Development Of Contrast Media Research Articles

Current concepts in nanostructured contrast media development for in vivo photoacoustic imaging.

Photoacoustic (PA) imaging is indeed one of the most promising bioimaging techniques for theranostics applications in humans, allowing for the visualization of blood vessels and melanomas with high spatial resolution. However, in order to overcome the endogenous contrast arising from interfering endogenous species such as haemoglobin and melanin, specific contrast agents need to be developed, allowing PAI to successfully identify targeted contrast in the range of wavelengths in which interference from the biomatrix is minimized. This has been first performed by small molecule dyes, which, however, suffer from some important limitations such as low hydrophilicity and short circulation times. For this reason, scientific research has recently directed its efforts towards the development of nanostructured contrast agents capable of providing efficient PA contrast at low concentrations with low toxicity and high biocompatibility. The principal nanostructures are based on (1) metal and semiconducting nanoparticles, amongst which variously shaped nano-gold plays the main role, (2) carbon nanomaterials, such as carbon nanotubes and graphene, and (3) conjugated polymer nanoparticles. In this review, the principal characteristics of this class of materials are reported and greater focus is directed towards in vivo studies. A detailed analysis is performed on various physical-chemical parameters that define the PA response of reported contrast agents, like absorption coefficients and photoacoustic efficiencies. By comparing the experimental data, this review provides a comprehensive tool for the evaluation of new nanostructured contrast agents for PA imaging.

25 Years of Contrast-Enhanced MRI: Developments, Current Challenges and Future Perspectives.

In 1988, the first contrast agent specifically designed for magnetic resonance imaging (MRI), gadopentetate dimeglumine (Magnevist®), became available for clinical use. Since then, a plethora of studies have investigated the potential of MRI contrast agents for diagnostic imaging across the body, including the central nervous system, heart and circulation, breast, lungs, the gastrointestinal, genitourinary, musculoskeletal and lymphatic systems, and even the skin. Today, after 25 years of contrast-enhanced (CE-) MRI in clinical practice, the utility of this diagnostic imaging modality has expanded beyond initial expectations to become an essential tool for disease diagnosis and management worldwide. CE-MRI continues to evolve, with new techniques, advanced technologies, and novel contrast agents bringing exciting opportunities for more sensitive, targeted imaging and improved patient management, along with associated clinical challenges. This review aims to provide an overview on the history of MRI and contrast media development, to highlight certain key advances in the clinical development of CE-MRI, to outline current technical trends and clinical challenges, and to suggest some important future perspectives.FundingBayer HealthCare.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0275-4) contains supplementary material, which is available to authorized users.

Contrast Media for X-ray and Magnetic Resonance Imaging: Development, Current Status and Future Perspectives.

Over the last 120 years, the extensive advances in medical imaging allowed enhanced diagnosis and therapy of many diseases and thereby improved the quality of life of many patient generations. From the beginning, all technical solutions and imaging procedures were combined with dedicated pharmaceutical developments of contrast media, to further enhance the visualization of morphology and physiology. This symbiosis of imaging hardware and contrast media development was of high importance for the development of modern clinical radiology. Today, all available clinically approved contrast media fulfill the highest requirements for clinical safety and efficacy. All new concepts to increase the efficacy of contrast media have also to consider the high clinical safety standards and cost of goods of current marketed contrast media. Nevertheless, diagnostic imaging will contribute significantly to the progresses in medicine, and new contrast media developments are mandatory to address the medical needs of the future.

Imaging the renal mass: a historical review.

A matter of months after Roentgen's landmark discovery in 1895, Roentgen's rays were focused on diseases and disorders of the urinary tract, specifically the kidney. At the dawn of the 20th century, urologists in the United States and around the world quickly recognized that by using a variety of metal stylets and radiopaque contrast agents, such as silver salts, the upper urinary tract, namely the ureter, pelvis, and calyces, could be depicted with radiography. Renal cysts and tumors were diagnosed on the basis of deformities in the kidney. Retrograde pyelography dominated the imaging evaluation of the kidney until the discovery of a safe intravenous method for urinary tract imaging (ie, intravenous pyelography). Pioneers and pathfinders in the field of contrast media development and radiologic procedures helped give radiologists the lead role in the work-up of renal masses, an area where urologists once held forth. The subspecialty of uroradiology was born in the middle of the 20th century. Intravenous urography, nephrotomography, and diagnostic angiography with pharmacologic manipulation followed by cyst or mass puncture and biopsy yielded unrivaled specificity for the diagnosis and staging of benign and malignant renal masses. The advent of cross-sectional and multiplanar imaging and the profound effects they had and continue to have on the discovery and characterization of renal masses has been detailed in the pages of Radiology since the 1920s. Ultrasonography, nuclear imaging, computed tomographic scanning, magnetic resonance imaging, and positron emission tomography each have made a claim to a part of the imaging algorithm of modern uroradiologic practice.

Advances in contrast media for vascular imaging of atherosclerosis

Atherosclerosis is a major cause of morbidity and mortality worldwide. Imaging plays a key role in its diagnosis and management, and contrast-enhanced imaging is widely integrated into current clinical practice for the imaging of atherosclerosis. Traditional imaging methods have focused on the degree of stenosis owing to atherosclerotic plaque; however, contrast media now allow for improved detection of plaque characteristics, which may aid in identifying at-risk lesions in cardiovascular and cerebrovascular disease. Developments in contrast media may allow imaging to play a much earlier role in diagnosis and, potentially, therapy for atherosclerosis in the future. This article focuses on the developments in contrast media for MRI, ultrasound and CT in relation to atherosclerosis.

Evolution of urological imaging

The evolution of urological imaging has had a major impact on the diagnosis and treatment of urological diseases since the discovery of the X-ray by Roentgen in 1895. Early developments included plain films of the abdomen, retrograde urographic techniques, development of contrast media, excretory urography, renal mass puncture, renal angiography, cystography and nuclear medicine procedures. These procedures led to the maturation of the specialties of diagnostic radiology and urology, and the development of the subspecialties of pediatric urology and urological radiology during the first seven decades of the 20th century. Subsequently, many imaging advances have occurred leading to changes in diagnosis and management of urological patients. Ultrasound and cross-sectional imaging technologies (computed tomography and magnetic resonance imaging) are increasingly applied in urological evaluation, treatment and surveillance. Current developments include dual energy computed tomography, positron emission tomography computed tomography, renal donor and renal transplant imaging, prostate magnetic resonance imaging, and microbubble contrast enhanced ultrasound. Imaging advances will continue. It is the responsibility of all physicians to assess the advantages of new developments while weighing those advantages against the additional radiation exposure and the costs associated with new procedures.

Contrast media: future aspects

In spite of the dramatic development in CT, there was no major breakthrough in the iodinated contrast media development. New agents based on hybrid between MRI and CT compounds may be a new innovative alternative. This new approach may also open new indications such as radiotherapy.

Contrast Media Research

This selective review highlights research in contrast media development and application in the field of diagnostic radiology in 1998 and 1999. The focus is on research published in Investigative Radiology, supplemented with work from other publications in the few areas not extensively covered by the journal. Studies continue to be performed, although at a low level, examining safety issues. Most preclinical investigations have focused on MR and ultrasound agents. In MR, the research effort is concentrated on the development of targeted agents; in ultrasound, work is focused on the characterization of basic contrast mechanisms. The demonstration of clinical applications is still dominated by work with MR, both in disease models and human investigations. The use of extracellular gadolinium chelates to enhance visualization of blood vessels (the field of contrast-enhanced MR angiography) is the largest single new clinical application of contrast media to emerge in several years. New clinical applications continue to be pursued with contrast media in CT, ultrasound, and x-ray angiography. As intravenously injected ultrasound contrast agents come to market, trials demonstrating clinical applications and subsequent scientific publications will increase in number.

Contrast-enhanced MRI for quantification of myocardial viability.

During the past 10 years substantial advances have taken place in magnetic resonance imaging (MRI) capabilities and in contrast media development. Furthermore, knowledge of in vivo contrast media interactions with surrounding water and distribution into tissue has increased, permitting regional quantification of concentration-time profiles in the myocardium. The combination of these advances has substantially improved the capability of contrast-enhanced MRI characterization of myocardial ischemic injury, including its ability to discriminate viable from nonviable zones. Discrimination of viable from nonviable myocardial subregions is important for patient management and for research applications. This review addresses recent progress toward the goal of defining viable and nonviable myocardium based on MRI detection of contrast media effects. J. Magn. Reson. Imaging 1999;10:694-702.

Aplicaciones del contraste en la ecocardiografía

The development of contrast media in ultrasound has been slow and sporadic, and there are no fully satisfactory agents for clinical imaging to date. Most contrast agents consist of air filled microbubbles which generate scattered echoes and enhance the ultrasound information. In this article we review the different phases of contrast echocardiography their potentials and clinical applications. First, right-sided echocontrast which is mainly used for the assessment of intracardiac shunts. Second, left-sided contrast agents with smaller and more stable microbubbles, that allow the visualization of the left ventricle after intravenous injection. With these agents, one it is now possible to study myocardial perfusion which is one of the most attractive potentials of these types of agents.

Assessment of myocardial perfusion using contrast-enhanced MR imaging: Current status and future developments

Excellent inherent tissue contrast is one of the great promises of clinical magnetic resonance (MR) imaging, but functional information is relatively limited. However, MR imaging complemented by the administration of contrast agents can provide such functional assessment. The perfusion status of the myocardium is one of the most important functional information in cardiovascular imaging. Because the clinical acceptance of a contrast agent is measured by its ability to improve patient outcome and to guide therapy, it is unlikely that detection of myocardial infarction, the final stage of ischemic heart disease, should be the target for contrast media development. It would obviously be better if occult regional myocardial perfusion deficits could be reliably detected. The current article was prepared to help the clinical radiologist to keep pace with new strategies for myocardial enhancement and their potential clinical applicability for detection of early perfusion deficits. Several techniques for noninvasive measurement of myocardial perfusion are currently evolving which have the potential to be introduced into routine MR imaging. Most investigators favor a first-pass analysis of the contrast agent bolus through the myocardium using ultrafast sequences. However, such a technique may require clinical introduction of a blood pool agent. There are good reasons to favor T1-weighted sequences over susceptibility imaging in such first-pass studies. In the future, assessment of myocardial perfusion status using contrast-enhanced MR imaging may be done producing perfusion maps with high spatial resolution (e.g., 256 x 128), with sequences available on most scanners without special hardware requirements (e.g., IR-Turboflash, keyhole imaging), and requiring only a short period of time for examination (approximately 3 min).

New developments in MRI contrast enhancement

Ongoing developments in contrast media for magnetic resonance imaging (MRI) should lead to an improvement in sensitivity for the detection of disease, better definition of normal and pathologic anatomy, added functional information, and an expansion of diagnostic MRI applications. Currently available for clinical use are four low-molecular-weight gadolinium complexes which distribute in the extracellular fluid space and highlight defects in the blood-brain barrier. An estimated 20–45% of patients undergoing MRI examination receive one of these governmental-approved gadolinium complexes. In addition, contrast agents differing in purpose and primary magnetic effect, both paramagnetic proton relaxation and magnetic susceptibility agents, are being developed. These include agents for enhancing the blood pool, myocardium, liver, lymph nodes, tumors, and gastrointestinal lumen. Criteria for suitability of new contrast agents include diagnostic efficacy, safety, stability, pharmacology, and cost.

New directions in the development of MR imaging contrast media.

Ongoing developments in contrast media for magnetic resonance (MR) imaging should lead to an improvement in sensitivity for the detection of disease, better definition of normal and pathologic anatomy, added functional information, and an expansion of diagnostic MR imaging applications. Currently, only gadopentetate dimeglumine, a contrast enhancer of the extracellular fluid space that is able to show defects in the blood-brain barrier, is governmentally approved for routine clinical use in North America. An estimated 25%-35% of patients undergoing MR imaging receive this drug. Multiple, potentially competitive formulations have been tested and may soon be approved. In addition, contrast agents differing in purpose and primary magnetic effect, both paramagnetic proton relaxation and magnetic susceptibility agents, are being developed. These include agents for enhancing the blood pool, myocardium, liver, lymph nodes, tumors, and gastrointestinal lumen. Criteria for suitability of new contrast agents include diagnostic efficacy, safety, stability, pharmacology, and cost.

Development of contrast media for magnetic resonance imaging.

Development of contrast media for magnetic resonance imaging.

The importance of nuclear magnetic relaxation dispersion (NMRD) profiles in MRI contrast media development.

Observation of the relaxivity of MRI contrast media over a wide range of magnetic fields is not only necessary for predicting their efficiency at any field but also compulsory for understanding and improving their mechanisms of action. The best experimental approach to this problem is the field cycling method, which allows the exploration of nuclear relaxation over a broad interval of magnetic field intensity but requires a specially dedicated instrument called a relaxometer. Particularly relevant are the relaxivity profiles of the two chelates Gd-DOTA and Gd-DTPA. Both show an important decrease from low to high fields within the current imaging range (0.02 T to 1.5 T). Although high field relaxivities of these chelates are similar, Gd-DTPA becomes less efficient in facilitating water protons relaxation at fields lower than 0.15 T. This behavior has to be related to different electronic relaxation times due to a different chelate symmetry.

Characteristics of Magnetic Resonance(M.R.) and Comprehension of its Imaging Mechanism

Magnetic Resonance (M.R.) is rapidly emerging technique that provides high quality images and potentially provides much more diagnostic information than do conventional imaging modalities. M.R.I. is conceptually quite different from currently used imaging methods. The complex nature of M.R.I. allows a great deal of flexibility in image product ion and available information, and key points are as follows. 1. M.R.I. offers a non-invasive technique with which to gene rate in vivo human images without ionizing radiation and with no known adverse biological effects. 2. Imaging mechanism of M.R.I. is quite different from conventional imaging modality and for more accurate diagnostic application, It is necessary for physician to understand imaging mechanism of M.R.I. 3. M.R. makes available basic chemical parameters that may provide to be useful for diagnostic medical imaging and more specific pathophysiologic information which are not available by alternate techniques. 4. M.R. can be produced by number of different methods. This flexibility allows the imaging technique to be applicated for particular clinical purpose. Multiplanar and three dimensional imaging may extend the imaging process beyond the single section available with current CT. 5. Future directions include efforts to; a. Further development of hard ware b. More fasternning scan time c. Respiratory and cardiac gated imaging d. Imaging of additional nuclei except hydrogen e. Further development of contrast media f. M.R. in vivo spectroscopy g. Real time M.R. imaging.

An evaluation of orabilex (bunamiodyl), a new medium for cholecystography.

The remarkable progress which has been made in the development of contrast media for oral cholecystography has led from time to time to the belief that the ideal medium has been found (1). More complete reports, however, have revealed certain disadvantages and limitations in all oral media currently employed. Of particular significance in this respect is occasional unexplained nonvisualization with a single dose of contrast material, necessitating a repeat examination with increased dosage. Other factors to be taken into consideration are the obscuring of disease by intestinal residue and the occurrence of gastrointestinal and urologic side-effects. The contrast medium of choice should provide maximum safety and patient-tolerance with a minimum of side-effects, effective and dependable visualization of the gallbladder, and freedom from secondary shadows due to retention in the intestinal tract. In studies in France, where it was first introduced, Orabilex (Bunamiodyl), a triiodinated compound—3(3-butyrylamino-2,4 6-triiodophenyl)-2 ethyl sodium acrylate—containing 57 per cent iodine by weight appeared to meet these criteria (2). The iodine content of iopanoic acid, or Telepague, is 66.7 per cent by weight. Absorption: Orabilex is absorbed readily from the small intestine, selectively excreted in the bile, and concentrated in the gallbladder. Optimal density of opacification of the gallbaldder is obtained in thirteen to sixteen hours. The butyrylation of the amine group is considered to permit adequate dosage essential for best results, with the incidence of side-effects considerably less than has been reported with other triiodinated compounds. Excretion: Orabilex is excreted largely through the kidney, without the attendant dysuria observed with similarly excreted agents. As a consequence, there is a much lower incidence of intestinal residue and the cholecystogram is unobscured. Toxicity: In acute intravenous toxicity studies in mice, the LD 50 value for Orabilex was found to be 570 mg. per kilogram as compared to 360 mg. per kilogram for iopanoic acid and 400 mg. per kilogram for iodoalphionic acid (3). When 200 mg. per kilogram, in the form of a 5.4 per cent solution, is administered to cats by means of a stomach tube, the animals show no signs of discomfort. Nor do rabbits exhibit any side-reactions when 200 mg. per kilogram in the form of a 5 per cent solution is introduced into the marginal vein of the ear. Dogs receiving Orabilex in doses up to 1.5 gm./kg. showed no impairment of liver or kidney function and, when the animals were sacrificed, gross and microscopic studies revealed no organ damage (4). Contraindications: As is the case with other cholecystographic media, Orabilex is contraindicated in patients with acute nephritis and uremia. It should not be administered in the presence of disorders of the gastrointestinal tract which might prevent its absorption.