multifunctional complex based on those NPs is a key issue to be addressed, for example, integration of anti-tumor agents with nanoprobes has been considered as one of the successful strategies for combined cancer diagnosis and therapy. In this paper, we develop paclitaxel (PTX)-loaded PEGylation KMnF3 NP, with the size ranged from 18 to 23 nm, as MRI contrast agents for cancer imaging and drug delivery for chemotherapy. Preliminary cell tests demonstrated that PTX@PEG-KMnF3 NP is highly biocompatible. The NP has high loading capacity of PTX (0.7 mg PTX/mg Mn ions), enhanced solubility of PTX (0.16 mg PTX/ml vs 0.02 mg PTX/ml), and high releasing ratio (90 %) in the weak acid solution. As it was applied for in vivo imaging and therapy, the NP enhanced contrast of tumor's MR images and PTX's anti-tumor effect profoundly. The signal noise ratio of the cancer image increased 170 % as comparison to pre-injection with the injection dose of 1.15 mg Mn/kg. The drug delivery's efficacy was also substantially improved, as the tumor growth inhibition effects reached 50 %, meanwhile only 30 % for pristine PTX. Our studies suggest that PTX-loaded KMnF3 NP might be useful as MR image-guided drug delivery for tumor treatment.

Computed Tomography Demonstration of the Production and Distribution of Oxygen Gas Following Intratumoral Injection of a New Radiosensitizer (KORTUC) for Patients with Breast Cancer-Is Intratumoral Injection Not an Ideal Approach to Solve the Major Problem of Tumor Hypoxia in Radiotherapy?

PubMed

Hayashi, Naoya; Ogawa, Yasuhiro; Kubota, Kei; Okino, Kazuhiro; Akima, Ryo; Morita-Tokuhiro, Shiho; Tsuzuki, Akira; Yaogawa, Shin; Nishioka, Akihito; Miyamura, Mitsuhiko

2016-04-01

We previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which contains hydrogen peroxide and sodium hyaluronate for injection into various types of tumors. For breast cancer treatment, the radiosensitization agent was injected into the tumor tissue twice a week under ultrasonographic guidance, immediately prior to each administration of radiation therapy. At approximately three hours after the second or third injection, computed tomography (CT) was performed to confirm the production and distribution of oxygen gas generated from the KORTUC radiosensitization agent by catalysis of peroxidases contained mainly in tumor tissue. The purpose of this study was to demonstrate that tumor hypoxia could be overcome by such a procedure and to evaluate the method of intratumoral injection in terms of confirming oxygen distribution in the target tumor tissue and around the tumor to be visualized on dedicated CT imaging. Three-dimensional reconstructed maximum intensity projection imaging of contrast-enhanced breast magnetic resonance imaging was used to compare the position of the tumor and that of the generated oxygen. Distributed oxygen gas was confirmed in the tumor tissue and around it in all 10 patients examined in the study. A region of oxygen gas was measured as an average value of -457.2 Hounsfield units (HU) as a region of interest. A slightly increased HU value compared to the density of air or oxygen was considered due to the presence of tumor tissue in the low-density area on 5-mm-thick reconstructed CT imaging. The results of this study showed that intratumoral oxygen was successfully produced by intratumoral KORTUC injection under ultrasonographic guidance, and that tumor hypoxia, which is considered a main cause of radioresistance in currently used Linac (linear accelerator) radiation therapy for malignant neoplasms, could be resolved by this method.

Positive contrast high-resolution 3D-cine imaging of the cardiovascular system in small animals using a UTE sequence and iron nanoparticles at 4.7, 7 and 9.4 T.

PubMed

Trotier, Aurélien J; Lefrançois, William; Van Renterghem, Kris; Franconi, Jean-Michel; Thiaudière, Eric; Miraux, Sylvain

2015-07-07

To show that 3D sequences with ultra-short echo times (UTEs) can generate a positive contrast whatever the magnetic field (4.7, 7 or 9.4 T) and whatever Ultra Small Particles of Iron Oxide (USPIO) concentration injected and to use it for 3D time-resolved imaging of the murine cardiovascular system with high spatial and temporal resolutions. Three different concentrations (50, 200 and 500 μmol Fe/kg) of USPIO were injected in mice and static images of the middle part of the animals were acquired at 4.7, 7 and 9.4 T pre and post-contrast with UTE (TE/TR = 0.05/4.5 ms) sequences. Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR) of blood and static tissus were evaluated before and after contrast agent injection. 3D-cine images (TE/TR = 0.05/3.5 ms, scan time < 12 min) at 156 μm isotropic resolution of the mouse cardiopulmonary system were acquired prospectively with the UTE sequence for the three magnetic fields and with an USPIO dose of 200 μmol Fe/kg. SNR, CNR and signal homogeneity of blood were measured. High spatial (104 μm) or temporal (3.5 ms) resolution 3D-cine imaging (scan time < 35 min) isotropic resolution were also performed at 7 T with a new sequence encoding scheme. UTE imaging generated positive contrast and higher SNR and CNR whatever the magnetic field and the USPIO concentration used compared to pre-contrast images. Time-resolved 3D acquisition enables high blood SNR (66.6 ± 4.5 at 7 T) and CNR (33.2 ± 4.2 at 7 T) without flow or motion artefact. Coronary arteries and aortic valve were visible on images acquired at 104 μm resolution. We have demonstrated that by combining the injection of iron nanoparticles with 3D-cine UTE sequences, it was possible to generate a strong positive contrast between blood and surrounding tissues. These properties were exploited to produce images of the cardiovascular system in small animals at high magnetic fields with a high spatial and temporal resolution. This approach might be useful to measure the functional cardiac parameters or to assess anatomical modifications to the blood vessels in cardio-vascular disease models.

[Value of combined conventional and contrast enhanced sonography in the evaluation of hepatic disorders].

PubMed

Tranquart, F; Bleuzen, A; Kissel, A

2004-06-01

To assess the value of combined conventional and contrast-material enhanced sonography for the characterization of focal liver lesions. Simultaneous imaging with grey scale and contrast enhanced US was performed in 90 patients following Levovist injection (Schering, Berlin, Germany) using the "Agent Detection Imaging" method (ADI, Siemens-Acuson, Mountain View, USA). US scanning was performed at least 4 minutes after contrast injection with review of both grayscale and contrast enhanced modes. Results for detection and characterization of lesions were compared to the selected gold standard imaging modality (CT or MRI). Final diagnoses included: 20 normal examinations, 41 patients with metastases, 6 patients with hepatocellular carcinoma, 13 patients with hemangioma, 6 patients with other benign lesions, 4 patients with cysts and 6 patients with two types of lesions. Delayed phase contrast enhanced US allowed diagnosis of all lesions except for one metastasis and all hepatocellular carcinomas. While the diagnosis of hepatoma could not be confirmed, the features suggested a malignant etiology. For 7 patients with metastases, more lesions were detected at ADI (4.9 lesions) than at conventional US (1.1 lesion). For 3 patients, CT showed more lesions than ADI US (3.3 versus 1.6 lesions). The accuracy of ADI US for differentiating between benign and malignant lesions was 98.7% compared to 49.6% for conventional US (p<0.001). The total number of lesions detected at ADI US was higher (p<0.01) than at conventional US and not significantly different from that obtained by the gold standard reference methods. Complete characterization was achieved in 92.2% of cases with ADI US compared to 59.2% with conventional US (p<0.001). Contrast-material enhanced US combined with conventional US markedly improves the diagnostic accuracy of US in terms of lesion detection and characterization.

Integrin αvβ3-targeted dynamic contrast-enhanced magnetic resonance imaging using a gadolinium-loaded polyethylene gycol-dendrimer-cyclic RGD conjugate to evaluate tumor angiogenesis and to assess early antiangiogenic treatment response in a mouse xenograft tumor model.

PubMed

Chen, Wei-Tsung; Shih, Tiffany Ting Fang; Chen, Ran-Chou; Tu, Shin-Yang; Hsieh, Wen-Yuen; Yang, Pang-Chyr

2012-01-01

The purpose of this study was to validate an integrin αvβ3-targeted magnetic resonance contrast agent, PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2, for its ability to detect tumor angiogenesis and assess early response to antiangiogenic therapy using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Integrin αvβ3-positive U87 cells and control groups were incubated with fluorescein-labeled cRGD-conjugated dendrimer, and the cellular attachment of the dendrimer was observed. DCE MRI was performed on mice bearing KB xenograft tumors using either PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 or PEG-G3-(Gd-DTPA)6-(cRAD-DTPA)2. DCE MRI was also performed 2 hours after anti-integrin αvβ3 monoclonal antibody treatment and after bevacizumab treatment on days 3 and 6t. Using DCE MRI, the 30-minute contrast washout percentage was significantly lower in the cRGD-conjugate injection groups. The enhancement patterns were different between the two contrast injection groups. In the antiangiogenic therapy groups, a rapid increase in 30-minute contrast washout percentage was observed in both the LM609 and bevacizumab treatment groups, and this occurred before there was an observable decrease in tumor size. The integrin αvβ3 targeting ability of PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 in vitro and in vivo was demonstrated. The 30-minute contrast washout percentage is a useful parameter for examining tumor angiogenesis and for the early assessment of antiangiogenic treatment response.

Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications.

PubMed

Shilo, Malka; Motiei, Menachem; Hana, Panet; Popovtzer, Rachela

2014-02-21

A critical problem in the treatment of neurodegenerative disorders and diseases, such as Alzheimer's and Parkinson's, is the incapability to overcome the restrictive mechanism of the blood-brain barrier (BBB) and to deliver important therapeutic agents to the brain. During the last decade, nanoparticles have gained attention as promising drug delivery agents that can transport across the BBB and increase the uptake of appropriate drugs in the brain. In this study we have developed insulin-targeted gold nanoparticles (INS-GNPs) and investigated quantitatively the amount of INS-GNPs that cross the BBB by the receptor-mediated endocytosis process. For this purpose, INS-GNPs and control GNPs were injected into the tail vein of male BALB/c mice. Major organs were then extracted and a blood sample was taken from the mice, and thereafter analyzed for gold content by flame atomic absorption spectroscopy. Results show that two hours post-intravenous injection, the amount of INS-GNPs found in mouse brains is over 5 times greater than that of the control, untargeted GNPs. Results of further experimentation on a rat model show that INS-GNPs can also serve as CT contrast agents to highlight specific brain regions in which they accumulate. Due to the fact that they can overcome the restrictive mechanism of the BBB, this approach could be a potentially valuable tool, helping to confront the great challenge of delivering important imaging and therapeutic agents to the brain for detection and treatment of neurodegenerative disorders and diseases.

Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications

NASA Astrophysics Data System (ADS)

Shilo, Malka; Motiei, Menachem; Hana, Panet; Popovtzer, Rachela

2014-01-01

A critical problem in the treatment of neurodegenerative disorders and diseases, such as Alzheimer's and Parkinson's, is the incapability to overcome the restrictive mechanism of the blood-brain barrier (BBB) and to deliver important therapeutic agents to the brain. During the last decade, nanoparticles have gained attention as promising drug delivery agents that can transport across the BBB and increase the uptake of appropriate drugs in the brain. In this study we have developed insulin-targeted gold nanoparticles (INS-GNPs) and investigated quantitatively the amount of INS-GNPs that cross the BBB by the receptor-mediated endocytosis process. For this purpose, INS-GNPs and control GNPs were injected into the tail vein of male BALB/c mice. Major organs were then extracted and a blood sample was taken from the mice, and thereafter analyzed for gold content by flame atomic absorption spectroscopy. Results show that two hours post-intravenous injection, the amount of INS-GNPs found in mouse brains is over 5 times greater than that of the control, untargeted GNPs. Results of further experimentation on a rat model show that INS-GNPs can also serve as CT contrast agents to highlight specific brain regions in which they accumulate. Due to the fact that they can overcome the restrictive mechanism of the BBB, this approach could be a potentially valuable tool, helping to confront the great challenge of delivering important imaging and therapeutic agents to the brain for detection and treatment of neurodegenerative disorders and diseases.

Up to 50-fold increase in urine viscosity with iso-osmolar contrast media in the rat.

PubMed

Seeliger, Erdmann; Becker, Klaus; Ladwig, Mechthild; Wronski, Thomas; Persson, Pontus B; Flemming, Bert

2010-08-01

To compare changes in urinary viscosity in the renal tubules following administration of a high-viscosity iso-osmolar contrast agent (iodixanol) to that observed following administration of a less viscous, higher osmolar contrast agent (iopromide) in anesthetized rats. A total of 43 rats were studied. Experiments were approved by the Berlin, Germany, animal protection administration. A viscometer was developed to measure viscosity in minute samples (7 microL). Urine was collected, viscosity was measured (at 37 degrees C), and glomerular filtration rate (GFR) was determined by means of creatinine clearance. Boluses of 1.5 mL of iodixanol (320 mg iodine per milliliter, iso-osmolar to plasma, high viscosity) or iopromide (370 mg iodine per milliliter, higher osmolality and lower viscosity than iodixanol) were injected into the thoracic aorta. There were five groups (seven rats per group). Groups 1 (iodixanol) and 2 (iopromide) had free access to water prior to the experiment; groups 3 (iodixanol) and 4 (iopromide) received an additional infusion of isotonic saline (4 mL/kg/h). Group 5 was treated as group 1 but received only 0.75 mL of iodixanol. The observation period was 100 minutes. Statistical comparisons were made by means of nonparametric procedures (Friedman test, Kruskal-Wallis test). Iodixanol increased urine viscosity from 0.69 to 36.7 mm(2)/sec; thus, urine became threefold more viscous than native iodixanol solution. The increase in urine viscosity after injection of iopromide was from 0.73 to 2.3 mm(2)/sec. While GFR was not significantly affected by iopromide, GFR transiently decreased by 50% after administration of iodixanol. Iopromide had a diuretic effect twofold greater than that of iodixanol. Saline infusion blunted the viscosity rise and transient decline in GFR caused by iodixanol, as did reducing the iodixanol dose by 50%. Contrast media, in particular iodixanol, increase urine viscosity (which is equal to tubular fluid viscosity in the collecting ducts); in response to iodixanol, GFR markedly decreases. Saline infusion attenuates this response, thus potentially explaining the protective effects of volume expansion in contrast medium-induced nephropathy.

Fluoroscopically Guided Epidural Injections of the Cervical and Lumbar Spine.

PubMed

Shim, Euddeum; Lee, Joon Woo; Lee, Eugene; Ahn, Joong Mo; Kang, Yusuhn; Kang, Heung Sik

2017-01-01

Advances in imaging and the development of injection techniques have enabled spinal intervention to become an important tool in managing chronic spinal pain. Epidural steroid injection (ESI) is one of the most widely used spinal interventions; it directly delivers drugs into the epidural space to relieve pain originating from degenerative spine disorders-central canal stenoses and neural foraminal stenoses-or disk herniations. Knowledge of the normal anatomy of the epidural space is essential to perform an effective and safe ESI and to recognize possible complications. Although computed tomographic (CT) or combined CT-fluoroscopic guidance has been increasingly used in ESI, conventional fluoroscopic guidance is generally performed. In ESI, drugs are delivered into the epidural space by interlaminar or transforaminal routes in the cervical spine or by interlaminar, transforaminal, or caudal routes in the lumbar spine. Epidurography is usually performed before drug delivery to verify the proper position of the needle in the epidural space. A small amount of contrast agent is injected with fluoroscopic guidance. Familiarity with the findings on a typical "true" epidurogram (demonstrating correct needle placement in the epidural space) permits proper performance of ESI. Findings on "false" epidurograms (demonstrating incorrect needle placement) include muscular staining and evidence of intravascular injection, inadvertent facet joint injection, dural puncture, subdural injection, and intraneural or intradiscal injection. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on December 22, 2016.

Application of organic IR788-loaded semi-interpenetrating network dyes for photoacoustic imaging

NASA Astrophysics Data System (ADS)

Phuc Nguyen, Van; Kim, Hyejin; Kang, Mingyeong; Kwak, Minseok; Kang, Hyun Wook

2017-07-01

In this study, we present the feasibility of a biocompatible Lumogen® IR788-loaded polymeric nanoparticle (NP) as a novel photoabsorbing agent for photoacoustic (PA) imaging. The NP was fabricated through a semi-interpenetrating network (sIPN) within the core of F127 resulting in IR788-sIPN formation. To evaluate the PA sensitivity of the material, tubing phantoms were injected with various concentrations of IR788-sIPN, and H1975 lung-tumor-bearing mice were intratumorally injected with IR788-sIPN. Compared with the background, the PA contrast was enhanced up to 80 and 40% in the phantom and in vivo experiments, respectively. IR788-sIPN can be a feasible IR-absorbing material for early cancer detection.

Fe3O4-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis

PubMed Central

Liu, Jia; Xu, Jie; Zhou, Jun; Zhang, Yu; Guo, Dajing; Wang, Zhigang

2017-01-01

Thrombotic disease is a great threat to human health, and early detection is particularly important. Magnetic resonance (MR) molecular imaging provides noninvasive imaging with the potential for early disease diagnosis. In this study, we developed Fe3O4-based poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface-modified with a cyclic Arg-Gly-Asp (cRGD) peptide as an MR contrast agent for the detection of thrombosis. The physical and chemical characteristics, biological toxicity, ability to target thrombi, and biodistribution of the NPs were studied. The Fe3O4-PLGA-cRGD NPs were constructed successfully, and hematologic and pathologic assays indicated no in vivo toxicity of the NPs. In a rat model of FeCl3-induced abdominal aorta thrombosis, the NPs readily and selectively accumulated on the surface of the thrombosis and under vascular endothelial cells ex vivo and in vivo. In the in vivo experiment, the biodistribution of the NPs suggested that the NPs might be internalized by the macrophages of the reticuloendothelial system in the liver and the spleen. The T2 signal decreased at the mural thrombus 10 min after injection and then gradually increased until 50 min. These results suggest that the NPs are suitable for in vivo molecular imaging of thrombosis under high shear stress conditions and represent a very promising MR contrast agent for sensitive and specific detection of thrombosis. PMID:28223802

Immobilization of iron oxide nanoparticles within alginate nanogels for enhanced MR imaging applications.

PubMed

Sun, Wenjie; Yang, Jia; Zhu, Jianzhi; Zhou, Yiwei; Li, Jingchao; Zhu, Xiaoyue; Shen, Mingwu; Zhang, Guixiang; Shi, Xiangyang

2016-10-20

We report the design of iron oxide (Fe3O4) nanoparticle (NP)-immobilized alginate (AG) nanogels (NGs) as a novel contrast agent for enhanced magnetic resonance (MR) imaging applications. In this study, an aqueous solution of AG activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride was double emulsified to form NGs, followed by in situ cross-linking with polyethyleneimine (PEI)-coated Fe3O4 NPs (PEI-Fe3O4 NPs). The resultant Fe3O4 NP-immobilized AG NGs (AG/PEI-Fe3O4 NGs) were characterized via different techniques. Our results reveal that the hybrid NGs with a size of 186.1 ± 33.1 nm are water dispersible, colloidally stable, and cytocompatible in the given concentration range. Importantly, these NGs have a high r2 relaxivity (170.87 mM(-1) s(-1)) due to the high loading of Fe3O4 NPs within the NGs, and can be more significantly uptaken by cancer cells when compared with carboxylated Fe3O4 NPs. The formed AG/PEI-Fe3O4 NGs are able to be used as an effective contrast agent for the MR imaging of cancer cells in vitro and the xenografted tumor model in vivo after intravenous injection. The developed AG/PEI-Fe3O4 NGs may hold great promise for use as a novel contrast agent for the enhanced MR imaging of different biological systems.

Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent.

PubMed

Jenjob, Ratchapol; Kun, Na; Ghee, Jung Yeon; Shen, Zheyu; Wu, Xiaoxia; Cho, Steve K; Lee, Don Haeng; Yang, Su-Geun

2016-04-01

In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd(3+), chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd(3+) in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd(3+) incubated with Ca(2+) was performed by using a dialysis membrane (MWCO 100-500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd(3+), the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd(3+) were released from Gd-DTPA-Pullulan after 2h incubation with Ca(2+) and Fe(2+), respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t1/2,α=0.43 h, t1/2,β=2.32 h), much longer than 0.11h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. Copyright © 2016 Elsevier B.V. All rights reserved.

Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution.

PubMed

Tran, Nhiem; Bye, Nicole; Moffat, Bradford A; Wright, David K; Cuddihy, Andrew; Hinton, Tracey M; Hawley, Adrian M; Reynolds, Nicholas P; Waddington, Lynne J; Mulet, Xavier; Turnley, Ann M; Morganti-Kossmann, M Cristina; Muir, Benjamin W

2017-02-01

Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapid treatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes and hexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. This is the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magnetic resonance (MR) imaging modalities in cubosomes and hexosomes. High-throughput screening was used to rapidly optimize formulations with desirable nano-architectures and low in vitro cytotoxicity. The dual-modal imaging nanoparticles in vivo biodistribution and organ specific contrast enhancement were then studied. The NIRF in vivo imaging results indicated accumulation of both cubosomes and hexosomes in the liver and spleen of mice up to 20h post-injection. Remarkably, the biodistribution of the nanoparticle formulations was affected by the mesophase (i.e. cubic or hexagonal), a finding of significant importance for the future use of these compounds, with hexosomes showing higher accumulation in the spleen than the liver compared to cubosomes. Furthermore, in vivo MRI data of animals injected with either type of lyotropic liquid crystal nanoparticle displayed enhanced contrast in the liver and spleen. Copyright © 2016 Elsevier B.V. All rights reserved.

In vivo magnetic resonance imaging of atherosclerotic lesions with a newly developed Evans blue-DTPA-gadolinium contrast medium in apolipoprotein-E-deficient mice.

PubMed

Yasuda, Satoshi; Ikuta, Kenjiro; Uwatoku, Toyokazu; Oi, Keiji; Abe, Kohtaro; Hyodo, Fuminori; Yoshimitsu, Kengo; Sugimura, Kohtaro; Utsumi, Hideo; Katayama, Yoshiki; Shimokawa, Hiroaki

2008-01-01

Magnetic resonance imaging (MRI) contrast agents that specifically detect atherosclerotic plaque may be useful for the noninvasive detection of the plaque. We have recently developed a new contrast agent, Evans blue-DTPA-gadolinium (EB-DTPA-Gd), which selectively accumulates vascular lesions with endothelial removal. In this study, we examined whether EB-DTPA-Gd is also useful for in vivo imaging of atherosclerotic plaques. We used male apolipoprotein-E-deficient (ApoE-/-) mice of different ages (3, 6 and 12 months old) and age-matched male wild-type mice. After a single intravenous administration of EB-DTPA-Gd (160 microM/kg body weight), MRI T(1) signal was obtained in vivo. Increased signal intensity in the aortic wall was noted within 10-20 min after intravenous injection of EB-DTPA-Gd and was maintained for 30 min. The MRI enhancement in the aorta of ApoE-/- mice was increased in accordance with age, whereas no such enhancement was noted in wild-type mice. Histological examination demonstrated that there was a topological correlation between the site of MRI enhancement and that of atherosclerotic plaque. These results indicate that EB-DTPA-Gd is a useful MRI contrast medium for the in vivo detection of atherosclerotic plaques. Copyright (c) 2007 S. Karger AG, Basel.

Application of a biodegradable macromolecular contrast agent in dynamic contrast enhanced MRI for assessing the efficacy of indocyanine green enhanced photothermal cancer therapy

PubMed Central

Feng, Yi; Emerson, Lyska; Jeong, Eun-Kee; Parker, Dennis L.; Lu, Zheng-Rong

2009-01-01

Purpose To investigate the effectiveness of a polydisulfide-based biodegradable macromolecular contrast agent, (Gd-DTPA)-cystamine copolymers (GDCC), in assessing the efficacy of indocyanine green enhanced photothermal cancer therapy using dynamic contrast enhanced MRI (DCE-MRI). Materials and Methods Breast cancer xenografts in mice were injected with indocyanine green and irradiated with laser. The efficacy was assessed using DCE-MRI with GDCC of 40 KDa (GDCC-40) at 4 hours and 7 days after the treatment. The uptake of GDCC-40 by the tumors was fit to a two-compartment model to obtain tumor vascular parameters, including fractional plasma volume (fPV), endothelium transfer coefficient (KPS), and permeability surface area product (PS). Results GDCC-40 resulted in similar tumor vascular parameters at three doses with larger standard deviations at lower doses. The values of fPV, KPS and PS of the treated tumors were smaller (p < 0.05) than those of untreated tumors at 4 hours after the treatment and recovered to pretreatment values (p > 0.05) at 7 days after the treatment. Conclusion DCE-MRI with GDCC-40 is effective for assessing tumor early response to dye-enhanced photothermal therapy and detecting tumor relapse after the treatment. GDCC-40 has a potential to non-invasively monitor anticancer therapies with DCE-MRI. PMID:19629979

Application of the HeartLander Crawling Robot for Injection of a Thermally Sensitive Anti-Remodeling Agent for Myocardial Infarction Therapy

PubMed Central

Chapman, Michael P.; López González, Jose L.; Goyette, Brina E.; Fujimoto, Kazuro L.; Ma, Zuwei; Wagner, William R.; Zenati, Marco A.; Riviere, Cameron N.

2011-01-01

The injection of a mechanical bulking agent into the left ventricular (LV) wall of the heart has shown promise as a therapy for maladaptive remodeling of the myocardium after myocardial infarct (MI). The HeartLander robotic crawler presented itself as an ideal vehicle for minimally-invasive, highly accurate epicardial injection of such an agent. Use of the optimal bulking agent, a thermosetting hydrogel developed by our group, presents a number of engineering obstacles, including cooling of the miniaturized injection system while the robot is navigating in the warm environment of a living patient. We present herein a demonstration of an integrated miniature cooling and injection system in the HeartLander crawling robot, that is fully biocompatible and capable of multiple injections of a thermosetting hydrogel into dense animal tissue while the entire system is immersed in a 37°C water bath. PMID:21096276

Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heyerdahl, Helen, E-mail: Helen.Heyerdahl@rr-research.no; Røe, Kathrine; Brevik, Ellen Mengshoel

2013-09-01

Purpose: The purpose of this study was to investigate the effect of α-particle-emitting {sup 227}Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of {sup 227}Th-trastuzumab. Methods and Materials: Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm{sup 3} (mean ± SEM) were treated with a single injection of either {sup 227}Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.9% NaCl (control group, n=10 tumors). Dynamic T1-weighted contrast-enhanced magnetic resonance imaging (DCEMRI) was used to study themore » effect of {sup 227}Th-trastuzumab on tumor vasculature. DCEMRI was performed before treatment and 1, 2, and 3 weeks after therapy. Tumor contrast-enhancement curves were extracted voxel by voxel and fitted to the Brix pharmacokinetic model. Pharmacokinetic parameters for the tumors that underwent radioimmunotherapy were compared with the corresponding parameters of control tumors. Results: Significant increases of k{sub ep}, the rate constant of diffusion from the extravascular extracellular space to the plasma (P<.05), and k{sub el,} the rate of clearance of contrast agent from the plasma (P<.01), were seen in the radioimmunotherapy group 2 and 3 weeks after injection, compared with the control group. The product of k{sub ep} and the amplitude parameter A, associated with increased vessel permeability and perfusion, was also significantly increased in the radioimmunotherapy group 2 and 3 weeks after injection (P<.01). Conclusions: Pharmacokinetic modeling of MRI contrast-enhancement curves evidenced significant alterations in parameters associated with increased tumor vessel permeability and tumor perfusion after {sup 227}Th-trastuzumab treatment of HER2-expressing ovarian cancer xenografts.« less

Modifications in dynamic contrast-enhanced magnetic resonance imaging parameters after α-particle-emitting ²²⁷Th-trastuzumab therapy of HER2-expressing ovarian cancer xenografts.

PubMed

Heyerdahl, Helen; Røe, Kathrine; Brevik, Ellen Mengshoel; Dahle, Jostein

2013-09-01

The purpose of this study was to investigate the effect of α-particle-emitting (227)Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of (227)Th-trastuzumab. Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm(3) (mean ± SEM) were treated with a single injection of either (227)Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.9% NaCl (control group, n=10 tumors). Dynamic T1-weighted contrast-enhanced magnetic resonance imaging (DCEMRI) was used to study the effect of (227)Th-trastuzumab on tumor vasculature. DCEMRI was performed before treatment and 1, 2, and 3 weeks after therapy. Tumor contrast-enhancement curves were extracted voxel by voxel and fitted to the Brix pharmacokinetic model. Pharmacokinetic parameters for the tumors that underwent radioimmunotherapy were compared with the corresponding parameters of control tumors. Significant increases of kep, the rate constant of diffusion from the extravascular extracellular space to the plasma (P<.05), and kel, the rate of clearance of contrast agent from the plasma (P<.01), were seen in the radioimmunotherapy group 2 and 3 weeks after injection, compared with the control group. The product of kep and the amplitude parameter A, associated with increased vessel permeability and perfusion, was also significantly increased in the radioimmunotherapy group 2 and 3 weeks after injection (P<.01). Pharmacokinetic modeling of MRI contrast-enhancement curves evidenced significant alterations in parameters associated with increased tumor vessel permeability and tumor perfusion after (227)Th-trastuzumab treatment of HER2-expressing ovarian cancer xenografts. Copyright © 2013 Elsevier Inc. All rights reserved.

MR imaging with i.v. superparamagnetic iron oxide: efficacy in the detection of focal hepatic lesions.

PubMed

Winter, T C; Freeny, P C; Nghiem, H V; Mack, L A; Patten, R M; Thomas, C R; Elliott, S

1993-12-01

The purpose of this study was to evaluate the efficacy of superparmagnetic iron oxide (SPIO) in the detection of focal hepatic lesions on MR images. The study included 21 patients with 115 focal hepatic lesions and eight patients without focal hepatic lesions. T1- and T2-weighted MR images were obtained at 1.5 T before and 60 min after the end of injection of an SPIO agent. Contrast-enhanced CT scans were obtained in all patients within 10 days after MR imaging. The effect of SPIO on the signal intensity of the liver and spleen was assessed by using quantitative analysis of the region of interest. Efficacy was evaluated by using multiple criteria and unenhanced and SPIO-enhanced images. Evaluations included subjective assessment of image quality, counting the number of lesions detected, and statistical analysis of quantitative changes in the signal intensity of lesions and of normal liver. By all criteria, SPIO-enhanced T2-weighted MR images were superior to unenhanced T2-weighted images and to contrast-enhanced CT scans. Conversely, by all criteria, SPIO-enhanced T1-weighted MR images were worse than unenhanced T1-weighted images and contrast-enhanced CT scans. The mean lesion-to-liver contrast on T2-weighted images was 317% on unenhanced images and 1745% on SPIO-enhanced images. For T1-weighted, the mean contrast was 26% on unenhanced images and 18% on SPIO-enhanced images. SPIO is an efficacious contrast agent for the detection of focal hepatic lesions when T2-weighted MR images are used.

Mesoporous silica nanoparticles as a breast cancer targeting contrast agent for ultrasound imaging

NASA Astrophysics Data System (ADS)

Milgroom, Andrew Carson

Current clinical use of ultrasound for breast cancer diagnostics is strictly limited to a role as a supplementary detection method to other modalities, such as mammography or MRI. A major reason for ultrasound’s role as a secondary method is its inability to discern between cancerous and non-cancerous bodies of similar density, like dense calcifications or benign fibroadenomas. Its detection capabilities are further diminished by the variable density of the surrounding breast tissue with the progression of age. Preliminary studies suggest that mesoporous silica nanoparticles (MSNs) are a good candidate as an in situ contrast agent for ultrasound. By tagging the silica particle surface with the cancer-targeting antibody trastuzumab (Herceptin), suspect regions of interest can be better identified in real time with standard ultrasound equipment. Once the silica-antibody conjugate is injected into the bloodstream and enters the cancerous growth’s vasculature, the antibody arm will bind to HER2, a cell surface receptor known to be dysfunctional or overexpressed in certain types of breast cancer. As more particles aggregate at the cell surface, backscatter of the ultrasonic waves increases as a result of the higher porous silica concentration. This translates to an increased contrast around the lesion boundary. Tumor detection through ultrasound contrast enhancement provides a tremendous advantage over current cancer diagnostics because is it significantly cheaper and can be monitored in real time. Characterization of MCM-41 type MSNs suggests that these particles have sufficient stability and particle size distribution to penetrate through fenestrated tumor vasculature and accumulate in HER2+ breast cancer cells through the enhanced permeation and retention (EPR) effect. A study of acoustic properties showed that particle concentration is linearly correlated to image contrast in clinical frequency-range ultrasound, although less pronounced than typical microbubble-type contrast agents. In vitro studies using cells with varied levels of HER2 expression demonstrated the selectivity of the MSN-Herceptin conjugate to cells with HER2 overexpression. Fluorescence imaging suggest these images remain surface-bound and are not incorporated into the cell body. This study demonstrates the potential of MSNs as a stable, safe, and effective imaging contrast agent for ultrasound-based cancer diagnostics. Ultimately this work will contribute towards the improvement of diagnostic alternatives to conventional ionizing radiation-intensive imaging—such as MRI or X-ray—without compromising the specificity of the test.

Contrast media extravasations in patients undergoing computerized tomography scanning: a systematic review and meta-analysis of risk factors and interventions.

PubMed

Ding, Sandrine; Meystre, Nicole Richli; Campeanu, Cosmin; Gullo, Giuseppe

2018-01-01

To identify risk factors and interventions preventing or reducing contrast medium extravasation. Computed tomography (CT) is a radiological examination essential for the diagnosis and monitoring of many diseases. It is often performed with the intravenous (IV) injection of contrast agents. Use of these products can result in a significant complication, extravasation, which is the accidental leakage of IV material into the surrounding tissue. Patients may feel a sharp pain and skin ulceration or necrosis may develop. This review considered studies that included patients (adults and children) undergoing a CT with IV administration of contrast media. The risk factors considered were patient demographics, comorbidities and medication history. This review also investigated any strategies related to: contrast agent, injection per se, material used for injection, apparatus used, healthcare professionals involved, and patient risk assessment performed by the radiology personnel. The comparators were other interventions or usual care. This review investigated randomized controlled trials and non-randomized controlled trials. When neither of these were available, other study designs, such as prospective and retrospective cohort studies, case-control studies and case series, were considered for inclusion. Primary outcomes considered were: extravasation frequency, volume, severity and complications. The databases PubMed, CINAHL, Embase, the Cochrane Register of Controlled Trials, Web of Science PsycINFO, ProQuest Dissertations and Theses A&I, TRIP Database and ClinicalTrials.gov were searched to find both published and unpublished studies from 1980 to September 2016. Papers were assessed by two independent reviewers for methodological validity using the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI). Data were extracted using the standardized data extraction tool from JBI SUMARI. In one case, quantitative data from two cohort studies were pooled in a statistical meta-analysis. However, generally, statistical pooling was not possible due to heterogeneity of the interventions, populations of interest or outcomes. Accordingly, the findings have been presented in narrative form. Fifteen articles were selected from a total of 2151 unique studies identified. Two were randomized controlled trials and 13 were quasi-experimental and observational studies. The quality of these studies was judged to be low to moderate. Some patient characteristics, such as female sex and inpatient status, appeared to be risk factors for extravasation. Additionally, injection rate, venous access site and catheter dwelling time could affect the volume extravasated. Preliminary studies seemed to indicate the potential of extravasation detection accessories to identify extravasation and reduce the volume extravasated. The other interventions either did not result in significant reduction in the frequency/volume of extravasation, or the results were mixed across the studies. The majority of the studies included in this review evaluated the outcomes of extravasation frequency and volume. Given the quality of the primary studies, this systematic review identified only potential risk factors and interventions. It further highlighted the research gap in this area and the importance of conducting trials with solid methodological designs.

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.

Needle Tip Position and Bevel Direction Have No Effect in the Fluoroscopic Epidural Spreading Pattern in Caudal Epidural Injections: A Randomized Trial

PubMed Central

Kwon, Won Kyoung; Kim, Ah Na; Lee, Pil Moo; Park, Cheol Hwan; Kim, Jae Hun

2016-01-01

Background. Caudal epidural steroid injections (CESIs) are an effective treatment for pain. If the injection spreads in a specific pattern depending on the needle position or bevel direction, it would be possible to inject the agent into a specific and desired area. Objectives. We conducted a prospective randomized trial to determine if the needle position and bevel direction have any effect on the epidural spreading pattern in CESI. Methods. Demographic data of the patient were collected. During CESI, the needle position (middle or lateral) and direction (ventral or dorsal) were randomly allocated. Following fluoroscope-guided injection of 4 mL contrast media and 10 mL of injectates, the epidural spreading patterns (ventral or dorsal, bilateral or lateral) were imaged. Results. In the 210 CESIs performed, the needle tip position and bevel direction did not influence the epidural spreading patterns at L4-5 and L5-S1 disc levels. A history of Lumbar spine surgery was associated with a significantly limited spread to each disc level. A midline needle tip position was more effective than the lateral position in spreading to the distant disc levels. Conclusions. Neither the needle tip position nor the bevel direction affected the epidural drug spreading pattern during CESI. PMID:27445609

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

Iodinated contrast media and contrast-induced nephropathy: is there a preferred cost-effective agent?

PubMed

Sharma, Samin K

2008-05-01

Over 20 years have passed since the introduction of the tri-iodinated low-osmolar nonionic contrast agents such as iopamidol, iohexol, ioversol and iopromide. During this time, most cardiology practices have switched to these nonionic agents to avoid the nuisance side effects and cardiac adverse events associated with the older ionic contrast agents. Although the improved tolerability of the nonionic agents is generally attributed to their decreased osmolality (approximately half that of the older ionic contrast agents), in fact, these contrast agents also differ from the older agents in their ionicity, viscosity and direct chemotoxicity. The impact of these properties on safety, together with cost differences, should be considered when selecting a contrast agent.

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles.

PubMed

Kim, Gi-Wook; Kang, Changsun; Oh, Young-Bin; Ko, Myoung-Hwan; Seo, Jeong-Hwan; Lee, Dongwon

2017-01-01

Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H 2 O 2 ) are known to be generated during tissue damages such as mechanical injury and therefore H 2 O 2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol- co -oxalate) (PVAX), which rapidly scavenges H 2 O 2 and exerts antioxidant and anti-inflammatory activity in H 2 O 2 -associated diseases. Based on the notion that PVAX nanoparticles generate CO 2 bubbles through H 2 O 2 -triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H 2 O 2 . In the agarose gel phantom study, PVAX nanoparticles continuously generated CO 2 bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H 2 O 2 in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries.

Novel Approaches for Targeting Antiviral Agents in the Treatment of Arena-, Bunya-, Flavi-, and Retroviral Infection

DTIC Science & Technology

1991-08-01

Group 3 on days 2, 4, and 6; and Group 4 on days 2, 4, 6 and 8. An additional group of mice was injected with Propionibacterium acnes (70 mg/kg) as a...with P. acnes exhibited the expected anti-tumor cytotoxic activity (data not shown). Similar results were obtained with CL 246738 (Table 14). C.2.1.4...nor liposome encapsulated drug was able to render peritoneal macrophages cytotoxic. In contrast P. acnes was highly effective. C.2.3.13 Peritoneal

Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

PubMed

Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P

1981-12-01

PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

Respiratory motion estimation in x-ray angiography for improved guidance during coronary interventions

NASA Astrophysics Data System (ADS)

Baka, N.; Lelieveldt, B. P. F.; Schultz, C.; Niessen, W.; van Walsum, T.

2015-05-01

During percutaneous coronary interventions (PCI) catheters and arteries are visualized by x-ray angiography (XA) sequences, using brief contrast injections to show the coronary arteries. If we could continue visualizing the coronary arteries after the contrast agent passed (thus in non-contrast XA frames), we could potentially lower contrast use, which is advantageous due to the toxicity of the contrast agent. This paper explores the possibility of such visualization in mono-plane XA acquisitions with a special focus on respiratory based coronary artery motion estimation. We use the patient specific coronary artery centerlines from pre-interventional 3D CTA images to project on the XA sequence for artery visualization. To achieve this, a framework for registering the 3D centerlines with the mono-plane 2D + time XA sequences is presented. During the registration the patient specific cardiac and respiratory motion is learned. We investigate several respiratory motion estimation strategies with respect to accuracy, plausibility and ease of use for motion prediction in XA frames with and without contrast. The investigated strategies include diaphragm motion based prediction, and respiratory motion extraction from the guiding catheter tip motion. We furthermore compare translational and rigid respiratory based heart motion. We validated the accuracy of the 2D/3D registration and the respiratory and cardiac motion estimations on XA sequences of 12 interventions. The diaphragm based motion model and the catheter tip derived motion achieved 1.58 mm and 1.83 mm median 2D accuracy, respectively. On a subset of four interventions we evaluated the artery visualization accuracy for non-contrast cases. Both diaphragm, and catheter tip based prediction performed similarly, with about half of the cases providing satisfactory accuracy (median error < 2 mm).

Synthesis and evaluation of novel polysaccharide-Gd-DTPA compounds as contrast agent for MRI

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Jing, Fengying; Pei, Fengkui; Liu, Maili

2003-09-01

Macromolecular conjugates of two kinds of natural polysaccharides, that from Panax quinquefolium linn (PQPS) and Ganoderma applanatum pat (GAPS), with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) have been synthesized and characterized by means of FTIR, elementary analysis and ICP-AES. Their stability was investigated by competition study with Ca 2+, EDTA (ethylenediaminetetraacetic acid) and DTPA. Polysaccharide-bound complexes exhibit T1 relaxivities of 1.5-1.7 times that of Gd-DTPA in D 2O at 25°C and 9.4 T. MR imaging of Sprague-Dawley (SD) rats showed remarkable enhancement in rat liver and kidney after i.v. injection of these two complexes: liver parenchyma 60.9±5.6%, 57.8±7.4% at 65-85 min; kidney 144.9±14.5%, 199.9±25.4% at 10-30 min for PQPS-Gd-DTPA, GAPS-Gd-DTPA at gadolinium dose of 0.083 and 0.082 mmol/kg, respectively. Our preliminary in vivo and in vitro study indicates that the two kinds of polysaccharide-bound complexes are potential tissue-specific contrast agents for MRI.

Contrast-enhanced small-animal PET/CT in cancer research: strong improvement of diagnostic accuracy without significant alteration of quantitative accuracy and NEMA NU 4-2008 image quality parameters.

PubMed

Lasnon, Charline; Quak, Elske; Briand, Mélanie; Gu, Zheng; Louis, Marie-Hélène; Aide, Nicolas

2013-01-17

The use of iodinated contrast media in small-animal positron emission tomography (PET)/computed tomography (CT) could improve anatomic referencing and tumor delineation but may introduce inaccuracies in the attenuation correction of the PET images. This study evaluated the diagnostic performance and accuracy of quantitative values in contrast-enhanced small-animal PET/CT (CEPET/CT) as compared to unenhanced small animal PET/CT (UEPET/CT). Firstly, a NEMA NU 4-2008 phantom (filled with 18F-FDG or 18F-FDG plus contrast media) and a homemade phantom, mimicking an abdominal tumor surrounded by water or contrast media, were used to evaluate the impact of iodinated contrast media on the image quality parameters and accuracy of quantitative values for a pertinent-sized target. Secondly, two studies in 22 abdominal tumor-bearing mice and rats were performed. The first animal experiment studied the impact of a dual-contrast media protocol, comprising the intravenous injection of a long-lasting contrast agent mixed with 18F-FDG and the intraperitoneal injection of contrast media, on tumor delineation and the accuracy of quantitative values. The second animal experiment compared the diagnostic performance and quantitative values of CEPET/CT versus UEPET/CT by sacrificing the animals after the tracer uptake period and imaging them before and after intraperitoneal injection of contrast media. There was minimal impact on IQ parameters (%SDunif and spillover ratios in air and water) when the NEMA NU 4-2008 phantom was filled with 18F-FDG plus contrast media. In the homemade phantom, measured activity was similar to true activity (-0.02%) and overestimated by 10.30% when vials were surrounded by water or by an iodine solution, respectively. The first animal experiment showed excellent tumor delineation and a good correlation between small-animal (SA)-PET and ex vivo quantification (r2 = 0.87, P < 0.0001). The second animal experiment showed a good correlation between CEPET/CT and UEPET/CT quantitative values (r2 = 0.99, P < 0.0001). Receiver operating characteristic analysis demonstrated better diagnostic accuracy of CEPET/CT versus UEPET/CT (senior researcher, area under the curve (AUC) 0.96 versus 0.77, P = 0.004; junior researcher, AUC 0.78 versus 0.58, P = 0.004). The use of iodinated contrast media for small-animal PET imaging significantly improves tumor delineation and diagnostic performance, without significant alteration of SA-PET quantitative accuracy and NEMA NU 4-2008 IQ parameters.

Dual-frequency transducer with a wideband PVDF receiver for contrast-enhanced, adjustable harmonic imaging

NASA Astrophysics Data System (ADS)

Kim, Jinwook; Lindsey, Brooks D.; Li, Sibo; Dayton, Paul A.; Jiang, Xiaoning

2017-04-01

Acoustic angiography is a contrast-enhanced, superharmonic microvascular imaging method. It has shown the capability of high-resolution and high-contrast-to-tissue-ratio (CTR) imaging for vascular structure near tumor. Dual-frequency ultrasound transducers and arrays are usually used for this new imaging technique. Stacked-type dual-frequency transducers have been developed for this vascular imaging method by exciting injected microbubble contrast agent (MCA) in the vessels with low-frequency (1-5 MHz), moderate power ultrasound burst waves and receiving the superharmonic responses from MCA by a high-frequency receiver (>10 MHz). The main challenge of the conventional dual-frequency transducers is a limited penetration depth (<25 mm) due to the insufficient receiving sensitivity for highfrequency harmonic signal detection. A receiver with a high receiving sensitivity spanning a wide superharmonic frequency range (3rd to 6th) enables selectable bubble harmonic detection considering the required penetration depth. Here, we develop a new dual-frequency transducer composed of a 2 MHz 1-3 composite transmitter and a polyvinylidene fluoride (PVDF) receiver with a receiving frequency range of 4-12 MHz for adjustable harmonic imaging. The developed transducer was tested for harmonic responses from a microbubble-injected vessel-mimicking tube positioned 45 mm away. Despite the long imaging distance (45 mm), the prototype transducer detected clear harmonic response with the contrast-to-noise ratio of 6-20 dB and the -6 dB axial resolution of 200-350 μm for imaging a 200 um-diameter cellulose tube filled with microbubbles.

In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent.

PubMed

Dewi, Novriana; Mi, Peng; Yanagie, Hironobu; Sakurai, Yuriko; Morishita, Yasuyuki; Yanagawa, Masashi; Nakagawa, Takayuki; Shinohara, Atsuko; Matsukawa, Takehisa; Yokoyama, Kazuhito; Cabral, Horacio; Suzuki, Minoru; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Nishiyama, Nobuhiro; Kataoka, Kazunori; Takahashi, Hiroyuki

2016-04-01

A more immediate impact for therapeutic approaches of current clinical research efforts is of major interest, which might be obtained by developing a noninvasive radiation dose-escalation strategy, and neutron capture therapy represents one such novel approach. Furthermore, some recent researches on neutron capture therapy have focused on using gadolinium as an alternative or complementary for currently used boron, taking into account several advantages that gadolinium offers. Therefore, in this study, we carried out feasibility evaluation for both single and multiple injections of gadolinium-based MRI contrast agent incorporated in calcium phosphate nanoparticles as neutron capture therapy agent. In vivo evaluation was performed on colon carcinoma Col-26 tumor-bearing mice irradiated at nuclear reactor facility of Kyoto University Research Reactor Institute with average neutron fluence of 1.8 × 10(12) n/cm(2). Antitumor effectivity was evaluated based on tumor growth suppression assessed until 27 days after neutron irradiation, followed by histopathological analysis on tumor slice. The experimental results showed that the tumor growth of irradiated mice injected beforehand with Gd-DTPA-incorporating calcium phosphate-based nanoparticles was suppressed up to four times higher compared to the non-treated group, supported by the results of histopathological analysis. The results of antitumor effectivity observed on tumor-bearing mice after neutron irradiation indicated possible effectivity of gadolinium-based neutron capture therapy treatment.

Outcome Differences between Intra-Arterial Iso- and Low-Osmolality Iodinated Radiographic Contrast Media in the Interventional Management of Stroke III Trial.

PubMed

Tomsick, T A; Foster, L D; Liebeskind, D S; Hill, M D; Carrozella, J; Goyal, M; von Kummer, R; Demchuk, A M; Dzialowski, I; Puetz, V; Jovin, T; Morales, H; Palesch, Y Y; Broderick, J; Khatri, P; Yeatts, S D

2015-11-01

Intracarotid arterial infusion of nonionic, low-osmolal iohexol contrast medium has been associated with increased intracranial hemorrhage in a rat middle cerebral artery occlusion model compared with saline infusion. Iso-osmolal iodixanol (290 mOsm/kg H2O) infusion demonstrated smaller infarcts and less intracranial hemorrhage compared with low-osmolal iopamidol and saline. No studies comparing iodinated radiographic contrast media in human stroke have been performed, to our knowledge. We hypothesized that low-osmolal contrast media may be associated with worse outcomes compared with iodixanol in the Interventional Management of Stroke III Trial (IMS III). We reviewed prospective iodinated radiographic contrast media data for 133 M1 occlusions treated with endovascular therapy. We compared 5 prespecified efficacy and safety end points (mRS 0-2 outcome, modified TICI 2b-3 reperfusion, asymptomatic and symptomatic intracranial hemorrhage, and mortality) between those receiving iodixanol (n = 31) or low-osmolal contrast media (n = 102). Variables imbalanced between iodinated radiographic contrast media types or associated with outcome were considered potential covariates for the adjusted models. In addition to the iodinated radiographic contrast media type, final covariates were those selected by using the stepwise method in a logistic regression model. Adjusted relative risks were then estimated by using a log-link regression model. Of baseline or endovascular therapy variables potentially linked to outcome, prior antiplatelet agent use was more common and microcatheter iodinated radiographic contrast media injections were fewer with iodixanol. Relative risk point estimates are in favor of iodixanol for the 5 prespecified end points with M1 occlusion. The percentage of risk differences are numerically greater for microcatheter injections with iodixanol. While data favoring the use of iso-osmolal iodixanol for reperfusion of M1 occlusion following IV rtPA are inconclusive, potential pathophysiologic mechanisms suggesting clinical benefit warrant further investigation. © 2015 by American Journal of Neuroradiology.

Effects of chronic exercise conditioning on thermal responses to lipopolysaccharide and turpentine abscess in female rats.

PubMed

Rowsey, Pamela Johnson; Metzger, Bonnie L; Carlson, John; Gordon, Christopher J

2006-02-01

Chronic exercise conditioning has been shown to alter basal thermoregulatory processes as well as the response to inflammatory agents. Two such agents, lipopolysaccharide (LPS) and turpentine (TPT) are inducers of fever in rats. LPS, given intraperitoneally (i.p.), involves a systemic inflammatory response whereas TPT given intramuscularly (i.m.) elicits a localized inflammation. We assessed if chronic exercise training in the rat would alter the thermoregulatory response to LPS and TPT. Core temperature (T (c)) and motor activity were monitored by radiotelemetry. Female Sprague Dawley rats were divided into two groups (trained and sedentary) and housed at an ambient temperature of 22 degrees C. Animals voluntarily trained on running wheels for 8 weeks. In the first study, trained and sedentary female rats were injected i.p. with LPS (50 microg/kg) or an equal volume of 0.9% normal saline. In another study, trained and sedentary female rats were injected i.m. with TPT (10 microl)/rat or an equal volume of 0.9% normal saline. The time course of the LPS fever was very short compared to TPT. TPT injected animals displayed a smaller but more prolonged fever compared to LPS; however, training accentuated the febrile response to LPS (DeltaT (c)=0.6 degrees C in sedentary and 1.2 degrees C in trained). Training had a slight suppression on TPT-induced fever during the daytime but had no effect on motor activity or nighttime T (c). In contrast, exercise training led to a marked increase in the pyrogenic effects of LPS. We conclude that the effect of exercise training and source of infection (i.e., systemic versus localized in muscle) on fever is directly linked to type of pyrogenic agent.

Multiphase contrast medium injection for optimization of computed tomographic coronary angiography.

PubMed

Budoff, Matthew Jay; Shinbane, Jerold S; Child, Janis; Carson, Sivi; Chau, Alex; Liu, Stephen H; Mao, SongShou

2006-02-01

Electron beam angiography is a minimally invasive imaging technique. Adequate vascular opacification throughout the study remains a critical issue for image quality. We hypothesized that vascular image opacification and uniformity of vascular enhancement between slices can be improved using multiphase contrast medium injection protocols. We enrolled 244 consecutive patients who were randomized to three different injection protocols: single-phase contrast medium injection (Group 1), dual-phase contrast medium injection with each phase at a different injection rate (Group 2), and a three-phase injection with two phases of contrast medium injection followed by a saline injection phase (Group 3). Parameters measured were aortic opacification based on Hounsfield units and uniformity of aortic enhancement at predetermined slices (locations from top [level 1] to base [level 60]). In Group 1, contrast opacification differed across seven predetermined locations (scan levels: 1st versus 60th, P < .05), demonstrating significant nonuniformity. In Group 2, there was more uniform vascular enhancement, with no significant differences between the first 50 slices (P > .05). In Group 3, there was greater uniformity of vascular enhancement and higher mean Hounsfield units value across all 60 images, from the aortic root to the base of the heart (P < .05). The three-phase injection protocol improved vascular opacification at the base of the heart, as well as uniformity of arterial enhancement throughout the study.

[Contrast-enhanced Ultrasound in Diagnostic Imaging of Muscle Injuries: Perfusion Imaging in the Early Arterial Phase].

PubMed

Hotfiel, T; Carl, H D; Swoboda, B; Engelhardt, M; Heinrich, M; Strobel, D; Wildner, D

2016-03-01

Ultrasound is a standard procedure widely used in the diagnostic investigation of muscle injuries and widely described in the literature. Its advantages include rapid availability, cost effectiveness and the possibility to perform a real-time dynamic examination with the highest possible spatial resolution. In the diagnostic work-up of minor lesions (muscle stiffness, muscle strain), plain ultrasound has so far been inferior to MRI. The case presented by us is an example of the possibilities offered by contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries compared with plain B-mode image ultrasound and MRI imaging of the affected region. This case report is about a high-performance football player who sustained a muscle injury. He underwent an ultrasound examination (S 2000, 9L4 Probe, Siemens, Germany), which was performed simultaneously in the conventional and contrast-enhanced mode at the level of the lesion. An intravenous bolus injection of 4.8 ml of intravascular contrast agent (SonoVue(®), Bracco, Italy) was given via a cubital intravenous line. After that, the distribution of contrast agent was visualised in the early arterial phase. In addition, a plain magnetic resonance imaging scan of both thighs was performed for reference. On conventional ultrasound, the lesion was not clearly distinguishable from neighbouring tissue, whereas contrast-enhanced ultrasound demonstrated a well delineated, circumscribed area of impaired perfusion with hypoenhancement compared with the surrounding muscles at the clinical level of the lesion in the arterial wash-in phase (0-30 sec, after intravenous administration). The MRI scan revealed an edema signal with perifascial fluid accumulation in the corresponding site. The use of intravascular contrast agent enabled the sensitive detection of a minor injury by ultrasound for the first time. An intramuscular edema seen in the MRI scan showed a functional arterial perfusion impairment on ultrasound, which was sensitively detected in the early phase. Further examinations must be performed on muscle injuries of various degrees of severity in order to validate the application of this procedure and to standardise the examination process. © Georg Thieme Verlag KG Stuttgart · New York.

The effect on cadaver blood DNA identification by the use of targeted and whole body post-mortem computed tomography angiography.

PubMed

Rutty, Guy N; Barber, Jade; Amoroso, Jasmin; Morgan, Bruno; Graham, Eleanor A M

2013-12-01

Post-mortem computed tomography angiography (PMCTA) involves the injection of contrast agents. This could have both a dilution effect on biological fluid samples and could affect subsequent post-contrast analytical laboratory processes. We undertook a small sample study of 10 targeted and 10 whole body PMCTA cases to consider whether or not these two methods of PMCTA could affect post-PMCTA cadaver blood based DNA identification. We used standard methodology to examine DNA from blood samples obtained before and after the PMCTA procedure. We illustrate that neither of these PMCTA methods had an effect on the alleles called following short tandem repeat based DNA profiling, and therefore the ability to undertake post-PMCTA blood based DNA identification.

Treatment of experimental staphylococcal osteomyelitis with rifampin and trimethoprim, alone and in combination.

PubMed Central

Norden, C W; Keleti, E

1980-01-01

Rifampin and trimethoprim were used alone and in combination in the treatment of chronic osteomyelitis due to Staphylococcus aureus in rabbits. Rifampicin levels in infected bone were well above the minimum inhibitory concentration of the infecting strain of S. aureus for at least 4 h after injection. In contrast, trimethoprim levels in diseased bone were below the minimum inhibitory concentration as early as 1 h after injection. Trimethoprim or rifampin, administered alone for 14 days, were ineffective in sterilizing infected rabbit bones. The combination of rifampin plus trimethoprim was significantly more effective (P less than 0.005) than either agents given alone for a comparable duration of time. Staphylococci isolated from the bones of rabbits treated with rifampin alone or rifampin plus trimethoprim were uniformly resistant to rifampin, but retained their susceptibility to trimethoprim. PMID:7396451

The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

NASA Astrophysics Data System (ADS)

Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

2016-07-01

We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.

Contrasting effects of systemic and central sibutramine administration on the intake of a palatable diet in the rat.

PubMed

Pratt, Wayne E; Connolly, Megan E

2010-10-22

Sibutramine hydrochloride monohydrate is the only centrally active weight-modifying agent currently approved by the FDA for long-term use in the treatment of obesity. Systemic sibutramine treatment has been shown to reduce food intake in humans and rodent models in a manner that is consistent with the enhancement of satiety mechanisms. Although it is generally assumed that the hypophagic effects of the drug are mediated by actions within the brain, the locus or loci of these effects remains unclear. These experiments compared the effects of systemic and intracranial injections of sibutramine on the intake of a palatable diet in non-deprived animals. Consistent with prior reports, systemic injections of sibutramine hydrochloride (at 0, 0.5, 1.0, or 3.0mg/kg sibutramine i.p.) dose-dependently reduced feeding on a high fat/high sucrose diet across a 2-h feeding session, but did not alter water intake or locomotor activity. In contrast, bilateral injections of sibutramine (at 0.0, 2.0, 4.0 and 10.0μg/0.5μl/side) into either the paraventricular nucleus of the hypothalamus (PVN) or the medial nucleus accumbens shell (ACb) significantly and dose-dependently increased food intake of the sweetened fat diet. ACb treatment also modestly inhibited locomotor behavior; intracranial injections had no effect on water consumption. These experiments are the first to suggest that sibutramine treatment may have distinct actions upon separate neural circuits that modulate food intake behavior in the rat. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Lung imaging in rodents using dual energy micro-CT

NASA Astrophysics Data System (ADS)

Badea, C. T.; Guo, X.; Clark, D.; Johnston, S. M.; Marshall, C.; Piantadosi, C.

2012-03-01

Dual energy CT imaging is expected to play a major role in the diagnostic arena as it provides material decomposition on an elemental basis. The purpose of this work is to investigate the use of dual energy micro-CT for the estimation of vascular, tissue, and air fractions in rodent lungs using a post-reconstruction three-material decomposition method. We have tested our method using both simulations and experimental work. Using simulations, we have estimated the accuracy limits of the decomposition for realistic micro-CT noise levels. Next, we performed experiments involving ex vivo lung imaging in which intact lungs were carefully removed from the thorax, were injected with an iodine-based contrast agent and inflated with air at different volume levels. Finally, we performed in vivo imaging studies in (n=5) C57BL/6 mice using fast prospective respiratory gating in endinspiration and end-expiration for three different levels of positive end-expiratory pressure (PEEP). Prior to imaging, mice were injected with a liposomal blood pool contrast agent. The mean accuracy values were for Air (95.5%), Blood (96%), and Tissue (92.4%). The absolute accuracy in determining all fraction materials was 94.6%. The minimum difference that we could detect in material fractions was 15%. As expected, an increase in PEEP levels for the living mouse resulted in statistically significant increases in air fractions at end-expiration, but no significant changes in end-inspiration. Our method has applicability in preclinical pulmonary studies where various physiological changes can occur as a result of genetic changes, lung disease, or drug effects.

Multimodal imaging of lymph nodes and tumors using glycol-chitosan-coated gold nanoparticles (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, In-Cheol; Dumani, Diego S.; Emelianov, Stanislav Y.

2017-03-01

A key step in staging cancer is the diagnosis of metastasis that spreads through lymphatic system. For this reason, researchers develop various methods of sentinel lymph node mapping that often use a radioactive tracer. This study introduces a safe, cost-effective, high-resolution, high-sensitivity, and real-time method of visualizing the sentinel lymph node: ultrasound-guided photoacoustic (US/PA) imaging augmented by a contrast agent. In this work, we use clearable gold nanoparticles covered by a biocompatible polymer (glycol chitosan) to enhance cellular uptake by macrophages abundant in lymph nodes. We incubate macrophages with glycol-chitosan-coated gold nanoparticles (0.05 mg Au/ml), and then fix them with paraformaldehyde solution for an analysis of in vitro dark-field microscopy and cell phantom. The analysis shows enhanced cellular uptake of nanoparticles by macrophages and strong photoacoustic signal from labeled cells in tissue-mimicking cell phantoms consisting gelatin solution (6 %) with silica gel (25 μm, 0.3%) and fixed macrophages. The in-vivo US/PA imaging of cervical lymph nodes in healthy mice (nu/nu, female, 5 weeks) indicates a strong photoacoustic signal from a lymph node 10 minutes post-injection (2.5 mg Au/ml, 80 μl). The signal intensity and the nanoparticle-labeled volume of tissue within the lymph node continues to increase until 4 h post-injection. Histological analysis further confirms the accumulation of gold nanoparticles within the lymph nodes. This work suggests the feasibility of molecular/cellular US/PA imaging with biocompatible gold nanoparticles as a photoacoustic contrast agent in the diagnosis of lymph-node-related diseases.

Enhanced Thermal Ablation by Combining Ultrasound Contrast Agents with a Miniature Flat Transducer

NASA Astrophysics Data System (ADS)

Murillo, A.; Goldendstedt, C.; Lafon, C.; Cathignol, D.; Chapelon, J.-Y.

2007-05-01

Miniature transducers can be used for performing interstitial thermal ablation. Increasing the frequency of non-focused transducers enhances energy deposition but limits the therapeutic range. In order to treat extended tumors, new therapeutic strategies must be explored. This work aimed to combine ultrasound contrast agents (UCA) with flat transducers for increasing the treatment depth. The idea consists in increasing attenuation away from the transducer to favor remote heat deposition. Thermal ablation is induced in three steps. 1- Attenuation raises by injecting UCA; 2- Destruction of bubbles next to the transducer by pulsed high intensity bursts, results in a gradient of attenuation; 3- Continuous ultrasound are applied for generating a localized thermal lesion. In vitro tests were performed on temperature-sensitive tissue phantoms in which the UCA BR14 (Bracco) was injected during the liquid phase. The feasibility of the idea was demonstrated in three stages. 1- The coefficient of attenuation was measured with the force balance as a function of the concentration of BR14. For 0.8 and 4.8% attenuation at 10MHz was found to be 0.35 and 1.33 Np/cm respectively. 2- Pulsed ultrasound was applied on phantoms to destroy UCA. Based on the echogenicity decay evidenced on ultrasound images, a 1MPa-pressure was required at 10MHz. 3- Heating beams were applied on phantoms presenting a gradient in attenuation. Lesions were 1.5 times larger than in phantoms with constant attenuation. This study demonstrates that UCA can be selectively destroyed in order to generate a gradient of attenuation and extended thermal lesions.

Complete penile corporeal septation: evaluation with contrast enhanced US.

PubMed

Bertolotto, Michele; Bucci, Stefano; Quaia, Emilio; Coss, Matteo; Liguori, Giovanni

2008-01-01

Complete penile corporeal septation is a rare malformation in which the corpora cavernosa are completely isolated. We describe a new method to reach the diagnosis of this malformation using contrast enhanced US. Two patients with complete penile corporeal septation underwent color Doppler and contrast enhanced US after bilateral cavernosal injection of 10 microg prostaglandin E1. Contrast enhanced US was performed using a contrast specific software (Contrast-Tuned imaging, EsaOte, Genoa, Italy) and a linear transducer designed to evaluate superficial structures. Microbubbles of SonoVue (Bracco, Milan, Italy) were injected in one corpus cavernosum. After cavernosal injection of microbubbles no adverse events were observed. Contrast enhanced US showed unilateral enhancement of the corpus cavernosum in which microbubbles were injected. Cavernosography confirmed unilateral corporeal opacification. Contrast enhanced US can be used effectively to diagnose complete penile corporeal septation.

Gadolinium-Based Contrast Agents for MR Cancer Imaging

PubMed Central

Zhou, Zhuxian; Lu, Zheng-Rong

2013-01-01

Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

Distribution of radiodense contrast medium after perineural injection of the palmar and palmar metacarpal nerves (low 4-point nerve block): an in vivo and ex vivo study in horses.

PubMed

Nagy, A; Bodò, G; Dyson, S J; Compostella, F; Barr, A R S

2010-09-01

Evidence-based information is limited on distribution of local anaesthetic solution following perineural analgesia of the palmar (Pa) and palmar metacarpal (PaM) nerves in the distal aspect of the metacarpal (Mc) region ('low 4-point nerve block'). To demonstrate the potential distribution of local anaesthetic solution after a low 4-point nerve block using a radiographic contrast model. A radiodense contrast medium was injected subcutaneously over the medial or the lateral Pa nerve at the junction of the proximal three-quarters and distal quarter of the Mc region (Pa injection) and over the ipsilateral PaM nerve immediately distal to the distal aspect of the second or fourth Mc bones (PaM injection) in both forelimbs of 10 mature horses free from lameness. Radiographs were obtained 0, 10 and 20 min after injection and analysed subjectively and objectively. Methylene blue and a radiodense contrast medium were injected in 20 cadaver limbs using the same techniques. Radiographs were obtained and the limbs dissected. After 31/40 (77.5%) Pa injections, the pattern of the contrast medium suggested distribution in the neurovascular bundle. There was significant proximal diffusion with time, but the main contrast medium patch never progressed proximal to the mid-Mc region. The radiological appearance of 2 limbs suggested that contrast medium was present in the digital flexor tendon sheath (DFTS). After PaM injections, the contrast medium was distributed diffusely around the injection site in the majority of the limbs. In cadaver limbs, after Pa injections, the contrast medium and the dye were distributed in the neurovascular bundle in 8/20 (40%) limbs and in the DFTS in 6/20 (30%) of limbs. After PaM injections, the contrast and dye were distributed diffusely around the injection site in 9/20 (45%) limbs and showed diffuse and tubular distribution in 11/20 (55%) limbs. Proximal diffusion of local anaesthetic solution after a low 4-point nerve block is unlikely to be responsible for decreasing lameness caused by pain in the proximal Mc region. The DFTS may be penetrated inadvertently when performing a low 4-point nerve block.

Alterations of the transverse ligament: an MRI study comparing patients with acute whiplash and matched control subjects.

PubMed

Ulbrich, Erika Jasmin; Eigenheer, Sandra; Boesch, Chris; Hodler, Juerg; Busato, André; Schraner, Christian; Anderson, Suzanne E; Bonel, Harald; Zimmermann, Heinz; Sturzenegger, Matthias

2011-10-01

The objective of our study was to evaluate whether there is injury to the transverse ligament of the atlas in patients with acute whiplash. Ninety patients with an acute (< 48 hours) symptomatic whiplash-associated injury and 90 healthy age- and sex-matched asymptomatic control subjects (mean age of patients and control subjects, 36 years) were included. The maximal sagittal thickness of the transverse ligament was measured on midsagittal T1 volumetric interpolated breath-hold examination (VIBE) images and transverse reformatted VIBE images. The signal intensity of the transverse ligament was measured on transverse STIR images and on transverse reformatted T1 VIBE images before and after IV administration of gadoterate. Contrast between the transverse ligament and CSF and alterations of contrast after gadoterate injection were calculated. Patients had a minimally thicker transverse ligament (posttraumatic swelling) than control subjects, and the difference in thickness was significant in men only (p = 0.03). In patients, a significant signal alteration of the transverse ligament (p = 0.03) was seen on STIR (posttraumatic edema) and native VIBE sequences. The contrast between the transverse ligament and the CSF on VIBE images was significantly (p = 0.005) lower in patients than in control subjects. With the application of a contrast agent, the contrast difference between the transverse ligament and CSF in patients and control subjects was less pronounced (p = 0.038). There was no abnormal uptake of contrast agent by the transverse ligament or CSF. The results of our study indicate possible involvement of the transverse ligament in whiplash injury. Although MRI may be helpful to study injury-related changes of anatomic structures in cohorts, it is not suited for individual diagnosis because the alterations are too small.

An analysis of the uncertainty and bias in DCE-MRI measurements using the spoiled gradient-recalled echo pulse sequence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Subashi, Ergys; Choudhury, Kingshuk R.; Johnson, G. Allan, E-mail: gjohnson@duke.edu

2014-03-15

Purpose: The pharmacokinetic parameters derived from dynamic contrast-enhanced (DCE) MRI have been used in more than 100 phase I trials and investigator led studies. A comparison of the absolute values of these quantities requires an estimation of their respective probability distribution function (PDF). The statistical variation of the DCE-MRI measurement is analyzed by considering the fundamental sources of error in the MR signal intensity acquired with the spoiled gradient-echo (SPGR) pulse sequence. Methods: The variance in the SPGR signal intensity arises from quadrature detection and excitation flip angle inconsistency. The noise power was measured in 11 phantoms of contrast agentmore » concentration in the range [0–1] mM (in steps of 0.1 mM) and in onein vivo acquisition of a tumor-bearing mouse. The distribution of the flip angle was determined in a uniform 10 mM CuSO{sub 4} phantom using the spin echo double angle method. The PDF of a wide range of T1 values measured with the varying flip angle (VFA) technique was estimated through numerical simulations of the SPGR equation. The resultant uncertainty in contrast agent concentration was incorporated in the most common model of tracer exchange kinetics and the PDF of the derived pharmacokinetic parameters was studied numerically. Results: The VFA method is an unbiased technique for measuringT1 only in the absence of bias in excitation flip angle. The time-dependent concentration of the contrast agent measured in vivo is within the theoretically predicted uncertainty. The uncertainty in measuring K{sup trans} with SPGR pulse sequences is of the same order, but always higher than, the uncertainty in measuring the pre-injection longitudinal relaxation time (T1{sub 0}). The lowest achievable bias/uncertainty in estimating this parameter is approximately 20%–70% higher than the bias/uncertainty in the measurement of the pre-injection T1 map. The fractional volume parameters derived from the extended Tofts model were found to be extremely sensitive to the variance in signal intensity. The SNR of the pre-injection T1 map indicates the limiting precision with which K{sup trans} can be calculated. Conclusions: Current small-animal imaging systems and pulse sequences robust to motion artifacts have the capacity for reproducible quantitative acquisitions with DCE-MRI. In these circumstances, it is feasible to achieve a level of precision limited only by physiologic variability.« less

Power port contrast medium flushing and trapping: impact of temperature, an in vitro experimental study.

PubMed

Guiffant, Gérard; Durussel, Jean Jacques; Flaud, Patrice; Royon, Laurent; Marcy, Pierre Yves; Merckx, Jacques

2013-01-01

The use of totally implantable venous access devices (TIVADs) certified as "high pressure resistant" or "power port" has begun to spread worldwide as a safe procedure for power contrast injection. Owing to the thermo-rheological properties of the contrast media, the primary aim of this work is to present an in vitro experimental impact study concerning the impact of the temperature level on flushing efficiency after contrast medium injection. Moreover, we report experimental data that confirms the role of needle bevel orientation. The secondary aim is to answer the following questions: Is there significant device contrast medium trapping after contrast medium injection? Is saline flushing efficient? And, finally, is it safe to inject contrast medium through an indwelled port catheter? The experimental results show that in addition to hydrodynamics, temperature is a key parameter for the efficiency of device flushing after contrast medium injection. It appears that this is the case when the cavity is incompletely rinsed after three calibrated flushing volumes of 10 mL saline solution, even by using the Huber needle bevel opposite to the port exit. This leads to a potentially important trapped volume of contrast medium in the port, and consequently to the possibility of subsequent salt precipitates and long term trisubstituted benzene nuclei delivery that might impair the solute properties, which may be further injected via the power port later on. We thus suggest, in TIVADS patients, the use of a temporary supplementary intravenous line rather than the port to perform contrast medium injections in daily radiology routine practice.

Power port contrast medium flushing and trapping: impact of temperature, an in vitro experimental study

PubMed Central

Guiffant, Gérard; Durussel, Jean Jacques; Flaud, Patrice; Royon, Laurent; Marcy, Pierre Yves; Merckx, Jacques

2013-01-01

Purpose The use of totally implantable venous access devices (TIVADs) certified as “high pressure resistant” or “power port” has begun to spread worldwide as a safe procedure for power contrast injection. Owing to the thermo-rheological properties of the contrast media, the primary aim of this work is to present an in vitro experimental impact study concerning the impact of the temperature level on flushing efficiency after contrast medium injection. Moreover, we report experimental data that confirms the role of needle bevel orientation. The secondary aim is to answer the following questions: Is there significant device contrast medium trapping after contrast medium injection? Is saline flushing efficient? And, finally, is it safe to inject contrast medium through an indwelled port catheter? Results The experimental results show that in addition to hydrodynamics, temperature is a key parameter for the efficiency of device flushing after contrast medium injection. It appears that this is the case when the cavity is incompletely rinsed after three calibrated flushing volumes of 10 mL saline solution, even by using the Huber needle bevel opposite to the port exit. This leads to a potentially important trapped volume of contrast medium in the port, and consequently to the possibility of subsequent salt precipitates and long term trisubstituted benzene nuclei delivery that might impair the solute properties, which may be further injected via the power port later on. Conclusion We thus suggest, in TIVADS patients, the use of a temporary supplementary intravenous line rather than the port to perform contrast medium injections in daily radiology routine practice. PMID:24043959

Effectiveness and safety of CEUS-guided haemostatic injection for blunt splenic trauma: an animal experiment.

PubMed

Li, W; Tang, J; Lv, F; Zhang, H; Zhang, S; An, L

2010-10-01

The aim of this study was to investigate whether complications occur after haemostatic agents are injected into blunt splenic injuries. After undergoing ultrasound (US), contrast-enhanced US (CEUS) and contrast-enhanced computed tomography (CECT) examinations, dogs with grade III-IV injury received the minimally invasive therapy. After treatment, CEUS was performed to observe changes in the regions treated. In the immediate group, dogs underwent laparotomy 30 min after treatment to observe the haemostatic effect. In the survival group, animals underwent CEUS and CECT examinations to observe the short-term healing outcome and complications at 3, 7, 14, and 21 days after the injection. After undergoing CEUS and CECT examinations, 12 dogs with grade III-IV injury received the minimally invasive therapy. Before injection, CEUS examinations showed anechoic and/or hypoechoic perfusion defects and active bleeding at the injury sites, and CECT showed traumatic lesions as low-density regions without enhancement. After treatment, CEUS demonstrated the disappearance of active bleeding, and hyperechoic spots emerged at the injury sites. Uneven density regions were displayed on CECT. Treated areas were covered by blood clots and glue membrane in the immediate-group animals. Three weeks later, CEUS showed a decrease of hyperechoic spots in the survival group, and the splenic parenchyma enhanced uniformly on CECT. Laparotomy showed that the greater omentum had moved upwards and partly covered the wound in four animals, and the injury sites had completely healed. Histopathological examination showed that fibrous connective tissue covered the splenic capsule and that the haemostatic glue had degraded. No complication occurred, such as delayed splenic haemorrhage, splenic abscesses, splenic pseudoaneurysms, intestinal obstruction or intestinal adhesions. CEUS-guided haemostatic injection is not only effective in stopping active bleeding immediately, but it is also safe in that no complications occurred during the 3 weeks of follow-up. This study indicates that CEUS-guided percutaneous injection may provide a safe, feasible and effective therapy for blunt splenic trauma.

Safety and efficacy of botulinum toxin injection therapy for esophageal achalasia in Japan

PubMed Central

Yamaguchi, Daisuke; Tsuruoka, Nanae; Sakata, Yasuhisa; Shimoda, Ryo; Fujimoto, Kazuma; Iwakiri, Ryuichi

2015-01-01

Botulinum toxin injection is an accepted treatment modality for esophageal achalasia in western countries. This pilot study aimed to clarify the effectiveness of botulinum toxin injection for esophageal achalasia in Japanese patients. We enrolled 10 patients diagnosed with esophageal achalasia between 2008 and 2014. A total of 100 U botulinum toxin A was divided into eight aliquots and injected around the esophagogastric junction. We compared the lower esophageal sphincter pressure before and 1 week after treatment. Scores of subjective symptoms for esophageal achalasia were assessed using a visual analog scale (VAS) before and after 1 week of follow-up of treatment. Barium passage was improved in barium esophagography and passage of contrast agent was also improved. Mean Eckardt score was reduced from 5.5 to 1.6 after treatment (p<0.001). By esophageal manometric study, mean lower esophageal sphincter pressure was reduced from 46.9 to 29.1 mmHg after treatment (p = 0.002). One week after treatment, mean VAS score was reduced from 10 to 3.9 (p<0.001). There were no side effects in any cases. Botulinum toxin injection for esophageal achalasia was safe and effective with few complications. Therefore, botulinum toxin could be used as minimally invasive therapy for esophageal achalasia in Japan. PMID:26566311

Safety and efficacy of botulinum toxin injection therapy for esophageal achalasia in Japan.

PubMed

Yamaguchi, Daisuke; Tsuruoka, Nanae; Sakata, Yasuhisa; Shimoda, Ryo; Fujimoto, Kazuma; Iwakiri, Ryuichi

2015-11-01

Botulinum toxin injection is an accepted treatment modality for esophageal achalasia in western countries. This pilot study aimed to clarify the effectiveness of botulinum toxin injection for esophageal achalasia in Japanese patients. We enrolled 10 patients diagnosed with esophageal achalasia between 2008 and 2014. A total of 100 U botulinum toxin A was divided into eight aliquots and injected around the esophagogastric junction. We compared the lower esophageal sphincter pressure before and 1 week after treatment. Scores of subjective symptoms for esophageal achalasia were assessed using a visual analog scale (VAS) before and after 1 week of follow-up of treatment. Barium passage was improved in barium esophagography and passage of contrast agent was also improved. Mean Eckardt score was reduced from 5.5 to 1.6 after treatment (p<0.001). By esophageal manometric study, mean lower esophageal sphincter pressure was reduced from 46.9 to 29.1 mmHg after treatment (p = 0.002). One week after treatment, mean VAS score was reduced from 10 to 3.9 (p<0.001). There were no side effects in any cases. Botulinum toxin injection for esophageal achalasia was safe and effective with few complications. Therefore, botulinum toxin could be used as minimally invasive therapy for esophageal achalasia in Japan.

Microangiography in Living Mice Using Synchrotron Radiation

NASA Astrophysics Data System (ADS)

Yuan, Falei; Wang, Yongting; Guan, Yongjing; Lu, Haiyan; Xie, Bohua; Tang, Yaohui; Xie, Honglan; Du, Guohao; Xiao, Tiqiao; Yang, Guo-Yuan

2010-07-01

Traditionally, there are no methods available to detect the fine morphologic changes of cerebrovasculature in small living animals such as rats and mice. Newly developed synchrotron radiation microangiography can achieve a fine resolution of several micrometers and had provided us with a powerful tool to study the cerebral vasculature in small animals. The purpose of this study is to identify the morphology of cerebrovasculature especially the structure of Lenticulostriate arteries (LSAs) in living mice using the synchrotron radiation source at Shanghai Synchrotron Radiation Facility (SSRF) in Shanghai, China. Adult CD-1 mice weighing 35-40 grams were anesthetized. Nonionic iodine (Omnipaque, 350 mg I /mL) was used as a contrast agent. The study was performed at the BL13W1 beam line at SSRF. The beam line was derived from a storage ring of electrons with an accelerated energy of 3.5 GeV and an average beam current of 200 mA. X-ray energy of 33.3 keV was used to produce the highest contrast image. Images were acquired every 172 ms by a x-ray camera (Photonic-Science VHR 1.38) with a resolution of 13 μm/pixel. The optimal dose of contrast agent is 100 μl per injection and the injecting rate is 33 μl/sec. The best position for imaging is to have the mouse lay on its right or left side, with ventral side facing the X-ray source. We observed the lenticulostriate artery for the first time in living mice. Our result show that there are 4 to 5 lenticulostriate branches originating from the root of middle cerebral artery in each hemisphere. LSAs have an average diameter of 43±6.8 μm. There were no differences between LSAs from the left and right hemisphere (p<0.05). These results suggest that synchrotron radiation may provide a unique tool for experimental stroke research.

Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

PubMed

Hou, Weixin; Toh, Tan Boon; Abdullah, Lissa Nurrul; Yvonne, Tay Wei Zheng; Lee, Kuan J; Guenther, Ilonka; Chow, Edward Kai-Hua

2017-04-01

Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl 2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn 2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Contrast enhanced spectroscopic optical coherence tomography

NASA Technical Reports Server (NTRS)

Xu, Chenyang (Inventor); Boppart, Stephen A. (Inventor)

2010-01-01

A method of forming an image of a sample includes performing SOCT on a sample. The sample may include a contrast agent, which may include an absorbing agent and/or a scattering agent. A method of forming an image of tissue may include selecting a contrast agent, delivering the contrast agent to the tissue, acquiring SOCT data from the tissue, and converting the SOCT data into an image. The contributions to the SOCT data of an absorbing agent and a scattering agent in a sample may be quantified separately.

Blood-pool contrast agent for pre-clinical computed tomography

NASA Astrophysics Data System (ADS)

Cruje, Charmainne; Tse, Justin J.; Holdsworth, David W.; Gillies, Elizabeth R.; Drangova, Maria

2017-03-01

Advances in nanotechnology have led to the development of blood-pool contrast agents for micro-computed tomography (micro-CT). Although long-circulating nanoparticle-based agents exist for micro-CT, they are predominantly based on iodine, which has a low atomic number. Micro-CT contrast increases when using elements with higher atomic numbers (i.e. lanthanides), particularly at higher energies. The purpose of our work was to develop and evaluate a lanthanide-based blood-pool contrast agent that is suitable for in vivo micro-CT. We synthesized a contrast agent in the form of polymer-encapsulated Gd nanoparticles and evaluated its stability in vitro. The synthesized nanoparticles were shown to have an average diameter of 127 +/- 6 nm, with good size dispersity. Particle size distribution - evaluated by dynamic light scattering over the period of two days - demonstrated no change in size of the contrast agent in water and saline. Additionally, our contrast agent was stable in a mouse serum mimic for up to 30 minutes. CT images of the synthesized contrast agent (containing 27 mg/mL of Gd) demonstrated an attenuation of over 1000 Hounsfield Units. This approach to synthesizing a Gd-based blood-pool contrast agent promises to enhance the capabilities of micro-CT imaging.

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

Contrast media extravasations in patients undergoing computerized tomography scanning: a systematic review and meta-analysis of risk factors and interventions

PubMed Central

Ding, Sandrine; Meystre, Nicole Richli; Campeanu, Cosmin; Gullo, Giuseppe

2018-01-01

ABSTRACT Objective: To identify risk factors and interventions preventing or reducing contrast medium extravasation. Introduction: Computed tomography (CT) is a radiological examination essential for the diagnosis and monitoring of many diseases. It is often performed with the intravenous (IV) injection of contrast agents. Use of these products can result in a significant complication, extravasation, which is the accidental leakage of IV material into the surrounding tissue. Patients may feel a sharp pain and skin ulceration or necrosis may develop. Inclusion criteria: This review considered studies that included patients (adults and children) undergoing a CT with IV administration of contrast media. The risk factors considered were patient demographics, comorbidities and medication history. This review also investigated any strategies related to: contrast agent, injection per se, material used for injection, apparatus used, healthcare professionals involved, and patient risk assessment performed by the radiology personnel. The comparators were other interventions or usual care. This review investigated randomized controlled trials and non-randomized controlled trials. When neither of these were available, other study designs, such as prospective and retrospective cohort studies, case-control studies and case series, were considered for inclusion. Primary outcomes considered were: extravasation frequency, volume, severity and complications. Methods: The databases PubMed, CINAHL, Embase, the Cochrane Register of Controlled Trials, Web of Science PsycINFO, ProQuest Dissertations and Theses A&I, TRIP Database and ClinicalTrials.gov were searched to find both published and unpublished studies from 1980 to September 2016. Papers were assessed by two independent reviewers for methodological validity using the Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI). Data were extracted using the standardized data extraction tool from JBI SUMARI. In one case, quantitative data from two cohort studies were pooled in a statistical meta-analysis. However, generally, statistical pooling was not possible due to heterogeneity of the interventions, populations of interest or outcomes. Accordingly, the findings have been presented in narrative form. Results: Fifteen articles were selected from a total of 2151 unique studies identified. Two were randomized controlled trials and 13 were quasi-experimental and observational studies. The quality of these studies was judged to be low to moderate. Some patient characteristics, such as female sex and inpatient status, appeared to be risk factors for extravasation. Additionally, injection rate, venous access site and catheter dwelling time could affect the volume extravasated. Preliminary studies seemed to indicate the potential of extravasation detection accessories to identify extravasation and reduce the volume extravasated. The other interventions either did not result in significant reduction in the frequency/volume of extravasation, or the results were mixed across the studies. Conclusions: The majority of the studies included in this review evaluated the outcomes of extravasation frequency and volume. Given the quality of the primary studies, this systematic review identified only potential risk factors and interventions. It further highlighted the research gap in this area and the importance of conducting trials with solid methodological designs. PMID:29324560

Optimization in modeling the ribs-bounded contour from computer tomography scan

NASA Astrophysics Data System (ADS)

Bilinskas, M. J.; Dzemyda, G.

2016-10-01

In this paper a method for analyzing transversal plane images from computer tomography scans is presented. A mathematical model that describes the ribs-bounded contour was created and the problem of approximation is solved by finding out the optimal parameters of the model in the least-squares sense. Such model would be useful in registration of images independently on the patient position on the bed and on the radio-contrast agent injection. We consider the slices, where ribs are visible, because many important internal organs are located here: liver, heart, stomach, pancreas, lung, etc.

Preliminary in vivo evaluation of [131I]-2-iodo-D-phenylalanine as a potential radionuclide therapeutic agent in R1M-fluc rhabdomyosarcoma tumor-bearing NuNu mice using bioluminescent imaging.

PubMed

Bauwens, Matthias; Wimana, Lena; Keyaerts, Marleen; Peleman, Cindy; Lahoutte, Tony; Kersemans, Ken; Snykers, Sarah; Vinken, Mathieu; Mertens, John; Bossuyt, Axel

2010-04-01

Carrier-added [(123)I]-2-iodo-D-phenylalanine (CA [(123)I]-2-I-D-Phe) was previously found to have a preferential retention in tumors with a high tumor background contrast in animal models. A previous human dosimetry study demonstrated a favorable biodistribution and radiation burden in human subjects. The aim of this study was to investigate the potential of CA [(131)I]-2-I-D-Phe as an agent for radionuclide therapy. Sixty (60) nude athymic mice were inoculated subcutaneously with firefly luciferase-transduced R1M rhabdomyosarcoma cells. The mice in the therapy group were injected intravenously (i.v.) with 148 MBq [(131)I]-2-I-D-Phe (432 GBq/mmol) in kit solution. Controls were injected with kit solution without radioactivity, with physiological saline, or with 148 MBq [(131)I](-) in physiological saline. Tumor growth was quantified using bioluminescent imaging and caliper measurements. [(131)I]-2-I-D-Phe clearly reduced tumor growth in the treated mice compared with the control groups. A tumor growth-rate reduction of at least 33% was found for mice receiving a therapeutic dose. There were no serious adverse side-effects of the therapy. In conclusion, i.v. injection of CA 148 MBq [(131)I]-2-I-D-Phe specifically reduces tumor growth in athymic nude mice without relevant side-effects on the animals' health.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weishaupt, Dominik; Hilfiker, Paul R.; Schmidt, Michaela

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 pulmonarymore » 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.« less

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles

PubMed Central

Kim, Gi-Wook; Kang, Changsun; Oh, Young-Bin; Ko, Myoung-Hwan; Seo, Jeong-Hwan; Lee, Dongwon

2017-01-01

Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H2O2) are known to be generated during tissue damages such as mechanical injury and therefore H2O2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H2O2 and exerts antioxidant and anti-inflammatory activity in H2O2-associated diseases. Based on the notion that PVAX nanoparticles generate CO2 bubbles through H2O2-triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H2O2. In the agarose gel phantom study, PVAX nanoparticles continuously generated CO2 bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H2O2 in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries. PMID:28744328

Benefits of Synchrotron Microangiography for Dynamic Studies of Smooth Muscle and Endothelial Roles in the Pathophysiology of Vascular Disease

NASA Astrophysics Data System (ADS)

Pearson, James T.; Schwenke, Daryl O.; Jenkins, Mathew J.; Edgley, Amanda J.; Sonobe, Takashi; Ishibashi-Ueda, Hatsue; Umetani, Keiji; Eppel, Gabriela A.; Evans, Roger G.; Okura, Yasuhiko; Shirai, Mikiyasu

2010-07-01

Changes in endothelial and smooth muscle function compromise organ perfusion in the chronic disease states of diabetes, atherosclerosis and hypertension. Moreover, vascular dysfunction increases the likelihood of lethal acute events such as myocardial infarction and stroke, which are now leading causes of adult mortality. Many circulating and local tissue factors in these disease states contribute to impaired vasomotor regulation of the arterial vessels, leading to spasm, chronic constriction and eventually vessel remodelling. X-ray contrast absorption imaging allows assessment of vessel lumen diameter and the factors contributing to steady-state vessel calibre, however, conventional clinical devices (>200 μm resolution) are not adequate to detect microvessels or accurately assess function in real time. Using synchrotron imaging we are now able to detect small vessel calibres (˜30 μm) and quantify regional differences in calibre even under conditions of high heart rate (>500 bpm). Herein we describe recent experiments that were conducted at the Japanese Synchrotron, SPring-8 using anaesthetised Sprague-Dawley rats and C57Bl/6 mice and a synchrotron radiation contrast angiography (single narrow energy bandwidth) approach based on selective arterial injection of iodine contrast agents. Application of this approach to imaging of the heart and other vasculatures are described. Our studies show that within-animal comparisons of 3-4 branching orders of arterial vessels are possible using small bolus contrast injections and appropriate contrast washout times (15-30 min) in many organ systems. Determination of relative calibre changes before and after any treatment allows us to evaluate the contributions of different endogenous factors and ligand-receptor pathways in the maintenance of vasomotor tone. Finally, we will present our findings relating to novel therapies to prevent endothelial dysfunction in heart failure.

Benefits of Synchrotron Microangiography for Dynamic Studies of Smooth Muscle and Endothelial Roles in the Pathophysiology of Vascular Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pearson, James T.; Department of Physiology, Monash University, 3800 Clayton; Schwenke, Daryl O.

2010-07-23

Changes in endothelial and smooth muscle function compromise organ perfusion in the chronic disease states of diabetes, atherosclerosis and hypertension. Moreover, vascular dysfunction increases the likelihood of lethal acute events such as myocardial infarction and stroke, which are now leading causes of adult mortality. Many circulating and local tissue factors in these disease states contribute to impaired vasomotor regulation of the arterial vessels, leading to spasm, chronic constriction and eventually vessel remodelling. X-ray contrast absorption imaging allows assessment of vessel lumen diameter and the factors contributing to steady-state vessel calibre, however, conventional clinical devices (>200 {mu}m resolution) are not adequatemore » to detect microvessels or accurately assess function in real time. Using synchrotron imaging we are now able to detect small vessel calibres ({approx}30 {mu}m) and quantify regional differences in calibre even under conditions of high heart rate (>500 bpm). Herein we describe recent experiments that were conducted at the Japanese Synchrotron, SPring-8 using anaesthetised Sprague-Dawley rats and C57Bl/6 mice and a synchrotron radiation contrast angiography (single narrow energy bandwidth) approach based on selective arterial injection of iodine contrast agents. Application of this approach to imaging of the heart and other vasculatures are described. Our studies show that within-animal comparisons of 3-4 branching orders of arterial vessels are possible using small bolus contrast injections and appropriate contrast washout times (15-30 min) in many organ systems. Determination of relative calibre changes before and after any treatment allows us to evaluate the contributions of different endogenous factors and ligand-receptor pathways in the maintenance of vasomotor tone. Finally, we will present our findings relating to novel therapies to prevent endothelial dysfunction in heart failure.« less

Biocompatible KMnF3 nanoparticular contrast agent with proper plasma retention time for in vivo magnetic resonance imaging.

PubMed

Liu, Zhi-jun; Song, Xiao-xia; Xu, Xian-zhu; Tang, Qun

2014-04-18

Nanoparticular MRI contrast agents are rapidly becoming suitable for use in clinical diagnosis. An ideal nanoparticular contrast agent should be endowed with high relaxivity, biocompatibility, proper plasma retention time, and tissue-specific or tumor-targeting imaging. Herein we introduce PEGylated KMnF3 nanoparticles as a new type of T1 contrast agent. Studies showed that the nanoparticular contrast agent revealed high bio-stability with bovine serum albumin in PBS buffer solution, and presented excellent biocompatibility (low cytotoxicity, undetectable hemolysis and hemagglutination). Meanwhile the new contrast agent possessed proper plasma retention time (circulation half-life t1/2 is approximately 2 h) in the body of the administrated mice. It can be delivered into brain vessels and maintained there for hours, and is mostly cleared from the body within 48 h, as demonstrated by time-resolved MRI and Mn-biodistribution analysis. Those distinguishing features make it suitable to obtain contrast-enhanced brain magnetic resonance angiography. Moreover, through the process of passive targeting delivery, the T1 contrast agent clearly illuminates a brain tumor (glioma) with high contrast image and defined shape. This study demonstrates that PEGylated KMnF3 nanoparticles represent a promising biocompatible vascular contrast agent for magnetic resonance angiography and can potentially be further developed into an active targeted tumor MRI contrast agent.

Retrospective analysis of the utility of multiparametric MRI for differentiating between benign and malignant breast lesions in women in China

PubMed Central

Fan, Wei Xiong; Chen, Xiao Feng; Cheng, Feng Yan; Cheng, Ya Bao; Xu, Tai; Zhu, Wen Biao; Zhu, Xiao Lei; Li, Gui Jin; Li, Shuai

2018-01-01

Abstract We explored the utility of time-resolved angiography with interleaved stochastic trajectories dynamic contrast-enhanced magnetic resonance imaging (TWIST DCE-MRI), readout segmentation of long variable echo-trains diffusion-weighted magnetic resonance imaging- diffusion-weighted magnetic resonance imaging (RESOLVE-DWI), and echo-planar imaging- diffusion-weighted magnetic resonance imaging (EPI-DWI) for distinguishing between malignant and benign breast lesions. This retrospective analysis included female patients with breast lesions seen at a single center in China between January 2016 and April 2016. Patients were allocated to a benign or malignant group based on pathologic diagnosis. All patients received routine MRI, RESOLVE-DWI, EPI-DWI, and TWIST DCE-T1WI. Variables measured included quantitative parameters (Ktrans, Kep, and Ve), semiquantitative parameters (rate of contrast enhancement for contrast agent inflow [W-in], rate of contrast decay for contrast agent outflow [W-out], and time-to-peak enhancement after contrast agent injection [TTP]) and apparent diffusion coefficient (ADC) values for RESOLVE-DWI (ADCr) and EPI-DWI (ADCe). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic utility of each parameter for differentiating malignant from benign breast lesions. A total of 87 patients were included (benign, n = 20; malignant, n = 67). Compared with the benign group, the malignant group had significantly higher Ktrans, Kep and W-in and significantly lower W-out, TTP, ADCe, and ADCr (all P < .05); Ve was not significantly different between groups. RESOLVE-DWI was superior to conventional EPI-DWI at illustrating lesion boundary and morphology, while ADCr was significantly lower than ADCe in all patients. Kep, W-out, ADCr, and ADCe showed the highest diagnostic efficiency (based on AUC value) for differentiating between benign and malignant lesions. Combining 3 parameters (Kep, W-out, and ADCr) had a higher diagnostic efficiency (AUC, 0.965) than any individual parameter and distinguished between benign and malignant lesions with high sensitivity (91.0%), specificity (95.0%), and accuracy (91.9%). An index combining Kep, W-out, and ADCr could potentially be used for the differential diagnosis of breast lesions. PMID:29369183

Retrospective analysis of the utility of multiparametric MRI for differentiating between benign and malignant breast lesions in women in China.

PubMed

Fan, Wei Xiong; Chen, Xiao Feng; Cheng, Feng Yan; Cheng, Ya Bao; Xu, Tai; Zhu, Wen Biao; Zhu, Xiao Lei; Li, Gui Jin; Li, Shuai

2018-01-01

We explored the utility of time-resolved angiography with interleaved stochastic trajectories dynamic contrast-enhanced magnetic resonance imaging (TWIST DCE-MRI), readout segmentation of long variable echo-trains diffusion-weighted magnetic resonance imaging- diffusion-weighted magnetic resonance imaging (RESOLVE-DWI), and echo-planar imaging- diffusion-weighted magnetic resonance imaging (EPI-DWI) for distinguishing between malignant and benign breast lesions.This retrospective analysis included female patients with breast lesions seen at a single center in China between January 2016 and April 2016. Patients were allocated to a benign or malignant group based on pathologic diagnosis. All patients received routine MRI, RESOLVE-DWI, EPI-DWI, and TWIST DCE-T1WI. Variables measured included quantitative parameters (K, Kep, and Ve), semiquantitative parameters (rate of contrast enhancement for contrast agent inflow [W-in], rate of contrast decay for contrast agent outflow [W-out], and time-to-peak enhancement after contrast agent injection [TTP]) and apparent diffusion coefficient (ADC) values for RESOLVE-DWI (ADCr) and EPI-DWI (ADCe). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic utility of each parameter for differentiating malignant from benign breast lesions.A total of 87 patients were included (benign, n = 20; malignant, n = 67). Compared with the benign group, the malignant group had significantly higher K, Kep and W-in and significantly lower W-out, TTP, ADCe, and ADCr (all P < .05); Ve was not significantly different between groups. RESOLVE-DWI was superior to conventional EPI-DWI at illustrating lesion boundary and morphology, while ADCr was significantly lower than ADCe in all patients. Kep, W-out, ADCr, and ADCe showed the highest diagnostic efficiency (based on AUC value) for differentiating between benign and malignant lesions. Combining 3 parameters (Kep, W-out, and ADCr) had a higher diagnostic efficiency (AUC, 0.965) than any individual parameter and distinguished between benign and malignant lesions with high sensitivity (91.0%), specificity (95.0%), and accuracy (91.9%).An index combining Kep, W-out, and ADCr could potentially be used for the differential diagnosis of breast lesions.

Induction of hypocalcemia by intracerebroventricular injection of calcitonin: evidence for control of blood calcium by the nervous system.

PubMed

Goltzman, D; Tannenbaum, G S

1987-07-21

Calcitonin (CT), when administered peripherally, is a potent hypocalcemic agent. This peptide can also exert a variety of profound effects through brain receptors after central injection. We examined the capacity of CT to alter plasma calcium of freely moving conscious rats after intracerebroventricular (i.c.v.) injection. A dose-dependent decrease in plasma calcium was seen after administration of 25 ng, 250 ng or 2500 ng of salmon calcitonin (sCT). The extent and duration of hypocalcemia after central injection was equal to, or greater than, that seen after giving the same doses of peptide intravenously (i.v.). Calcitonin gene-related peptide (CGRP), when administered centrally at a 50-fold molar excess, produced only a transient decrease in plasma calcium. No increase in plasma levels of sCT could be detected by RIA after i.c.v. injection, although measurable levels were obtained by i.v. injection. Centrally administered sCT did not appear to produce hypocalcemia by enhancing the release of endogenous rat CT. In contrast to the rise in rat immunoreactive parathyroid hormone (PTH) seen after i.v. injection of sCT, no significant elevation occurred after central administration of the peptide despite induction of comparable levels of hypocalcemia. Consequently, reduced PTH release may contribute to the central hypocalcemic action of CT. The results indicate that peptides acting through the brain CT receptor may modulate peripheral blood calcium.

Fast frame rate rodent cardiac x-ray imaging using scintillator lens coupled to CMOS camera

NASA Astrophysics Data System (ADS)

Swathi Lakshmi, B.; Sai Varsha, M. K. N.; Kumar, N. Ashwin; Dixit, Madhulika; Krishnamurthi, Ganapathy

2017-03-01

Micro-Computed Tomography (MCT) systems for small animal imaging plays a critical role for monitoring disease progression and therapy evaluation. In this work, an in-house built micro-CT system equipped with a X-ray scintillator lens coupled to a commercial CMOS camera was used to test the feasibility of its application to Digital Subtraction Angiography (DSA). Literature has reported such studies being done with clinical X-ray tubes that can be pulsed rapidly or with rotating gantry systems, thus increasing the cost and infrastructural requirements.The feasibility of DSA was evaluated by injected Iodinated contrast agent (ICA) through the tail vein of a mouse. Projection images of the heart were acquired pre and post contrast using the high frame rate X-ray detector and processing done to visualize transit of ICA through the heart.

Pressure and Flow Rate Changes During Contrast Injections in Cerebral Angiography: Correlation to Reflux Length.

PubMed

Kovarovic, Brandon; Woo, Henry H; Fiorella, David; Lieber, Baruch B; Sadasivan, Chander

2018-03-01

Cerebral angiography involves the antegrade injection of contrast media through a catheter into the vasculature to visualize the region of interest under X-ray imaging. Depending on the injection and blood flow parameters, the bolus of contrast can propagate in the upstream direction and proximal to the catheter tip, at which point contrast is said to have refluxed. In this in vitro study, we investigate the relationship of fundamental hemodynamic variables to this phenomenon. Contrast injections were carried out under steady and pulsatile flow using various vessel diameters, catheter sizes, working fluid flow rates, and injection rates. The distance from the catheter tip to the proximal edge of the contrast bolus, called reflux length, was measured on the angiograms; the relation of this reflux length to different hemodynamic parameters was evaluated. Results show that contrast reflux occurs when the pressure distal to the catheter tip increases to be greater than the pressure proximal to the catheter tip. The ratio of this pressure difference to the baseline flow rate, called reflux resistance here, was linearly correlated to the normalized reflux length (reflux length/vessel diameter). Further, the ratio of blood flow to contrast fluid momentums, called the Craya-Curtet number, was correlated to the normalized reflux length via a sigmoid function. A sigmoid function was also found to be representative of the relationship between the ratio of the Reynolds numbers of blood flow to contrast and the normalized reflux length. As described by previous reports, catheter based contrast injections cause substantial increases in local flow and pressure. Contrast reflux should generally be avoided during standard antegrade angiography. Our study shows two specific correlations between contrast reflux length and baseline and intra-injection parameters that have not been published previously. Further studies need to be conducted to fully characterize the phenomena and to extract reliable indicators of clinical utility. Parameters relevant to cerebral angiography are studied here, but the essential principles are applicable to all angiographic procedures involving antegrade catheter injections.

Nanoscale Metal-Organic Frameworks Decorated with Graphene Oxide for Magnetic Resonance Imaging Guided Photothermal Therapy.

PubMed

Meng, Jing; Chen, Xiujin; Tian, Yang; Li, Zhongfeng; Zheng, Qingfeng

2017-12-11

Imaging-guided photothermal therapy (PTT) provides an attractive way to treat cancer. A composite material of a nanoscale metal-organic framework (NMOF) and graphene oxide (GO) has been prepared for potential use in tumor-guided PTT with magnetic resonance imaging (MRI). The NMOFs containing Fe 3+ were prefabricated with an octahedral morphology through a solvothermal reaction to offer a strong T 2 -weighted contrast in MRI. Then the NMOFs were decorated with GO nanosheets, which had good photothermal properties. After decoration, zeta-potential characterization shows that the aqueous stability of the composite material is enhanced, UV/Vis and near-infrared (NIR) spectra confirm that NIR absorption is also increased, and photothermal experiments reveal that the composite materials express higher photothermal conversion effects and conversion stability. The fabricated NMOF/GO shows low cytotoxicity, effective T 2 -weighted contrast of MRI, and positive PTT behavior for a tumor model in vitro. The performance of the composite NMOF/GO for MRI and PTT was also tested upon injection into A549 tumor-bearing mice. The studies in vivo revealed that the fabricated NMOF/GO was efficient in T 2 -weighted imaging and ablation of the A549 tumor with low cytotoxicity, which implied that the prepared composite contrast agent was a potential multifunctional nanotheranostic agent. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Entropy of Ultrasound-Contrast-Agent Velocity Fields for Angiogenesis Imaging in Prostate Cancer.

PubMed

van Sloun, Ruud J G; Demi, Libertario; Postema, Arnoud W; Jmch De La Rosette, Jean; Wijkstra, Hessel; Mischi, Massimo

2017-03-01

Prostate cancer care can benefit from accurate and cost-efficient imaging modalities that are able to reveal prognostic indicators for cancer. Angiogenesis is known to play a central role in the growth of tumors towards a metastatic or a lethal phenotype. With the aim of localizing angiogenic activity in a non-invasive manner, Dynamic Contrast Enhanced Ultrasound (DCE-US) has been widely used. Usually, the passage of ultrasound contrast agents thought the organ of interest is analyzed for the assessment of tissue perfusion. However, the heterogeneous nature of blood flow in angiogenic vasculature hampers the diagnostic effectiveness of perfusion parameters. In this regard, quantification of the heterogeneity of flow may provide a relevant additional feature for localizing angiogenesis. Statistics based on flow magnitude as well as its orientation can be exploited for this purpose. In this paper, we estimate the microbubble velocity fields from a standard bolus injection and provide a first statistical characterization by performing a spatial entropy analysis. By testing the method on 24 patients with biopsy-proven prostate cancer, we show that the proposed method can be applied effectively to clinically acquired DCE-US data. The method permits estimation of the in-plane flow vector fields and their local intricacy, and yields promising results (receiver-operating-characteristic curve area of 0.85) for the detection of prostate cancer.

Comparison of two ultrasound-guided injection techniques targeting the sacroiliac joint region in equine cadavers.

PubMed

Stack, John David; Bergamino, Chiara; Sanders, Ruth; Fogarty, Ursula; Puggioni, Antonella; Kearney, Clodagh; David, Florent

2016-09-20

To compare the accuracy and distribution of injectate for cranial (CR) and caudomedial (CM) ultrasound-guided injections of equine sacroiliac joints. Both sacroiliac joints from 10 lumbosacropelvic specimens were injected using cranial parasagittal (CR; curved 18 gauge, 25 cm spinal needles) and caudomedial (CM; straight 18 gauge, 15 cm spinal needles) ultrasound-guided approaches. Injectate consisted of 4 ml iodinated contrast and 2 ml methylene blue. Computed tomographical (CT) scans were performed before and after injections. Time for needle guidance and repositioning attempts were recorded. The CT sequences were analysed for accuracy and distribution of contrast. Intra-articular contrast was detected in sacroiliac joints following 15/40 injections. The CR and CM approaches deposited injectate ≤2 cm from sacroiliac joint margins following 17/20 and 20/20 injections, respectively. Median distance of closest contrast to the sacroiliac joint was 0.4 cm (interquartile range [IQR]: 1.5 cm) for CR approaches and 0.6 cm (IQR: 0.95 cm) for CM approaches. Cranial injections resulted in injectate contacting lumbosacral intertransverse joints 15/20 times. Caudomedial injections were perivascular 16/20 times. Safety and efficacy could not be established. Cranial and CM ultrasound-guided injections targeting sacroiliac joints were very accurate for periarticular injection, but accuracy was poor for intra-articular injection. Injectate was frequently found in contact with interosseous sacroiliac ligaments, as well as neurovascular and synovial structures in close vicinity of sacroiliac joints.

INDIRECT COMPUTED TOMOGRAPHIC LYMPHOGRAPHY FOR ILIOSACRAL LYMPHATIC MAPPING IN A COHORT OF DOGS WITH ANAL SAC GLAND ADENOCARCINOMA: TECHNIQUE DESCRIPTION.

PubMed

Majeski, Stephanie A; Steffey, Michele A; Fuller, Mark; Hunt, Geraldine B; Mayhew, Philipp D; Pollard, Rachel E

2017-05-01

Sentinel lymph node mapping can help to direct surgical oncologic staging and metastatic disease detection in patients with complex lymphatic pathways. We hypothesized that indirect computed tomographic lymphography (ICTL) with a water-soluble iodinated contrast agent would successfully map lymphatic pathways of the iliosacral lymphatic center in dogs with anal sac gland carcinoma, providing a potential preoperative method for iliosacral sentinel lymph node identification in dogs. Thirteen adult dogs diagnosed with anal sac gland carcinoma were enrolled in this prospective, pilot study, and ICTL was performed via peritumoral contrast injection with serial caudal abdominal computed tomography scans for iliosacral sentinel lymph node identification. Technical and descriptive details for ICTL were recorded, including patient positioning, total contrast injection volume, timing of contrast visualization, and sentinel lymph nodes and lymphatic pathways identified. Indirect CT lymphography identified lymphatic pathways and sentinel lymph nodes in 12/13 cases (92%). Identified sentinel lymph nodes were ipsilateral to the anal sac gland carcinoma in 8/12 and contralateral to the anal sac gland carcinoma in 4/12 cases. Sacral, internal iliac, and medial iliac lymph nodes were identified as sentinel lymph nodes, and patterns were widely variable. Patient positioning and timing of imaging may impact successful sentinel lymph node identification. Positioning in supported sternal recumbency is recommended. Results indicate that ICTL may be a feasible technique for sentinel lymph node identification in dogs with anal sac gland carcinoma and offer preliminary data to drive further investigation of iliosacral lymphatic metastatic patterns using ICTL and sentinel lymph node biopsy. © 2017 American College of Veterinary Radiology.

Spectral CT data acquisition with Medipix3.1

NASA Astrophysics Data System (ADS)

Walsh, M. F.; Nik, S. J.; Procz, S.; Pichotka, M.; Bell, S. T.; Bateman, C. J.; Doesburg, R. M. N.; De Ruiter, N.; Chernoglazov, A. I.; Panta, R. K.; Butler, A. P. H.; Butler, P. H.

2013-10-01

This paper describes the acquisition of spectral CT images using the Medipix3.1 in spectroscopic mode, in which the chip combines 2 × 2 pixel clusters to increase the number of energy thresholds and counters from 2 to 8. During preliminary measurements, it was observed that the temperature, DAC and equalisation stability of the Medipix3.1 outperformed the Medipix3.0, while maintaining similar imaging quality. In this paper, the Medipix3.1 chips were assembled in a quad (2 × 2) layout, with the four ASICs bump-bonded to a silicon semiconductor doped as an np-junction diode. To demonstrate the biological imaging quality that is possible with the Medipix3.1, an image of a mouse injected with gold nano-particle contrast agent was obtained. CT acquisition in spectroscopic mode was enabled and examined by imaging a customised phantom containing multiple contrast agents and biological materials. These acquisitions showed a limitation of imaging performance depending on the counter used. Despite this, identification of multiple materials in the phantom was demonstrated using an in-house material decomposition algorithm. Furthermore, gold nano-particles were separated from biological tissues and bones within the mouse by means of image rendering.

18F-positron-emitting/fluorescent labeled erythrocytes allow imaging of internal hemorrhage in a murine intracranial hemorrhage model

PubMed Central

Wang, Ye; An, Fei-Fei; Chan, Mark; Friedman, Beth; Rodriguez, Erik A; Tsien, Roger Y; Aras, Omer

2017-01-01

An agent for visualizing cells by positron emission tomography is described and used to label red blood cells. The labeled red blood cells are injected systemically so that intracranial hemorrhage can be visualized by positron emission tomography (PET). Red blood cells are labeled with 0.3 µg of a positron-emitting, fluorescent multimodal imaging probe, and used to non-invasively image cryolesion induced intracranial hemorrhage in a murine model (BALB/c, 2.36 × 108 cells, 100 µCi, <4 mm hemorrhage). Intracranial hemorrhage is confirmed by histology, fluorescence, bright-field, and PET ex vivo imaging. The low required activity, minimal mass, and high resolution of this technique make this strategy an attractive alternative for imaging intracranial hemorrhage. PET is one solution to a spectrum of issues that complicate single photon emission computed tomography (SPECT). For this reason, this application serves as a PET alternative to [99mTc]-agents, and SPECT technology that is used in 2 million annual medical procedures. PET contrast is also superior to gadolinium and iodide contrast angiography for its lack of clinical contraindications. PMID:28054494

Luminescent gold nanoparticles for bioimaging

NASA Astrophysics Data System (ADS)

Zhou, Chen

Inorganic nanoparticles (NPs) with tunable and diverse material properties hold great potential as contrast agents for better disease management. Over the past decades, luminescent gold nanoparticles (AuNPs) with intrinsic emissions ranging from the visible to the near infrared have been synthesized and emerge as a new class of fluorophores for bioimaging. This dissertation aims to fundamentally understand the structure-property relationships in luminescent AuNPs and apply them as contrast agents to address some critical challenges in bioimaging at both the in vitro and in vivo level. In Chapter 2, we described the synthesized ~20 nm polycrystalline AuNPs (pAuNPs), which successfully integrated and enhanced plasmonic and fluorescence properties into a single AuNP through the grain size effect. The combination of these properties in one NP enabled AuNPs to serve as a multimodal contrast agent for in vitro optical microscopic imaging, making it possible to develop correlative microscopic imaging techniques. In Chapters 3-5, we proposed a feasible approach to optimize the in vivo kinetics and clearance profile of nanoprobes for multimodality in vivo bioimaging applications by using straightforward surface chemistry with luminescent AuNPs as a model. Luminescent glutathione-coated AuNPs of ~2 nm were synthesized. Investigation of the biodistribution showed that these glutathione-coated AuNPs (GS-AuNPs) exhibit stealthiness to the reticuloendothelial system (RES) organs and efficient renal clearance, with only 3.7+/-1.9% and 0.3+/-0.1% accumulating in the liver and spleen, and over 65% of the injection dose cleared out via the urine within the first 72 hours. In addition, ~2.5 nm NIR-emitting radioactive glutathione-coated [198Au]AuNPs (GS-[198Au]AuNPs) were synthesized for further evaluation of the pharmacokinetic profile of GS-AuNPs and potential multimodal imaging. The results showed that the GS-[198Au]AuNPs behave like small-molecule contrast agents in pharmacokinetics while remaining renal clearable. With a rapid distribution half-life and a desirable elimination half-life, these NPs are highly promising for single-photon emission computed tomography (SPECT) and fluorescence dual-modality imaging.

Functional Nanoparticles for Magnetic Resonance Imaging

PubMed Central

Mao, Xinpei; Xu, Jiadi; Cui, Honggang

2016-01-01

Nanoparticle-based magnetic resonance imaging (MRI) contrast agents have received much attention over the past decade. By virtue of a high payload of magnetic moieties, enhanced accumulation at disease sites, and a large surface area for additional modification with targeting ligands, nanoparticle-based contrast agents offer promising new platforms to further enhance the high resolution and sensitivity of MRI for various biomedical applications. T2* superparamagnetic iron oxide nanoparticles (SPIONs) first demonstrated superior improvement on MRI sensitivity. The prevailing SPION attracted growing interest in the development of refined nanoscale versions of MRI contrast agents. Afterwards, T1-based contrast agents were developed, and became the most studied subject in MRI due to the positive contrast they provide that avoids the susceptibility associated with MRI signal reduction. Recently, chemical exchange saturation transfer (CEST) contrast agents have emerged and rapidly gained popularity. The unique aspect of CEST contrast agents is that their contrast can be selectively turned “on” and “off” by radiofrequency (RF) saturation. Their performance can be further enhanced by incorporating a large number of exchangeable protons into well-defined nanostructure. Besides activatable CEST contrast agents, there is growing interest in developing nanoparticle-based activatable MRI contrast agents responsive to stimuli (pH, enzyme, etc.), which improves sensitivity and specificity. In this review, we summarize the recent development of various types of nanoparticle-based MRI contrast agents, and have focused our discussions on the key advantages of introducing nanoparticles in MRI. PMID:27040463

Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model

PubMed Central

ZUNINO, SUSAN J.; STORMS, DAVID H.; NEWMAN, JOHN W.; PEDERSEN, THERESA L.; KEEN, CARL L.; DUCORE, JONATHAN M.

2013-01-01

In this study, the efficacy of orally and parenter-ally administered curcumin was evaluated in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice (NOD.CB17-Prkdcscid/J mice) engrafted with the human t(4;11) acute lymphoblastic leukemia line, SEM. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, the chemotherapeutic potential was examined by injecting mice intraperitoneally with curcumin (5 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). The intraperitoneal administration of curcumin did not inhibit the growth of the leukemia cells. To determine the efficacy of oral curcumin, mice were fed a control diet or a diet containing 0.5% w/w curcumin 3 weeks prior to the injection of the leukemia cells and throughout the experimental period (n=16 per group). To determine whether dietary curcumin can enhance the efficacy of a conventional chemotherapeutic agent, vincristine was injected intraperitoneally into leukemic mice fed the different diets. Dietary curcumin did not delay the engraftment or growth of leukemia cells, or sensitize the cells to vincristine. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed that curcumin rapidly metabolized to glucuronidated and sulfated forms within 1 h post-injection and these were the major curcumin metabolites found in the sera of the mice fed the curcumin diet. In contrast to the findings in previous in vitro models, the current data indicate that orally or parenterally administered curcumin is not a potent preventive agent against high-risk t(4;11) acute lymphoblastic leukemia. PMID:23232667

Color Doppler Ultrasound and Gamma Imaging of Intratumorally Injected 500 nm Iron-Silica Nanoshells

PubMed Central

Liberman, Alexander; Wu, Zhe; Barback, Christopher V.; Viveros, Robert; Blair, Sarah L.; Ellies, Lesley G.; Vera, David R.; Mattrey, Robert F.; Kummel, Andrew C.; Trogler, William C.

2013-01-01

Perfluoropentane gas filled iron-silica nanoshells have been developed as stationary ultrasound contrast agents for marking tumors to guide surgical resection. It is critical to establish their long term imaging efficacy, as well as biodistribution. This work shows that 500 nm Fe-SiO2 nanoshells can be imaged by color Doppler ultrasound over the course of 10 days in Py8119 tumor bearing mice. The 500 nm non-biodegradable SiO2 and biodegradable Fe-SiO2 nanoshells were functionalized with diethylenetriamine pentaacetic acid (DTPA) ligand and radiolabeled with 111In3+ for biodistribution studies in nu/nu mice. The majority of radioactivity was detected in the liver and kidneys following intravenous (IV) administration of nanoshells to healthy animals. By contrast, after nanoshells were injected intratumorally, most of the radioactivity remained at the injection site; however, some nanoshells escaped into circulation and were distributed similarly as those given intravenously. For intratumoral delivery of nanoshells and IV delivery to healthy animals, little difference was seen between the biodistribution of SiO2 and biodegradable Fe-SiO2 nanoshells. However, when nanoshells were administered IV to tumor bearing mice, a significant increase was observed in liver accumulation of SiO2 nanoshells relative to biodegradable Fe-SiO2 nanoshells. Both SiO2 and Fe-SiO2 nanoshells accumulate passively in proportion to tumor mass, during intravenous delivery of nanoshells. This is the first report of the biodistribution following intratumoral injection of any biodegradable silica particle, as well as the first report demonstrating the utility of DTPA-111In labeling for studying silica nanoparticle biodistributions. PMID:23802554

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.

Comparison between nonspecific and necrosis-avid gadolinium contrast agents in vascular disrupting agent-induced necrosis of rodent tumors at 3.0T.

PubMed

Wang, Huaijun; Miranda Cona, Marlein; Chen, Feng; Li, Junjie; Yu, Jie; Feng, Yuanbo; Peeters, Ronald; De Keyzer, Frederik; Marchal, Guy; Ni, Yicheng

2011-09-01

: To compare a commercial contrast agent (CA) Dotarem and a necrosis-avid CA (NACA) for their ability to evaluate the therapeutic necrosis with a vascular disrupting agent (VDA) on magnetic resonance imaging in rodent liver tumors to determine which could better correlate with the histopathologic outcome. : After the VDA treatment, 16 rats with 32 liver rhabdomyosarcomas were randomized into Dotarem and NACA groups (n = 8 per group) for both interindividual and intraindividual comparisons. T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1-weighted imaging (CE-T1WI), and diffusion-weighted imaging were performed at baseline, after VDA treatment and CA injections. The enhancing efficacy of CAs at immediate and delayed enhancement on CE-T1WI in viable tumor and necrosis was compared. Tumor necrosis ratios calculated from NACA and Dotarem were compared and correlated with gold-standard histopathology. : On the immediate CE-T1WI, viable tumor was enhanced by either CA. On the delayed CE-T1WI at 30 minutes, both CAs failed to demarcate viable tumor from necrosis. At 24 hours post-NACA, the necrosis was clearly distinguished from viable tumor and thus derived necrosis ratio matched that from histopathology (P = 0.99); necrosis ratio from Dotarem was significantly lower than that from NACA and histopathology (P < 0.05, both), with a higher correlation of NACA than that of Dotarem with histopathology (r = 0.99 vs. r = 0.82). : NACA better evaluated VDA-induced tumor necrosis than nonspecific CA on T1WI in tumor models of rat liver. NACA showed a closer correlation with histopathology than nonspecific CA for the delineation of true necrosis. Delayed enhancement on T1WI with nonspecific CA is not suitable for the assessment of VDA-induced tumor necrosis.

Using molecular imaging to assess the delivery and infection of protease activated virus in animal model of myocardial infarction

NASA Astrophysics Data System (ADS)

Zhu, Banghe; Guenther, Caitlin; Kwon, Sunkuk; Sevick-Muraca, Eva M.; Suh, Junghae

2017-02-01

Cardiovascular diseases remain the greatest cause of death in the US and gene therapy has the potential to be an effective therapy. In this study, we demonstrated MMP-9 based protease-activatable virus (PAV) for selective infection of myocardial infarct (MI) that is associated with active MMP-9 expression. To test the specificity of PAV, we used expression of a far-red fluorescence protein (iRFP) delivered by the PAV together with a dual PET/NIRF imaging agent specific for active MMP-9 activity at the site of MI in a murine model. Calibrated fluorescence imaging employed a highly-sensitive intensified camera, laser diode excitation sources, and filtration schemes based upon the spectra of iRFP and the NIRF agent. One to two days after ligation of the left anterior descending artery, the PAV or WT AAV9 virus encoding for iRFP (5x1010 genomic particles) and radiolabeled MMP-9 imaging agent (3 nmol) were injected intravenously (i.v.). PET imaging showed MMP activity was associated with adverse tissue remodeling at the site of the MI. One week after, animals were again injected i.v. with the MMP-9 agent (3 nmol) and 18-24 h later, the animals were euthanized and the hearts were harvested, sliced, and imaged for congruent iRFP transgene expression and NIRF signals associated with MMP-9 tissue activity. The fluorescent margins of iRFP and NIRF contrasted tissues were quantified in terms Standard International units of mW/cm2/sr. The sensitivity, specificity, and accuracy of PAV and WT targeting to sites of MI was determined from these calibrated fluorescence measurements. The PAV demonstrated significantly higher delivery performance than that of the WT AAV9 virus.

In vivo diffusion characteristics following perineural injection of the deep branch of the lateral plantar nerve with mepivacaine or iohexol in horses.

PubMed

Contino, E K; King, M R; Valdés-Martínez, A; McIlwraith, C W

2015-03-01

Hindlimb proximal suspensory desmopathy is a common injury of sport horses but diagnosis can be difficult because diagnostic analgesia of the region lacks specificity. Perineural analgesia of the deep branch of the lateral plantar nerve (DBLPN) has been proposed as a more specific method of isolating pain of the proximal aspect of the suspensory ligament but the technique has not been evaluated in vivo. To determine the extent of diffusion of contrast medium and mepivacaine following DBLPN analgesia using a single-needle injection technique and to determine if there is inadvertent involvement of the tarsal sheath and/or tarsometatarsal (TMT) joint using this technique. In vivo experimental study. Perineural injection of the DBLPN was performed in 16 limbs with 3 ml of either mepivacaine hydrochloride or positive contrast medium. Contrast medium-injected limbs were radiographed 5, 15, and 30 min post injection and diffusion characteristics were described. In mepivacaine-injected limbs, synovial fluid from the TMT joint was obtained 10 and 20 min post injection and mepivacaine concentrations were analysed. At 5, 15 and 30 min post injection, the contrast medium extended, on average, 19.6, 20.6 and 21.0 mm proximal and 38.0, 43.5 and 51.9 mm distal to the injection site, respectively. Three of 8 (37.5%) limbs had evidence of contrast medium in the tarsal sheath. Two of 8 (25%) limbs had mepivacaine concentrations within the TMT joint sufficient to produce analgesia (>300 mg/l) at 10 min post injection. Contrast medium diffused further in a distal direction than in a proximal direction. Analgesia of the DBLPN can result in inadvertent involvement of the tarsal sheath and/or TMT joint. © 2014 EVJ Ltd.

Glenohumeral joint injection: a comparative study of ultrasound and fluoroscopically guided techniques before MR arthrography.

PubMed

Rutten, Matthieu J C M; Collins, James M P; Maresch, Bas J; Smeets, Jacques H J M; Janssen, Caroline M M; Kiemeney, Lambertus A L M; Jager, Gerrit J

2009-03-01

To assess the variability in accuracy of contrast media introduction, leakage, required time and patient discomfort in four different centres, each using a different image-guided glenohumeral injection technique. Each centre included 25 consecutive patients. The ultrasound-guided anterior (USa) and posterior approach (USp), fluoroscopic-guided anterior (FLa) and posterior (FLp) approach were used. Number of injection attempts, effect of contrast leakage on diagnostic quality, and total room, radiologist and procedure times were measured. Pain was documented with a visual analogue scale (VAS) pain score. Access to the joint was achieved in all patients. A successful first attempt significantly occurred more often with US (94%) than with fluoroscopic guidance (72%). Leakage of contrast medium did not cause interpretative difficulties. With US guidance mean room, procedure and radiologist times were significantly shorter (p < 0.001). The USa approach was rated with the lowest pre- and post-injection VAS scores. The four image-guided injection techniques are successful in injection of contrast material into the glenohumeral joint. US-guided injections and especially the anterior approach are significantly less time consuming, more successful on the first attempt, cause less patient discomfort and obviate the need for radiation and iodine contrast.

Pharmacokinetic and in vivo evaluation of a self-assembled gadolinium(III)-iron(II) contrast agent with high relaxivity.

PubMed

Parac-Vogt, Tatjana N; Vander Elst, Luce; Kimpe, Kristof; Laurent, Sophie; Burtéa, Carmen; Chen, Feng; Van Deun, Rik; Ni, Yicheng; Muller, Robert N; Binnemans, Koen

2006-01-01

A high-molecular weight tetrametallic supramolecular complex [(Ln-DTPA-phen)3Fe]- (Ln = Gd, Eu, La) has been obtained upon self-assembly around one iron(II) ion of three 1,10-phenantroline-based molecules substituted in 5'-position with the polyaminocarboxylate diethylenetriamine-N,N,N',N',N'-pentaacetate, DTPA-phen(4-). The ICP-MS measurements indicated that the lanthanide:iron ratio is 3:1. Photoluminescence spectra of [Eu-DTPA-phen](-) and of [(Eu-DTPA-phen)3Fe]- are nearly identical, implying that the first coordination sphere of the lanthanide(III) ion has not been changed upon coordination of phenantroline unit to iron(II) ion. NMRD measurements revealed that at 20 MHz and 310 K the relaxivity of the [(Gd-DTPA-phen)3Fe]- is equal to 9.5 +/- 0.3 s(-1) mM(-1) of Gd (28.5 s(-1) per millimole per liter of complex) which is significantly higher than that for Gd-DTPA (3.9 s(-1) mM(-1)). The pharmacokinetic parameters of [(Gd-DTPA-phen)3Fe]- in rats indicate that the elimination of [(Gd-DTPA-phen)3Fe]- is significantly slower than that of Gd-DTPA and is correlated with a reduced volume of distribution. The low volume of distribution and the longer elimination time (T(e1/2)) suggest that the agent is confined to the blood compartment, so it could have an important potential as a blood pool contrast agent. The biodistribution profile of [(Gd-DTPA-phen)3Fe]- 2 h after injection indicates significantly higher concentrations of [(Gd-DTPA-phen)3Fe]- as compared with Gd-DTPA in kidney, liver, lungs, heart and spleen. The images obtained on rats by MR angiography show the enhancement of the abdominal blood vessels. The signal intensity reaches a maximum of 55% at 7 min post-contrast and remains around 25% after 90 min. MRI-histomorphological correlation studies of [Gd-DTPA-phen]- and [(Gd-DTPA-phen)3Fe]- showed that both agents displayed potent contrast enhancement in organs including the liver. The necrosis avidity tests indicated that, in contrast to the [Gd-DTPA-phen](-) precursor complex, the supramolecular complex [(Gd-DTPA-phen)3Fe]- exhibits necrosis avidity. Copyright 2006 John Wiley & Sons, Ltd.

Dendrimer-stabilized bismuth sulfide nanoparticles: synthesis, characterization, and potential computed tomography imaging applications.

PubMed

Fang, Yi; Peng, Chen; Guo, Rui; Zheng, Linfeng; Qin, Jinbao; Zhou, Benqing; Shen, Mingwu; Lu, Xinwu; Zhang, Guixiang; Shi, Xiangyang

2013-06-07

We report here a general approach to synthesizing dendrimer-stabilized bismuth sulfide nanoparticles (Bi2S3 DSNPs) for potential computed tomography (CT) imaging applications. In this study, ethylenediamine core glycidol hydroxyl-terminated generation 4 poly(amidoamine) dendrimers (G4.NGlyOH) were used as stabilizers to first complex the Bi(III) ions, followed by reaction with hydrogen sulfide to generate Bi2S3 DSNPs. By varying the molar ratio of Bi atom to dendrimer, stable Bi2S3 DSNPs with an average size range of 5.2-5.7 nm were formed. The formed Bi2S3 DSNPs were characterized via different techniques. X-ray absorption coefficient measurements show that the attenuation of Bi2S3 DSNPs is much higher than that of iodine-based CT contrast agent at the same molar concentration of the active element (Bi versus iodine). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay and hemolysis assay reveal that the formed Bi2S3 DSNPs are noncytotoxic and have a negligible hemolysis effect in the studied concentration range. Furthermore, we show that cells incubated with the Bi2S3 DSNPs are able to be imaged using CT, a prominent enhancement at the point of rabbit injected subcutaneously with the Bi2S3 DSNPs is able to be visualized via CT scanning, and the mouse's pulmonary vein can be visualized via CT after intravenous injection of the Bi2S3 DSNPs. With the good biocompatibility, enhanced X-ray attenuation property, and tunable dendrimer chemistry, the designed Bi2S3 DSNPs should be able to be further functionalized, allowing them to be used as a highly efficient contrast agent for CT imaging of different biological systems.

Simultaneous magnetic resonance imaging and pharmacokinetic analysis of intramuscular depots.

PubMed

Probst, Mareike; Kühn, Jens-Peter; Scheuch, Eberhard; Seidlitz, Anne; Hadlich, Stefan; Evert, Katja; Oswald, Stefan; Siegmund, Werner; Weitschies, Werner

2016-04-10

The present pilot study introduces a method that might give novel insights in drug absorption processes from intramuscularly administered depots. An oily suspension or an aqueous solution of paracetamol (6 mg/kg body mass), prednisolone or its hemisuccinate sodium salt for the aqueous solutions (10mg/kg body mass) or diclofenac (10mg/kg body mass) was injected into the muscle tissue of the hind leg of female Lewis-rats (n=47). For the oily suspensions the micronized particles were suspended in medium-chain triglycerides. The aqueous solutions were buffered to a pH of 7.4 ± 0.5. Polyethylene glycol was added as a cosolvent in the formulations containing paracetamol (acetaminophen) and diclofenac and sodium chloride was added to the aqueous solutions of prednisolone hemisuccinate sodium to achieve nearly isotonic formulations. The formed depot was visualized by magnetic resonance imaging (MRI) and characterized with regard to volume and surface area. A 7 T-small animal scanner was used and T1-weighted and T2-weighted sequences including a fat saturation were performed. Simultaneously blood samples were taken and the drugs were quantitatively analyzed. The water based solvent and the oily dispersion agent were visible in the MRI images without the use of contrast agents. Since a free hand injection mostly led to an application directly into the fascia, resulting in a fast removal of the depot, MRI-guided injection was conducted. Comparing pharmacokinetic data with MRI data it was observed that maximal blood levels occurred before the solvent and the dispersion agent were removed from the muscle tissue. Thus, the drug is not absorbed together with the depot. Furthermore, no correlation was found between the shape of the depot and the rate of absorption. Consequently, a higher surface area or volume of the depot did not result in a faster release or absorption of the drugs from the tested formulations. In contrast to the paracetamol and prednisolone formulations the formulations containing diclofenac led to a massive accumulation of interstitial fluid around the injection area being a sign for an acute local reaction. Histological analysis of the muscle tissue revealed a clear correspondence between the amount of interstitial fluid and the extent of infiltrating lymphocytes and granulocytes indicating a tissue response. In conclusion combining MRI with pharmacokinetic data is a suitable method to gain deeper insights into drug absorption processes from intramuscular depots. Furthermore, MRI offers a great possibility detecting local side effects caused by an intramuscularly applied dosage form. This might be very useful in preclinical phases during the development of new intramuscular formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Soft-tissue tumor differentiation using 3D power Doppler ultrasonography with echo-contrast medium injection.

PubMed

Chiou, Hong-Jen; Chou, Yi-Hong; Chen, Wei-Ming; Chen, Winby; Wang, Hsin-Kai; Chang, Cheng-Yen

2010-12-01

We aimed to evaluate the ability of 3-dimensional power Doppler ultrasonography to differentiate soft-tissue masses from blood flow and vascularization with contrast medium. Twenty-five patients (mean age, 44.1 years; range, 12-77 years) with a palpable mass were enrolled in this study. Volume data were acquired using linear and convex 3-dimensional probes and contrast medium injected manually by bolus. Data were stored and traced slice by slice for 12 slices. All patients were scanned by the same senior sonologist. The vascular index (VI), flow index (FI), and vascular-flow index (VFI) were automatically calculated after the tumor was completely traced. All tumors were later confirmed by pathology. The study included 8 benign (mean, 36.5 mL; range, 2.4-124 mL) and 17 malignant (mean, 319.4 mL; range, 9.9-1,179.6 mL) tumors. Before contrast medium injection, mean VI, FI and VFI were, respectively, 3.22, 32.26 and 1.07 in benign tumors, and 1.97, 29.33 and 0.67 in malignant tumors. After contrast medium injection, they were, respectively, 20.85, 37.33 and 8.52 in benign tumors, and 40.12, 41.21 and 17.77 in malignant tumors. The mean differences between with and without contrast injection for VI, FI and VFI were, respectively, 17.63, 5.07 and 7.45 in benign tumors, and 38.15, 11.88 and 16.55 in malignant tumors. Tumor volume, VI, FI and VFI were not significantly different between benign and malignant tumors before and after echo-contrast medium injection. However, VI, FI and VFI under self-differentiation (differences between with and without contrast injection) were significantly different between malignant and benign tumors. Three-dimensional power Doppler ultrasound is a valuable tool for differential diagnosis of soft-tissue tumors, especially with the injection of an echo-contrast medium. Copyright © 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

Tissue gadolinium deposition in renally impaired rats exposed to different gadolinium-based MRI contrast agents: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

PubMed

Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Kanki, Akihiko; Watanabe, Shigeru; Nishimura, Hirotake; Tanimoto, Daigo; Higashi, Hiroki; Yamamoto, Akira

2013-10-01

To quantify tissue gadolinium (Gd) deposition in renally impaired rats exposed to Gd-EOB-DTPA and other Gd-based MRI contrast agents by means of inductively coupled plasma mass spectrometry (ICP-MS), and to compare the differences in distribution among major organs as possible triggers for nephrogenic systemic fibrosis (NSF). A total of 15 renally impaired rats were injected with Gd-EOB-DTPA, Gd-DTPA-BMA and Gd-HP-DO3A. Gd contents of skin, liver, kidney, lung, heart, spleen, diaphragm and femoral muscle were measured by inductively coupled plasma mass spectrometry (ICP-MS). Histological assessment was also conducted. Tissue Gd deposition in all organs was significantly higher (P=0.005~0.009) in the Gd-DTPA-BMA group than in the Gd-HP-DO3A and Gd-EOB-DTPA groups. In the Gd-DTPA-BMA group, Gd was predominantly deposited in kidney (1306±605.7μg/g), followed by skin, liver, lung, spleen, femoral muscle, diaphragm and heart. Comparing Gd-HP-DO3A and Gd-EOB-DTPA groups, Gd depositions in the kidney, liver and lung were significantly lower (P=0.009~0.011) in the Gd-EOB-DTPA group than in the Gd-HP-DO3A group although no significant differences were seen for any other organs. Gd-EOB-DTPA is a stable and safe Gd-based contrast agent (GBCA) showing lower Gd deposition in major organs in renally impaired rats, compared with other GBCAs. This fact suggests that the risk of NSF onset would be low in the use of Gd-EOB-DTPA. Copyright © 2013 Elsevier Inc. All rights reserved.

Improving ovarian cancer imaging with LHRH-NBs: an experimental study.

PubMed

Li, Wenjuan; Zhang, Lingping; Zhu, Yuanfang; Zhang, Jinyi; Shen, Li; Huang, Shuying; Fang, Shanyu

2016-09-01

Our previous study used freeze-drying and biotin-avidin binding methods and obtained nontargeted nanobubbles (N-NBs) and ovarian cancer-targeting nanobubbles (LHRH-NBs, luteinizing hormone-releasing hormone nanobubbles). Our study also identified the physical and chemical properties of these two contrast agents, and validated the targeting ability and underlying mechanisms of LHRH-NBs in vitro. The present study investigated the imaging of N-NBs and LHRH-NBs in nude mice and their binding with tissues. The nude mice models of xenografts were divided into three groups, N-NB, LHRH-NB, and SonoVue. These contrast agents were injected via the caudal vein to observe the imaging of ovarian cancer. Fluorescence microscope was used to observe the penetration of N-NBs and LHRH-NBs through the vascular endothelial gaps. Immunofluorescence was used to observe the penetration of N-NBs and LHRH-NBs through vascular endothelial gaps and binding to the tumor cells. The imaging intensity and duration were not significantly different between N-NBs and LHRH-NBs. The imaging intensity in the N-NB and LHRH-NB groups was not significantly different compared with the SonoVue group; however, the imaging duration in the N-NB and LHRH-NB groups was significantly longer than in the SonoVue group (P < 0.001). Both N-NBs and LHRH-NBs penetrated through the vascular endothelial gaps. After penetrating through the vascular endothelial gapes, LHRH-NBs could target and bind to the tumor cells. N-NBs and LHRH-NBs are of good imaging effectiveness and relatively long imaging duration. LHRH-NB is a potent contrast agent for imaging ovarian cancer, while achieving targeted delivery of drugs to the site of ovarian cancer.

Discrimination of benign and malignant lymph nodes at 7.0T compared to 1.5T magnetic resonance imaging using ultrasmall particles of iron oxide: a feasibility preclinical study.

PubMed

Kinner, Sonja; Maderwald, Stefan; Albert, Juliane; Parohl, Nina; Corot, Claire; Robert, Philippe; Baba, Hideo A; Barkhausen, Jörg

2013-12-01

To investigate the feasibility and performance of 7T magnetic resonance imaging compared to 1.5T imaging to discriminate benign (normal and inflammatory changed) from tumor-bearing lymph nodes in rabbits using ultrasmall particles of iron oxide (USPIO)-based contrast agents. Six New Zealand White rabbits were inoculated with either complete Freund's adjuvant cell suspension (n = 3) to induce reactively enlarged lymph nodes or with VX2 tumor cells to produce metastatic lymph nodes (n = 3). Image acquisition was performed before and 24 hours after bolus injection of an USPIO contrast agent at 1.5T and afterward at 7T using T1-weighted and T2*-weighted sequences. Sensitivities, specificities, and negative and positive predictive values for the detection of lymph node metastases were calculated for both field strengths with histopathology serving as reference standard. Sizes of lymph nodes with no, inflammatory, and malignant changes were compared using a Mann-Whitney U-test. All 24 lymph nodes were detected at 1.5T as well as at 7T. At 1.5T, sensitivity amounted to 0.67, while specificity reached a value of 1. At the higher field strength (7T), imaging was able to reach sensitivity and specificity values of 1. No statistical differences were detected concerning lymph node sizes. Magnetic resonance lymphography with USPIO contrast agents allows for differentiation of normal and reactively enlarged lymph nodes compared to metastatic nodes. First experiments at 7T show promising results compared to 1.5T, which have to be evaluated in further trials. Copyright © 2013. Published by Elsevier Inc.

Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes

NASA Astrophysics Data System (ADS)

Hu, Fengqin; Zhao, Yong Sheng

2012-09-01

Magnetic resonance imaging (MRI) yields high spatially resolved contrast with anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning. To improve imaging sensitivity, adding contrast agents accelerates the relaxation rate of water molecules, thereby greatly increasing the contrast between specific issues or organs of interest. Currently, the majority of T1 contrast agents are paramagnetic molecular complexes, typically Gd(iii) chelates. Various nanoparticulate T1 and T1/T2 contrast agents have recently been investigated as novel agents possessing the advantages of both the T1 contrast effect and nanostructural characteristics. In this minireview, we describe the recent progress of these inorganic nanoparticle-based MRI contrast agents. Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and ultrasmall iron oxide/ferrite nanoparticles.

Retrospective Analysis of the Accuracy of Ultrasound-Guided Magnetic Resonance Arthrogram Injections of the Hip in the Office Setting.

PubMed

Jernick, Michael; Walker Gallego, Edward; Nuzzo, Michael

2017-12-01

Ultrasound (US)-guided intra-articular hip injections have been proposed in the literature to be accurate, reliable, and safe alternatives to fluoroscopy-guided injections. To evaluate the accuracy of US-guided magnetic resonance (MR) arthrogram injections of the hip performed in the office setting by a single orthopaedic surgeon and elucidate the potential effects that patient age, sex, and body mass index (BMI) have on contrast placement. Case series; Level of evidence, 4. From a review of the senior author's office database, 89 patients (101 hips) who had US-guided MR arthrogram injections performed between December 2014 and June 2016 were identified. Official radiology reports were evaluated to determine whether extra-articular contrast was noted. Patient variables, including BMI, age, and sex, were evaluated between patients who had inappropriately placed contrast and those who did not. Of the 101 hip injections, there were 6 cases that demonstrated inadequate contrast placement within the joint, likely secondary to extravasation or incorrect placement; however, an MR arthrogram was adequately interpreted in all cases. There were no significant differences noted between those with appropriate versus inappropriate contrast placement when evaluating BMI ( P = .57), age ( P = .33), or sex ( P = .67), and neither group had an adverse event. US-guided injections are safe and accurate alternatives to fluoroscopy-guided injections in the office setting, with 94% accuracy. Furthermore, BMI, age, and sex did not play a statistically significant role among patients with inappropriately placed contrast.

Magnetic resonance-guided motorized transcranial ultrasound system for blood-brain barrier permeabilization along arbitrary trajectories in rodents.

PubMed

Magnin, Rémi; Rabusseau, Fabien; Salabartan, Frédéric; Mériaux, Sébastien; Aubry, Jean-François; Le Bihan, Denis; Dumont, Erik; Larrat, Benoit

2015-01-01

Focused ultrasound combined with microbubble injection is capable of locally and transiently enhancing the permeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) guidance enables to plan, monitor, and characterize the BBB disruption. Being able to precisely and remotely control the permeabilization location is of great interest to perform reproducible drug delivery protocols. In this study, we developed an MR-guided motorized focused ultrasound (FUS) system allowing the transducer displacement within preclinical MRI scanners, coupled with real-time transfer and reconstruction of MRI images, to help ultrasound guidance. Capabilities of this new device to deliver large molecules to the brain on either single locations or along arbitrary trajectories were characterized in vivo on healthy rats and mice using 1.5 MHz ultrasound sonications combined with microbubble injection. The efficacy of BBB permeabilization was assessed by injecting a gadolinium-based MR contrast agent that does not cross the intact BBB. The compact motorized FUS system developed in this work fits into the 9-cm inner diameter of the gradient insert installed on our 7-T preclinical MRI scanners. MR images acquired after contrast agent injection confirmed that this device can be used to enhance BBB permeability along remotely controlled spatial trajectories of the FUS beam in both rats and mice. The two-axis motor stage enables reaching any region of interest in the rodent brain. The positioning error when targeting the same anatomical location on different animals was estimated to be smaller than 0.5 mm. Finally, this device was demonstrated to be useful for testing BBB opening at various acoustic pressures (0.2, 0.4, 0.7, and 0.9 MPa) in the same animal and during one single ultrasound session. Our system offers the unique possibility to move the transducer within a high magnetic field preclinical MRI scanner, thus enabling the delivery of large molecules to virtually any rodent brain area in a non-invasive manner. It results in time-saving and reproducibility and could be used to either deliver drugs over large parts of the brain or test different acoustic conditions on the same animal during the same session, therefore reducing physiological variability.

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

Gadolinium chloride as a contrast agent for imaging wood composite components by magnetic resonance

Treesearch

Thomas L. Eberhardt; Chi-Leung So; Andrea Protti; Po-Wah So

2009-01-01

Although paramagnetic contrast agents have an established track record in medical uses of magnetic resonance imaging (MRI), only recently has a contrast agent been used for enhancing MRI images of solid wood specimens. Expanding on this concept, wood veneers were treated with a gadolinium-based contrast agent and used in a model system comprising three-ply plywood...

Assessing the Risk of Contrast-Induced Nephropathy Using a Finger Stick Analysis in Recalls from Breast Screening: The CINFIBS Explorative Study.

PubMed

Houben, I P L; van Berlo, C J L Y; Bekers, O; Nijssen, E C; Lobbes, M B I; Wildberger, J E

2017-01-01

To evaluate whether a handheld point-of-care (POC) device is able to predict and discriminate patients at potential risk of contrast-induced nephropathy (CIN) prior to iodine-based contrast media delivery. Between December 2014 and June 2016, women undergoing contrast-enhanced spectral mammography (CESM) with an iodine-based contrast agent were asked to have their risk of CIN assessed by a dedicated POC device (StatSensor CREAT) and a risk factor questionnaire based on national guidelines. Prior to contrast injection, a venous blood sample was drawn to compare the results of POC with regular laboratory testing. A total of 351 patients were included; 344 were finally categorized as low risk patients by blood creatinine evaluation. Seven patients had a eGFR below 60 ml/min/1.73 m 2 , necessitating additional preparation prior to contrast delivery. The POC device failed to categorize six out of seven patients (86%), leading to (at that stage) unwanted contrast administration. Two patients subsequently developed CIN after 2-5 days, which was self-limiting after 30 days. The POC device tested was not able to reliably assess impairment of renal function in our patient cohort undergoing CESM. Consequently, we still consider classic clinical laboratory testing preferable in patients at potential risk for developing CIN.

A new technical contribution for ultrasound-guided injections of sacro-iliac joints.

PubMed

Migliore, A; Bizzi, E; Massafra, U; Vacca, F; Martin-Martin, L S; Granata, M; Tormenta, S

2010-05-01

Sacroiliac joint (SIJ) represents a difficult location for local therapies, as intra-articular injections may be hard to execute, especially in particular conditions such as chronic inflammatory diseases. However, in selected patients, local therapies may be considered. Some recent studies demonstrated the feasibility of ultrasound (US)-guided injection of SIJ, but still a complete explanation and definition of the technique is needed. Seven patients, four males and 3 females, affected by mono or bilateral sacroiliitis entered the study. Each patient received 40 mg of acetonide triamcinolone for each SIJ, intra articular (IA) US-guided injection. The technical originality proposed in this study consists in the spinal needle insertion in the middle of the cranial long side of the linear transducer with an orientation of about 10 degrees, determining shorter needle insertion for reaching joint space and consequently probably granting lesser pain and traumatism for patients. A total of 22 injections was performed. The longer follow-up time obtained was 18 months in 3 patients. All patients reached at least a 6 month follow-up. All patients reported an amelioration in pain that lasted for at least 6 months. No systemic adverse events were reported or observed. Complete visualization of SIJ and of needle placement was performed by US imaging, while compound proper injection was also visualized by Color-Doppler US imaging. Actually, sacroiliac joint intraarticular injections are often performed under fluoroscopy or Computerized Tomography guidance. Such techniques present several limitations, especially for repeated injections, such as the use of ionizing radiations, the need of a contrast agent and the direct and indirect costs connected. US guidance in IA SIJ injections may represent an easily repeatable imaging technique for needle placement and a precious tool for detecting inflammatory activity of the joint.

[New methods for the evaluation of bone quality. Bone anabolic agents and bone quality.

PubMed

Yamamoto, Norio; Tsuchiya, Hiroyuki

Teriparatide(TPTD)products that can be used clinically in Japan include a daily subcutaneous injection form produced by genetic engineering and a weekly subcutaneous injectable TPTD acetate form produced by chemical synthesis. Published reports indicate that both forms exhibit excellent antifracture efficacy, and as the only anabolic agents that promote osteogenesis, TPTD products now occupy a prominent position. However, the two forms differ considerably, not only in frequency of administration, but also in mechanism of action. The daily form stimulates osteogenesis and accompanying resorption through more radical high bone turnover, and early in the course of treatment, intracortical porosity and apatite crystallization decrease, while immature collagen crosslinking increases. However, because daily formulations also produce an increase in cortical surface area or cortical thickness, the effects are counterbalanced, and bone strength is maintained. In contrast, the weekly form prioritizes osteogenesis, and by concurrently lowering turnover below pretreatment levels, improves trabecular bone mass and structure, and enhances strength without leading to cortical porosity and other undesirable phenomena. Abaloparatide, a PTHrP(1-34)analog that is homologous with the biologically active site of PTH drugs, is currently under development, and we eagerly anticipate further clarification of the mechanism of action of each formulation on bone.

Contrast-enhanced spectral mammography based on a photon-counting detector: quantitative accuracy and radiation dose

NASA Astrophysics Data System (ADS)

Lee, Seungwan; Kang, Sooncheol; Eom, Jisoo

2017-03-01

Contrast-enhanced mammography has been used to demonstrate functional information about a breast tumor by injecting contrast agents. However, a conventional technique with a single exposure degrades the efficiency of tumor detection due to structure overlapping. Dual-energy techniques with energy-integrating detectors (EIDs) also cause an increase of radiation dose and an inaccuracy of material decomposition due to the limitations of EIDs. On the other hands, spectral mammography with photon-counting detectors (PCDs) is able to resolve the issues induced by the conventional technique and EIDs using their energy-discrimination capabilities. In this study, the contrast-enhanced spectral mammography based on a PCD was implemented by using a polychromatic dual-energy model, and the proposed technique was compared with the dual-energy technique with an EID in terms of quantitative accuracy and radiation dose. The results showed that the proposed technique improved the quantitative accuracy as well as reduced radiation dose comparing to the dual-energy technique with an EID. The quantitative accuracy of the contrast-enhanced spectral mammography based on a PCD was slightly improved as a function of radiation dose. Therefore, the contrast-enhanced spectral mammography based on a PCD is able to provide useful information for detecting breast tumors and improving diagnostic accuracy.

Model and reconstruction of a K-edge contrast agent distribution with an X-ray photon-counting detector

PubMed Central

Meng, Bo; Cong, Wenxiang; Xi, Yan; De Man, Bruno; Yang, Jian; Wang, Ge

2017-01-01

Contrast-enhanced computed tomography (CECT) helps enhance the visibility for tumor imaging. When a high-Z contrast agent interacts with X-rays across its K-edge, X-ray photoelectric absorption would experience a sudden increment, resulting in a significant difference of the X-ray transmission intensity between the left and right energy windows of the K-edge. Using photon-counting detectors, the X-ray intensity data in the left and right windows of the K-edge can be measured simultaneously. The differential information of the two kinds of intensity data reflects the contrast-agent concentration distribution. K-edge differences between various matters allow opportunities for the identification of contrast agents in biomedical applications. In this paper, a general radon transform is established to link the contrast-agent concentration to X-ray intensity measurement data. An iterative algorithm is proposed to reconstruct a contrast-agent distribution and tissue attenuation background simultaneously. Comprehensive numerical simulations are performed to demonstrate the merits of the proposed method over the existing K-edge imaging methods. Our results show that the proposed method accurately quantifies a distribution of a contrast agent, optimizing the contrast-to-noise ratio at a high dose efficiency. PMID:28437900

Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats

NASA Astrophysics Data System (ADS)

Luo, Binhua; Wang, Siqi; Rao, Rong; Liu, Xuhan; Xu, Haibo; Wu, Yun; Yang, Xiangliang; Liu, Wei

2016-04-01

The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T 2 relaxation rate ( r 2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM-1 s-1. In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian blue staining of the section clearly showed the retention of Lf-M-PAEEP-PLLA-NPs in tumor tissues. The results from the in vitro and in vivo MRI indicated that Lf-M-PAEEP-PLLA-NPs possessed strong, long-lasting, tumor targeting, and enhanced tumor MRI contrast ability. Lf-M-PAEEP-PLLA-NPs represent a promising nano-sized MRI contrast agent for brain glioma targeting MRI.

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

Ultrasound image-guided therapy enhances antitumor effect of cisplatin.

PubMed

Sasaki, Noboru; Kudo, Nobuki; Nakamura, Kensuke; Lim, Sue Yee; Murakami, Masahiro; Kumara, W R Bandula; Tamura, Yu; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

2014-01-01

The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model. Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 10(7) microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times. The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm(3), P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice. Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

PubMed Central

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M.; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders. PMID:24782720

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations.

PubMed

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

Ultrasound-guided injection for MR arthrography of the hip: comparison of two different techniques.

PubMed

Kantarci, Fatih; Ozbayrak, Mustafa; Gulsen, Fatih; Gencturk, Mert; Botanlioglu, Huseyin; Mihmanli, Ismail

2013-01-01

The purpose of this study was to prospectively evaluate the two different ultrasound-guided injection techniques for MR arthrography of the hip. Fifty-nine consecutive patients (21 men, 38 women) referred for MR arthrographies of the hip were prospectively included in the study. Three patients underwent bilateral MR arthrography. The two injection techniques were quantitatively and qualitatively compared. Quantitative analysis was performed by the comparison of injected contrast material volume into the hip joint. Qualitative analysis was performed with regard to extraarticular leakage of contrast material into the soft tissues. Extraarticular leakage of contrast material was graded as none, minimal, moderate, or severe according to the MR images. Each patient rated discomfort after the procedure using a visual analogue scale (VAS). The injected contrast material volume was less in femoral head puncture technique (mean 8.9 ± 3.4 ml) when compared to femoral neck puncture technique (mean 11.2 ± 2.9 ml) (p < 0.05). The chi-squared test showed significantly more contrast leakage by femoral head puncture technique (p < 0.05). Statistical analysis showed no difference between the head and neck puncture groups in terms of feeling of pain (p = 0.744) or in the body mass index (p = 0.658) of the patients. The femoral neck injection technique provides high intraarticular contrast volume and produces less extraarticular contrast leakage than the femoral head injection technique when US guidance is used for MR arthrography of the hip.

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. © 2015 Wiley Periodicals, Inc.

"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

Strategies for Optimizing Water-Exchange Rates of Lanthanide-Based Contrast Agents for Magnetic Resonance Imaging

PubMed Central

Siriwardena-Mahanama, Buddhima N.; Allen, Matthew J.

2013-01-01

This review describes recent advances in strategies for tuning the water-exchange rates of contrast agents for magnetic resonance imaging (MRI). Water-exchange rates play a critical role in determining the efficiency of contrast agents; consequently, optimization of water-exchange rates, among other parameters, is necessary to achieve high efficiencies. This need has resulted in extensive research efforts to modulate water-exchange rates by chemically altering the coordination environments of the metal complexes that function as contrast agents. The focus of this review is coordination-chemistry-based strategies used to tune the water-exchange rates of lanthanide(III)-based contrast agents for MRI. Emphasis will be given to results published in the 21st century, as well as implications of these strategies on the design of contrast agents. PMID:23921796

Enhancement of high-resolution photoacoustic imaging with indocyanine green-conjugated carbon nanotubes

NASA Astrophysics Data System (ADS)

Phuc Nguyen, Van; Oh, Yunok; Ha, Kanglyeol; Oh, Junghwan; Kang, Hyun Wook

2015-07-01

The current study indicates the feasibility of photoacoustic imaging (PAI) enhanced with contrast agents. A single-element ultrasound transducer (20 MHz) was used to detect PA signals for image reconstruction. To improve PA sensitivity, single-walled carbon nanotubes (SWNTs) conjugated with indocyanine green (ICG) were injected into samples at various concentrations. PA signal amplitudes linearly increased with SWNT-ICG concentration owing to strong light absorption. Compared with SWNTs, SWNT-ICG augmented the signal intensity by approximately 2-fold (concentration: 300 nM). The enhanced optical absorption can allow the application of SWNT-ICG to enable PAI for specifically identifying tumors with high sensitivity.

Ultrasonic Analysis of Peptide- and Antibody-Targeted Microbubble Contrast Agents for Molecular Imaging of αvβ3-Expressing Cells

PubMed Central

Dayton, Paul A.; Pearson, David; Clark, Jarrod; Simon, Scott; Schumann, Patricia A.; Zutshi, Reena; Matsunaga, Terry O.; Ferrara, Katherine W.

2008-01-01

The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. In this manuscript, three distinct contrast agents targeted to the αvβ3 integrin are examined. The αvβ3 integrin has been shown to be highly expressed on metastatic tumors and endothelial cells during neovascularization, and its expression has been shown to correlate with tumor grade. Specific adhesion of these contrast agents to αvβ3-expressing cell monolayers is demonstrated in vitro, and compared with that of nontargeted agents. Acoustic studies illustrate a backscatter amplitude increase from monolayers exposed to the targeted contrast agents of up to 13-fold (22 dB) relative to enhancement due to control bubbles. A linear dependence between the echo amplitude and bubble concentration was observed for bound agents. The decorrelation of the echo from adherent targeted agents is observed over successive pulses as a function of acoustic pressure and bubble density. Frequency–domain analysis demonstrates that adherent targeted bubbles exhibit high-amplitude narrowband echo components, in contrast to the primarily wideband response from free microbubbles. Results suggest that adherent targeted contrast agents are differentiable from free-floating microbubbles, that targeted contrast agents provide higher sensitivity in the detection of angiogenesis, and that conventional ultrasound imaging techniques such as signal subtraction or decorrelation detection can be used to detect integrin-expressing vasculature with sufficient signal-to-noise. PMID:15296677

Contrast echocardiography: new agents.

PubMed

Miller, Andrew P; Nanda, Navin C

2004-04-01

In this report, we review the history, rationale, current status and future directions of contrast agents in echocardiography. First, we discuss the historic development of contrast agents through a review of important physical principles of microbubbles in ultrasonography. Second, we identify attributes of an ideal contrast agent and review those that are currently available or in the "pipeline" for clinical use. Third, we review indications for contrast echocardiography, including endocardial border detection, perfusion quantification and reperfusion assessment, and validate these observations by comparisons with other imaging modalities. Then, we briefly review different methodologies of performing a contrast study, including interrupted, real-time and a hybrid modality. Finally, we identify novel future applications of the newest contrast agents. These newer concepts in contrast echocardiography should form a foundation for nearly limitless application of echocardiography in improved anatomical assessment, perfusion imaging and even special applications, such as detection of vascular inflammation and site-specific drug delivery.

Molecular Magnetic Resonance Imaging of Angiogenesis In Vivo using Polyvalent Cyclic RGD-Iron Oxide Microparticle Conjugates

PubMed Central

Melemenidis, Stavros; Jefferson, Andrew; Ruparelia, Neil; Akhtar, Asim M; Xie, Jin; Allen, Danny; Hamilton, Alastair; Larkin, James R; Perez-Balderas, Francisco; Smart, Sean C; Muschel, Ruth J; Chen, Xiaoyuan; Sibson, Nicola R; Choudhury, Robin P

2015-01-01

Angiogenesis is an essential component of tumour growth and, consequently, an important target both therapeutically and diagnostically. The cell adhesion molecule αvβ3 integrin is a specific marker of angiogenic vessels and the most prevalent vascular integrin that binds the amino acid sequence arginine-glycine-aspartic acid (RGD). Previous studies using RGD-targeted nanoparticles (20-50 nm diameter) of iron oxide (NPIO) for magnetic resonance imaging (MRI) of tumour angiogenesis, have identified a number of limitations, including non-specific extravasation, long blood half-life (reducing specific contrast) and low targeting valency. The aim of this study, therefore, was to determine whether conjugation of a cyclic RGD variant [c(RGDyK)], with enhanced affinity for αvβ3, to microparticles of iron oxide (MPIO) would provide a more sensitive contrast agent for imaging of angiogenic tumour vessels. Cyclic RGD [c(RGDyK)] and RAD [c(RADyK)] based peptides were coupled to 2.8 μm MPIO, and binding efficacy tested both in vitro and in vivo. Significantly greater specific binding of c(RGDyK)-MPIO to S-nitroso-n-acetylpenicillamine (SNAP)-stimulated human umbilical vein endothelial cells in vitro than PBS-treated cells was demonstrated under both static (14-fold increase; P < 0.001) and flow (44-fold increase; P < 0.001) conditions. Subsequently, mice bearing subcutaneous colorectal (MC38) or melanoma (B16F10) derived tumours underwent in vivo MRI pre- and post-intravenous administration of c(RGDyK)-MPIO or c(RADyK)-MPIO. A significantly greater volume of MPIO-induced hypointensities were found in c(RGDyK)-MPIO injected compared to c(RADyK)-MPIO injected mice, in both tumour models (P < 0.05). Similarly, administration of c(RGDyK)-MPIO induced a greater reduction in mean tumour T2* relaxation times than the control agent in both tumour models (melanoma P < 0.001; colorectal P < 0.0001). Correspondingly, MPIO density per tumour volume assessed immunohistochemically was significantly greater for c(RGDyK)-MPIO than c(RADyK)-MPIO injected animals, in both melanoma (P < 0.05) and colorectal (P < 0.0005) tumours. In both cases, binding of c(RGDyK)-MPIO co-localised with αvβ3 expression. Comparison of RGD-targeted and dynamic contrast enhanced (DCE) MRI assessment of tumour perfusion indicated sensitivity to different vascular features. This study demonstrates specific binding of c(RGDyK)-MPIO to αvβ3 expressing neo-vessels, with marked and quantifiable contrast and rapid clearance of unbound particles from the blood circulation compared to NPIO. Combination of this molecular MRI approach with conventional DCE MRI will enable integrated molecular, anatomical and perfusion tumour imaging. PMID:25767618

The use of intravitreal anti-vascular endothelial growth factor injection and its complications in Chiang Mai University Hospital.

PubMed

Kunavisarut, Paradee; Saenpen, Nithiracht; Ittipunkul, Nimitr; Patikulsila, Direk; Choovuthayakorn, Janejit; Watanachai, Nawat; Pathanapitoon, Kessara

2013-11-01

To report the use of intravitreal (IVT) injections of anti-vascular endothelial growth factor agents (anti-VEGF) and its complications. The authors performed a retrospective review of consecutive patients treated with IVT injection of anti-VEGF between May 2006 and December 2010 at Chiang Mai University Hospital. Demographic data and complications were registered. The present study included 1,006 eyes of 878 patients. Mean age was 60 years (range 1 month to 91 years). Mean follow-up time was 12 months (range 1 month to 54 months). Total injections were 2,077 given as 47, 210, 399, 575, and 846 injection per year between 2006 and 2010, respectively. Anti-VEGF agents were bevacizumab (1,878; 90.42%), ranibizumab (190; 9.15%), and pegaptanib (9; 0.43%). Indications for injection based on primary diagnosis were neovascular macular degeneration (38.5%), diabetic retinopathy (38%), and retinal vein occlusion (15.9%). The incidence of endophthalmitis was 0.048% (1/2,077) for all injections and 0.053% (1/1878)for bevacizumab. The use of IVT injections of anti-VEGF is increasing, especially the use of bevacizumab. Incidence of ocular and systemic complications after IVT injection of anti- VEGF was low with no significant difference among the three anti-VEGFs agents.

Application of gold nanoparticles as contrast agents in confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Lemelle, A.; Veksler, B.; Kozhevnikov, I. S.; Akchurin, G. G.; Piletsky, S. A.; Meglinski, I.

2009-01-01

Confocal laser scanning microscopy (CLSM) is a modern high-resolution optical technique providing detailed image of tissue structure with high (down to microns) spatial resolution. Aiming at a concurrent improvement of imaging depth and image quality the CLSM requires the use of contrast agents. Commonly employed fluorescent contrast agents, such as fluorescent dyes and proteins, suffer from toxicity, photo-bleaching and overlapping with the tissues autofluorescence. Gold nanoparticles are potentially highly attractive to be applied as a contrast agent since they are not subject to photo-bleaching and can target biochemical cells markers associated with the specific diseases. In current report we consider the applicability of gold nano-spheres as a contrast agent to enhance quality of CLSM images of skin tissues in vitro versus the application of optical clearing agent, such as glycerol. The enhancement of CLSM image contrast was observed with an application of gold nano-spheres diffused within the skin tissues. We show that optical clearing agents such as a glycerol provide better CLSM image contrast than gold nano-spheres.

Evaluation of lumbar transforaminal epidural injections with needle placement and contrast flow patterns: a prospective, descriptive report.

PubMed

Manchikanti, Laxmaiah; Cash, Kim A; Pampati, Vidyasagar; Damron, Kim S; McManus, Carla D

2004-04-01

Transforaminal epidural steroid injection is one of the commonly employed modalities of treatment in managing nerve root pain. However, there have been no controlled prospective evaluations of epidural and nerve root contrast distribution patterns and other aspects of fluoroscopically directed lumbosacral transforaminal epidural steroid injections. To evaluate contrast flow patterns and intravascular needle placement of fluoroscopically guided lumbosacral transforaminal epidural injections. A prospective, observational study. A total of 100 consecutive patients undergoing fluoroscopically guided transforaminal epidural steroid injections were evaluated. The contrast flow patterns, ventral or dorsal epidural filling, nerve root filling, C-arm time, and intravascular needle placement were evaluated. Ventral epidural filling was seen in 88% of the procedures, in contrast to dorsal filling noted in 9% of the procedures. Nerve root filling was seen in 97% of the procedures. Total intravenous placement of the needle was noted in 22% of the procedures, whereas negative flashback and aspiration was noted in 5% of the procedures. Lumbosacral transforaminal epidural injections, performed under fluoroscopic visualization, provide excellent nerve root filling and ventral epidural filling patterns. However, unrecognized intravascular needle placement with negative flashback or aspiration was noted in 5% of the procedures.

Use of gadoxetic acid for computed tomographic cholangiography in healthy dogs.

PubMed

Chau, Jennifer; Podadera, Juan M; Young, Alex C; Makara, Mariano A

2017-07-01

OBJECTIVE To evaluate the effect of gadoxetic acid (contrast) dose on biliary tract enhancement, determine the optimal time after contrast injection for CT image acquisition, and assess the feasibility of CT cholangiography in sedated dogs. ANIMALS 8 healthy dogs. PROCEDURES The study had 2 parts. In part 1, 4 dogs were anesthetized and underwent CT cholangiography twice. Gadoxetic acid was administered IV at a low dose (0.025 mmol/kg) for the first procedure and high dose (0.3 mmol/kg) for the second procedure. Serial CT scans were obtained at predetermined times after contrast injection. In part 2, 4 dogs were sedated and underwent CT angiography 85 minutes after IV administration of the high contrast dose. Contrast enhancement of the biliary tract on all scans was objectively assessed by measurement of CT attenuation and qualitatively assessed by use of a subjective 4-point scoring system by 3 independent reviewers. All measurements were compared over time and between contrast doses for the dogs of part 1. Subjective measurements were compared between the sedated dogs of part 2 and anesthetized dogs of part 1. RESULTS Enhancement of the biliary tract was positively associated with contrast dose and time after contrast injection. Optimal enhancement was achieved 65 minutes after contrast injection. Subjective visualization of most biliary structures did not differ significantly between sedated and anesthetized dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated CT cholangiography with gadoxetic acid was feasible in sedated dogs. The high contrast dose provided better visualization of biliary structures than the low dose; CT scans should be obtained 65 minutes after contrast injection.

Intact Imaging of Human Heart Structure Using X-ray Phase-Contrast Tomography.

PubMed

Kaneko, Yukihiro; Shinohara, Gen; Hoshino, Masato; Morishita, Hiroyuki; Morita, Kiyozo; Oshima, Yoshihiro; Takahashi, Masashi; Yagi, Naoto; Okita, Yutaka; Tsukube, Takuro

2017-02-01

Structural examination of human heart specimens at the microscopic level is a prerequisite for understanding congenital heart diseases. It is desirable not to destroy or alter the properties of such specimens because of their scarcity. However, many of the currently available imaging techniques either destroy the specimen through sectioning or alter the chemical and mechanical properties of the specimen through staining and contrast agent injection. As a result, subsequent studies may not be possible. X-ray phase-contrast tomography is an imaging modality for biological soft tissues that does not destroy or alter the properties of the specimen. The feasibility of X-ray phase-contrast tomography for the structural examination of heart specimens was tested using infantile and fetal heart specimens without congenital diseases. X-ray phase-contrast tomography was carried out at the SPring-8 synchrotron radiation facility using the Talbot grating interferometer at the bending magnet beamline BL20B2 to visualize the structure of five non-pretreated whole heart specimens obtained by autopsy. High-resolution, three-dimensional images were obtained for all specimens. The images clearly showed the myocardial structure, coronary vessels, and conduction bundle. X-ray phase-contrast tomography allows high-resolution, three-dimensional imaging of human heart specimens. Intact imaging using X-ray phase-contrast tomography can contribute to further structural investigation of heart specimens with congenital heart diseases.

Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors

PubMed Central

2017-01-01

Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field 1H MRI techniques. PMID:28776023

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging

PubMed Central

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-01-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane–modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. PMID:26874280

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Thermographic visualization of the superficial vein and extravasation using the temperature gradient produced by the injected materials

NASA Astrophysics Data System (ADS)

Nakamura, Katsumasa; Sasaki, Tomonari; Ohga, Saiji; Yoshitake, Tadamasa; Terashima, Kotaro; Asai, Kaori; Matsumoto, Keiji; Shinoto, Makoto; Shioyama, Yoshiyuki; Nishie, Akihoro; Honda, Hiroshi

2014-11-01

There are few effective methods to detect or prevent the extravasation of injected materials such as chemotherapeutic agents and radiographic contrast materials. To investigate whether a thermographic camera could visualize the superficial vein and extravasation using the temperature gradient produced by the injected materials, an infrared thermographic camera with a high resolution of 0.04 °C was used. At the room temperature of 26 °C, thermal images and the time course of the temperature changes of a paraffin phantom embedded with rubber tubes (diameter 3.2 mm, wall thickness 0.8 mm) were evaluated after the tubes were filled with water at 15 °C or 25 °C. The rubber tubes were embedded at depths of 0 mm, 1.5 mm, and 3.0 mm from the surface of the phantom. Temperature changes were visualized in the areas of the phantom where the tubes were embedded. In general, changes were more clearly detected when greater temperature differences between the phantom and the water and shallower tube locations were employed. The temperature changes of the surface of a volunteer's arm were also examined after a bolus injection of physiological saline into the dorsal hand vein or the subcutaneous space. The injection of 5 ml room-temperature (26 °C) saline into the dorsal hand vein enabled the visualization of the vein. When 3 ml of room-temperature saline was injected through the vein into the subcutaneous space, extravasation was detected without any visualization of the vein. The subtraction image before and after the injection clearly showed the temperature changes induced by the saline. Thermography may thus be useful as a monitoring system to detect extravasation of the injected materials.

Practice patterns for the use of iodinated i.v. contrast media for pediatric CT studies: a survey of the Society for Pediatric Radiology.

PubMed

Callahan, Michael J; Servaes, Sabah; Lee, Edward Y; Towbin, Alexander J; Westra, Sjirk J; Frush, Donald P

2014-04-01

There are limited data available on the use of i.v. contrast media for CT studies in the pediatric population. The purpose of this study is to determine the practice patterns of i.v. contrast media usage for pediatric CT by members of the Society for Pediatric Radiology (SPR). SPR members were surveyed regarding the use of i.v. contrast media for pediatric CT studies. Questions pertained to information required before administering i.v. contrast media, types of central catheters for injecting i.v. contrast media, injection rates based on angiocatheter size and study type, and management of i.v. contrast media extravasation. The response rate of 6% (88/1545) represented practice patterns of 26% (401/1545) of the SPR membership. Most respondents thought the following clinical information was mandatory before i.v. contrast media administration: allergy to i.v. contrast media (97%), renal insufficiency (97%), current metformin use (72%), significant allergies (61%), diabetes (54%), and asthma (52%). Most administered i.v. contrast media through nonimplanted central venous catheters (78%), implanted venous ports (78%), and peripherally inserted central catheters (72%). The most common maximum i.v. contrast media injection rates were 5.0 mL/s or greater for a 16-gauge angiocatheter, 4.0 mL/s for an 18-gauge angiocatheter, 3.0 mL/s for a 20-gauge angiocatheter, and 2.0 mL/s for a 22-gauge angiocatheter. For soft-tissue extravasation of i.v. contrast media, 95% elevate the affected extremity, 76% use ice, and 45% use heat. The results of this survey illustrate the collective opinion of a subset of SPR members relating to the use of i.v. contrast media in pediatric CT, providing guidelines for clinical histories needed before i.v. contrast media, maximum i.v. contrast injection rates for standard angiocatheters, contrast media injection rates for specific CT studies, and management of i.v. contrast media soft-tissue extravasation.

Polydisulfide Manganese(II) Complexes as Non-Gadolinium Biodegradable Macromolecular MRI Contrast Agents

PubMed Central

Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Tan, Mingqian; Yin, Shouyu; Lu, Zheng-Rong

2011-01-01

Purpose To develop safe and effective manganese(II) based biodegradable macromolecular MRI contrast agents. Materials and Methods In this study, we synthesized and characterized two polydisulfide manganese(II) complexes, Mn-DTPA cystamine copolymers and Mn-EDTA cystamine copolymers, as new biodegradable macromolecular MRI contrast agents. The contrast enhancement of the two manganese based contrast agents were evaluated in mice bearing MDA-MB-231 human breast carcinoma xenografts, in comparison with MnCl2. Results The T1 and T2 relaxivities were 4.74 and 10.38 mM−1s−1 per manganese at 3T for Mn-DTPA cystamine copolymers (Mn=30.50 kDa) and 6.41 and 9.72 mM−1s−1 for Mn-EDTA cystamine copolymers (Mn= 61.80 kDa). Both polydisulfide Mn(II) complexes showed significant liver, myocardium and tumor enhancement. Conclusion The manganese based polydisulfide contrast agents have a potential to be developed as alternative non-gadolinium contrast agents for MR cancer and myocardium imaging. PMID:22031457

The use of innovative gadolinium-based contrast agent for MR-diagnosis of cancer in the experiment

NASA Astrophysics Data System (ADS)

Chernov, V.; Medvedeva, A.; Sinilkin, I.; Zelchan, R.; Grigorev, E.; Frolova, I.; Nam, I.

2016-02-01

The present study of the functional suitability and specific activity of the contrast agent gadolinium-based for magnetic resonance imaging demonstrated that the investigated contrast agent intensively accumulates in organs and anatomical structures of the experimental animals. In the model of tumor lesions in animals, study have shown that investigational contrast agent accumulates in the tumor tissue and retained there in for a long enough time.

Pain & resistance in patients with adhesive capsulitis during contrast material injection phase of MR arthrography.

PubMed

Yilmaz, Mehmet Halit; Kantarci, Fatih; Adaletli, Ibrahim; Ulus, Sila; Gulsen, Fatih; Ozer, Harun; Aktas, Ilknur; Akgun, Kenan; Kanberoglu, Kaya

2007-04-01

Adhesive capsulitis of the shoulder is a condition of unknown aetiology that results in the development of restricted active and passive glenohumeral motion. It has been reported that magnetic resonance (MR) imaging is useful in diagnosing adhesive capsulitis. We carried out this study to assess how pain and/or resistance during contrast material injection affects the diagnosis of adhesive capsulitis on magnetic resonance (MR) arthrography. The study included MR arthrography examinations of 21 patients with a diagnosis of adhesive capsulitis. The control group consisted of 20 patients who presented clinically with rotator cuff tear. The pain (visual analog scale, VAS), resistance to injection and the amount of contrast material that could be injected during injection phase of MR arthrography was assessed and compared between groups. The patients in adhesive capsulitis group (mean VAS score 66.5+/-25.5) experienced more pain when compared with the control group (mean VAS score 34.9+/-27.7, P<0.001). A statistically significant difference (P<0.001) in terms of the amount of the injected fluid (4.3+/-2.6 ml for adhesive capsulitis group, and 10.9+/-4.1 ml for control group) was seen into the joint cavity. Resistance to injection was significantly more (P<0.001) in patients with adhesive capsulitis when compared to control group. Experience of pain during injection, a decreased amount of contrast material injected and resistance to injection in patients during injection phase of MR arthrography may suggest adhesive capsulitis.

Metal artifact reduction for flat panel detector intravenous CT angiography in patients with intracranial metallic implants after endovascular and surgical treatment

PubMed Central

Pjontek, Rastislav; Önenköprülü, Belgin; Scholz, Bernhard; Kyriakou, Yiannis; Schubert, Gerrit A; Othman, Ahmed; Wiesmann, Martin; Brockmann, Marc A

2016-01-01

Background Flat panel detector CT angiography with intravenous contrast agent injection (IV CTA) allows high-resolution imaging of cerebrovascular structures. Artifacts caused by metallic implants like platinum coils or clips lead to degradation of image quality and are a significant problem. Objective To evaluate the influence of a prototype metal artifact reduction (MAR) algorithm on image quality in patients with intracranial metallic implants. Methods Flat panel detector CT after intravenous application of 80 mL contrast agent was performed with an angiography system (Artis zee; Siemens, Forchheim, Germany) using a 20 s rotation protocol (200° rotation angle, 20 s acquisition time, 496 projections). The data before and after MAR of 26 patients with a total of 34 implants (coils, clips, stents) were independently evaluated by two blinded neuroradiologists. Results MAR improved the assessability of the brain parenchyma and small vessels (diameter <1 mm) in the neighborhood of metallic implants and at a distance of 6 cm (p<0.001 each, Wilcoxon test). Furthermore, MAR significantly improved the assessability of parent vessel patency and potential aneurysm remnants (p<0.005 each, McNemar test). MAR, however, did not improve assessability of stented vessels. Conclusions When an intravenous contrast protocol is used, MAR significantly ameliorates the assessability of brain parenchyma, vessels, and treated aneurysms in patients with intracranial coils or clips. PMID:26346458

Prussian blue coated gold nanoparticles for simultaneous photoacoustic/CT bimodal imaging and photothermal ablation of cancer.

PubMed

Jing, Lijia; Liang, Xiaolong; Deng, Zijian; Feng, Shanshan; Li, Xiaoda; Huang, Maomao; Li, Changhui; Dai, Zhifei

2014-07-01

The combination of CT imaging and photoacoustic (PA) imaging represents not only high resolution and ease of forming 3D visual image for locating tissues of interest, but also good soft tissue contrast and excellent high sensitivity, which is very beneficial to the precise guidance for photothermal therapy (PTT). The near infrared (NIR) absorbing Au nanostructures take advantages to operate as a CT contrast agent due to high absorption coefficient of X-ray and outstanding biocompatibility, but show obvious deficiency for PA imaging and PTT because of low photostability. Attacking this problem head on, the Au nanoparticles (NPs) were coated with Prussian blue (PB) which is a typical FDA-approved drug in clinic for safe and effective treatment of radioactive exposure. The obtained core/shell NPs of Au@PB NPs of 17.8 ± 2.3 nm were found to be an excellent photoabsorbing agent for both PTT and PA imaging due to high photostability and high molar extinction coefficient in NIR region. Their gold core of 9.1 ± 0.64 nm ensured a remarkable contrast enhancement for CT imaging. Through a one-time treatment of NIR laser irradiation after intravenous injection of Au@PB NPs, 100 mm(3) sized tumors in nude mice could be completely ablated without recurrence. Such versatile nanoparticles integrating effective cancer diagnosis with noninvasive therapy might bring opportunities to future cancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel Application of Postmortem CT Angiography for Evaluation of the Intracranial Vascular Anatomy in Cadaver Heads.

PubMed

van Eijk, Ruben P A; van der Zwan, Albert; Bleys, Ronald L A W; Regli, Luca; Esposito, Giuseppe

2015-12-01

Postmortem CT angiography is a common procedure used to visualize the entire human vasculature. For visualization of a specific organ's vascular anatomy, casting is the preferred method. Because of the permanent and damaging nature of casting, the organ cannot be further used as an experimental model after angiography. Therefore, there is a need for a minimally traumatic method to visualize organ-specific vascular anatomy. The purpose of this study was to develop and evaluate a contrast enhancement technique that is capable of visualizing the intracranial vascular anatomy while preserving the anatomic integrity in cadaver heads. Seven human heads were used in this study. Heads were prepared by cannulating the vertebral and internal carotid arteries. Contrast agent was injected as a mixture of tap water, polyethylene glycol 600, and an iodinated contrast agent. Postmortem imaging was executed on a 64-MDCT scanner. Primary image review and 3D reconstruction were performed on a CT workstation. Clear visualization of the major cerebral arteries and smaller intracranial branches was achieved. Adequate visualization was obtained for both the anterior and posterior intracranial circulation. The minimally traumatic angiography method preserved the vascular integrity of the cadaver heads. A novel application of postmortem CT angiography is presented here. The technique can be used for radiologic evaluation of the intracranial circulation in cadaver heads. After CT angiography, the specimen can be used for further experimental or laboratory testing and teaching purposes.

Effects of iodinated contrast agent, xylocaine and gadolinium concentration on the signal emitted in magnetic resonance arthrography: a samples study*

PubMed Central

da Silva, Yvana Lopes Pinheiro; Costa, Rita Zanlorensi Visneck; Pinho, Kátia Elisa Prus; Ferreira, Ricardo Rabello; Schuindt, Sueliton Miyamoto

2015-01-01

Objective To investigate the effects of dilution of paramagnetic contrast agent with iodinated contrast and xylocaine on the signal intensity during magnetic resonance arthrography, and to improve the paramagnetic contrast agent concentration utilized in this imaging modality. Materials and Methods Samples specially prepared for the study with three different concentrations of paramagnetic contrast agent diluted in saline, iodinated contrast agent and xylocaine were imaged with fast spin echo T1-weighted sequences with fat saturation. The samples were placed into flasks and graphical analysis of the signal intensity was performed as a function of the paramagnetic contrast concentration. Results As compared with samples of equal concentrations diluted only with saline, the authors have observed an average signal intensity decrease of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the increased gadolinium concentration in the samples caused decrease in signal intensity with all the dilutions. Conclusion Minimizing the use of iodinated contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5 mmol/L diluted in saline will improve the sensitivity of magnetic resonance arthrography. PMID:25987746

Feasibility of Retrograde Ureteral Contrast Injection to Guide Ultrasonographic Percutaneous Renal Access in the Nondilated Collecting System.

PubMed

Usawachintachit, Manint; Tzou, David T; Mongan, John; Taguchi, Kazumi; Weinstein, Stefanie; Chi, Thomas

2017-02-01

Ultrasound-guided percutaneous nephrolithotomy (PCNL) has become increasingly utilized. Patients with nondilated collecting systems represent a challenge: the target calix is often difficult to visualize. Here we report pilot study results for retrograde ultrasound contrast injection to aid in percutaneous renal access during ultrasound-guided PCNL. From April to July 2016, consecutive patients over the age of 18 years with nondilated collecting systems on preoperative imaging who presented for PCNL were enrolled. B-mode ultrasound imaging was compared with contrast-enhanced mode with simultaneous retrograde injection of Optison™ via an ipsilateral ureteral catheter. Five patients (four males and one female) with renal stones underwent PCNL with retrograde ultrasound contrast injection during the study period. Mean body mass index was 28.3 ± 5.6 kg/m 2 and mean stone size was 24.5 ± 12.0 mm. Under B-mode ultrasound, all patients demonstrated nondilated renal collecting systems that appeared as hyperechoic areas, where it was difficult to identify a target calix for puncture. Retrograde contrast injection facilitated delineation of all renal calices initially difficult to visualize under B-mode ultrasound. Renal puncture was then performed effectively in all cases with a mean puncture time of 55.4 ± 44.8 seconds. All PCNL procedures were completed without intraoperative complications and no adverse events related to ultrasound contrast injection occurred. Retrograde ultrasound contrast injection as an aide for renal puncture during PCNL is a feasible technique. By improving visualization of the collecting system, it facilitates needle placement in challenging patients without hydronephrosis. Future larger scale studies comparing its use to standard ultrasound-guided technique will be required to validate this concept.

3.0 Tesla high spatial resolution contrast-enhanced magnetic resonance angiography (CE-MRA) of the pulmonary circulation: initial experience with a 32-channel phased array coil using a high relaxivity contrast agent.

PubMed

Nael, Kambiz; Fenchel, Michael; Krishnam, Mayil; Finn, J Paul; Laub, Gerhard; Ruehm, Stefan G

2007-06-01

To evaluate the technical feasibility of high spatial resolution contrast-enhanced magnetic resonance angiography (CE-MRA) with highly accelerated parallel acquisition at 3.0 T using a 32-channel phased array coil, and a high relaxivity contrast agent. Ten adult healthy volunteers (5 men, 5 women, aged 21-66 years) underwent high spatial resolution CE-MRA of the pulmonary circulation. Imaging was performed at 3 T using a 32-channel phase array coil. After intravenous injection of 1 mL of gadobenate dimeglumine (Gd-BOPTA) at 1.5 mL/s, a timing bolus was used to measure the transit time from the arm vein to the main pulmonary artery. Subsequently following intravenous injection of 0.1 mmol/kg of Gd-BOPTA at the same rate, isotropic high spatial resolution data sets (1 x 1 x 1 mm3) CE-MRA of the entire pulmonary circulation were acquired using a fast gradient-recalled echo sequence (TR/TE 3/1.2 milliseconds, FA 18 degrees) and highly accelerated parallel acquisition (GRAPPA x 6) during a 20-second breath hold. The presence of artifact, noise, and image quality of the pulmonary arterial segments were evaluated independently by 2 radiologists. Phantom measurements were performed to assess the signal-to-noise ratio (SNR). Statistical analysis of data was performed by using Wilcoxon rank sum test and 2-sample Student t test. The interobserver variability was tested by kappa coefficient. All studies were of diagnostic quality as determined by both observers. The pulmonary arteries were routinely identified up to fifth-order branches, with definition in the diagnostic range and excellent interobserver agreement (kappa = 0.84, 95% confidence interval 0.77-0.90). Phantom measurements showed significantly lower SNR (P < 0.01) using GRAPPA (17.3 +/- 18.8) compared with measurements without parallel acquisition (58 +/- 49.4). The described 3 T CE-MRA protocol in addition to high T1 relaxivity of Gd-BOPTA provides sufficient SNR to support highly accelerated parallel acquisition (GRAPPA x 6), resulting in acquisition of isotopic (1 x 1 x 1 mm3) voxels over the entire pulmonary circulation in 20 seconds.

Contrast agent enhanced pQCT of articular cartilage

NASA Astrophysics Data System (ADS)

Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

2007-02-01

The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded articular cartilage in vitro. As high resolution imaging of e.g. the knee joint is possible with pQCT, the present technique may be further developed for in vivo quantification of PG depletion in osteoarthritic cartilage. However, careful in vitro and in vivo characterization of diffusion mechanics and optimal contrast agent concentrations are needed before diagnostic applications are feasible.

Dependency of the effect of a vascular disrupting agent on sensitivity to tirapazamine and gamma-ray irradiation upon the timing of its administration and tumor size, with reference to the effect on intratumor quiescent cells.

PubMed

Masunaga, Shin-ichiro; Nagasawa, Hideko; Nagata, Kenji; Suzuki, Minoru; Uto, Yoshihiro; Hori, Hitoshi; Kinashi, Yuko; Ono, Koji

2007-01-01

The effect of vascular disrupting agent ZD6126 with time on the sensitivity to the hypoxic cytotoxin tirapazamine (TPZ) and gamma-rays was examined in large and small solid tumors. Mice bearing SCC VII tumors 1 or 1.5 cm in diameter received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells, followed by injection with or without ZD6126. In the absence of ZD6126, or 1 or 24 h following ZD6126 injection, the response to TPZ or gamma-ray irradiation in quiescent (Q) cells was assessed in terms of induced micronucleus (MN) frequency using immunofluorescence staining for BrdU. The MN frequency in the total cell population was determined from the tumors not pretreated with BrdU. Another group of tumor-bearing mice received a series of test doses of gamma-rays while alive or after tumor clamping to obtain hypoxic fractions (HFs) in the tumors. One hour after ZD6126 injection, both small and large tumors showed lower and higher sensitivity, and 24 h after, higher and lower sensitivity, to gamma-rays and TPZ, respectively, than the tumors not treated with ZD6126. Further, they showed larger and smaller HFs 1 and 24 h after ZD6126 injection, respectively. Without ZD6126 and 1 h after injection, small tumors were more sensitive to gamma-rays and less sensitive to TPZ than large tumors, probably due to the smaller HFs than large tumors. In contrast, 24 h after the injection, these differences in sensitivity and the HF between small and large tumors were reversed. The changes in sensitivity and the size of the HF were more marked in the total cell population than in Q cells. Following ZD6126 treatment, in terms of tumor control, especially large tumors and total tumor cell population, administering TPZ 1 h later and gamma-ray irradiation 24 h later were effective. Intratumor physiologic factors such as the size of the HF, depending on the time after ZD6126 injection, have to be taken into account when combining another treatment with ZD6126.

Safe Use of Contrast Media: What the Radiologist Needs to Know.

PubMed

Beckett, Katrina R; Moriarity, Andrew K; Langer, Jessica M

2015-10-01

Iodinated and gadolinium-based contrast media are used on a daily basis in most radiology practices. These agents often are essential to providing accurate diagnoses, and are nearly always safe and effective when administered correctly. However, reactions to contrast media do occur and can be life threatening. Therefore, it is critical for faculty and staff to know how reactions to contrast agents manifest and how to treat them promptly. The decline in renal function seen occasionally after intravenous administration of iodinated contrast agents is poorly understood and likely multifactorial, and its association with the contrast medium may be overemphasized. However, it is important that radiologists be aware of current understanding and strategies to decrease the incidence of renal dysfunction. Nephrogenic systemic fibrosis, a skin disease, is an adverse reaction related to use of some gadolinium-based contrast agents in patients with chronic renal failure. The types of gadolinium most often associated with this condition and the indications for withholding gadolinium are important and are discussed in this article. The use of enteric contrast agents and contrast agents during pregnancy and nursing are reviewed briefly. Current knowledge for safe use of contrast media and key concepts that all radiologists should know are summarized in this review. © RSNA, 2015.

Role of Arrival Time Difference Between Lesions and Lung Tissue on Contrast-Enhanced Sonography in the Differential Diagnosis of Subpleural Pulmonary Lesions.

PubMed

Bai, Jing; Yang, Wei; Wang, Song; Guan, Rui-Hong; Zhang, Hui; Fu, Jing-Jing; Wu, Wei; Yan, Kun

2016-07-01

The purpose of this study was to explore the diagnostic value of the arrival time difference between lesions and surrounding lung tissue on contrast-enhanced sonography of subpleural pulmonary lesions. A total of 110 patients with subpleural pulmonary lesions who underwent both conventional and contrast-enhanced sonography and had a definite diagnosis were enrolled. After contrast agent injection, the arrival times in the lesion, lung, and chest wall were recorded. The arrival time differences between various tissues were also calculated. Statistical analysis showed a significant difference in the lesion arrival time, the arrival time difference between the lesion and lung, and the arrival time difference between the chest wall and lesion (all P < .001) for benign and malignant lesions. Receiver operating characteristic curve analysis revealed that the optimal diagnostic criterion was the arrival time difference between the lesion and lung, and that the best cutoff point was 2.5 seconds (later arrival signified malignancy). This new diagnostic criterion showed superior diagnostic accuracy (97.1%) compared to conventional diagnostic criteria. The individualized diagnostic method based on an arrival time comparison using contrast-enhanced sonography had high diagnostic accuracy (97.1%) with good feasibility and could provide useful diagnostic information for subpleural pulmonary lesions.

Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation

PubMed Central

Gustafsson, Björn; Youens, Susan; Louie, Angelique Y.

2008-01-01

Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the sub-clinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI. PMID:16536488

Evidence on Possible Mycoplasma Etiology of Aster Yellows Disease II. Suppression of Aster Yellows in Insect Vectors

PubMed Central

Whitcomb, R. F.; Davis, R. E.

1970-01-01

Chlortetracycline or chloramphenicol (but not kanamycin, penicillin, or erythromycin), when administered in hydroponic solution to diseased aster, reduced the availability of the aster yellows (AY) agent to nymphs of Macrosteles fascifrons (Stål). Insects exposed to healthy plants whose roots were immersed in chlortetracycline were able to acquire AY agent from diseased plants the day after removal from the antibiotic-treated plants, but the latent period of the ensuing disease in the insects was prolonged. Chlortetracycline or tylosin tartrate blocked AY infection in nymphs injected with a mixture of antibiotic and the AY agent, but polymyxin, neomycin, vancomycin, penicillin, carbomycin, or chloramphenicol did not. All tetracyclines tested, methacycline, oxytetracycline, and chlortetracycline, produced a dramatic reduction in the ability of infected vectors to transmit AY agent. Tylosin tartrate also reduced transmission when injected into AY-transmitting vectors, but carbomycin, spectinomycin, cycloserine, penicillin, erythromycin, or kanamycin had no such effect. During the first 10 days after injection of tylosin tartrate or oxytetracycline into transmitting vectors, ability of the insects to transmit AY decayed rapidly. Transmission by insects injected with buffer alone, after decreasing the first day after injection, gradually returned to its normal level in less than 1 week. By 2 to 3 weeks after injection with tylosin or oxytetracycline, ability to transmit AY was regained by vectors. The results suggest that tetracycline antibiotics and tylosin tartrate inhibit multiplication of AY agent in the insect. The spectrum of antibiotic activity in the insect is consistent with the hypothesis that AY and other plant yellows diseases are caused by mycoplasma-like organisms. PMID:16557821

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

PubMed

Daryaei, Iman; Pagel, Mark D

2015-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

Magneto acoustic tomography with short pulsed magnetic field for in-vivo imaging of magnetic iron oxide nanoparticles.

PubMed

Mariappan, Leo; Shao, Qi; Jiang, Chunlan; Yu, Kai; Ashkenazi, Shai; Bischof, John C; He, Bin

2016-04-01

Nanoparticles are widely used as contrast and therapeutic agents. As such, imaging modalities that can accurately estimate their distribution in-vivo are actively sought. We present here our method Magneto Acoustic Tomography (MAT), which uses magnetomotive force due to a short pulsed magnetic field to induce ultrasound in the magnetic nanoparticle labeled tissue and estimates an image of the distribution of the nanoparticles in-vivo with ultrasound imaging resolution. In this study, we image the distribution of superparamagnetic iron oxide nanoparticles (IONP) using MAT method. In-vivo imaging was performed on live, nude mice with IONP injected into LNCaP tumors grown subcutaneously within the hind limb of the mice. Our experimental results indicate that the MAT method is capable of imaging the distribution of IONPs in-vivo. Therefore, MAT could become an imaging modality for high resolution reconstruction of MNP distribution in the body. Many magnetic nanoparticles (MNPs) have been used as contrast agents in magnetic resonance imaging. In this study, the authors investigated the use of ultrasound to detect the presence of MNPs by magneto acoustic tomography. In-vivo experiments confirmed the imaging quality of this new approach, which hopefully would provide an alternative method for accurate tumor detection. Copyright © 2015 Elsevier Inc. All rights reserved.

Gold-Loaded Polymeric Micelles for Computed Tomography-Guided Radiation Therapy Treatment and Radiosensitization

PubMed Central

2013-01-01

Gold nanoparticles (AuNPs) have generated interest as both imaging and therapeutic agents. AuNPs are attractive for imaging applications since they are nontoxic and provide nearly three times greater X-ray attenuation per unit weight than iodine. As therapeutic agents, AuNPs can sensitize tumor cells to ionizing radiation. To create a nanoplatform that could simultaneously exhibit long circulation times, achieve appreciable tumor accumulation, generate computed tomography (CT) image contrast, and serve as a radiosensitizer, gold-loaded polymeric micelles (GPMs) were prepared. Specifically, 1.9 nm AuNPs were encapsulated within the hydrophobic core of micelles formed with the amphiphilic diblock copolymer poly(ethylene glycol)-b-poly(ε-capralactone). GPMs were produced with low polydispersity and mean hydrodynamic diameters ranging from 25 to 150 nm. Following intravenous injection, GPMs provided blood pool contrast for up to 24 h and improved the delineation of tumor margins via CT. Thus, GPM-enhanced CT imaging was used to guide radiation therapy delivered via a small animal radiation research platform. In combination with the radiosensitizing capabilities of gold, tumor-bearing mice exhibited a 1.7-fold improvement in the median survival time, compared with mice receiving radiation alone. It is envisioned that translation of these capabilities to human cancer patients could guide and enhance the efficacy of radiation therapy. PMID:24377302

The effect of various immunosuppressive agents on mouse peritoneal macrophages and on the in vitro phagocytosis of Escherichia coli O4:K3:H5 and degradation of 125I-labelled HSA-antibody complexes by these cells.

PubMed Central

Gadeberg, O V; Rhodes, J M; Larsen, S O

1975-01-01

Large doses of hydrocortisone, cyclophosphamide, and methotrexate injected subcutaneously, and whole-body irradiation (500 rads) caused a reduction in the number of peritoneal cells (PE cells) obtained after intraperitoneal injection of the treated mice with proteose-peptone. The same dose of cyclophosphamide and irradiation induced morphological changes in PE macrophages. There were more giant cells in the peritoneal exudates from treated mice as compared to control mice. 'Pharmacological' and larger doses of hydrocortisone, methotrexate and azathioprine or anti-lymphocyte globulin had no effect on the in vitro phagocytic capacity of proteose-peptone-stimulated mouse PE macrophages. This also applied to doses of up to 50 mg/kg of cyclophosphamide. In contrast, whole-body irradiation (500 rad) and 100 mg/kg of cyclophosphamide decreased the phagocytic capacity of mouse macrophages in vitro and reduced the ability of PE cells to degrade 125I-labelled HSA-antibody complexes in vitro. The greatest effect was noted 4-5 days after whole-body irradiation or four to five subcutaneous injections of cyclophosphamide. Images Figure 1 Figure 2 PMID:1090520

Optical coherence tomography and computer-aided diagnosis of a murine model of chronic kidney disease

NASA Astrophysics Data System (ADS)

Wang, Bohan; Wang, Hsing-Wen; Guo, Hengchang; Anderson, Erik; Tang, Qinggong; Wu, Tongtong; Falola, Reuben; Smith, Tikina; Andrews, Peter M.; Chen, Yu

2017-12-01

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function over time. Histopathological analysis of the condition of glomeruli and the proximal convolutional tubules over time can provide valuable insights into the progression of CKD. Optical coherence tomography (OCT) is a technology that can analyze the microscopic structures of a kidney in a nondestructive manner. Recently, we have shown that OCT can provide real-time imaging of kidney microstructures in vivo without administering exogenous contrast agents. A murine model of CKD induced by intravenous Adriamycin (ADR) injection is evaluated by OCT. OCT images of the rat kidneys have been captured every week up to eight weeks. Tubular diameter and hypertrophic tubule population of the kidneys at multiple time points after ADR injection have been evaluated through a fully automated computer-vision system. Results revealed that mean tubular diameter and hypertrophic tubule population increase with time in post-ADR injection period. The results suggest that OCT images of the kidney contain abundant information about kidney histopathology. Fully automated computer-aided diagnosis based on OCT has the potential for clinical evaluation of CKD conditions.

An Imaging Biomarker for Assessing Hepatic Function in Patients with Primary Sclerosing Cholangitis.

PubMed

Schulze, Jennifer; Lenzen, Henrike; Hinrichs, Jan B; Ringe, Burckhardt; Manns, Michael P; Wacker, Frank; Ringe, Kristina I

2018-05-15

We aimed to evaluate the potential of hepatobiliary phase magnetic resonance imaging (MRI) as parameter for assessment of hepatocellular function in patients with primary sclerosing cholangitis (PSC). We collected data from 111 patients (83 male, 28 female; median, 44 years old), from March 2012 through March 2016, with a confirmed diagnosis of PSC who underwent MRI evaluation before and after injection (hepatobiliary phase) of a hepatocyte-specific contrast agent (gadoxetate disodium). Signal intensities were measured in each liver segment. Mean relative enhancement values were calculated and correlated with findings from liver functions tests, prognostic scoring systems (model for end-stage liver disease [MELD] score; Mayo risk score; Amsterdam-Oxford-PSC score), abnormalities detected by endoscopic retrograde cholangiopancreatography (using the Amsterdam cholangiographic classification system), and clinical endpoints (liver transplantation, cholangiocarcinoma, liver-related death). Our primary aim was to associate relative enhancement values with liver function and patient outcomes. Most patients had moderate-stage disease and had intermediate levels of risk (median MELD score, 8 and median Mayo score, 0.27). Clinical endpoints were reached by 21 patients (6 developed cholangiocarcinoma, 8 underwent liver transplantation, and 7 patients died). The highest levels of correlations were observed for relative enhancement 20 min after contrast injection and level of alkaline phosphatase (r= -0.636), bilirubin (r= -0.646), albumin (r= 0.538); as well as international normalized ratio (r=0.456); MELD score (r= -0.587); Mayo risk score (r= -0.535), and Amsterdam-Oxford model score (r= -0.595) (P<.0001). Relative enhancement correlated with all clinical endpoints (all P<.05). A cutoff relative enhancement value of 0.65 identified patients with a clinical endpoint with 73.9% sensitivity 92.9% specificity (area under the receiver operating characteristic curve, 0.901; likelihood ratio, 10.34; P<.0001). In an analysis of 111 patients with PSC, we found MRI-measured relative enhancement, using a hepatocyte-specific contrast agent, to identify patients with clinical outcomes with 73.9% sensitivity 92.9% specificity. Long-term, multicenter studies are needed to further evaluate this marker of PSC progression. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Label free measurement of retinal blood cell flux, velocity, hematocrit and capillary width in the living mouse eye

PubMed Central

Guevara-Torres, A.; Joseph, A.; Schallek, J. B.

2016-01-01

Measuring blood cell dynamics within the capillaries of the living eye provides crucial information regarding the health of the microvascular network. To date, the study of single blood cell movement in this network has been obscured by optical aberrations, hindered by weak optical contrast, and often required injection of exogenous fluorescent dyes to perform measurements. Here we present a new strategy to non-invasively image single blood cells in the living mouse eye without contrast agents. Eye aberrations were corrected with an adaptive optics camera coupled with a fast, 15 kHz scanned beam orthogonal to a capillary of interest. Blood cells were imaged as they flowed past a near infrared imaging beam to which the eye is relatively insensitive. Optical contrast of cells was optimized using differential scatter of blood cells in the split-detector imaging configuration. Combined, these strategies provide label-free, non-invasive imaging of blood cells in the retina as they travel in single file in capillaries, enabling determination of cell flux, morphology, class, velocity, and rheology at the single cell level. PMID:27867728

Label free measurement of retinal blood cell flux, velocity, hematocrit and capillary width in the living mouse eye.

PubMed

Guevara-Torres, A; Joseph, A; Schallek, J B

2016-10-01

Measuring blood cell dynamics within the capillaries of the living eye provides crucial information regarding the health of the microvascular network. To date, the study of single blood cell movement in this network has been obscured by optical aberrations, hindered by weak optical contrast, and often required injection of exogenous fluorescent dyes to perform measurements. Here we present a new strategy to non-invasively image single blood cells in the living mouse eye without contrast agents. Eye aberrations were corrected with an adaptive optics camera coupled with a fast, 15 kHz scanned beam orthogonal to a capillary of interest. Blood cells were imaged as they flowed past a near infrared imaging beam to which the eye is relatively insensitive. Optical contrast of cells was optimized using differential scatter of blood cells in the split-detector imaging configuration. Combined, these strategies provide label-free, non-invasive imaging of blood cells in the retina as they travel in single file in capillaries, enabling determination of cell flux, morphology, class, velocity, and rheology at the single cell level.

[Retention of contrast media in the history of radiology : Sequelae of the former use of thorotrast and new challenges].

PubMed

van Kaick, G; Delorme, S

2016-12-01

Detection of gadolinium deposits in patients who have repeatedly been administered intravenous gadolinium chelates have given rise to concern regarding the long-term safety of magnetic resonance imaging (MRI) contrast media. Nevertheless, negative long-term clinical effects have not yet been observed. In some publications parallels have been drawn to the sequelae of thorotrast that was formerly used for arterial angiography. In this article the history of thorotrast use is briefly described and in particular why, despite warnings, this substance was used frequently and worldwide. A brief summary of the results of the German Thorotrast Study revealed that high excess rates were only observed for primary malignant liver tumors after a 15-year or longer latency period and to a lesser degree of leukemias, as well as for severe local complications due to paravascular injections, particularly in the neck region. Based on this historical review, we will venture to take stock of the outcome from the "success story" of this contrast agent.

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.

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.

Automated contrast medium monitoring system for computed tomography--Intra-institutional audit.

PubMed

Lauretti, Dario Luca; Neri, Emanuele; Faggioni, Lorenzo; Paolicchi, Fabio; Caramella, Davide; Bartolozzi, Carlo

2015-12-01

The aim of this study was to analyze the usage and the data recorded by a RIS-PACS-connected contrast medium (CM) monitoring system (Certegra(®), Bayer Healthcare, Leverkusen, Germany) over 19 months of CT activity. The system used was connected to two dual syringe power injectors (each associated with a 16-row and a high definition 64-row multidetector CT scanner, respectively), allowing to manage contrast medium injection parameters and to send and retrieve CT study-related information via RIS/PACS for any scheduled contrast-enhanced CT examination. The system can handle up to 64 variables and can be accessed via touchscreen by CT operators as well as via a web interface by registered users with three different hierarchy levels. Data related to CM injection parameters (i.e. iodine concentration, volume and flow rate of CM, iodine delivery rate and iodine dose, CM injection pressure, and volume and flow rate of saline), patient weight and height, and type of CT study over a testing period spanning from 1 June 2013 to 10 January 2015 were retrieved from the system. Technical alerts occurred for each injection event (such as system disarm due to technical failure, disarm due to operator's stop, incomplete filling of patient data fields, or excessively high injection pressure), as well as interoperability issues related to data sending and receiving to/from the RIS/PACS were also recorded. During the testing period, the CM monitoring system generated a total of 8609 reports, of which 7629 relative to successful injection events (88.6%). 331 alerts were generated, of which 40 resulted in injection interruption and 291 in CM flow rate limitation due to excessively high injection pressure (>325 psi). Average CM volume and flow rate were 93.73 ± 17.58 mL and 3.53 ± 0.89 mL/s, and contrast injection pressure ranged between 5 and 167 psi. A statistically significant correlation was found between iodine concentration and peak IDR (rs=0.2744, p<0.0001), as well as between iodine concentration and iodine dose (rs=0.3862, p<0.0001) for all CT studies. Automated contrast management systems can provide a full report of contrast use with the possibility to systematically compare different contrast injection protocols, minimize errors, and optimize organ-specific contrast enhancement for any given patient and clinical application. This can be useful to improve and harmonize the quality and consistency of contrast CT procedures within the same radiological department and across the hospital, as well as to monitor potential adverse events and overall costs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of contrast media for visualization of the colon of healthy dogs during computed tomography and ultrasonography.

PubMed

Cheon, Byunggyu; Moon, Sohyeon; Park, Seungjo; Lee, Sang-Kwon; Hong, Sunghwa; Cho, Hyun; Choi, Jihye

2016-11-01

OBJECTIVE To evaluate contrast agents for their ability to improve visualization of the colon wall and lumen during CT and ultrasonography. ANIMALS 10 healthy adult Beagles. PROCEDURES Food was withheld from dogs for 36 hours, after which dogs consumed 250 mL of polyethylene glycol solution. Dogs were then anesthetized, a contrast agent (tap water, diluted barium, or air; order randomly assigned) was administered rectally, iodine contrast medium (880 mg of I/kg) was administered IV, and CT and ultrasonography of the colon were performed. After a 1-week washout period, this process was repeated with a different contrast agent until all agents had been evaluated. Two investigators reviewed the CT and ultrasonographic images for colon wall thickness, conspicuity, artifacts, wall layering, and degree of lumen dilation at 4 sites. RESULTS Thickness of the colon wall was greatest in CT and ultrasonographic images with water used as contrast agent, followed by barium and then air. The CT images obtained after water administration had a smooth appearance that outlined the colonic mucosa and had the highest score of the 3 contrast agents for wall conspicuity. Although no substantial artifacts related to any of the contrast agents were identified on CT images, barium- and gas-induced shadowing and reverberation artifacts hindered wall evaluation during ultrasonography. For ultrasonography, the degree of conspicuity was highest with barium in the near-field wall and with water in the far-field wall. In contrast to CT, ultrasonography could be used to distinguish wall layering, and the mucosal and muscular layers were distinct with all contrast agents. CONCLUSIONS AND CLINICAL RELEVANCE Use of water as a contrast agent for both CT and ultrasonography of the colon in dogs compensated for each imaging modality's disadvantages and could be beneficial in the diagnosis of colon disease.

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

PubMed

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-04-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents

PubMed Central

Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A.; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

2017-01-01

Objectives Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Materials and Methods Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. Results No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological nephrogenic systemic fibrosis–like skin lesions. The Gd concentrations observed in the skin/brain samples (in nanomole Gd per gram of tissue) for each agent were as follows: gadodiamide: 1472 ± 115/11.1 ± 5.1, gadopentetate dimeglumine: 80.8 ± 6.2/13.1 ± 7.3, gadobutrol: 1.1 ± 0.5/0.7 ± 0.4, and gadoteridol: 1.7 ± 0.8/0.5 ± 0.2. The average detected residual Gd concentration in the brain was approximately 15-fold higher for linear than for macrocyclic GBCAs. The highest amounts of Gd found in brain corresponded to less than 0.0002% of the injected dose per gram of tissue. Using LA-ICP-MS, high Gd concentrations in the deep cerebellar nuclei and in the granular layer of the cerebellar cortex were detected only for linear gadodiamide and gadopentetate dimeglumine but not for gadoteridol or gadobutrol. The energy dispersive x-ray spectroscopy analysis revealed Gd-containing spots in the skin of animals administered gadodiamide and gadopentetate dimeglumine. Transmission electron microscopy revealed several Gd-containing spots in the region of the dentate nuclei in the brain of 1 animal injected with gadodiamide. Conclusions After repeated high dosing, nephrogenic systemic fibrosis–like macroscopic and histopathological lesions of the skin were observed only in some of the gadodiamide-treated animals. No histopathological findings were detected in the rodent brain. The administration of linear GBCAs was associated with significantly higher Gd concentrations in the brain and skin compared with macrocyclic GBCA administration. The results of LA-ICP-MS demonstrated local accumulation of Gd within the deep cerebellar nuclei and the granular layer only after the administration of linear agents. In summary, the detected low Gd concentrations in the skin and brain were well correlated with the higher kinetic stability of macrocyclic GBCA. PMID:28323657

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PubMed

Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

2017-06-01

Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological nephrogenic systemic fibrosis-like skin lesions. The Gd concentrations observed in the skin/brain samples (in nanomole Gd per gram of tissue) for each agent were as follows: gadodiamide: 1472 ± 115/11.1 ± 5.1, gadopentetate dimeglumine: 80.8 ± 6.2/13.1 ± 7.3, gadobutrol: 1.1 ± 0.5/0.7 ± 0.4, and gadoteridol: 1.7 ± 0.8/0.5 ± 0.2. The average detected residual Gd concentration in the brain was approximately 15-fold higher for linear than for macrocyclic GBCAs. The highest amounts of Gd found in brain corresponded to less than 0.0002% of the injected dose per gram of tissue. Using LA-ICP-MS, high Gd concentrations in the deep cerebellar nuclei and in the granular layer of the cerebellar cortex were detected only for linear gadodiamide and gadopentetate dimeglumine but not for gadoteridol or gadobutrol. The energy dispersive x-ray spectroscopy analysis revealed Gd-containing spots in the skin of animals administered gadodiamide and gadopentetate dimeglumine. Transmission electron microscopy revealed several Gd-containing spots in the region of the dentate nuclei in the brain of 1 animal injected with gadodiamide. After repeated high dosing, nephrogenic systemic fibrosis-like macroscopic and histopathological lesions of the skin were observed only in some of the gadodiamide-treated animals. No histopathological findings were detected in the rodent brain. The administration of linear GBCAs was associated with significantly higher Gd concentrations in the brain and skin compared with macrocyclic GBCA administration. The results of LA-ICP-MS demonstrated local accumulation of Gd within the deep cerebellar nuclei and the granular layer only after the administration of linear agents. In summary, the detected low Gd concentrations in the skin and brain were well correlated with the higher kinetic stability of macrocyclic GBCA.

Ultrasonic contrast agents in transcranial perfusion sonography (TPS) for follow-up of patients with high grade gliomas.

PubMed

Ickenstein, G W; Valaikiene, J; Koch, H; Hau, P; Erban, P; Schlachetzki, F

2008-04-01

The aim of this study was to evaluate brain perfusion differences in patients with high grade gliomas after partial tumor resection and irradiation/chemotherapy between tumor and non-tumor hemisphere by transcranial perfusion sonography (TPS) employing a contrast burst imaging (CBI) technique. Six patients with glioblastoma (WHO Grade IV) in the temporoparietal region within the defined axial diencephalic scanning plane were examined by TPS during follow-up. All subjects had an adequate acoustic temporal bone window. Transtemporal insonation on brain tumor and non-tumor hemisphere was performed with a bolus-injection of sulphur hexafluoride-based contrast agent (10 mg i.v., 5mg/ml--SonoVue, Bracco, Altana, Switzerland). Recorded images were analysed off-line by Quanticon Software (3D-Echotech, Munich, Germany) and time intensity curve parameters [area under the curve (AUC, dB s), peak intensity (PI, dB), time to peak (TTP, s)] in five regions of interest (ROI) [thalamus anterior, thalamus posterior, nucleus lentiformis, white matter, whole hemisphere] were evaluated. Statistical analyses were performed. Perfusion differences between brain tumor and non-tumor hemispheres were detected with contrast burst imaging (CBI) technique with a significantly greater mean AUC (5343.69 dB s vs. 4625.04 dB s, p<0.028) and a significantly prolonged TTP (32.72 s vs. 28.91 s, p<0.046) in the tumor hemisphere. Within our study population, TTP and AUC seem to be the most robust parameters for the evaluation of cerebral perfusion differences assessed by transcranial perfusion sonography with CBI technique. We hypothesize that these results correlate with microvascular changes due to treatment regimens, such as microvessel necrosis after irradiation and chemotherapy. Above that, TPS may be of value for the long-term follow-up of brain tumor therapy concept.

In vivo cleavage rate of a dextran-bound magnetic resonance imaging contrast agent: preparation and intravascular pharmacokinetic characteristics in the rabbit.

PubMed

Hals, Petter Arnt; Sontum, Per Christian; Holtz, Eckart; Klaveness, Jo; Rongved, Pål

2013-02-01

Earlier described dextran-based contrast agents for magnetic resonance imaging (MRI) comprising the gadolinium chelate diethylenetriamine pentaacetic acid (GdDTPA, 1) have shown significantly shorter in vivo contrast duration in rat than what would be expected from the initial average molecular weight (Mw) of the dextran fraction (71.4 kD). To investigate this further, four dextran fractions with given initial average molecular weight (Mw) of 10.4, 41.0, 71.4 and 580 kD were used as starting material to prepare products 2-5 where one of the carboxylic acid functionalities in GdDTPA was used as a direct covalent ester linker to hydroxyl groups in dextrans. A fifth derivative (6) was an amide-ester bound β-alanine-DTPAGd conjugate with dextran having Mw 71.4 kD. The reference compound GdDTPA (1) and gadoliniumlabelled dextran derivatives 2-6 were injected intravenously in rabbits. Pharmacokinetic parameters showed that when GdDTPA is ester-bound directly to dextran hydroxyls, the cleavage rates of 2-5 were only moderately dependent on the molecular weights of the dextrans, having blood pool half-lives comparable to the low-molecular reference compound (t 1/2,β 0.3 - 0.5 hrs.). Presence of a β-alanine spacer in 6 prolonged the plasma half-life t 1/2,β to 6.9 hours, rendering a blood residence time suitable for blood pool slow release of GdDTPA. Biological cleavage regenerates the clinically acceptable carrier dextran and the β-alanine derivative of GdDTPA, pointing at a clinically acceptable product class for blood-pool contrast in MRI.

Contrast agents in dynamic contrast-enhanced magnetic resonance imaging

PubMed Central

Yan, Yuling; Sun, Xilin; Shen, Baozhong

2017-01-01

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive method to assess angiogenesis, which is widely used in clinical applications including diagnosis, monitoring therapy response and prognosis estimation in cancer patients. Contrast agents play a crucial role in DCE-MRI and should be carefully selected in order to improve accuracy in DCE-MRI examination. Over the past decades, there was much progress in the development of optimal contrast agents in DCE-MRI. In this review, we describe the recent research advances in this field and discuss properties of contrast agents, as well as their advantages and disadvantages. Finally, we discuss the research perspectives for improving this promising imaging method. PMID:28415647

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.

Imaging-related medications: a class overview

PubMed Central

2007-01-01

Imaging-related medications (contrast agents) are commonly utilized to improve visualization of radiographic, computed tomography (CT), and magnetic resonance (MR) images. While traditional medications are used specifically for their pharmacological actions, the ideal imaging agent provides enhanced contrast with little biological interaction. The radiopaque agents, barium sulfate and iodinated contrast agents, confer “contrast” to x-ray films by their physical ability to directly absorb x-rays. Gadolinium-based MR agents enhance visualization of tissues when exposed to a magnetic field. Ferrous-ferric oxide–based paramagnetic agents provide negative contrast for MR liver studies. This article provides an overview of clinically relevant information for the imaging-related medications commonly in use. It reviews the safety improvements in new generations of drugs; risk factors and precautions for the reduction of severe adverse reactions (i.e., extravasation, contrast-induced nephropathy, metformin-induced lactic acidosis, and nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis); and the significance of diligent patient screening before contrast exposure and appropriate monitoring after exposure. PMID:17948119

A Pictorial Review of Hepatobiliary Magnetic Resonance Imaging With Hepatocyte-Specific Contrast Agents: Uses, Findings, and Pitfalls of Gadoxetate Disodium and Gadobenate Dimeglumine.

PubMed

Scali, Elena P; Walshe, Triona; Tiwari, Hina Arif; Harris, Alison C; Chang, Silvia D

2017-08-01

Magnetic resonance imaging (MRI) has a well-established role as a highly specific and accurate modality for characterizing benign and malignant focal liver lesions. In particular, contrast-enhanced MRI using hepatocyte-specific contrast agents (HSCAs) improves lesion detection and characterization compared to other imaging modalities and MRI techniques. In this pictorial review, the mechanism of action of gadolinium-based MRI contrast agents, with a focus on HSCAs, is described. The clinical indications, protocols, and emerging uses of the 2 commercially available combined contrast agents available in the United States, gadoxetate disodium and gadobenate dimeglumine, are discussed. The MRI features of these agents are compared with examples of focal hepatic masses, many of which have been obtained within the same patient therefore allowing direct lesion comparison. Finally, the pitfalls in the use of combined contrast agents in liver MRI are highlighted. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging

PubMed Central

Daryaei, Iman; Pagel, Mark D

2016-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a “double-agent” approach to molecular imaging. Exogenous T2-exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T1 and T2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as “secret agents” in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging. PMID:27747191

Intramuscular injection of malignant hyperthermia trigger agents induces hypermetabolism in susceptible and nonsusceptible individuals.

PubMed

Metterlein, Thomas; Schuster, Frank; Kranke, Peter; Roewer, Norbert; Anetseder, Martin

2010-01-01

A new minimally invasive metabolic test for the diagnosis of susceptibility for malignant hyperthermia measuring intramuscular p(CO(2)) and lactate following local application of caffeine and halothane in humans was recently proposed. The present study tested the hypothesis that a more simplified test protocol allows a differentiation between malignant hyperthermia susceptible (MHS) and malignant hyperthermia nonsusceptible (MHN) and control individuals. With approval of the local ethics committee and informed consent, microdialysis and p(CO(2)) probes with attached microtubing were placed into the lateral vastus muscle of six MHS, seven MHN and seven control individuals. Following equilibration, boluses of 500 microl caffeine 80 mmol l(-1) and halothane 10 vol% dissolved in soybean oil were injected locally. p(CO(2)) and lactate were measured spectrophotometrically. The maximal rate of p(CO(2)) increase was significantly higher in MHS than in MHN and control individuals following application of halothane and caffeine, respectively. Intramuscular caffeine injection leads to a significantly higher increase of local lactate levels in MHS than in MHN and control individuals, whereas halothane increased local lactate levels in all investigated groups. Haemodynamic and systemic metabolic parameters did not differ between the investigated groups. Local caffeine and halothane injection increased intramuscular metabolism in MHS individuals significantly more than in the two other groups. In contrast to previous investigations, direct injection of the concentrations of halothane described here increased lactate and p(CO(2)) even in MHN skeletal muscle.

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

THE REMOVAL OF CARTILAGE MATRIX, IN VIVO, BY PAPAIN

PubMed Central

McCluskey, Robert T.; Thomas, Lewis

1958-01-01

The intravenous injection of crystalline papain into young rabbits results in depletion of cartilage matrix throughout the body, with loss of rigidity and collapse of the ears, provided the enzyme is inactivated by oxidation or sulfhydryl blocking agents prior to administration. Cysteine-activated crystalline papain, when injected intravenously, produces little or no change in cartilage. The changes which occur in cartilage following an injection of inactivated crystalline papain are indistinguishable from those produced by crude papain. Activation of crude papain by cysteine prior to injection results in loss of its capacity to produce in vivo changes in cartilage. The progressive changes which take place in cartilage in vivo also occur in vitro in isolated rabbit ears removed shortly after an injection of crude papain or inactivated crystalline papain. In vitro ear collapse occurs rapidly at 37°C. and does not occur at 4°C. Collapse is enhanced by exposing the cartilage to cysteine and prevented by exposure to iodoacetamide or p-chloromercuribenzoate. The direct action of crystalline papain on plates of normal cartilage, in vitro, results in the same gross and histological changes which were observed in vivo. The direct action is accelerated by cysteine and inhibited by iodoacetamide or p-chloromercuribenzoate. The intravenous injection of iodoacetamide-treated bromelin produces the same in vivo changes in cartilage as papain. Untreated bromelin has no demonstrable effect on cartilage. It is suggested that the reason for the failure of activated papain to enter cartilage, after being injected intravenously, is that it probably reacts with a substrate or substrates in the blood. Oxidized or otherwise inactivated papain, in contrast, is readily taken up by cartilage and there converted to its active form. PMID:13575673

Dual Contrast CT Method Enables Diagnostics of Cartilage Injuries and Degeneration Using a Single CT Image.

PubMed

Saukko, Annina E A; Honkanen, Juuso T J; Xu, Wujun; Väänänen, Sami P; Jurvelin, Jukka S; Lehto, Vesa-Pekka; Töyräs, Juha

2017-12-01

Cartilage injuries may be detected using contrast-enhanced computed tomography (CECT) by observing variations in distribution of anionic contrast agent within cartilage. Currently, clinical CECT enables detection of injuries and related post-traumatic degeneration based on two subsequent CT scans. The first scan allows segmentation of articular surfaces and lesions while the latter scan allows evaluation of tissue properties. Segmentation of articular surfaces from the latter scan is difficult since the contrast agent diffusion diminishes the image contrast at surfaces. We hypothesize that this can be overcome by mixing anionic contrast agent (ioxaglate) with bismuth oxide nanoparticles (BINPs) too large to diffuse into cartilage, inducing a high contrast at the surfaces. Here, a dual contrast method employing this mixture is evaluated by determining the depth-wise X-ray attenuation profiles in intact, enzymatically degraded, and mechanically injured osteochondral samples (n = 3 × 10) using a microCT immediately and at 45 min after immersion in contrast agent. BiNPs were unable to diffuse into cartilage, producing high contrast at articular surfaces. Ioxaglate enabled the detection of enzymatic and mechanical degeneration. In conclusion, the dual contrast method allowed detection of injuries and degeneration simultaneously with accurate cartilage segmentation using a single scan conducted at 45 min after contrast agent administration.

[Injection Pressure Evaluation of the New Venous Catheter with Side Holes for Contrast-enhanced CT/MRI].

PubMed

Fukuda, Junya; Arai, Keisuke; Miyazawa, Hitomi; Kobayashi, Kyouko; Nakamura, Junpei; Suto, Takayuki; Tsushima, Yoshito

2018-01-01

The simulation study was conducted for the new venous catheter with side holes of contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) to evaluate the infusion pressure on four contrast media and several injection speeds. All infusion pressure of the new venous catheter with side holes were less than 15 kg/cm 2 as limitation of extension tube and also reduced the infusion pressure by 15% at the maximum compared to the catheter with single hole. The results suggest that the new venous catheter with side holes can reduce the infusion pressure by power injection of contrast-enhanced CT and MRI.

Multimodal imaging approach to examine biodistribution kinetics of Cabotegravir (GSK1265744) long acting parenteral formulation in rat.

PubMed

Jucker, Beat M; Alsaid, Hasan; Rambo, Mary; Lenhard, Stephen C; Hoang, Bao; Xie, Fang; Groseclose, M Reid; Castellino, Stephen; Damian, Valeriu; Bowers, Gary; Gupta, Manish

2017-12-28

Long-Acting Parenterals (LAPs) have been used in the clinic to provide sustained therapeutic drug levels at a target site, and thereby reducing the frequency of dosing required. In an effort to understand the factors associated with long-acting cabotegravir (GSK1265744 LAP) pharmacokinetic variability, the current study was designed to investigate the temporal relationship between intramuscular (IM) or subcutaneous (SC) drug depot morphology and distribution kinetics with plasma pharmacokinetics. Therefore, a multi-modal molecular imaging (MRI & MALDI IMS) approach was employed to examine the temporal GSK1265744 LAP biodistribution in rat following either IM or SC administration. Serial MRI was performed immediately post drug administration, and then at day 1 (24h post), 2, 3, 4, 7, and 14. In a separate cohort of rats, an MRI contrast agent, Feraheme® (USPIO), was administered 2days post IM drug injection in order to investigate the potential involvement of macrophages trafficking to the GSK1265744 LAP and Vehicle depot sites. The GSK1265744 LAP depot volume increased rapidly by day 2 in the IM injected rats (~3-7 fold) compared with a ~1 fold increase in the SC injected rats. In addition, the USPIO contrast agent labeled macrophages were shown to be present in the depot region of the GSK1265744 LAP injected gastrocnemius while the Vehicle injected gastrocnemius appeared to show reduced uptake. Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) of muscle and abdominal tissue sections identified the drug content primarily within the depot. Co-registration of the GSK1265744 ion images with immunohistochemical images established that the drug was taken up by macrophages associated with the depot. Linear regression analysis demonstrated that the drug depot characteristics including volume, surface area, and perimeter assessed by MRI at day 2 correlated with early time point plasma drug concentrations. In summary, a multimodal molecular imaging approach was used to identify the drug depot location and volumetric/physiologic changes in both IM and SC locations following GSK1265744 LAP administration. The IM depot volume increased rapidly to a maximum volume at 2days post-GSK1265744 LAP administration, while the Vehicle depot did not suggesting that the active drug substance and/or related particle was a key driver for drug depot evolution. The depot expansion was associated with an increase in macrophage infiltration and edema in and around the depot region and was correlated to plasma drug concentration at early time points (0-4days). Consequently, molecular imaging approaches may be used in patients to help understand the biodistribution of GSK1265744 LAP and its associated pharmacokinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances in cardiac CT contrast injection and acquisition protocols.

PubMed

Scholtz, Jan-Erik; Ghoshhajra, Brian

2017-10-01

Cardiac computed tomography (CT) imaging has become an important part of modern cardiovascular care. Coronary CT angiography (CTA) is the first choice imaging modality for non-invasive visualization of coronary artery stenosis. In addition, cardiac CT does not only provide anatomical evaluation, but also functional and valvular assessment, and myocardial perfusion evaluation. In this article we outline the factors which influence contrast enhancement, give an overview of current contrast injection and acquisition protocols, with focus on current emerging topics such as pre-transcatheter aortic valve replacement (TAVR) planning, cardiac CT for congenital heart disease (CHD) patients, and myocardial CT perfusion (CTP). Further, we point out areas where we see potential for future improvements in cardiac CT imaging based on a closer interaction between CT scanner settings and contrast injection protocols to tailor injections to patient- and exam-specific factors.

Advances in cardiac CT contrast injection and acquisition protocols

PubMed Central

Scholtz, Jan-Erik

2017-01-01

Cardiac computed tomography (CT) imaging has become an important part of modern cardiovascular care. Coronary CT angiography (CTA) is the first choice imaging modality for non-invasive visualization of coronary artery stenosis. In addition, cardiac CT does not only provide anatomical evaluation, but also functional and valvular assessment, and myocardial perfusion evaluation. In this article we outline the factors which influence contrast enhancement, give an overview of current contrast injection and acquisition protocols, with focus on current emerging topics such as pre-transcatheter aortic valve replacement (TAVR) planning, cardiac CT for congenital heart disease (CHD) patients, and myocardial CT perfusion (CTP). Further, we point out areas where we see potential for future improvements in cardiac CT imaging based on a closer interaction between CT scanner settings and contrast injection protocols to tailor injections to patient- and exam-specific factors. PMID:29255688

SU-E-QI-06: Design and Initial Validation of a Precise Capillary Phantom to Test Perfusion Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, R; Iacobucci, G; Khobragade, P

2014-06-15

Purpose: To design a precise perfusion phantom mimicking capillaries of the brain vasculature which could be used to test various perfusion protocols and algorithms which generate perfusion maps. Methods: A perfusion phantom was designed in Solidworks and built using additive manufacturing. The phantom was an overall cylindrical shape of diameter and height 20mm and containing capillaries of 200μm or 300μm which were parallel and in contact making up the inside volume where flow was allowed. We created a flow loop using a peristaltic pump and contrast agent was injected manually. Digital Subtraction Angiographic images and low contrast images with conemore » beam CT were acquired after the contrast was injected. These images were analyzed by our own code in LabVIEW software and Time-Density Curve, MTT and TTP was calculated. Results: Perfused area was visible in the cone beam CT images; however, individual capillaries were not distinguishable. The Time-Density Curve acquired was accurate, sensitive and repeatable. The parameters MTT, and TTP offered by the phantom were very sensitive to slight changes in the TDC shape. Conclusion: We have created a robust calibrating model for evaluation of existing perfusion data analysis systems. This approach is extremely sensitive to changes in the flow due to the high temporal resolution and could be used as a golden standard to assist developers in calibrating and testing of imaging perfusion systems and software algorithms. Supported by NIH Grant: 2R01EB002873 and an equipment grant from Toshiba Medical Systems Corporation.« less

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer

PubMed Central

Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S.; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J.; Liu, Xuewu; Decuzzi, Paolo

2015-01-01

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1,000 × 400 nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities – small pore (SP: ~ 5 nm) and huge pore (HP: ~ 40 nm) – and of bulk, non-porous silica beads (1,000 nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ~ 17 (mM·s)−1, which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases. PMID:24931336

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer.

PubMed

Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J; Liu, Xuewu; Decuzzi, Paolo

2014-09-28

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1000×400nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities - small pore (SP: ∼5nm) and huge pore (HP: ∼40nm) - and of bulk, non-porous silica beads (1000nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ∼17 (mMs)(-)(1), which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review.

PubMed

Lenz, David E; Yeung, David; Smith, J Richard; Sweeney, Richard E; Lumley, Lucille A; Cerasoli, Douglas M

2007-04-20

Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE; PharmAthene Inc.) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable with a half-life (t(1/2)) and pharmacokinetic profile that resembled that of plasma-derived huBuChE. Guinea pigs were injected with 140mg/kg (i.m.) of pegylated r-HuBuChE 18h prior to exposure (sc) to 5.5xLD(50) VX or soman. VX and soman were administered in a series of three injections of 1.5xLD(50), 2.0xLD(50), and 2.0xLD(50), respectively, with injections separated by 2h. Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent toxicity following exposure. Assessments of motor activity, coordination, and acquisition of spatial memory were performed for 2 weeks following nerve agent exposure. There were no measurable decreases in motor or cognitive function during this period. In contrast, animals receiving 1.5xLD(50) challenges of soman or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50 and 100% survival, respectively, but exhibited marked decrements in motor function and, in the case of GD, impaired spatial memory acquisition. The advances in this field have resulted in the decision to select both the plasma-derived and the recombinant form of BuChE for advanced development and transition to clinical trials. Efforts have now been expanded to identify a catalytic protein capable of not only binding, but also rapidly hydrolyzing the standard threat nerve agents. Recent work has focused on paraoxonase-1 (PON1), a naturally occurring human serum enzyme with the capacity to catalyze the hydrolysis of nerve agents, albeit too slowly to afford dramatic protection. Using rational design, several amino acids involved in substrate binding have been identified and site-directed mutations have revealed that residue H115 plays an important role in binding. In addition, the stereospecificity of PON1 for the catalytic hydrolysis of soman has been examined. The enzyme exhibits a slight stereospecificity for the C+P+ isomer of soman, which is due more to preferential binding than to selective hydrolysis of this isomer. The results suggest that it may be possible to engineer a mutant form of PON1 with enhanced activity and stereospecificity for the most toxic nerve agent isoforms.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogunlade, Olumide, E-mail: o.ogunlade@ucl.ac.uk; 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 substancemore » 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. Conclusions: It is concluded that gadolinium based contrast agents, iron oxide particles, and single walled carbon nanotubes have little intrinsic merit as thermoacoustic contrast agents. Simple electrolytes such as saline which yield high contrast based on ionic conductivity provide much higher dielectric contrast per unit solute concentration and are likely to be significantly more effective as contrast agents.« less

Evaluation of carrier agents for hyperpolarized xenon MRI

NASA Technical Reports Server (NTRS)

Venkatesh, A. K.; Zhao, L.; Balamore, D.; Jolesz, F. A.; Albert, M. S.

2000-01-01

Several biocompatible carrier agents, in which xenon is highly soluble and has a long T(1), were tested, and injected in living rats. These included saline, Intralipid suspension, perfluorocarbon emulsion and (129)Xe gas-filled liposomes. The T(1) of (129)Xe in these compounds ranged from 47 to 116 s. Vascular injection of these carrier agents was tolerated well, encouraging their use for further experiments in live animals. In vivo spectra, obtained from gas-filled liposomes and perfluorocarbon solutions, suggest that these carrier agents have potential for use in angiography and perfusion imaging. Copyright 2000 John Wiley & Sons, Ltd.

Endocytosis and exocytosis of nanoparticles in mammalian cells

PubMed Central

Oh, Nuri; Park, Ji-Ho

2014-01-01

Engineered nanoparticles that can be injected into the human body hold tremendous potential to detect and treat complex diseases. Understanding of the endocytosis and exocytosis mechanisms of nanoparticles is essential for safe and efficient therapeutic application. In particular, exocytosis is of significance in the removal of nanoparticles with drugs and contrast agents from the body, while endocytosis is of great importance for the targeting of nanoparticles in disease sites. Here, we review the recent research on the endocytosis and exocytosis of functionalized nanoparticles based on various sizes, shapes, and surface chemistries. We believe that this review contributes to the design of safe nanoparticles that can efficiently enter and leave human cells and tissues. PMID:24872703

Solute Transport of Negatively Charged Contrast Agents Across Articular Surface of Injured Cartilage.

PubMed

Kokkonen, H T; Chin, H C; Töyräs, J; Jurvelin, J S; Quinn, T M

2017-04-01

Solute transport through the extracellular matrix (ECM) is crucial to chondrocyte metabolism. Cartilage injury affects solute transport in cartilage due to alterations in ECM structure and solute-matrix interactions. Therefore, cartilage injury may be detected by using contrast agent-based clinical imaging. In the present study, effects of mechanical injury on transport of negatively charged contrast agents in cartilage were characterized. Using cartilage plugs injured by mechanical compression protocol, effective partition coefficients and diffusion fluxes of iodine- and gadolinium-based contrast agents were measured using high resolution microCT imaging. For all contrast agents studied, effective diffusion fluxes increased significantly, particularly at early times during the diffusion process (38 and 33% increase after 4 min, P < 0.05 for iodine and Gd-DTPA; and 76% increase after 10 min for diatrizoate, P < 0.05). Effective partition coefficients were unaffected in mechanically injured cartilage. Mechanical injury reduced PG content and collagen integrity in cartilage superficial zone. This study suggests that alterations in contrast agent diffusion flux, a non-equilibrium transport parameter, provides a more sensitive indicator for assessment of cartilage matrix integrity than partition coefficient and the equilibrium distribution of solute. These findings may help in developing clinical methods of contrast agent-based imaging to detect cartilage injury.

Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

PubMed

Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

2016-12-01

While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively). In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination. © 2016 by American Journal of Neuroradiology.

Molecular Contrast Optical Coherence Tomography: A Review¶

PubMed Central

Yang, Changhuei

2005-01-01

This article reviews the current state of research on the use of molecular contrast agents in optical coherence tomography (OCT) imaging techniques. After a brief discussion of the basic principle of OCT and the importance of incorporating molecular contrast agent usage into this imaging modality, we shall present an overview of the different molecular contrast OCT (MCOCT) methods that have been developed thus far. We will then discuss several important practical issues that define the possible range of contrast agent choice, the design criteria for engineered molecular contrast agent and the implementability of a given MCOCT method for clinical or biological applications. We will conclude by outlining a few areas of pursuit that deserve a greater degree of research and development. PMID:15588122

Novel strategy for prevention of esophageal stricture after endoscopic surgery.

PubMed

Mizutani, Taro; Tadauchi, Akimitsu; Arinobe, Manabu; Narita, Yuji; Kato, Ryuji; Niwa, Yasumasa; Ohmiya, Naoki; Itoh, Akihiro; Hirooka, Yoshiki; Honda, Hiroyuki; Ueda, Minoru; Goto, Hidemi

2010-01-01

Recently, novel endoscopic surgery, including endoscopic submucosal dissection (ESD), was developed to resect a large superficial gastrointestinal cancer. However, circumferential endoscopic surgery in the esophagus can lead to esophageal stricture that affects the patient's quality of life. This major complication is caused by scar formation, and develops during the two weeks after endoscopic surgery. We hypothesized that local administration of a controlled release anti-scarring agent can prevent esophageal stricture after endoscopic surgery. The aims of this study were to develop an endoscopically injectable anti-scarring drug delivery system, and to verify the efficacy of our strategy to prevent esophageal stricture. We focused on 5-Fluorouracil (5-FU) as an anti-scarring agent, which has already been shown to be effective not only for treatment of cancers, but also for treatment of hypertrophic skin scars. 5-FU was encapsulated by liposome, and then mixed with injectable 2% atelocollagen (5FLC: 5FU-liposome-collagen) to achieve sustained release. An in vitro 5-FU releasing test from 5FLC was performed using high-performance liquid chromatography (HPLC). Inhibition of cell proliferation was investigated using normal human dermal fibroblast cells (NHDF) with 5FLC. In addition, a canine esophageal mucosal resection was carried out, and 5FLC was endoscopically injected into the ulcer immediately after the operation, and compared with a similar specimen injected with saline as a control. 5-FU was gradually released from 5FLC for more than 2 weeks in vitro. The solution of 5-FU released from 5FLC inhibited NHDF proliferation more effectively than 5-FU alone. In the canine model, no findings of stricture were observed in the 5FLC-treated dog at 4 weeks after the operation and no vomiting occurred. In contrast, marked esophageal strictures were observed with repeated vomiting in the control group. Submucosal fibrosis was markedly reduced histologically in the 5FLC-treated dog compared with the control. 5FLC showed sustained release of 5-FU and decreased cell proliferation in vitro. The clinically relevant canine model demonstrated that local endoscopic injection of 5FLC can prevent post-operative esophageal stricture. These results suggest that our strategy may be useful for preventing post-operative esophageal stricture.

Pig lumbar spine anatomy and imaging-guided lateral lumbar puncture: a new large animal model for intrathecal drug delivery.

PubMed

Pleticha, Josef; Maus, Timothy P; Jeng-Singh, Christian; Marsh, Michael P; Al-Saiegh, Fadi; Christner, Jodie A; Lee, Kendall H; Beutler, Andreas S

2013-05-30

Intrathecal (IT) administration is an important route of drug delivery, and its modelling in a large animal species is of critical value. Although domestic swine is the preferred species for preclinical pharmacology, no minimally invasive method has been established to deliver agents into the IT space. While a "blind" lumbar puncture (LP) can sample cerebrospinal fluid (CSF), it is unreliable for drug delivery in pigs. Using computed tomography (CT), we determined the underlying anatomical reasons for this irregularity. The pig spinal cord was visualised terminating at the S2-S3 level. The lumbar region contained only small amounts of CSF found in the lateral recess. Additional anatomical constraints included ossification of the midline ligaments, overlapping lamina with small interlaminar spaces, and a large bulk of epidural adipose tissue. Accommodating the the pig CT anatomy, we developed a lateral LP (LLP) injection technique that employs advanced planning of the needle path and monitoring of the IT injection progress. The key features of the LLP procedure involved choosing a vertebral level without overlapping lamina or spinal ligament ossification, a needle trajectory crossing the midline, and entering the IT space in its lateral recess. Effective IT delivery was validated by the injection of contrast media to obtain a CT myelogram. LLP represents a safe and reliable method to deliver agents to the lumbar pig IT space, which can be implemented in a straightforward way by any laboratory with access to CT equipment. Therefore, LLP is an attractive large animal model for preclinical studies of IT therapies. Copyright © 2013 Elsevier B.V. All rights reserved.

POOLED ESTIMATES OF INCIDENCE OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS WITH AND WITHOUT TOPICAL ANTIBIOTIC PROPHYLAXIS.

PubMed

Reibaldi, Michele; Pulvirenti, Alfredo; Avitabile, Teresio; Bonfiglio, Vincenza; Russo, Andrea; Mariotti, Cesare; Bucolo, Claudio; Mastropasqua, Rodolfo; Parisi, Guglielmo; Longo, Antonio

2018-01-01

To assess the effect of topical antibiotic prophylaxis on postoperative endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. A systematic literature search was performed from inception to March 2016 using PubMed, Medline, Web of Science, Embase, and the Cochrane Library, to identify articles that reported cases of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. We used a pooled analysis to estimate the incidence of cases of endophthalmitis who developed after injections performed with and without topical antibiotic prophylaxis. We used regression analysis to explore the effects of study characteristics on heterogeneity. From our search of electronic databases, we identified and screened 4,561 unique records. We judged 60 articles to have reported findings for cohorts of patients who met our inclusion criteria, (12 arms of randomized clinical trials, 11 prospective cohort studies, and 37 retrospective cohort studies), which included 244 cases of endophthalmitis and 639,391 intravitreal injections of anti-vascular endothelial growth factor agents. The final pooled estimate endophthalmitis proportions were 9/10,000 (95% confidence interval, 7/10,000-12/10,000) in the antibiotic-treated group and 3/10,000 (95% confidence interval, 2/10,000-5/10,000) in the untreated group. The estimated incidence of endophthalmitis with topical antibiotic prophylaxis was approximated three times the incidence without prophylaxis. Random effects regression showed that none of the study characteristics significantly affected the effect size in either group. Topical antibiotic after intravitreal injection of anti-vascular endothelial growth factor agents is associated with a higher risk of endophthalmitis.

Ballooning of the papilla during contrast injection: the semaphore of a choledochocele.

PubMed

Kim, M H; Myung, S J; Lee, S K; Yoo, B M; Seo, D W; Lee, M H; Jung, S A; Kim, Y S; Min, Y I

1998-09-01

Choledochocele is a rare abnormality involving the intramural segment of the common bile duct. ERCP is essential to demonstrate a choledochocele. The aim of this study was to investigate the duodenoscopic and cholangiographic findings during ERCP. Over a 4-year period, 17 symptomatic patients (8 men, 9 women; age range 45 to 83 years) were identified as having choledochoceles. The diagnosis of choledochocele was made by both duodenoscopic and cholangiographic findings. As a characteristic duodenoscopic finding, the enlarged bulging papilla was noted in 8 patients (47%), whereas a normal-appearing papilla was noted in 9 patients (53%) before the injection of contrast media. However, in all 17 patients progressive enlargement or ballooning of the papilla was noted during contrast injection. The maximum diameter of the choledochocele, determined by cholangiography, was significantly larger (19 +/-4 mm) in patients with initially bulging papilla than in those with normal-appearing papilla (9+/-3 mm) (p < 0.05). Ballooning of the papilla during contrast injection may be a specific duodenoscopic finding for choledochocele. To avoid missing the diagnosis of a choledochocele, especially when it is small, it is important to watch the papilla carefully during contrast injection.