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Purpose: To investigate the relationship between magnetic resonance (MR) imaging markers of iron content and disease severity in patients with multiple sclerosis (MS) over a 2-year period., Materials and Methods: This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. Seventeen patients with MS and 17 control subjects were examined twice, 2 years apart, by using phase imaging and transverse relaxation (R2*) mapping at 4.7 T. Quantitative differences in iron content in deep gray matter between patients and control subjects were evaluated with repeated-measures multivariate analysis of variance separately for R2* mapping and phase imaging. Multiple regression analysis was used to evaluate correlations of MR imaging measures, both 2-year-difference and single-time measurements, to baseline disease severity., Results: R2* mapping using 2-year-difference measurements had the highest correlation to disease severity (r = 0.905, P < .001) compared with R2* mapping using single-time measurements (r = 0.560, P = .019) and phase imaging by using either single-time (r = 0.539, P = .026) or 2-year-difference (r = 0.644, P = .005) measurements. Significant increases in R2* occur during 2 years in the substantia nigra (P < .001) and globus pallidus (P = .035), which are both predictors of disease in regression analysis, in patients compared with control subjects. There were group differences in the substantia nigra, globus pallidus, pulvinar thalamus, thalamus, and caudate nucleus, compared with control subjects with R2* mapping (P < .05), and group differences in the caudate nucleus and pulvinar thalamus, compared with control subjects with phase imaging (P < .05)., Conclusion: There are significant changes in deep gray matter iron content in MS during 2 years measured with MR imaging, changes that are strongly related to physical disability. Longitudinal measurements may produce a higher correlation to disease severity compared with single-time measurements because baseline iron content of deep gray matter is variable among subjects., (©RSNA, 2013.)

Background: Magnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Preclinical and postmortem studies show that chronic stress and MDD may affect hippocampal subfields differently, but MRI spatial resolution has previously been insufficient to measure subfield volumes., Methods: Twenty MDD participants (9 unmedicated and 11 medicated, both > 6 months) and 27 healthy control subjects were studied. We used T2-weighted two-dimensional fast spin echo and T1-weighted three-dimensional magnetization prepared rapid acquisition gradient-echo sequences at 4.7 T to compare hippocampal subfield volumes at .09 μL voxel volume., Results: Unmedicated MDD participants had a lower dentate gyrus volume than control subjects or medicated MDD participants and a lower cornu ammonis (CA1-3) volume in the hippocampal body subregion than control subjects., Conclusions: Hippocampal volumes in unmedicated MDD showed evidence of localization to specific subfields and subregions, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. Strengths include in vivo measurement of entire hippocampal subfields and separation between unmedicated and medicated MDD. Limitations include power to control for multiple comparisons and that MRI landmarks approximate the subfields defined by cellular microstructure., (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the relationship between iron staining and magnetic resonance (MR) imaging measurements in postmortem subjects with multiple sclerosis (MS)., Materials and Methods: Institutional ethical approval was obtained, and informed consent was obtained from the subjects and/or their families. Four MR imaging methods based on transverse relaxation (T2 weighting, R2 mapping, and R2* mapping) and phase imaging were performed by using a 4.7-T system in three in situ postmortem patients with MS less than 28 hours after death and in one in vivo patient 1 year before death. Iron staining with the Perls iron reaction was performed after brain extraction. Region-of-interest measurements from six subcortical gray matter structures were obtained from MR imaging and then correlated with corresponding locations on photographs of iron-stained pathologic slices by using a separate linear least-squares regression in each subject. Iron status of white matter lesions, as determined by staining, was compared with appearance on MR images., Results: R2* mapping had the highest intrasubject correlations with iron in subcortical gray matter (R(2) = 0.857, 0.628, and 0.685; all P < .001), while R2 mapping (R(2) = 0.807, 0.615, 0.628, and 0.489; P < .001 and P = .001, .034, and .001, respectively), phase imaging (R(2) = 0.672, 0.441, 0.596, 0.548; all P ≤ .001), and T2-weighted imaging (R(2) = 0.463, 0.582, 0.650, and 0.551; all P < .001) had lower but still strong correlations. Within lesions, hypointense areas on phase images did not always represent iron. A hyperintense rim surrounding lesions on R2* maps was only present with iron staining, yet not all iron-staining lesions had R2* rim hyperintensity., Conclusion: All four MR imaging methods had significant linear correlations with iron and could potentially be used to determine iron status of subcortical gray matter structures in MS, with R2* mapping being preferred. A reliable method of determining iron status within MS lesions was not established., (© RSNA, 2013.)

Background and Purpose: CSM is a common neurologic disease that results in progressive disability and eventual paralysis without appropriate treatment. Imaging plays a significant role in the evaluation of CSM and has evolved with recent technical advances. We sought to systematically explore the relationship between clinical disease severity and DTI in CSM, and to investigate the potential use of DTI in surgical decision-making models., Materials and Methods: MR imaging studies and clinical assessments were prospectively collected on 30 patients with CSM. Spearman correlations were used to investigate associations between clinical disease severity and FA at the time of diagnosis. Clinical assessment was performed using mJOA, Nurick, Short Form-36, and NDI scores. Fifteen patients with CSM subsequently underwent decompressive surgery; Spearman correlation and logistic regression were applied to this cohort to study the relationship between baseline DTI measurements and postoperative outcome. Conventional imaging (spinal cord T2 signal intensity and degree of stenosis) was evaluated for comparison with DTI., Results: At diagnosis, FA demonstrated a strong correlation with baseline mJOA (r = 0.62, P < .01) and Nurick (r = -0.46, P = .01) scores. After surgery, recovery of function demonstrated by improvement in NDI score was associated with higher FA values on preoperative DTI (r = -0.61, P = .04). Severely affected patients with CSM with disproportionately high FA tended to achieve greater mJOA scores after surgery compared with subjects with lower FA (P = .08). T2 signal intensity was associated with functional status at baseline but did not predict postoperative outcome; degree of stenosis lacked any significant correlation with clinical parameters., Conclusions: DTI may be a useful diagnostic tool for assessing disease severity in CSM. The predictive value of DTI regarding postoperative outcome may improve surgical decision-making and facilitate health care outcomes research.

High risk behaviors such as narcotic use or physical fighting can be caused by impulsive decision making in emotionally-charged situations. Improved neuroscientific understanding of how emotional context interacts with the control of impulsive behaviors may lead to advances in public policy and/or treatment approaches for high risk groups, including some high-risk adolescents or adults with poor impulse control. Inferior frontal gyrus (IFG) is an important contributor to response inhibition (behavioral impulse control). IFG also has a role in processing emotional stimuli and regulating emotional responses. The mechanism(s) whereby response inhibition processes interact with emotion processing in IFG are poorly understood. We used 4.7 T fMRI in 20 healthy young adults performing a rapid event-related emotional Go/NoGo task. This task combined the Go/NoGo task, which is a classic means of recruiting response inhibition processes, with emotionally neutral and aversive distractor images. In IFG, both response inhibition in an emotionally neutral context (neutral NoGo trials) and aversive emotional picture processing (aversive Go trials) evoked activation greater than the simple response baseline (neutral Go trials). These results are consistent with the literature. Activation for response inhibition in aversive contexts (aversive NoGo-neutral Go trials) was approximately the sum of response inhibition activation (neutral NoGo-neutral Go) and aversive emotional distractor activation (aversive Go-neutral Go). We conclude that response inhibition and aversive emotional stimulus processing activities combine additively (linearly) in IFG, rather than interfering with each other (sub-linearly) or mutually-enhancing each other (super-linearly). We also found previously undocumented interaction effects between response inhibition (NoGo vs. Go) and emotional context (aversive vs. neutral distractor pictures) in bilateral posterior middle temporal gyrus and angular gyrus, right frontal eye field, and other brain regions. These results may reflect the interaction of attention processes driven by emotional stimuli with conflict resolution processes related to Go/NoGo performance., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Concomitant gradient fields are transverse magnetic field components that are necessarily present to satisfy Maxwell's equations when magnetic field gradients are utilized in magnetic resonance imaging. They can have deleterious effects that are more prominent at lower static fields and/or higher gradient strengths. In diffusion tensor imaging schemes that employ large gradients that are not symmetric about a refocusing radiofrequency pulse (unlike Stejskal-Tanner, which is symmetric), concomitant fields may cause phase accrual that could corrupt the diffusion measurement. Theory predicting the error from this dephasing is described and experimentally validated for both Reese twice-refocused and split gradient single spin-echo diffusion gradient schemes. Bias in apparent diffusion coefficient values was experimentally found to worsen with distance from isocenter and with increasing duration of gradient asymmetry in both a phantom and in the brain. The amount of error from concomitant gradient fields depends on many variables, including the diffusion gradient pattern, pulse sequence timing, maximum effective gradient amplitude, static magnetic field strength, voxel size, slice distance from isocenter, and partial Fourier fraction. A prospective correction scheme that can reduce concomitant gradient errors is proposed and verified for diffusion imaging., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: In addition to neuronal injury, inflammatory, and demyelinating processes, evidence suggests multiple sclerosis (MS) is also associated with increased iron deposition in the basal ganglia. Magnetic resonance imaging (MRI), particularly at very high field strengths, is sensitive to iron accumulation and may enable visualization and quantification of iron associated with MS., Objectives: To investigate the sub-cortical gray matter in patients with early-stage relapsing-remitting MS using multiple, and novel, quantitative MRI measures at very high field., Methods: In total, 22 patients with relapsing-remitting MS and 22 control subjects were imaged at 4.7 Tesla. Transverse relaxation rates (R₂ and R₂*) and susceptibility phase were quantified in four basal ganglia nuclei, the thalamus, and the red nuclei. Parameters in patients with MS were compared with those in healthy subjects and correlated with clinical scores., Results: Significant abnormalities were observed in most structures, most notably in the pulvinar sub-nucleus. Significant correlations with disability were observed in the pulvinar; marginally significant correlations were also observed in the thalamus and red nucleus. No significant correlations were observed with duration since index relapse., Conclusions: Widespread abnormalities are present in the deep gray matter nuclei of patients recently diagnosed with MS; these abnormalities can be detected via multi-modal high-field MRI. Imaging metrics, particularly R₂*, relate to disease severity in the pulvinar and other gray matter regions.

Presented is a fitting model for transverse relaxometry data acquired with the multiple-refocused spin-echo sequence. The proposed model, requiring no additional data input or pulse sequence modifications, compensates for imperfections in the transmit field and radiofrequency (RF) profiles. Exploiting oscillatory echo behavior to estimate alternate coherence pathways, the model compensates for prolonged signal decay from stimulated echo pathways yielding precise monoexponential T(2) quantification. Verified numerically and experimentally at 4.7 T in phantoms and the human brain, over 95% accuracy is readily attainable in realistic imaging situations without sacrificing multislice capabilities or requiring composite or adiabatic RF pulses. The proposed model allows T(2) quantitation in heterogeneous transmit fields and permits thin refocusing widths for efficient multislice imaging.

Several neuropsychiatric disorders involving hippocampal structural changes have been studied extensively using volumetric magnetic resonance imaging (MRI). These studies have mostly measured total hippocampal volume while the present study aimed to delineate and measure hippocampal subfields within the whole hippocampus and subdivisions along its longitudinal axis. Images were acquired at 4.7 T in 11 healthy subjects (5 males and 6 females, aged 23-56 years), using a fast spin echo (FSE) sequence with 0.52 x 0.68 x 1.0 mm(3) native resolution, collecting 90 contiguous coronal slices. Subiculum, cornu ammonis (CA1-3), and dentate gyrus were traced manually within the hippocampal head, body, and tail. We reported volumes for the subfields and demonstrated differences in the distribution within the hippocampus and its parts. The biggest part of the dentate gyrus was located in the hippocampal body, following the hippocampal head and tail. In contrast, the hippocampal head had the largest part of CA1-3, following the hippocampal body and tail. The hippocampal tail had the smallest portion of the subiculum compared to hippocampal head and tail. Subfield volumes were consistent between hemispheres and showed distributions within the longitudinal subdivisions that were consistent with histological data. Direct measurements of subfield distribution along the longitudinal axis of the hippocampus may be more sensitive to detecting disease effects than total volume measures and the differential distribution of subfield volumes may aid in the interpretation of measurements obtained at lower field strength and spatial resolution.

Purpose: To demonstrate 4.7 Tesla (T) imaging methods for visualizing lesions in multiple sclerosis in the human brain using phase susceptibility-weighting and T2 weighting., Materials and Methods: Seven patients with relapsing-remitting multiple sclerosis were imaged at 4.7T using three-dimensional (3D) susceptibility-weighted imaging (SWI) with 0.90 mm(3) voxel volumes, and with 2D T2-weighted fast spin echo (T2WFSE) with 0.34 mm(3) voxels and 1.84 mm(3) voxels. The visibility of MS lesions at 4.7T with phase SWI and T2WFSE was assessed by independent lesion counts made by an experienced neuroradiologist, and by quantitative measures., Results: High resolution T2WFSE at 4.7T provided excellent depiction of hyperintense lesions. When combined with phase SWI, 124 total lesions were identified of which 18% were only visible on phase SWI and not on T2WFSE. The phase lesions had a mean phase shift relative to local background of -11.15 +/- 5.97 parts per billion., Conclusion: Imaging at 4.7T can provide both high quality, high resolution T2WFSE and SWI for visualization of lesions in multiple sclerosis. Phase susceptibility-weighting can identify additional lesions that are not visible with high resolution T2WFSE., ((c) 2009 Wiley-Liss, Inc.)

An implementation of fast spin echo at 4.7 T designed for versatile and time-efficient T(2)-weighted imaging of the human brain is presented. Reduced refocusing angles (alpha < 180 degrees) were employed to overcome specific absorption rate (SAR) constraints and their effects on image quality assessed. Image intensity and tissue contrast variations from heterogeneous RF transmit fields and incidental magnetization transfer effects were investigated at reduced refocusing angles. We found that intraslice signal variations are minimized with refocusing angles near 180 degrees, but apparent gray/white matter contrast is independent of refocusing angle. Incidental magnetization transfer effects from multislice acquisitions were shown to attenuate white matter intensity by 25% and gray matter intensity by 15% at 180 degrees; less than 5% attenuation was seen in all tissues at flip angles below 60 degrees. We present multislice images acquired without excess delay time for SAR mitigation using a variety of protocols. Subsecond half Fourier acquisition single-shot turbo spin echo (HASTE) images were obtained with a novel variable refocusing angle echo train (20 degrees < alpha < 58 degrees) and high-resolution scans with a voxel volume of 0.18 mm(3) were acquired in 6.5 min with refocusing angles of 100 degrees., ((c) 2009 Wiley-Liss, Inc.)

We present a simple and intuitive means for determining the flip angles (FAs) required for smooth transitions between static pseudo steady states (SPSSs) in fast spin echo (FSE) imaging with variable FA (VFA) echo trains. We demonstrate the effectiveness of single and multiple transition pulses to successfully vary refocusing FAs while retaining high signal levels. The graphical interpretation presented here is consistent with previous analytical techniques and permits accurate signal-intensity predictions along the echo train., ((c) 2007 Wiley-Liss, Inc.)

Magnetic resonance microscopy using magnetically labeled cells is an emerging discipline offering the potential for non-destructive studies targeting numerous cellular events in medical research. The present work develops a technique to quantify superparamagnetic iron-oxide (SPIO) loaded cells using fully balanced steady state free precession (b-SSFP) imaging. An analytic model based on phase cancellation was derived for a single particle and extended to predict mono-exponential decay versus echo time in the presence of multiple randomly distributed particles. Numerical models verified phase incoherence as the dominant contrast mechanism and evaluated the model using a full range of tissue decay rates, repetition times, and flip angles. Numerical simulations indicated a relaxation rate enhancement (DeltaR(2b)=0.412 gamma . LMD) proportional to LMD, the local magnetic dose (the additional sample magnetization due to the SPIO particles), a quantity related to the concentration of contrast agent. A phantom model of SPIO loaded cells showed excellent agreement with simulations, demonstrated comparable sensitivity to gradient echo DeltaR(*) (2) enhancements, and 14 times the sensitivity of spin echo DeltaR(2) measurements. We believe this model can be used to facilitate the generation of quantitative maps of targeted cell populations., (Magn Reson Med, 2006. (c) 2006 Wiley-Liss, Inc.)