A. Water Exchange 2326 B. Proton Exchange 2327 C. Electronic Relaxation 2327 D. Relaxivity 2331 E. Outerand Second-Sphere Relaxivity 2334 F. Methods of Improving Relaxivity 2336 V. Macromolecular Conjugates 2336 A. Introduction 2336 B. General Conjugation Methods 2336 C. Synthetic Linear Polymers 2336 D. Synthetic Dendrimer-Based Agents 2338 E. Naturally Occurring Polymers (Proteins, Polysaccharides, and Nucleic Acids) 2339

https://mriquestions.com/uploads/3/4/5/7/34572113/lauffer_1999_review.pdf

Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications

Magnetism in medicine has had a long and interesting history In the 10 th century AD, Egyptian physician and philosopher Avicenna prescribed a grain of magnetite dissolved in milk for the accidental swallowing of rust reasoning that magnetite would render the poisonous iron inert by attracting it and accelerating its excretion through the intestine1 A thousand years later on July 3, 1977, “Indomitable”, the little machine that could, labored for five hours to produce one image, an event that used magnetism to change the landscape of modern medicine 2 Looking at the homemade superconducting magnet constructed from 30 miles of niobiumtitanium wire that now resides in its rightful place at the Smithsonian Institution, it is incredible to comprehend how in a mere 30 years magnetic resonance imaging (MRI) has gone from its crude, almost ugly, human scan to where physicians can now regularly order MRIs off their menu of diagnostic tools because of its exquisite anatomical resolution, routinely down to 05 to 1 mm When the field was first reviewed in this journal in 1987, 3 only 39 papers were found in Medline with keywords “gado-“ and “MRI” 4 Today, this same search on PubMed pulls out over 250,000 records, of which a significant component has been development of MR contrast agents The human body is essentially a super-sized water bottle, with about two-thirds of its weight consisting of water Water's hydrogen atoms are able to act as microscopic compass needles that stand “at attention” when placed in a strong magnetic field When submitted to pulses of radio waves, their magnetic alignment is disrupted and the differences in how they relax to the previous state are used to generate images Contrast agents can act to catalyze the process of the return to the ground relaxed state Now commonplace in the clinic, paramagnetic or superparamagnetic metal ions are administered in 40–50% of the 7–10 million MR examinations per year 5 These image-enhancing contrast agents add significant morphological and functional information to unenhanced MR images, allowing for enhanced tissue contrast, characterization of lesions, and evaluation of perfusion and flow-related abnormalities In this review, we will introduce small molecule agents, but focus primarily on macromolecular MR contrast agents, particularly those containing gadolinium (Gd 3+ ) that are assembled or based in part on these same small molecules A brief discussion on iron oxide and manganese (Mn 2+ ) agents is also provided

/pdf/macromolecules-dendrimers-and-nanomaterials-in-magnetic-q5ck3wg08k.pdf

Macromolecules, Dendrimers, and Nanomaterials in Magnetic Resonance Imaging: The Interplay between Size, Function, and Pharmacokinetics

Angiogenesis has long been established as a key element in the pathophysiology of tumor growth and metastasis. Increasingly, new molecularly targeted antiangiogenic drugs are being developed in the fight against cancer. These drugs bring with them a need for an accurate means of diagnosing tumor angiogenesis and monitoring response to treatment. Imaging techniques can offer this in a noninvasive way, while also providing functional information about the tumor. Among the many clinical imaging techniques available, MRI alone can provide relatively good spatial resolution and specificity, without ionizing radiation and with limited side effects. Arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) imaging techniques can be employed to confer indirect measures of angiogenesis, such as blood flow and blood volume, without the need for external contrast agents. Dynamic contrast-enhanced (DCE)-MRI is rapidly emerging as a standard method for directly measuring angiogenesis during angiogenesis-inhibitor drug trials. As macromolecular MR contrast agents become available, they will inevitably be utilized in the assessment of tumor perfusion and vessel permeability. Meanwhile, technological advances have made imaging at a molecular level a possibility. They have brought the potential to directly target MR contrast agents to markers of angiogenesis, such as the alpha(v)beta(3) integrin. Before this is used clinically, however, substantial gains in sensitivity brought about by improved coils, pulse sequences, and contrast agents will be needed. Herein we discuss the techniques currently available for MRI of angiogenesis, along with their respective advantages and disadvantages, and what the future holds for this evolving field of imaging.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmri.20991

MRI of tumor angiogenesis.

Tissue-specific MR contrast agents

Purpose: To evaluate the feasibility of first-pass contrastenhanced magnetic resonance angiography (MRA) using ferumoxytol in humans. Materials and Methods: First-pass and equilibrium phase MRA were performed using ferumoxytol in one healthy volunteer and 11 patients with a fast three-dimensional spoiled gradient recalled (SPGR) pulse sequence. The examined vessels included carotid arteries, thoracic aorta, abdominal aorta, and peripheral arteries. A dose of either 71.6 mol Fe/kg (n 9), or 35.8 mol Fe/kg (n 3) was used. Based on a phantom study, the agent with initial concentration of 537.2 mol Fe/mL was diluted by either four-fold (134.3 mol Fe/mL) or eight-fold (67.1 mol Fe/ mL) for first-pass MRA. Results: All subjects completed their studies without adverse events. First-pass MRA showed selective arterial enhancement, with both arterial and venous enhancement on delayed acquisitions. Selective venous enhancement could be obtained by subtraction of arterial phase images from equilibrium phase images. The findings in ferumoxytol MRA were consistent with the results of original vascular tests. Conclusion: Our preliminary experience supports the feasibility of first-pass MRA with ferumoxytol. Satisfactory arterial enhancement during first-pass imaging is obtained with injection of diluted contrast agent. With ferumoxytol, arteries and veins can be selectively depicted in a single exam.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmri.20235

First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent

PURPOSE: To evaluate the imaging performance and patient tolerance of a blood-pool contrast agent (MS-325) for magnetic resonance (MR) angiography. MATERIALS AND METHODS: Imaging of peripheral and carotid vessels was performed in seven healthy volunteers in a phase I clinical trial of the gadolinium chelate MS-325. Each volunteer received an intravenous injection of 0.05 mmol/kg MS-325 over 30 seconds. Dynamic (arterial phase) and steady-state (arterial-venous phase) three-dimensional gradient-echo MR angiograms were acquired during, immediately after, and approximately 50 minutes after injection. Images were ranked (1 [poor] to 5 [excellent]) for overall image quality, and signal-to-noise ratio (S/N) and contrast-to-noise ratio (C/N) were measured by using standard techniques. RESULTS: All volunteers tolerated the procedure well. The MS-325-enhanced studies demonstrated intense vascular signal. Mean peripheral arterial C/N was 12.9 +/- 4.8 (standard deviation), 78.8 +/- 29.4, 46.1 +/- 10.9, and 41.9 +/- ...

E K Yucel

Papers

Steady-state and dynamic MR angiography with MS-325: initial experience in humans.