Analytical Methods for Characterizing Magnetic Resonance Probes (original) (raw)

Amplification strategies in MR imaging: Activation and accumulation of sensing contrast agents (SCAs

Journal of Magnetic Resonance Imaging, 2006

We review new strategies for the development of Gd3+-based T1-relaxation agents and paramagnetic chemical exchange saturation transfer (PARACEST) “sensing” contrast agents (SCAs) designed specifically to detect small molecules or enzymatic activity in living systems. The first class of agents exhibits molecular “sensing” properties as a result of water coordination sphere effects, cleavage, or synthesis of reactive precursor compounds that recombine with macromolecules with the resultant formation of immobilized or rotationally constrained paramagnetic cations. This effect results in changes of water proton relaxation times. The second class (PARACEST) comprises a family of lanthanide-based paramagnetic compounds suitable for CEST imaging. The need for both types of MR agents is justified by efforts to utilize magnetic resonance imaging (MRI) to visualize fine structures in living tissue, and to increase the molecular specificity of MRI. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Off-resonance experiments and contrast agents to improve magnetic resonance imaging

Magnetic Resonance in Medicine, 1998

The effect of off-resonance irradiation on the water proton NMR signal intensity has been investigated as follows: (a) in the presence of a paramagnetic probe like manganese(l1); (b) in the presence of bovine serum albumin (BSA) and two gadolinium(lll) complexes, Gd-DTPA and Gd-BOPTA; (c) in the presence of cross-linked BSA and the two above-mentioned gadolinium(lll) complexes. The experimental data have been rationalized on the basis of the available theoretical models.

Uptake of a superparamagnetic contrast agent imaged by MR with high spectral and spatial resolution

Magnetic Resonance in Medicine, 2000

Conventional MRI implicitly treats the proton signal as a single, narrow Lorentzian. However, water signals in vivo are often inhomogeneously broadened and have multiple resolvable components. These components represent discrete populations of water molecules within each pixel which are affected differently by physiology and contrast agents. Accurate measurement of each component of the water resonance can improve anatomic and functional MR images and provide insight into the structure and dynamics of subpixelar microenvironments. This report describes high spectral and spatial resolution (HiSS) MR imaging of rodent prostate tumors before and after injection of a superparamagnetic contrast agent. HiSS datasets were used to synthesize images in which intensity is proportional to peak height, peak frequency, and linewidth. These images showed anatomic features which were not clearly delineated in conventional T 2 and gradient echo images. HiSS images obtained after injection of the contrast agent showed T * 2 and T 1 changes which were not seen in conventional images. These changes are associated with microvessel density and permeability. The results suggest HiSS with superparamagnetic contrast agents has the potential to improve characterization of tumors.

Magnetic resonance in the era of molecular imaging of cancer

Magnetic Resonance Imaging, 2011

MRI has played an important role in the diagnosis and management of cancer since it was first developed, but other modalities also continue to advance and provide complementary information on the status of tumors. In the future there will be a major continuing role for non-invasive imaging in order to obtain information on the location and extent of cancer, as well as assessments of tissue characteristics that can monitor and predict treatment response and guide patient management. Developments are currently being undertaken that aim to provide improved imaging methods for the detection and evaluation of tumors, for identifying important characteristics of tumors such as the expression levels of cell surface receptors that may dictate what types of therapy will be effective, and for evaluating their response to treatments. Molecular imaging techniques based mainly on radionuclide imaging can depict numerous, specific, cellular and molecular markers of disease and have unique potential to address important clinical and research challenges. In this review we consider what continuing and evolving roles will be played by MRI in this era of molecular imaging. We discuss some of the challenges for MRI of detecting imaging agents that report on molecular events, but highlight also the ability of MRI to assess other features such as cell density, blood flow and metabolism which are not specific hallmarks of cancer but which reflect molecular changes. We discuss the future role of MRI in cancer and describe the use of selected quantitative imaging techniques for characterizing tumors that can be translated to clinical applications, particularly in the context of evaluating novel treatments.

In vivo MRI visualization of different cell populations labeled with PARACEST agents

Magnetic Resonance in Medicine, 2013

Conventional T 1-or T 2-MRI contrast agents do not allow to track the distribution of different cell populations simultaneously because the effects of relaxation enhancers are additive. Herein, it is shown that paramagnetic chemical exchange saturation transfer agents offer the opportunity to visualize different cell populations in vitro and in vivo by 1 H-MRI. Yband Eu-HPDO3A complexes have been used to label murine macrophages (J774.A1) and melanoma cells (B16-F10), respectively. By selective irradiation of the highly-shifted OH resonances of the two chemical exchange saturation transfer agents, it has been shown that tracking of the two cell types is possible. These PARAmagnetic Chemical Exchange Saturation Transfer agents have a tremendous potential for clinical translation as they share the same stability and in vivo pharmacokinetic properties of Gd-HPDO3A (ProHance V R), which is a widely used clinically approved MRI agent. Magn Reson Med 000:000-000, 2012. V

Nanomedicine strategies for molecular targets with MRI and optical imaging

Future Medicinal Chemistry, 2010

The science of 'theranostics' plays a crucial role in personalized medicine, which represents the future of patient management. Over the last decade an increasing research effort has focused on the development of nanoparticle-based molecular-imaging and drug-delivery approaches, emerging as a multidisciplinary field that shows promise in understanding the components, processes, dynamics and therapies of a disease at a molecular level. The potential of nanometer-sized agents for early detection, diagnosis and personalized treatment of diseases is extraordinary. They have found applications in almost all clinically relevant biomedical imaging modality. In this review, a number of these approaches will be presented with a particular emphasis on MRI and optical imaging-based techniques. We have discussed both established molecular-imaging approaches and recently developed innovative strategies, highlighting the seminal studies and a number of successful examples of theranostic nanomedicine, especially in the areas of cardiovascular and cancer therapy. Nanotechnology is starting to invade different areas of science and 'theranostic' biomedical science is no exception [1][2][3]. The science of theranostics plays a critical role in personalized medicine, which represents the future of patient management. Nanoparticle-based medicinal approaches have emerged as an interdisciplinary area, that shows promise in understanding the components, processes, dynamics and therapies of disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases have found application in every biomedical imaging modality. These include noninvasive cellular and molecular-imaging techniques, including ultrasound (US) [5], optical [6], PET [7], computed tomography [8-9] and MRI [10-14].

An overview of responsive MRI contrast agents for molecular imaging

Frontiers in Bioscience, 2008

Introduction 3. MRI contrast mechanisms 4. Exogenous MRI contrast agents 5. Responsive MRI contrast agents 5.1. Molecular imaging of proteins 5.1.1. Contrast agents that bind to proteins 5.1.2. Contrast agents that are catalyzed by enzymes 5.2. Molecular imaging of nucleic acids 5.3. Molecular imaging of metabolites 5.4. Molecular imaging of oxygen 5.5. Molecular imaging of metal ions 5.6. Molecular imaging of pH 5.7. Molecular imaging of temperature 6. Future Directions 7. Acknowledgements 8. References

New MRI method with contrast based on the macromolecular characteristics of tissues

Magnetic Resonance in Medicine, 2003

A new MRI method with a contrast that is derived from the macromolecular composition and spin dynamics in the tissue is described and demonstrated on excised mouse brain and rat spinal cord. In the method, magnetization is selectively excited in the macromolecules by using a double quantum filter and subsequently transferred to water. The new imaging method differs from previous methods that rely on magnetization transfer contrast (MTC) in that it enables a separate and independent control of the effect of the macromolecule characteristics, chemical exchange, and water-related parameters on the images. Magn Reson Med 50:229 -234, 2003.

Responsive MRI agents for sensing metabolism in vivo

Accounts of chemical …, 2009

M agnetic resonance imaging (MRI) has inherent advantages in safety, three-dimensional output, and clinical relevance when compared with optical and radiotracer imaging methods. However, MRI contrast agents are inherently less sensitive than agents used in other imaging modalities primarily because MRI agents are detected indirectly by changes in either the water proton relaxation rates (T 1 , T 2 , and T 2 * ) or water proton intensities (chemical exchange saturation transfer and paramagnetic chemical exchange saturation transfer, CEST and PARACEST). Consequently, the detection limit of an MRI agent is determined by the characteristics of the background water signal; by contrast, optical and radiotracer-based methods permit direct detection of the agent itself. By virtue of responding to background water (which reflects bulk cell properties), however, MRI contrast agents have considerable advantages in "metabolic" imaging, that is, spatially resolving tissue variations in pH, redox state, oxygenation, or metabolite levels. In this Account, we begin by examining sensitivity limits in targeted contrast agents and then address contrast agents that respond to a physiological change; these responsive agents are effective metabolic imaging sensors.