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Contrast reagents (CRs) may enter the tissue interstitium for a period after a vascular bolus injection. As the amount of interstitial CR increases, the longitudinal relaxographic NMR "shutter-speed" (T

At present, the diagnosis of multiple sclerosis (MS) relies heavily on the use of MRI, which can demonstrate disease dissemination in space and time [1][2][3][4] . The current 2010 McDonald criteria have enabled earlier diagnosis 5,6 and initiation of disease-modifying treatment, with substantial benefits for disease outcome 7,8 , but they still have imperfect sensitivity and specificity 9,10 . The limited accuracy of the criteria results in challenging cases and misdiagnosis, which are prevalent problems in MS 11,12 . Therefore, more-accurate and pathologically specific MRI criteria are still needed to exclude other disorders that can mimic MS 13,14 .The MRI-detectable central vein inside white matter lesions has recently been proposed as a biomarker of inflammatory demyelination and, thus, may aid the diagnosis of MS 15 . The 'central vein sign' (CVS) has been investigated in various neurological conditions by several groups, and evidence has accumulated that the CVS may have the ability to accurately differentiate MS from its mimics [15][16][17][18][19][20][21] . As a consequence, recent guidelines from the Magnetic Resonance Imaging in MS (MAGNIMS) group 1,4 and the Consortium of MS Centers (CMSC) task force 22 have acknowledged the potential of the CVS and its dedicated MRI acquisitions for the differential diagnosis of MS, while calling for further research before considering a possible modification of the diagnostic criteria. However, the lack of standardization for the definition and imaging of the CVS, as well as a dearth of large-scale prospective studies evaluating the CVS for MS diagnosis, are currently preventing the clinical validation of this potential biomarker 1,23 .This Consensus Statement aims to provide recommendations for the definition, standardization and clinical evaluation of the CVS in the diagnosis of MS. These statements are based on a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative. E X P E RT C O N S E N S U S D O C U M E N T on behalf of the NAIMS CooperativeAbstract | Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Mult...

Superparamagnetic iron oxide nanoparticles have diverse diagnostic and potential therapeutic applications in the central nervous system (CNS). They are useful as magnetic resonance imaging (MRI) contrast agents to evaluate: areas of blood-brain barrier (BBB) dysfunction related to tumors and other neuroinflammatory pathologies, the cerebrovasculature using perfusion-weighted MRI sequences, and in vivo cellular tracking in CNS disease or injury. Novel, targeted, nanoparticle synthesis strategies will allow for a rapidly expanding range of applications in patients with brain tumors, cerebral ischemia or stroke, carotid atherosclerosis, multiple sclerosis, traumatic brain injury, and epilepsy. These strategies may ultimately improve disease detection, therapeutic monitoring, and treatment efficacy especially in the context of antiangiogenic chemotherapy and antiinflammatory medications. The purpose of this review is to outline the current status of superparamagnetic iron oxide nanoparticles in the context of biomedical nanotechnology as they apply to diagnostic MRI and potential therapeutic applications in neurooncology and other CNS inflammatory conditions.

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An extensive protocol for the study of tissue resonances of spin 3/2 nuclei is described. The roles of the most relevant multiple pulse experiments are indicated. Their theory is organized in terms of irreducible tensor operators and the pulse and quadrupolar relaxation transfer functions which relate them for a type c spectrum. A systematic approach to the interpretation of the temperature and/or magnetic field dependences of all six of the relaxation rate constants of the resonance of a single population of isolated spins in fast exchange, and giving rise to a type c spectrum, is presented. An experimental calibration and an application of this protocol are presented in an accompanying paper. The comprehensive method we describe has a number of practical benefits in the interpretation of the physiological spectra obtained from conventional one pulse experiments. A consideration of the appropriate transverse relaxation transfer function leads to an analytical expression for the heretofore empirical NMR visibility factor. This includes factors which account for relaxation during the receiver 'dead' time and relaxation during the pulse itself. Also, consideration of realistic transverse relaxation times likely to be observed in tissue leads to a reasonable strategy for the quantitative resolution and integration of in vivo spectra obtained in the presence of hyperfine shift reagents.

Contrast-enhanced magnetic resonance imaging (MRI) is a commonly used diagnostic tool. Compared to the standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of intravenous (IV) ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacological, metabolic and imaging properties, ferumoxytol may play a crucial role in future MR imaging of the central nervous system (CNS), various organs outside the CNS, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in MRI. In order to more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available as supplementary material online.