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Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults., Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session., Results: Significant MRI site and vendor effects (p ​< ​.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p ​< ​1.39E-36). In particular, volumes larger than 200 ​mm 3 (for amygdalar nuclei) and 300 ​mm 3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε ​< ​5% and DICE ​> ​0.80)., Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer's disease (AD)., Methods: We included 88 patients with dementia due to AD from the Amsterdam Dementia Cohort. Mean follow-up was 2 ± 1 years. Linear mixed models were used to determine associations of lower whole brain and regional pseudo-continuous arterial spin labelling measured CBF with rate of cognitive decline as measured with repeated mini-mental state examination (MMSE). Model 1 was adjusted for age, sex, and education. Model 2 was additionally adjusted for normalized gray matter volume, medial temporal lobe atrophy, white matter hyperintensities, microbleeds, and lacunes. Analyses were repeated after partial volume correction (PVC) of CBF. Statistical significance was set at p ≤ 0.05., Results: Patients were 65 ± 7 years old, 44 (50 %) were women, and mean baseline MMSE was 22 ± 4. Annual decline (β[SE]) on the MMSE was estimated at -2.11 (0.25) points per year. Lower whole brain (β[SE]-0.50[0.25]; p ≤ 0.05) and parietal (β[SE]-0.59[0.25]; p < 0.05) CBF were associated with faster cognitive decline. PVC cortical CBF was not associated with cognitive decline., Conclusions: Lower CBF, in particular in the posterior brain regions, may have value as a prognostic marker for rate of cognitive decline in AD., Key Points: • In AD, lower CBF is associated with more rapid cognitive decline. • Decreasing CBF does not reach a plateau early in AD. • PcASL-CFB has additive value to conventional structural MRI measures in AD.

Purpose To investigate whether multivariate pattern recognition analysis of arterial spin labeling (ASL) perfusion maps can be used for classification and single-subject prediction of patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) and subjects with subjective cognitive decline (SCD) after using the W score method to remove confounding effects of sex and age. Materials and Methods Pseudocontinuous 3.0-T ASL images were acquired in 100 patients with probable AD; 60 patients with MCI, of whom 12 remained stable, 12 were converted to a diagnosis of AD, and 36 had no follow-up; 100 subjects with SCD; and 26 healthy control subjects. The AD, MCI, and SCD groups were divided into a sex- and age-matched training set (n = 130) and an independent prediction set (n = 130). Standardized perfusion scores adjusted for age and sex (W scores) were computed per voxel for each participant. Training of a support vector machine classifier was performed with diagnostic status and perfusion maps. Discrimination maps were extracted and used for single-subject classification in the prediction set. Prediction performance was assessed with receiver operating characteristic (ROC) analysis to generate an area under the ROC curve (AUC) and sensitivity and specificity distribution. Results Single-subject diagnosis in the prediction set by using the discrimination maps yielded excellent performance for AD versus SCD (AUC, 0.96; P < .01), good performance for AD versus MCI (AUC, 0.89; P < .01), and poor performance for MCI versus SCD (AUC, 0.63; P = .06). Application of the AD versus SCD discrimination map for prediction of MCI subgroups resulted in good performance for patients with MCI diagnosis converted to AD versus subjects with SCD (AUC, 0.84; P < .01) and fair performance for patients with MCI diagnosis converted to AD versus those with stable MCI (AUC, 0.71; P > .05). Conclusion With automated methods, age- and sex-adjusted ASL perfusion maps can be used to classify and predict diagnosis of AD, conversion of MCI to AD, stable MCI, and SCD with good to excellent accuracy and AUC values. © RSNA, 2016.

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The relevance of cortical grey matter pathology in multiple sclerosis has become increasingly recognized over the past decade. Unfortunately, a large part of cortical lesions remain undetected on magnetic resonance imaging using standard field strength. In vivo studies have shown improved detection by using higher magnetic field strengths up to 7 T. So far, a systematic histopathological verification of ultra-high field magnetic resonance imaging pulse sequences has been lacking. The aim of this study was to determine the sensitivity of 7 T versus 3 T magnetic resonance imaging pulse sequences for the detection of cortical multiple sclerosis lesions by directly comparing them to histopathology. We obtained hemispheric coronally cut brain sections of 19 patients with multiple sclerosis and four control subjects after rapid autopsy and formalin fixation, and scanned them using 3 T and 7 T magnetic resonance imaging systems. Pulse sequences included T1-weighted, T2-weighted, fluid attenuated inversion recovery, double inversion recovery and T2*. Cortical lesions (type I-IV) were scored on all sequences by an experienced rater blinded to histopathology and clinical data. Staining was performed with antibodies against proteolipid protein and scored by a second reader blinded to magnetic resonance imaging and clinical data. Subsequently, magnetic resonance imaging images were matched to histopathology and sensitivity of pulse sequences was calculated. Additionally, a second unblinded (retrospective) scoring of magnetic resonance images was performed. Regardless of pulse sequence, 7 T magnetic resonance imaging detected more cortical lesions than 3 T. Fluid attenuated inversion recovery (7 T) detected 225% more cortical lesions than 3 T fluid attenuated inversion recovery (Z = 2.22, P < 0.05) and 7 T T2* detected 200% more cortical lesions than 3 T T2* (Z = 2.05, P < 0.05). Sensitivity of 7 T magnetic resonance imaging was influenced by cortical lesion type: 100% for type I (T2), 11% for type II (FLAIR/T2), 32% for type III (T2*), and 68% for type IV (T2). We conclude that ultra-high field 7 T magnetic resonance imaging more than doubles detection of cortical multiple sclerosis lesions, compared to 3 T magnetic resonance imaging. Unfortunately, (subpial) cortical pathology remains more extensive than 7 T magnetic resonance imaging can reveal., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate arterial spin-labelling (ASL) cerebral blood flow (CBF) changes in predementia stages of Alzheimer's disease (AD)., Methods: Data were obtained from 177 patients with subjective complaints, mild cognitive impairment and AD from the Amsterdam Dementia Cohort. AD stages were based on diagnosis and cerebrospinal fluid biomarkers amyloid-β (Aβ) and total-tau (tau). General-linear-models were used to assess relationships between AD stages and total and regional CBF, correcting for age and sex., Results: Decreasing CBF was related to more advanced AD stages in all supratentorial regions (p for trend < 0.05). Post-hoc testing revealed that CBF was lower in AD compared to controls and stage-1 predementia patients (i.e. abnormal Aβ and normal tau) in temporal and parietal regions, and compared to stage-2 predementia patients (i.e. abnormal Aβ and tau) in temporal regions. CBF values of stage-2 predementia patients were numerically in between those of stage-1 predementia patients and AD., Conclusion: The continuing decrease of CBF along the continuum of AD indicates the potential of ASL-CBF as a measure for disease progression., Key Points: • Decreasing CBF relates to more advanced AD stages in all supratentorial regions. • The reduction of CBF does not reach a bottom level. • ASL-CBF has potential as a measure for disease progression in AD.

To date, limited data are available regarding the inter-site consistency of test-retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0T using vendor-provided sequences. Each site scanned a group of 5 healthy elderly participants twice, at least a week apart. We evaluated inter-site differences and test-retest reproducibility of both temporal signal-to-noise ratio (tSNR) and functional connectivity measurements derived from: i) seed-based analysis (SBA) with seed in the posterior cingulate cortex (PCC), ii) group independent component analysis (ICA) separately for each site (site ICA), and iii) consortium ICA, with group ICA across the whole consortium. Despite protocol harmonization, significant and quantitatively important inter-site differences remained in the tSNR of resting-state fMRI data; these were plausibly driven by hardware and pulse sequence differences across scanners which could not be harmonized. Nevertheless, the tSNR test-retest reproducibility in the consortium was high (ICC=0.81). The DMN was consistently extracted across all sites and analysis methods. While significant inter-site differences in connectivity scores were found, there were no differences in the associated test-retest error. Overall, ICA measurements were more reliable than PCC-SBA, with site ICA showing higher reproducibility than consortium ICA. Across the DMN nodes, the PCC yielded the most reliable measurements (≈4% test-retest error, ICC=0.85), the medial frontal cortex the least reliable (≈12%, ICC=0.82) and the lateral parietal cortices were in between (site ICA). Altogether these findings support usage of harmonized multisite studies of resting-state functional connectivity to characterize longitudinal effects in studies that assess disease progression and treatment response., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Object: The current study assesses the multicenter feasibility of pharmacological arterial spin labeling (ASL) by comparing a caffeine-induced relative cerebral blood flow decrease (%CBF↓) measured with two pseudo-continuous ASL sequences as provided by two major vendors., Materials and Methods: Twenty-two healthy volunteers were scanned twice with both a 3D spiral (GE) and a 2D EPI (Philips) sequence. The inter-session reproducibility was evaluated by comparisons of the mean and within-subject coefficient of variability (wsCV) of the %CBF↓, both for the total cerebral gray matter and on a voxel level., Results: The %CBF↓ was larger when measured with the 3D spiral sequence (23.9 ± 5.9 %) than when measured with the 2D EPI sequence (19.2 ± 5.6 %) on a total gray matter level (p = 0.02), and on a voxel level in the posterior watershed area (p < 0.001). There was no difference between the gray matter wsCV of the 3D spiral (57.3 %) and 2D EPI sequence (66.7 %, p = 0.3), whereas on a voxel level, the wsCV was visibly different between the sequences., Conclusion: The observed differences between ASL sequences of both vendors can be explained by differences in the employed readout modules. These differences may seriously hamper multicenter pharmacological ASL, which strongly encourages standardization of ASL implementations.

Objectives: Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD., Methods: Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed., Results: Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68)., Conclusions: Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET., Key Points: • Similar patterns of hypoperfusion and hypometabolism were observed in patients with dementia. • For both imaging modalities, parietal abnormalities were found in Alzheimer's disease. • For both imaging modalities, prefrontal abnormalities were found in frontotemporal dementia.

Recently, there has been an increased interest in the use of automatically segmented subfields of the human hippocampal formation derived from magnetic resonance imaging (MRI). However, little is known about the test-retest reproducibility of such measures, particularly in the context of multisite studies. Here, we report the reproducibility of automated Freesurfer hippocampal subfields segmentations in 65 healthy elderly enrolled in a consortium of 13 3T MRI sites (five subjects per site). Participants were scanned in two sessions (test and retest) at least one week apart. Each session included two anatomical 3D T1 MRI acquisitions harmonized in the consortium. We evaluated the test-retest reproducibility of subfields segmentation (i) to assess the effects of averaging two within-session T1 images and (ii) to compare subfields with whole hippocampus volume and spatial reliability. We found that within-session averaging of two T1 images significantly improved the reproducibility of all hippocampal subfields but not that of the whole hippocampus. Volumetric and spatial reproducibility across MRI sites were very good for the whole hippocampus, CA2-3, CA4-dentate gyrus (DG), subiculum (reproducibility error∼2% and DICE > 0.90), good for CA1 and presubiculum (reproducibility error ∼ 5% and DICE ∼ 0.90), and poorer for fimbria and hippocampal fissure (reproducibility error ∼ 15% and DICE < 0.80). Spearman's correlations confirmed that test-retest reproducibility improved with volume size. Despite considerable differences of MRI scanner configurations, we found consistent hippocampal subfields volumes estimation. CA2-3, CA4-DG, and sub-CA1 (subiculum, presubiculum, and CA1 pooled together) gave test-retest reproducibility similar to the whole hippocampus. Our findings suggest that the larger hippocampal subfields volume may be reliable longitudinal markers in multisite studies., (© 2015 Wiley Periodicals, Inc.)

Purpose: To evaluate intervertebral disc (IVD) degeneration and treatments, an objective diagnostic tool is needed. Recently, T2* relaxation time mapping was proposed as a technique to assess early IVD degeneration, yet the correlation with biochemical content and histological features has not been investigated previously. Our objective was to validate T2* mapping for disc degeneration by correlating this technique with accepted parameters of IVD degeneration., Methods: Mildly and severely degenerated lumbar discs were obtained from an in vivo large animal study; two healthy goat spines were acquired as control. In total, 48 IVDs were analysed using T2-weighted MRI, T2* relaxation time mapping, biochemical assays, macroscopic and histological scoring. Correlations between variables were expressed with Spearman's rho (ρ) coefficients., Results: A complete range of degenerative grades were obtained (mean histological grade 2.2, range 0-6). A linear positive correlation was observed between T2* relaxation time and glycosaminoglycan content (ρ = 0.64, p < 0.001). T2* relaxation time decreased linearly with increasing degeneration as assessed with Pfirrmann scoring system (ρ = -0.67, p < 0.001), macroscopic (ρ = -0.33, p < 0.05) and histological (ρ = -0.45, p < 0.05) grading., Conclusions: T2* mapping is an MRI technique for IVD evaluation which allows for measurements on a continuous scale thus minimising observer bias compared to grading systems. Although limited by a small sample size, this study showed a relatively good and linear correlation between T2* relaxation time and accepted parameters of disc degeneration. This suggests that T2* mapping is a promising tool to assess disc degeneration in clinical practice.

Objective: To assess the effect of fasting and eating on estimates of apparent diffusion coefficient (ADC) in the livers of healthy volunteers using a diffusion-weighted MRI protocol with b-values of 100, 500 and 900 s mm(-2) in a multicentre study at 1.5 T., Methods: 20 volunteers were scanned using 4 clinical 1.5-T MR scanners. Volunteers were scanned after fasting for at least 4 h and after eating a meal; the scans were repeated on a subsequent day. Median ADC estimates were calculated from all pixels in three slices near the centre of the liver. Analysis of variance (ANOVA) was used to assess the difference between ADC estimates in fasted and non-fasted states and between ADC estimates on different days., Results: ANOVA showed no difference between ADC estimates in fasted and non-fasted states (p = 0.8) nor between ADC estimates on different days (p = 0.8). The repeatability of the measurements was good, with coefficients of variation of 5.1% and 4.6% in fasted and non-fasted states, respectively., Conclusion: There was no significant difference in ADC estimates between fasted and non-fasted measurements, indicating that the perfusion sensitivity of ADC estimates obtained from b-values of 100, 500 and 900 s mm(-2) is sufficiently low that changes in blood flow in the liver after eating are undetectable beyond the variability in the measurements., Advances in Knowledge: Assessment of the effect of prandial state on ADC estimates is critical, in order to determine the appropriate patient preparation for biological validation in clinical trials.

Purpose: To compare cerebral blood flow (CBF) values measured using magnetic resonance imaging (MRI) arterial spin labeling (ASL) with those obtained with [(15)O]H2O positron emission tomography (PET), the gold standard for measuring CBF in vivo., Materials and Methods: Data were collected in 11 healthy men and in 20 age- and body mass index (BMI)-matched type 1 diabetic men. Pseudo-continuous ASL (PCASL) data were acquired at 3 T and [(15)O]H2O PET scans were acquired using a high-resolution PET scanner. Input functions were obtained using on-line arterial blood sampling. Whole brain and regional CBF values were compared., Results: For both modalities, whole brain CBF was similar in both subject groups. In groups combined, average whole brain CBF was 0.30 ± 0.05 mL · cm(-3) · min(-1) for [(15)O]H2O PET and 0.34 ± 0.05 mL · cm(-3) · min(-1) for ASL MRI (P < 0.01). A significant correlation between methods was observed for whole brain, gray and white matter. In 12 out of 33 brain regions a significant difference between methods was observed., Conclusion: PCASL provides CBF values that correlate with [(15)O]H2O PET-derived values, but is less accurate. PCASL may be an attractive alternative when absolute quantification is not needed., (© 2013 Wiley Periodicals, Inc.)

Conflicting results on differentiating edema and glioma by diffusion tensor imaging (DTI) are possibly attributable to dissimilar spatial distribution of the lesions. Combining DTI-parameters and enhanced registration might improve prediction. Regions of edema surrounding 22 metastases were compared to tumor-infiltrated regions from WHO grade 2 (12), 3 (10) and 4 (18) gliomas. DTI data was co-registered using Tract Based Spatial Statistics (TBSS), to measure Fractional Anisotropy (FA) and Mean Diffusivity (MD) for white matter only, and relative changes compared to matching reference regions (dFA and dMD). A two-factor principal component analysis (PCA) on metastasis and grade 2 glioma was performed to explore a possible differentiating combined factor. Edema demonstrated equal MD and higher FA compared to grade 2 and 3 glioma (P < 0.001), but did not differ from glioblastoma. Differences were non-significant when corrected for spatial distribution, since reference regions differed strongly (P < 0.001). The second component of the PCA (PCA-C2) did differentiate edema and low-grade tumor (sensitivity 91.7%, specificity 86.4%). PCA-C2 scores were plotted voxel-wise as a probability-map, discerning distinct areas of presumed edema or tumor infiltration. Correction of spatial dependency appears essential when differentiating glioma from edema. A tumor-infiltration probability-map is presented, based on supplementary information of multiple DTI parameters and spatial normalization.

Objectives: To compare pseudo-continuous arterial spin-labelled (PCASL) magnetic resonance imaging (MRI) measured quantitative cerebral blood flow (CBF) of patients with frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), Alzheimer's disease (AD) and controls, in a region of interest (ROI) and voxel-wise fashion., Methods: We analysed whole-brain 3D fast-spin-echo PCASL images of 20 FTD patients, 14 DLB patients, 48 AD patients and 50 controls from the Amsterdam Dementia Cohort. Regional CBF patterns were compared using analyses of variance for repeated measures. Permutation tests were used for voxel-wise comparisons. Analyses were performed using uncorrected and partial volume corrected (PVC) maps. All analyses were corrected for age and sex., Results: There was an interaction between diagnosis and region (p < 0.001), implying differences in regional CBF changes between diagnostic groups. In AD patients, CBF was decreased in all supratentorial regions, most prominently so in the posterior regions. DLB patients showed lowest CBF values throughout the brain, but temporal CBF was preserved. Supratentorial PVC cortical CBF values were lowest in the frontal lobes in FTD patients, and in the temporal lobes in AD patients., Conclusions: Patients with AD, FTD and DLB display distinct patterns of quantitative regional CBF changes. 3D-PCASL may provide additional value in the workup of dementia patients., Key Points: Patterns of regional CBF changes differ between AD, FTD and DLB patients. CBF is lower throughout the brain in DLB than AD and FTD. 3D-PCASL MRI is a potential non-invasive and easily accessible alternative to FDG-PET. 3D-PCASL MRI may be of additional value in the workup of dementia.

Purpose: Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips., Material and Methods: 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level., Results: Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM., Conclusion: These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors.

Recently, a new MRI technique was developed at 3 Tesla (T), called fluid attenuated inversion recovery* (FLAIR*). In this study, we implemented FLAIR* in an existing MS cohort at 7 T, to investigate whether we could corroborate results of previous 7 T studies that introduced specific MS lesion characteristics. Furthermore, we aimed to investigate the meaning of these lesion characteristics by relating them to clinical characteristics of the MS patient. Three-dimensional FLAIR and T2*-weighted images of 33 MS patients and 7 healthy controls were fused into FLAIR* images. Lesion type, signal intensity and morphology were analysed on FLAIR*, side-by-side with the original FLAIR and T2*, and correlated with clinical characteristics using Spearman's rho. Three morphological features of MS lesions were visualised: (1) central vessel (CV) within lesions, present in 78 % of total MS lesions; (2) hypointense rims around MS lesions, present in eight patients; (3) FLAIR* lesions that were hypointense at T2*, present in 13 patients. The presence of hypointense (rims around) lesions was not related to clinical characteristics. The simultaneous presence of rimlike lesions and hypointense lesions within MS patients was significantly correlated (ρ = 0.52, P < 0.01). We conclude that the implementation of the new MRI technique FLAIR* at ultra-high-field 7 T combines and corroborates the results of preceding 7 T research, by showing three morphological features of MS lesions. In addition, our study shows that these phenomena do not show a relation to patient's clinical characteristics and cannot be allocated to certain MS disease subtypes.

Aim: A pilot study to phenotype young adults (< 40 years) with Type 2 diabetes mellitus., Methods: Twenty people with Type 2 diabetes (aged 18-40 years), 10 lean and 10 obese control subjects underwent detailed assessment, including tagged cardiac magnetic resonance imaging, inflammatory proteins, lipids, vitamin D and maximal oxygen uptake. Outcomes were compared between the group with Type 2 diabetes and the control group., Results: Mean (standard deviation) age, Type 2 diabetes duration and BMI in the group with Type 2 diabetes were 31.8 (6.6) years, 4.7 (4.0) years and 33.9 (5.8) kg/m(2) respectively. Compared with lean control subjects, those with Type 2 diabetes had more deleterious profiles of hyperlipidaemia, vitamin D deficiency, inflammation and maximal oxygen uptake relative to body mass. However, there was no difference between the group with Type 2 diabetes and the obese control group. The group with Type 2 diabetes had a higher left ventricular mass and a trend towards concentric remodelling compared with the lean control group (P = 0.002, P = 0.052) but not the obese control group (P > 0.05). Peak early diastolic strain rate was reduced in the group with Type 2 diabetes [1.51 (0.24)/s] compared with the lean control [1.97 (0.34)/s, P = 0.001] and obese control [1.78 (0.39)/s, P = 0.042] group., Conclusions: Young adults with Type 2 diabetes and those with obesity have similar adverse cardiovascular risk profiles, higher left ventricular mass and a trend towards left ventricular concentric remodelling. In addition, those with Type 2 diabetes demonstrate diastolic dysfunction, a known risk marker for future heart failure and mortality., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Objectives: To investigate whether a new magnetic resonance image (MRI) technique called T2*-weighted fluid attenuation inversion recovery (FLAIR*) can differentiate between multiple sclerosis (MS) and vascular brain lesions, at 7 Tesla (T)., Methods: We examined 16 MS patients and 16 age-matched patients with (risk factors for) vascular disease. 3D-FLAIR and T2*-weighted images were combined into FLAIR* images. Lesion type and intensity, perivascular orientation and presence of a hypointense rim were analysed., Results: In total, 433 cerebral lesions were detected in MS patients versus 86 lesions in vascular patients. Lesions in MS patients were significantly more often orientated in a perivascular manner: 74 % vs. 47 % (P < 0.001). Ten MS lesions (2.3 %) were surrounded by a hypointense rim on FLAIR*, and 24 MS lesions (5.5 %) were hypointense on T2*. No lesions in vascular patients showed any rim or hypointensity. Specificity of differentiating MS from vascular lesions on 7-T FLAIR* increased when the presence of a central vessel was taken into account (from 63 % to 88 %), most obviously for deep white matter lesions (from 69 % to 94 %). High sensitivity remained (81 %)., Conclusion: 7-T FLAIR* improves differentiation between MS and vascular lesions based on lesion location, perivascular orientation and presence of hypointense (rims around) lesions., Key Points: • A new MRI technique T2*-weighted fluid attenuation inversion recovery (FLAIR*) was investigated. • FLAIR* at 7-T MRI combines FLAIR and T2* images into a single image. • FLAIR* at 7 T does not require enhancement with contrast agents. •High-resolution 7-T FLAIR* improves differentiation between MS and vascular brain lesions. • FLAIR* revealed a central vessel more frequently in MS than vascular lesions.

Objective: To determine prevalence, topography, and severity of cortical superficial siderosis (SS), a recently recognized manifestation of cerebral amyloid angiopathy, and its possible association with Alzheimer disease (AD) in a memory clinic patient cohort., Methods: We included 809 patients (56% men, aged 66 ± 10 years) from the Amsterdam Dementia Cohort between November 2010 and November 2012 scanned on a 3-tesla MRI system. We analyzed prevalence and topography of cortical SS according to demographic, clinical, and MRI data. Agreement for SS detection between 2 neuroradiologists was calculated by using Cohen κ., Results: Agreement for detection of SS was excellent (unweighted κ of 0.81). In 17 patients (2.1%), cortical SS was found without a known cause. The prevalence of idiopathic SS differed according to diagnostic groups (p < 0.001): nearly 5% (95% confidence interval [CI] 2.8%-8.2%) in patients with AD (n = 168) vs 2% (95% CI 0.7%-6.0%) in patients with mild cognitive impairment (n = 143) and 2.5% (95% CI 0.7%-8.7%) in other types of dementia (n = 80). By contrast, SS was not found in patients with subjective complaints (n = 168) or in those with other disorders (n = 157). Presence of SS was associated with APOE ε4, microbleeds, and white matter hyperintensities (all p < 0.05) independent of diagnosis., Conclusion: The prevalence of cortical SS in a memory clinic setting is higher than reported in the general population but lower than reported in cerebral amyloid angiopathy. The relatively high prevalence of SS in AD suggests that SS is a relevant radiologic manifestation of amyloid pathology in AD. Presence of SS does not seem to predict severity of AD. Further longitudinal research is needed to investigate clinical relevance.

Background and Purpose: 7T MR imaging has led to improved detection and classification of cortical MS lesions, mainly based on T2*-weighted gradient-echo sequences. Depiction of cortical GM by using the recommended MS imaging protocol has not yet been investigated at 7T. We aimed to investigate prospectively which recommended sequence for clinical use has the highest value at 7T, in terms of GM and WM lesion detection., Materials and Methods: Thirty-seven patients with MS (mean age, 43.8 years; 25 women) and 7 healthy controls (mean age, 40.4 years; 5 women) underwent multicontrast 7T MR imaging including the recommended clinical 2D-T2WI, 3D-T1WI, 3D-FLAIR, and GM-specific 3D-DIR. Lesions were scored and categorized anatomically by 3 raters, in consensus. The value of sequences was evaluated lesion-wise and patient-wise (Wilcoxon signed-rank test)., Results: At 7T, 3D-FLAIR detected the highest number of total cortical GM lesions (217), 89% more than 3D-DIR and 87% and 224% more than 2D-T2WI and 3D-T1WI. Patient-wise analysis showed that this difference between 3D-FLAIR and 3D-DIR was statistically significant (P<.04), and most pronounced for the number of mixed lesions (P<.03). 3D-FLAIR also detected the highest number of total WM lesions (2605), but the difference with 3D-DIR and 3D-T1WI was not significant., Conclusions: When using recommended clinical sequences at 7T, the best way to detect cortical GM lesions is with 3D-FLAIR and not by GM-specific 3D-DIR or by conventional 2D-T2WI and 3D-T1WI sequences.

Purpose: To compare quantitative cerebral blood flow (CBF) values in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and subjects with subjective complaints by using a whole-brain three-dimensional (3D) pseudocontinuous arterial spin-labeling (ASL) technique at 3.0 T., Materials and Methods: The local institutional review board approved the study. All subjects provided informed consent. Whole-brain 3D fast spin-echo pseudocontinuous ASL images were acquired at 3.0 T in 71 patients with AD (mean age, 65 years ± 7; 55% women), 35 patients with MCI (mean age, 65 years ± 8; 42% women), and 73 subjects with subjective complaints (mean age, 60 years ± 9; 39% women) who visited a memory clinic. Analyses were performed by using both uncorrected maps and maps corrected for partial volume effects. Regional CBF was compared by using analyses of variance; permutation tests were used for voxel-wise comparisons. Associations with cognition (Mini-Mental State Examination) were investigated by using linear regression analyses. All analyses were corrected for age and sex., Results: Uncorrected CBF was decreased in patients with AD compared with subjects with subjective complaints (27 mL/100 g/min ± 5 vs 33 mL/100 g/min ± 5; P < .001), with strongest reductions in the parietal lobes (22 mL/100 g/min ± 6 vs 30 mL/100 g/min ± 5; ie, decrease of 27%). Corrected cortical CBF showed similar results. In patients with MCI, CBF was decreased in the precuneus and the parietal and occipital lobes compared with subjects with subjective complaints. Voxel-wise comparisons confirmed the region of interest-based findings, showing the largest CBF differences in the precuneus and bilateral parietal cortex. Uncorrected and corrected cortical CBF were associated with cognition across diagnostic groups (β = 0.46 and β = 0.42, P < .001) and within the AD group (β = 0.41 and β = 0.42, P < .001)., Conclusion: CBF measured with 3D pseudocontinuous ASL MR imaging helps detect functional changes in the prodromal and more advanced stages of AD and is a marker for disease severity., (RSNA, 2012)

Purpose: With the introduction of hybrid PET∕MRI systems, it has become more likely that the cyclotron and MRI systems will be located close to each other. This study considered the interference between a cyclotron and a superconducting MRI system., Methods: Interactions between cyclotrons and MRIs are theoretically considered. The main interference is expected to be the perturbation of the magnetic field in the MRI due to switching on or off the magnetic field of the cyclotron. MR imaging is distorted by a dynamic spatial gradient of an external inplane magnetic field larger than 0.5-0.04 μT∕m, depending on the specific MR application. From the design of a cyclotron, it is expected that the magnetic fringe field at large distances behaves as a magnetic dipolar field. This allows estimation of the full dipolar field and its spatial gradients from a single measurement. Around an 18 MeV cyclotron (Cyclone, IBA), magnetic field measurements were performed on 5 locations and compared with calculations based upon a dipolar field model., Results: At the measurement locations the estimated and measured values of the magnetic field component and its spatial gradients of the inplane component were compared, and found to agree within a factor 1.1 for the magnetic field and within a factor of 1.5 for the spatial gradients of the field. In the specific case of the 18 MeV cyclotron with a vertical magnetic field and a 3T superconducting whole body MR system, a minimum distance of 20 m has to be considered to prevent interference., Conclusions: This study showed that a dipole model is sufficiently accurate to predict the interference of a cyclotron on a MRI scanner, for site planning purposes. The cyclotron and a whole body MRI system considered in this study need to be placed more than 20 m apart, or magnetic shielding should be utilized.

Background and Purpose: Noninvasive evaluation of retinoblastoma treatment response has become more important due to increased use of eye-sparing treatments. We evaluated the relation between DCE-MR imaging and histopathologic parameters to determine the value of DCE-MR imaging in assessing tumor angiogenesis and prognostic features., Materials and Methods: Fifteen consecutive patients with retinoblastoma (mean age, 24 months; range, 2-70 months) undergoing enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was evaluated by 2 observers by using curve-pattern analysis, with the first 5 minutes of each curve and the full time-series described as κ(5min) and κ(17min), respectively. Assessed histopathologic and immunologic parameters included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and expression of VEGF and Flt-1., Results: The median value of κ(5min) was 1.28 (range, 0.87-2.07) and correlated positively with MVD (P = .008). The median value of κ(17min) was 1.33 (range, 0.35-3.08) and correlated negatively with tumor necrosis (P = .002). Other histopathologic and immunohistopathologic parameters did not correlate with DCE-MR imaging parameters. Interobserver agreement was 0.53 for κ(5min) and 0.91 for κ(17min)., Conclusions: In retinoblastoma, the early phase of the DCE time curve positively correlates with MVD, while the presence of late enhancement is correlated with necrosis. Thus, the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and necrosis in retinoblastoma is promising and warrants further investigation.

There is growing interest in the use of stereotactic body radiation therapy (SBRT) for spinal metastases. With the need for accurate target definition and conformal avoidance of critical normal structures, high-quality multimodal imaging has emerged as a key component at each stage of the treatment process. Multidisciplinary collaboration is necessary to optimize imaging protocols and implement imaging advances into routine patient care., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To test whether a 3D imaging sequence with phase contrast (PC) velocity encoding based on steady-state free precession (SSFP) improves 3D velocity quantification in the heart compared to the currently available gradient echo (GE) approach., Materials and Methods: The 3D PC-SSFP sequence with 1D velocity encoding was compared at the mitral valve in 12 healthy subjects with 3D PC-GE at 1.5T. Velocity measurements, velocity-to-noise-ratio efficiency (VNR(eff)), intra- and interobserver variability of area and velocity measurements, contrast-to-noise-ratio (CNR), and artifact sensitivity were evaluated in both long- and short-axis orientation., Results: Descending aorta mean and peak velocities correlated well (r(2) = 0.79 and 0.93) between 3D PC-SSFP and 3D PC-GE. At the mitral valve, mean velocity correlation was moderate (r(2) = 0.70 short axis, 0.56 long axis) and peak velocity showed good correlation (r(2) = 0.94 short axis, 0.81 long axis). In some cases VNR(eff) was higher, in others lesser, depending on slab orientation and cardiac phase. Intra- and interobserver variability was generally better for 3D PC-SSFP. CNR improved significantly, especially at end systole. Artifact levels did not increase., Conclusion: 3D SSFP velocity quantification was successfully tested in the heart. Blood-myocardium contrast improved significantly, resulting in more reproducible velocity measurements for 3D PC-SSFP at 1.5T.

Objectives: The aim of this study was to evaluate the effects of alcohol septal ablation (ASA) on coronary blood flow in symptomatic hypertrophic obstructive cardiomyopathy (HOCM) using cardiac MR (CMR) coronary flow measurements. Background CMR flow mapping enables quantification of coronary blood flow in a noninvasive way. Both left ventricular outflow tract (LVOT) gradient reduction and myocardial scarring after ASA are expected to influence left anterior descending (LAD) coronary blood flow., Methods: Cine, contrast-enhanced (CE) imaging and breath-hold CMR phase contrast velocity mapping were performed at baseline and 1 and 6 months after ASA in seven patients. Changes of coronary blood flow were related to left ventricular (LV) mass reduction, enzyme release, volume of ethanol administered, LVOT gradient reduction, and LV rate pressure product (LVRPP)., Results: A significant mass reduction was observed both in the target septal myocardium and in the total myocardium (both P < 0.01). Mean myocardial infarct size was 23 +/- 12 g (range 7.3-41.6 g). LVRPP decreased from 13,268 +/- 2,212 to 10,685 +/- 3,918 at 1 month (P = 0.05) and 9,483 +/- 2,496 mmHg beats/min at 6 months' follow-up (P < 0.01). LAD coronary blood flow decreased from 100 +/- 37 ml/min at baseline to 84 +/- 54 ml/min (P = 0.09) at 1 month and 67 +/- 33 ml/min at 6 months follow-up (P < 0.01). A significant correlation was found between the change in LVRPP and LAD coronary flow at 1 month follow-up (r = 0.83, P = 0.02). CE-infarct size tended to modulate the blood flow changes over time (P = 0.12); no correlation was observed between enzyme release, volume of ethanol or both septal and total mass reduction and coronary blood flow., Conclusion: The reduction in coronary blood flow is primarily associated with diminished LV loading conditions, whereas the induction of metabolically inactive myocardial scar tissue by ASA did not significantly influence the changes in coronary blood flow.

Purpose: To compare left ventricular (LV) torsion represented as the circumferential-longitudinal (CL) shear angle between 2D and 3D quantification, using cardiovascular magnetic resonance (CMR)., Methods: CMR tagging was performed in six healthy volunteers. From this, LV torsion was calculated using a 2D and a 3D method. The cross-correlation between both methods was evaluated and comparisons were made using Bland-Altman analysis., Results: The cross-correlation between the curves was r2 = 0.97 +/- 0.02. No significant time-delay was observed between the curves. Bland-Altman analysis revealed a significant positive linear relationship between the difference and the average value of both analysis methods, with the 2D results showing larger values than the 3D. The difference between both methods can be explained by the definition of the 2D method., Conclusion: LV torsion represented as CL shear quantified by the 2D and 3D analysis methods are strongly related. Therefore, it is suggested to use the faster 2D method for torsion calculation.

Multiecho phase-contrast steady-state free precession (PC-SSFP) is a recently introduced sequence for flow quantification. In this multiecho approach, a phase reference and a velocity-encoded readout were acquired at different echo times after a single excitation. In this study, the sequence is validated in vitro for stationary flow. Subsequently, the sequence was evaluated on cardiac output measurements in vivo for through-plane flow in comparison to regular single gradient echo velocity quantification [phase-contrast spoiled gradient echo (PC-GE)]. In vitro results agreed with regular flow meters (RMS 0.1 cm/s). Cardiac output measurements with multiecho PC-SSFP on 10 healthy subjects gave on average the same results as the standard PC-GE. However, the limits of repeatability of PC-SSFP were significantly larger than those of PC-GE (2 l/min and 0.5 l/min, respectively, P=.001). The multiecho approach introduced some specific problems in vivo. The difference in echo times made the velocity maps sensitive for water-fat shifts and B(0)-drifts, which in turn made velocity offset correction problematic. Also, the addition of a single bipolar gradient cancelled the flow compensated nature of the SSFP sequence. In combination with the prolonged TR, this resulted in flow artifacts caused by high and pulsatile through-plane flow, affecting repeatability. Given the significantly lower repeatability of PC-SSFP, cardiac output in turn is less reliable, thus impairing the use of multiecho PC-SSFP.

Purpose: A change in surface area of the capsular bag and a change in volume of the lens can indicate whether a change in the shape of the lens during accommodation is due to the compressibility or the elasticity of the lens material., Methods: 3D magnetic resonance imaging (MRI) was used to image the complete shape of the lens in a group of five healthy subjects between 18 and 35 years of age. A parametric representation of the cross-sectional shape was fitted to the edges of the lens, which were determined with a Canny edge filter. Based on a partition of the lens into eight parts, the parametric shape makes it possible to calculate the mean cross-sectional area, the volume, and the surface area as a function of accommodation. Corrected Scheimpflug imaging was used to validate the results obtained with MRI., Results: No significant difference in central anterior and posterior radius of curvature and thickness was found between the MRI and Scheimpflug measurements. In accordance with the Helmholtz accommodation theory, a decrease in the anterior and posterior radius of curvature and equatorial diameter and an increase in lens thickness occurred with accommodation. During accommodation, the mean cross-sectional area increased and the surface area decreased. However, no significant change in lens volume was found., Conclusions: The preservation of lens volume implies that the internal human lens material can be assumed to be incompressible and is undergoing elastic deformation. Furthermore, the change in surface area indicates that the capsular bag also undergoes elastic deformation.

Study Objectives: Although subjective complaints about daytime cognitive functioning are an essential symptom of chronic insomnia, abnormalities in functional brain activation have not previously been investigated. This study was designed to investigate functional brain activation differences as a possible result of chronic insomnia, and the reversibility of these differences after nonmedicated sleep therapy., Design: Insomniacs and carefully matched controls underwent functional magnetic resonance imaging (fMRI) scanning during the performance of a category and a letter fluency task. Insomniacs were randomly assigned to either a 6-week period of nonpharmacological sleep therapy or a wait list period, after which fMRI scanning was repeated using parallel tasks. Task-related brain activation and number of generated words were considered as outcome measures., Setting: The outpatient sleep clinic of the VU University Medical Center, Department of Clinical Neurophysiology; fMRI was performed at the Department of Radiology., Participants: Twenty-one patients suffering from chronic insomnia and 12 matched controls., Interventions: Nonpharmacological sleep therapy for 6 weeks, consisting of cognitive behavioral therapy, body temperature and bright light interventions, sleep hygiene, and physical activity counseling., Measurement and Results: Compared to controls, insomnia patients showed hypoactivation of the medial and inferior prefrontal cortical areas (Brodmann Area 9, 44-45), which recovered after sleep therapy but not after a wait list period., Conclusions: Insomnia interferes in a reversible fashion with activation of the prefrontal cortical system during daytime task performance.

Considering that there are several theoretical reasons why fMRI data is correlated to variations in heart rate, these correlations are explored using experimental resting state data. In particular, the possibility is discussed that the "default network", being a brain area that deactivates during non-specific general tasks, is a hemodynamic effect caused by heart rate variations. Of fifteen healthy controls ECG, EEG and fMRI were co-registered. Slice time dependent heart rate regressors were derived from the ECG data and correlated to fMRI using a linear correlation analysis where the impulse response is estimated from the data. It was found that in most subjects substantial correlations between heart rate variations and fMRI exist, both within the brain and at the ventricles. The brain areas with high correlation to heart rate are different from the "default network" and the response functions deviate from the canonical hemodynamic response function. Furthermore, a general negative correlation was found between heart beat intervals (reverse of heart rate) and alpha power. We interpret this finding by assuming that subject's state varies between drowsiness and wakefulness. Finally, given this large correlation, we re-examined the contribution of heart rate variations to earlier reported fMRI/alpha band correlations, by adding heart rate regressors as confounders. It was found that inclusion of these confounders most often had a negligible effect. From its strong correlation to alpha power, we conclude that the heart rate variations contain important physiological information about subject's resting state. However, it does not provide a full explanation of the behaviour of the "default network". Its application as confounder in fMRI experiments is a relatively small computational effort, but may have a substantial impact in paradigms where heart rate is controlled by the stimulus.

Background and Purpose: On MR imaging, white matter hyperintensities (WMH) on T2-weighted images are generally considered as a surrogate marker of ischemic small vessel disease in elderly subjects. Pulsed arterial spin-labeling (PASL) is a noninvasive MR perfusion-weighted technique. We hypothesized that elderly subjects with diffuse confluent WMH should have lower cerebral blood flow (CBF) measurements than subjects with punctiform or beginning confluent WMH., Materials and Methods: MR images of 21 subjects (13 women; mean age, 76 years; SD, 5), stratified for the degree of WMH, from a single center within the multinational Leukoaraiosis and Disability (LADIS) study, were investigated. CBF images were obtained by means of quantitative imaging of perfusion by using a single-subtraction second version, with thin-section TI periodic saturation PASL. Values of cortical gray matter, subcortical (including white matter and deep gray matter), and global CBF were calculated. CBF measurements of subjects with diffuse confluent WMH (n = 7) were compared with those of subjects with punctiform or beginning confluent WMH (n = 14)., Results: Subjects with diffuse confluent WMH were found to have approximately 20% lower mean global CBF (43.5 mL/100 mL/min; SD, 6.3) than subjects with punctiform or beginning confluent WMH (57.9 mL/100 mL/min; SD, 8.6; P < .01), as well as approximately 20% lower mean subcortical (P < .01) and cortical gray matter CBF (P < .05)., Conclusion: PASL revealed a significant reduction of CBF measurements in elderly subjects with diffuse confluent WMH.

Purpose: To introduce a standardized method for calculation of left ventricular torsion by CMR tagging and to determine the accuracy of torsion analysis in regions using an analytical model., Methods: Torsion between base and apex, base and mid, and mid and apex levels was calculated using CSPAMM tagging and Harmonic Phase tracking. The accuracy of torsion analysis on a regional basis (circumferential segments and transmural layers) was analyzed using an analytical model of a deforming cylinder with a displaced axis of rotation (AoR). Regional peak torsion values from twelve healthy volunteers calculated by the described method were compared to literature., Results: The deviation from the analytical torsion per % AoR-displacement (of the radius) was 0.90 +/- 0.44% for the circumferential segments and only 0.05% for the transmural layers. In the subjects, circumferentially, anterolateral torsion was larger than inferior (12.4 +/- 3.9 degrees vs. 5.0 +/- 3.3 degrees , N.S.). Transmurally, endocardial torsion was smaller than epicardial (7.5 +/- 1.3 degrees vs. 8.0 +/- 1.5 degrees , p < 0.001)., Conclusion: Variability in the position of the AoR causes a large variability in torsion in circumferential segments. This effect was negligible for global torsion, and torsion calculated in transmural layers. Results were documented for the healthy human heart and are in agreement with data from literature.

Brain activation in studies using blood oxygenation level dependent (BOLD) FMRI is associated with an increase in T2* weighted signal between baseline and an active condition. This BOLD technique is often applied to study differences in brain activation between patients and healthy controls. However, the baseline T2* signal itself may also be different between groups, as shown in the hippocampus in Alzheimer's disease using the resting oxygen or ROXY approach (Small et al. [2002]: Ann Neurol 51:290-295). In the current study, we analyzed whole brain, voxel-wise T2* weighted signal of averaged baseline scans of a BOLD FMRI experiment in 41 healthy elderly controls and 46 patients with mild cognitive impairment or Alzheimer's disease. In each subject, T2* weighted images were normalized to the CSF signal of the same image. Additionally, gray matter probability maps of high-resolution structural scans were also compared between groups to assess atrophy. T2* signal was decreased in dementia in the hippocampus, insula/putamen, posterior and middle cingulate cortex, and parietal cortex. Most of these regions also showed decreased gray matter, except insula/putamen. Hippocampal and posterior cingulate gray matter differences were significantly larger than T2* differences. Therefore, decreased T2* signal in most regions are likely to be caused by gray matter atrophy, although decreased metabolism or perhaps iron deposition are also factors that may contribute. We conclude that in FMRI studies of dementia, not only the dynamic BOLD signal (activation and deactivation) but also the average baseline signal is diminished in certain regions. The method we applied may also be used in task-rel, ((copyright) 2007 Wiley-Liss, Inc.)

Objective: Co-registration of EEG (electroencephalogram) and fMRI (functional magnetic resonance imaging) remains a challenge due to the large artifacts induced on the EEG by the MR (magnetic resonance) sequence magnetic fields. Thus, we present an algorithm, based on the average-subtraction method, which is able to correct EEG data for gradient and pulse artifacts., Methods: MR sequence timing parameters are estimated from the EEG data and both slice and volume artifact templates are subtracted from the data. A clustering algorithm is proposed to account for the variability of the pulse artifact., Results: The algorithm is able to keep the spontaneous EEG as well as visual evoked potentials (VEPs), while removing gradient and pulse artifacts with only a subtraction of selectively averaged data. In the frequency domain, the artifact frequencies are strongly attenuated. Estimated MR sequence time parameters showed that the correction is extremely sensitive to the slice time value. Pulse artifact clustering showed that most of the variability is due to the time jitter of the pulse artifact markers., Conclusions: Selective subtraction of averages in combination with proper time alignment is enough to remove most of the MR-induced artifacts., Significance: Clean EEG can be obtained from raw signals that are corrupted by MR-induced artifacts during simultaneous EEG-fMRI scanning without using dedicated hardware to synchronize EEG and fMRI clocks.

Our aim was to determine the diagnostic value of myocardial tagging sequences with regard to the evaluable share of the cardiac cycle. Thirty-three patients were examined at 1.5 T using tagging sequences with gradient-echo (GRE) readout, 18 patients at 1.5 T with steady-state free precession (SSFP), and 11 patients at 3 T using GRE. Two observers graded image quality and determined the share of the cardiac cycle for which postprocessing could be performed (1, optimal; 2, little interaction; 3, whole cycle assessable; 4, diastole non-assessable; 5, systole incomplete; 6, non-diagnostic). With GRE at 1.5 T, median image quality was 4.0 (95% CI 4.0-5.0), while it was significantly better with 2.0 (2.0-3.0) using the SSFP technique and similar at 3 T with 2.9 (1.7-3.5). With GRE at 1.5 T, systole could be assessed in 69% of patients, and an evaluation of the whole cardiac cycle was not possible. With the SSFP sequence at 1.5 T and GRE at 3 T, an evaluation of the whole cardiac cycle was possible in 71% and 70% of the patients, respectively, and systole was assessable in all patients. Tagging sequences with SSFP readout at 1.5 T make a semi-automatic evaluation of the whole cardiac cycle feasible in a large share of patients.

Glucocorticoids (GCs, cortisol in human) are associated with impairments in declarative memory retrieval. Brain regions hypothesized to mediate these effects are the hippocampus and prefrontal cortex (PFC). Our aim was to use fMRI in localizing the effects of GCs during declarative memory retrieval. Therefore, we tested memory retrieval in 21 young healthy males in a randomized placebo-controlled crossover design. Participants encoded word lists containing neutral and emotional words 1 h prior to ingestion of 20 mg hydrocortisone. Memory retrieval was tested using an old/new recognition paradigm in a rapid event-related design. It was found that hydrocortisone decreased brain activity in both the hippocampus and PFC during successful retrieval of neutral words. These observations are consistent with previous animal and human studies suggesting that glucocorticoids modulate both hippocampal and prefrontal brain regions that are crucially involved in memory processing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11682-007-9003-2) contains supplementary material, which is available to authorized users.

EEG was recorded during fMRI scanning of 16 normal controls in resting condition with eyes closed. Time variations of the occipital alpha band amplitudes were correlated to the fMRI signal variations to obtain insight into the hemodynamic correlates of the EEG alpha activity. Contrary to earlier studies, no a priori assumptions were made on the expected shape of the alpha band response function (ARF). The ARF of different brain regions and subjects were explored and compared. It was found that: (1) the ARF of the thalamus is mainly positive. (2) The ARFs at the occipital and left and right parietal points are similar in amplitude and timing. (3) The peak time of the thalamus is a few seconds earlier than that of occipital and parietal cortex. (4) No systematic BOLD activity was found preceding the alpha band activity, although in the two subjects with the strongest alpha band power such correlation was present. (5) There is a strong and immediate positive correlation at the eyeball, and a strong negative correlation at the back of the eye. Furthermore, it was found that in one subject the cortical ARF was positive, contrary to the other subjects. Finally, a cluster analysis of the observed ARF, in combination with a Modulated Sine Model (MSM) fit to the estimated ARF, revealed that within the cortex the ARF peak time shows a spatial pattern that may be interpreted as a traveling wave. The spatial pattern of alpha band response function represents the combined effect of local differences in electrical alpha band activity and local differences in the hemodynamic response function (HRF) onto these electrical activities. To disentangle the contributions of both factors, more advanced integration of EEG inverse modeling and hemodynamic response modeling is required in future studies.

The response to cardiac resynchronization therapy (CRT), which is applied to patients with heart failure (HF) and left bundle-branch block (LBBB), can be predicted from the mechanical dyssynchrony measured on circumferential strain. Circumferential strain can be assessed by either 2D or 3D strain analysis. In this study was evaluated the difference between 2D and 3D circumferential strain using MR tagging with high temporal resolution (14 ms). Six healthy volunteers and five patients with LBBB were evaluated. We compared the 2D and 3D circumferential strains by computing the mechanical dyssynchrony and the cross correlation (r) between 2D and 3D strain curves, and by quantifying the differences in peak circumferential shortening, time to onset, and time to peak of shortening. The obtained maximum r(2) values were 0.97 +/- 0.03 and 0.87 +/- 0.16 for the healthy and LBBB populations, respectively, and thus showed a good similarity between 2D and 3D strain curves. No significant difference was observed between 2D and 3D in time to onset, time to peak, or peak circumferential shortening. Thus, to measure dyssynchrony, 2D strain analysis will suffice. Since 2D analysis is easier to implement than 3D analysis, this finding brings the application of MRI tagging and strain analysis closer to the clinical routine.

Co-registration of EEG (Electroencephalogram)- and fMRI (functional magnetic resonance imaging) remains a challenge due to the large artifacts induced on the EEG by the MR (magnetic resonance) sequence gradient and RF pulses. We present an algorithm, based on the average-subtraction method, which is able to correct EEG data for gradient and RF pulse artifacts. We optimized artifact reduction by correcting the misalignment of EEG and fMRI data samples, resulting from the asynchronous sampling of EEG and fMRI data, through interpolation of EEG data. A clustering algorithm is proposed to account for the variability of the pulse artifact. Results show that the algorithm was able to keep the spontaneous brain activity while removing gradient and pulse artifacts with only a subtraction of selectively averaged data. Pulse artifact clustering showed that most of the variability was due to the time jitter of the pulse artifact markers. We show that artifact reduction by average-subtraction is optimized by interpolating the EEG data to correct for asynchronously sampled EEG and fMRI data.

Purpose: To discuss differences between displacement encoding with stimulated echoes (DENSE) and the harmonic phase (HARP) in imaging and reconstruction strategies., Materials and Methods: HARP and DENSE are presented in their historical context: while the HARP method was developed from the framework of myocardial tagging, DENSE arose from the framework of stimulated echo and displacement encoding using bipolar gradients. Both techniques have evolved since their introduction, thereby becoming more similar over time and losing their distinct features. Newly introduced improvements have successfully been applied in both methods. Differences between both methods are discussed point by point., Results: From this discussion it follows that almost all apparent differences are in fact nonexistent., Conclusion: In the literature, both techniques are still regarded as distinctly different techniques, where a more general treatment of the technique is justified. Once it is realized that both frameworks are easily merged, the benefits are 1) less confusion about the (dis)advantages of either technique, and 2) understanding of phase-based strain imaging that is more general than HARP or DENSE alone., ((c) 2006 Wiley-Liss, Inc.)

The purpose of this study was to develop and prospectively evaluate the feasibility of a single-slab three-dimensional (3D) double inversion-recovery, or DIR, sequence for magnetic resonance imaging at 1.5 T. The study was approved by the local ethics committee, and informed consent was obtained from six healthy control subjects (one woman, five men; age range, 26-47 years) and two patients with multiple sclerosis (one woman, aged 39; one man, aged 56). Gray matter (GM)-only images were obtained by selectively suppressing cerebrospinal fluid (CSF) and white matter (WM) signals. Whole-brain high-spatial-resolution 3D images (1.2 x 1.2 x 1.3 mm) were acquired within 10 minutes. Cortical and deep GM structures were clearly delineated from WM and CSF, and there were regional differences in GM signal intensity. No flow artifacts from blood or CSF were observed. These GM images with high spatial resolution are suitable to identify cortical pathologic conditions and can potentially be used for segmentation purposes to determine cortical thickness or volume., ((c) RSNA, 2006.)

Aims: Alcohol septal ablation (ASA) has been successful in the treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of this study is to evaluate the effects of ethanol-induced myocardial infarcts on regional myocardial function using cardiac magnetic resonance (CMR) tissue tagging and 3-dimensional (3D) strain analysis., Methods and Results: In nine patients (age 52+/-15 years) who underwent ASA, CMR was performed prior to and 6 months after the procedure. Regional myocardial mass was evaluated using cine imaging. Myocardial tagging was used to calculate systolic 3D myocardial strain values. These strain values were used to calculate the shortening index (SI), a robust parameter for myocardial contraction. Maximum end-systolic (ES) SI and systolic SI rate were quantified in three circumferential segments: septum, adjacent, and remote (lateral) myocardium. Compared with baseline, septal and non-septal mass decreased at follow-up (from 72+/-27 to 59+/-21 g; P=0.008 and from 131+/-34 to 109+/-30 g; P=0.008, respectively). In the septum, maximum ES SI and SI rate remained unchanged after ASA. In adjacent myocardium, ES SI remained unchanged, whereas SI rate improved (from -56.5+/-21.1 to -70.0+/-16.7%/s; P=0.02). Both ES SI and SI rate improved significantly in remote myocardium (from -16.9+/-2.8 to -18.8+/-3.2%; P=0.02 and from -70.3+/-9.2 to -86.1+/-15.0%/s; P=0.01, respectively)., Conclusion: Reduction of left ventricular (LV) outflow tract obstruction in symptomatic HOCM is associated with a significant reduction in myocardial mass and improvement of intramural systolic function in the lateral (remote) wall, indicating reversed LV remodelling.

Background: Regional differences in resting myocardial blood flow (MBF) have been observed in patients with hypertrophic cardiomyopathy (HCM), but their determinants are currently unknown. This study verifies whether MBF at rest in HCM is related to delayed contrast enhancement (DCE) or regional systolic function (or both) as determined by magnetic resonance imaging., Methods and Results: Fourteen patients with HCM were studied. MBF was measured with positron emission tomography by use of oxygen 15-labeled water. DCE and tissue tagging, to calculate end-systolic circumferential shortening (Ecc), were obtained with magnetic resonance imaging. The mean resting MBF was 0.78 +/- 0.19 mL x min(-1) x mL(-1), and there was a trend toward reduced MBF in the septum (0.72 +/- 0.11 mL x min(-1) x mL(-1)) compared with that in the lateral wall (0.84 +/- 0.29 mL x min(-1) x mL(-1)) (P = .092). The distribution patterns of DCE and Ecc were both heterogeneous, displaying significantly increased enhancement and impaired regional systolic function in the hypertrophic septum compared with the lateral wall (both P < .001). Resting MBF was inversely related to the extent of DCE (r = -0.30, P < .001), whereas MBF was not significantly related to Ecc (r = -0.15, P = .072)., Conclusions: Regional heterogeneity of resting perfusion in HCM is related to the extent of DCE but not to regional systolic function.

Purpose: To extend the harmonic phase (HARP) tracking method in order to track the myocardial tissue that appears near the epicardial contour during systole and reappears near the endocardial contour during diastole, due to the longitudinal motion and conical shape of the heart., Materials and Methods: A mathematical model of myocardial deformation was used to quantify the accuracy of the extended HARP tracking and of the strain computation. For six healthy volunteers, the number of tracked points and the two-dimensional strain components were computed with the extended and with the original HARP tracking version., Results: High accuracy was obtained for the circumferential strain (maximum error is 0.5% relative to analytical strain). The extended version tracked 22 +/- 7%, 51 +/- 19%, and 67 +/- 20% more points than the original version on the basal, mid, and apical slices, respectively (P < or = 0.001 for each slice), and yielded a decreased circumferential shortening (relative decrease: 2 +/- 4%, 9 +/- 4%, and 12 +/- 5% for the three slices; P < 0.005 for mid and apex), at end systole. These differences in circumferential strain were related to the more complete coverage of the myocardial wall with tracked points., Conclusion: The extended HARP tracking also provides strain values from myocardial regions that were not covered by the original HARP tracking., (Copyright 2006 Wiley-Liss, Inc.)

Simultaneous recording of electroencephalogram/functional magnetic resonance images (EEG/fMRI) was applied to identify blood oxygenation level-dependent (BOLD) changes associated with spontaneous variations of the alpha rhythm, which is considered the hallmark of the brain resting state. The analysis was focused on inter-subject variability associated with the resting state. Data from 7 normal subjects are presented. Confirming earlier findings, three subjects showed a negative correlation between the BOLD signal and the average power time series within the alpha band (8--12 Hz) in extensive areas of the occipital, parietal and frontal lobes. In small thalamic areas, the BOLD signal was positively correlated with the alpha power. For subjects 3 and 4, who displayed two different states during the data acquisition time, it was shown that the corresponding correlation patterns were different, thus demonstrating the state dependency of the results. In subject 5, the changes in BOLD were observed mainly in the frontal and temporal lobes. Subject 6 only showed positive correlations, thus contradicting the negative BOLD alpha power cortical correlations that were found in most subjects. Results suggest that the resting state varies over subjects and, sometimes, even within one subject. As the resting state plays an important role in many fMRI experiments, the inter-subject variability of this state should be addressed when comparing fMRI results from different subjects.