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BackgroundMRI is the imaging modality of choice for diagnosis and intervention assessment in neurological disease. Its full potential has not been realized due in part to challenges in harmonizing advanced techniques across multiple sites.PurposeTo develop a method for the assessment of reliability and repeatability of advanced multisite-multisession neuroimaging studies and specifically to assess the reliability of an advanced MRI protocol, including multiband fMRI and diffusion tensor MRI, in a multisite setting.Study typeProspective.PopulationTwice repeated measurement of a single subject with stable relapsing-remitting multiple sclerosis (MS) at seven institutions.Field strength/sequenceA 3 T MRI protocol included higher spatial resolution anatomical scans, a variable flip-angle longitudinal relaxation rate constant (R1 ≡ 1/T1 ) measurement, quantitative magnetization transfer imaging, diffusion tensor imaging, and a resting-state fMRI (rsFMRI) series.AssessmentMultiple methods of assessing intrasite repeatability and intersite reliability were evaluated for imaging metrics derived from each sequence.Statistical testsStudent's t-test, Pearson's r, and intraclass correlation coefficient (ICC) (2,1) were employed to assess repeatability and reliability. Two new statistical metrics are introduced that frame reliability and repeatability in the respective units of the measurements themselves.ResultsIntrasite repeatability was excellent for quantitative R1 , magnetization transfer ratio (MTR), and diffusion-weighted imaging (DWI) based metrics (r > 0.95). rsFMRI metrics were less repeatable (r = 0.8). Intersite reliability was excellent for R1 , MTR, and DWI (ICC >0.9), and moderate for rsFMRI metrics (ICC∼0.4).Data conclusionFrom most reliable to least, using a new reliability metric introduced here, MTR > R1 > DWI > rsFMRI; for repeatability, MTR > DWI > R1 > rsFMRI. A graphical method for at-a-glance assessment of reliability and repeatability, effect sizes, and outlier identification in multisite-multisession neuroimaging studies is introduced.Level of evidence1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:878-888.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with 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 i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, 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 magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis and have implications for non-relapsing biological progression. In recent years, the discovery of innovative MRI and PET-derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with multiple sclerosis, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted and T2-weighted scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification and monitoring is lacking. To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a consensus statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this consensus statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge. [ABSTRACT FROM AUTHOR]

Objective: Magnetic resonance (MR) measures of muscle quality are highly sensitive to disease progression and predictive of meaningful functional milestones in Duchenne muscular dystrophy (DMD). This investigation aimed to establish the reproducibility, responsiveness to disease progression, and minimum clinically important difference (MCID) for multiple MR biomarkers at different disease stages in DMD using a large natural history dataset. Methods: Longitudinal MR imaging and spectroscopy outcomes and ambulatory function were measured in 180 individuals with DMD at three sites, including repeated measurements on two separate days (within 1 week) in 111 participants. These data were used to calculate day‐to‐day reproducibility, responsiveness (standardized response mean, SRM), minimum detectable change, and MCID. A survey of experts was also performed. Results: MR spectroscopy fat fraction (FF), as well as MR imaging transverse relaxation time (MRI‐T2), measures performed in multiple leg muscles, and had high reproducibility (Pearson's R > 0.95). Responsiveness to disease progression varied by disease stage across muscles. The average FF from upper and lower leg muscles was highly responsive (SRM > 0.9) in both ambulatory and nonambulatory individuals. MCID estimated from the distribution of scores, by anchoring to function, and via expert opinion was between 0.01 and 0.05 for FF and between 0.8 and 3.7 ms for MRI‐T2. Interpretation: MR measures of FF and MRI T2 are reliable and highly responsive to disease progression. The MCID for MR measures is less than or equal to the typical annualized change. These results confirm the suitability of these measures for use in DMD and potentially other muscular dystrophies. [ABSTRACT FROM AUTHOR]

Evidence mounts that the steady‐state cellular water efflux (unidirectional) first‐order rate constant (kio [s−1]) magnitude reflects the ongoing, cellular metabolic rate of the cytolemmal Na+, K+‐ATPase (NKA), cMRNKA (pmol [ATP consumed by NKA]/s/cell), perhaps biology's most vital enzyme. Optimal 1H2O MR kio determinations require paramagnetic contrast agents (CAs) in model systems. However, results suggest that the homeostatic metabolic kio biomarker magnitude in vivo is often too large to be reached with allowable or possible CA living tissue distributions. Thus, we seek a noninvasive (CA‐free) method to determine kio in vivo. Because membrane water permeability has long been considered important in tissue water diffusion, we turn to the well‐known diffusion‐weighted MRI (DWI) modality. To analyze the diffusion tensor magnitude, we use a parsimoniously primitive model featuring Monte Carlo simulations of water diffusion in virtual ensembles comprising water‐filled and ‐immersed randomly sized/shaped contracted Voronoi cells. We find this requires two additional, cytometric properties: the mean cell volume (V [pL]) and the cell number density (ρ [cells/μL]), important biomarkers in their own right. We call this approach metabolic activity diffusion imaging (MADI). We simulate water molecule displacements and transverse MR signal decays covering the entirety of b‐space from pure water (ρ = V = 0; kio undefined; diffusion coefficient, D0) to zero diffusion. The MADI model confirms that, in compartmented spaces with semipermeable boundaries, diffusion cannot be described as Gaussian: the nanoscopic D (Dn) is diffusion time‐dependent, a manifestation of the "diffusion dispersion". When the "well‐mixed" (steady‐state) condition is reached, diffusion becomes limited, mainly by the probabilities of (1) encountering (ρ, V), and (2) permeating (kio) cytoplasmic membranes, and less so by Dn magnitudes. Importantly, for spaces with large area/volume (A/V; claustrophobia) ratios, this can happen in less than a millisecond. The model matches literature experimental data well, with implications for DWI interpretations. [ABSTRACT FROM AUTHOR]

We introduce a new 1H2O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion‐weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady‐state trans‐membrane water cycling (AWC), kio reflects the cytolemmal Na+, K+ATPase (NKA) homeostatic cellular metabolic rate (cMRNKA). A digital 3D "library" contains thousands of simulated single diffusion‐encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel‐by‐pixel experimental SDE decay library matchings that can be used to advantage. They yield proof‐of‐concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s−1; likely reflecting mostly exchange within myelin. The kio•V product map displays brain tissue cMRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting‐state brain 18FDG‐PET tissue glucose consumption rate (tMRglucose) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented. [ABSTRACT FROM AUTHOR]