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We study the multifractal behavior of coherent states projected in the energy eigenbasis of the spin-boson Dicke Hamiltonian, a paradigmatic model describing the collective interaction between a single bosonic mode and a set of two-level systems. By examining the linear approximation and parabolic correction to the mass exponents, we find ergodic and multifractal coherent states and show that they reflect details of the structure of the classical phase space, including chaos, regularity, and features of localization. The analysis of multifractality stands as a sensitive tool to detect changes and structures in phase space, complementary to classical tools to investigate it. We also address the difficulties involved in the multifractal analyses of systems with unbounded Hilbert spaces.

In magnetic resonance imaging (MRI), the perception of substandard image quality may prompt repetition of the respective image acquisition protocol. Subsequently selecting the preferred high-quality image data from a series of acquisitions can be challenging. An automated workflow may facilitate and improve this selection. We therefore aimed to investigate the applicability of an automated image quality assessment for the prediction of the subjectively preferred image acquisition. Our analysis included data from 11,347 participants with whole-body MRI examinations performed as part of the ongoing prospective multi-center German National Cohort (NAKO) study. Trained radiologic technologists repeated any of the twelve examination protocols due to induced setup errors and/or subjectively unsatisfactory image quality and chose a preferred acquisition from the resultant series. Up to 11 quantitative image quality parameters were automatically derived from all acquisitions. Regularized regression and standard estimates of diagnostic accuracy were calculated. Controlling for setup variations in 2342 series of two or more acquisitions, technologists preferred the repetition over the initial acquisition in 1116 of 1396 series in which the initial setup was retained (79.9%, range across protocols: 73-100%). Image quality parameters then commonly showed statistically significant differences between chosen and discarded acquisitions. In regularized regression across all protocols, 'structured noise maximum' was the strongest predictor for the technologists' choice, followed by 'N/2 ghosting average'. Combinations of the automatically derived parameters provided an area under the ROC curve between 0.51 and 0.74 for the prediction of the technologists' choice. It is concluded that automated image quality assessment can, despite considerable performance differences between protocols and anatomical regions, contribute substantially to identifying the subjective preference in a series of MRI acquisitions and thus provide effective decision support to readers., (© 2023. The Author(s).)

We present a detailed analysis of the connection between chaos and the onset of thermalization in the spin-boson Dicke model. This system has a well-defined classical limit with two degrees of freedom, and it presents both regular and chaotic regions. Our studies of the eigenstate expectation values and the distributions of the off-diagonal elements of the number of photons and the number of excited atoms validate the diagonal and off-diagonal eigenstate thermalization hypothesis (ETH) in the chaotic region, thus ensuring thermalization. The validity of the ETH reflects the chaotic structure of the eigenstates, which we corroborate using the von Neumann entanglement entropy and the Shannon entropy. Our results for the Shannon entropy also make evident the advantages of the so-called "efficient basis" over the widespread employed Fock basis when investigating the unbounded spectrum of the Dicke model. The efficient basis gives us access to a larger number of converged states than what can be reached with the Fock basis.

Background: Reproducible image quality is of high relevance for large cohort studies and can be challenging for magnetic resonance imaging (MRI). Automated image quality assessment may contribute to conducting radiologic studies effectively., Purpose: The aims of this study were to assess protocol repetition frequency in population-based whole-body MRI along with its effect on examination time and to examine the applicability of automated image quality assessment for predicting decision-making regarding repeated acquisitions., Materials and Methods: All participants enrolled in the prospective, multicenter German National Cohort (NAKO) study who underwent whole-body MRI at 1 of 5 sites from 2014 to 2016 were included in this analysis (n = 11,347). A standardized examination program of 12 protocols was used. Acquisitions were carried out by certified radiologic technologists, who were authorized to repeat protocols based on their visual perception of image quality. Eleven image quality parameters were derived fully automatically from the acquired images, and their discrimination ability regarding baseline acquisitions and repetitions was tested., Results: At least 1 protocol was repeated in 12% (n = 1359) of participants, and more than 1 protocol in 1.6% (n = 181). The repetition frequency differed across protocols (P < 0.001), imaging sites (P < 0.001), and over the study period (P < 0.001). The mean total scan time was 62.6 minutes in participants without and 67.4 minutes in participants with protocol repetitions (mean difference, 4.8 minutes; 95% confidence interval, 4.5-5.2 minutes). Ten of the automatically derived image quality parameters were individually retrospectively predictive for the repetition of particular protocols; for instance, "signal-to-noise ratio" alone provided an area under the curve of 0.65 (P < 0.001) for repetition of the Cardio Cine SSFP SAX protocol. Combinations generally improved prediction ability, as exemplified by "image sharpness" plus "foreground ratio" yielding an area under the curve of 0.89 (P < 0.001) for repetition of the Neuro T1w 3D MPRAGE protocol, versus 0.85 (P < 0.001) and 0.68 (P < 0.001) as individual parameters., Conclusions: Magnetic resonance imaging protocol repetitions were necessary in approximately 12% of scans even in the highly standardized setting of a large cohort study. Automated image quality assessment shows predictive value for the technologists' decision to perform protocol repetitions and has the potential to improve imaging efficiency., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

By employing Husimi quasiprobability distributions, we show that a bounded portion of an unbounded phase space induces a finite effective dimension in an infinite-dimensional Hilbert space. We compare our general expressions with numerical results for the spin-boson Dicke model in the chaotic energy regime, restricting its unbounded four-dimensional phase space to a classically chaotic energy shell. This effective dimension can be employed to characterize quantum phenomena in infinite-dimensional systems, such as localization and scarring.

The deviation between chronological age and age predicted from neuroimaging data has been identified as a sensitive risk marker of cross-disorder brain changes, growing into a cornerstone of biological age research. However, machine learning models underlying the field do not consider uncertainty, thereby confounding results with training data density and variability. Also, existing models are commonly based on homogeneous training sets, often not independently validated, and cannot be shared because of data protection issues. Here, we introduce an uncertainty-aware, shareable, and transparent Monte Carlo dropout composite quantile regression (MCCQR) Neural Network trained on N = 10,691 datasets from the German National Cohort. The MCCQR model provides robust, distribution-free uncertainty quantification in high-dimensional neuroimaging data, achieving lower error rates compared with existing models. In two examples, we demonstrate that it prevents spurious associations and increases power to detect deviant brain aging. We make the pretrained model and code publicly available.

Since the experimental observation of the violation of the Bell-CHSH inequalities, much has been said about the non-local and contextual character of the underlying system. However, the hypothesis from which Bell's inequalities are derived differ according to the probability space used to write them. The violation of Bell's inequalities can, alternatively, be explained by assuming that the hidden variables do not exist at all, that they exist but their values cannot be simultaneously assigned, that the values can be assigned but joint probabilities cannot be properly defined, or that averages taken in different contexts cannot be combined. All of the above are valid options, selected by different communities to provide support to their particular research program.

Measuring the degree of localization of quantum states in phase space is essential for the description of the dynamics and equilibration of quantum systems, but this topic is far from being understood. There is no unique way to measure localization, and individual measures can reflect different aspects of the same quantum state. Here we present a general scheme to define localization in measure spaces, which is based on what we call Rényi occupations, from which any measure of localization can be derived. We apply this scheme to the four-dimensional unbounded phase space of the interacting spin-boson Dicke model. In particular, we make a detailed comparison of two localization measures based on the Husimi function in the regime where the model is chaotic, namely, one that projects the Husimi function over the finite phase space of the spin and another that uses the Husimi function defined over classical energy shells. We elucidate the origin of their differences, showing that in unbounded spaces the definition of maximal delocalization requires a bounded reference subspace, with different selections leading to contextual answers.

In a classically chaotic system that is ergodic, any trajectory will be arbitrarily close to any point of the available phase space after a long time, filling it uniformly. Using Born's rules to connect quantum states with probabilities, one might then expect that all quantum states in the chaotic regime should be uniformly distributed in phase space. This simplified picture was shaken by the discovery of quantum scarring, where some eigenstates are concentrated along unstable periodic orbits. Despite that, it is widely accepted that most eigenstates of chaotic models are indeed ergodic. Our results show instead that all eigenstates of the chaotic Dicke model are actually scarred. They also show that even the most random states of this interacting atom-photon system never occupy more than half of the available phase space. Quantum ergodicity is achievable only as an ensemble property, after temporal averages are performed.

We study dynamical signatures of quantum chaos in one of the most relevant models in many-body quantum mechanics, the Bose-Hubbard model, whose high degree of symmetries yields a large number of invariant subspaces and degenerate energy levels. The standard procedure to reveal signatures of quantum chaos requires classifying the energy levels according to their symmetries, which may be experimentally and theoretically challenging. We show that this classification is not necessary to observe manifestations of spectral correlations in the temporal evolution of the survival probability, which makes this quantity a powerful tool in the identification of chaotic many-body quantum systems.

Quantum chaos refers to signatures of classical chaos found in the quantum domain. Recently, it has become common to equate the exponential behavior of out-of-time order correlators (OTOCs) with quantum chaos. The quantum-classical correspondence between the OTOC exponential growth and chaos in the classical limit has indeed been corroborated theoretically for some systems and there are several projects to do the same experimentally. The Dicke model, in particular, which has a regular and a chaotic regime, is currently under intense investigation by experiments with trapped ions. We show, however, that for experimentally accessible parameters, OTOCs can grow exponentially also when the Dicke model is in the regular regime. The same holds for the Lipkin-Meshkov-Glick model, which is integrable and also experimentally realizable. The exponential behavior in these cases are due to unstable stationary points, not to chaos.

Quantum systems whose classical counterparts are chaotic typically have highly correlated eigenvalues and level statistics that coincide with those from ensembles of full random matrices. A dynamical manifestation of these correlations comes in the form of the so-called correlation hole, which is a dip below the saturation point of the survival probability's time evolution. In this work, we study the correlation hole in the spin-boson (Dicke) model, which presents a chaotic regime and can be realized in experiments with ultracold atoms and ion traps. We derive an analytical expression that describes the entire evolution of the survival probability and allows us to determine the time scales of its relaxation to equilibrium. This expression shows remarkable agreement with our numerical results. While the initial decay and the time to reach the minimum of the correlation hole depend on the initial state, the dynamics beyond the hole up to equilibration is universal. We find that the relaxation time of the survival probability for the Dicke model increases linearly with system size.

The exponential growth of the out-of-time-ordered correlator (OTOC) has been proposed as a quantum signature of classical chaos. The growth rate is expected to coincide with the classical Lyapunov exponent. This quantum-classical correspondence has been corroborated for the kicked rotor and the stadium billiard, which are one-body chaotic systems. The conjecture has not yet been validated for realistic systems with interactions. We make progress in this direction by studying the OTOC in the Dicke model, where two-level atoms cooperatively interact with a quantized radiation field. For parameters where the model is chaotic in the classical limit, the OTOC increases exponentially in time with a rate that closely follows the classical Lyapunov exponent.

Pseudo-random number generators are widely used in many branches of science, mainly in applications related to Monte Carlo methods, although they are deterministic in design and, therefore, unsuitable for tackling fundamental problems in security and cryptography. The natural laws of the microscopic realm provide a fairly simple method to generate non-deterministic sequences of random numbers, based on measurements of quantum states. In practice, however, the experimental devices on which quantum random number generators are based are often unable to pass some tests of randomness. In this review, we briefly discuss two such tests, point out the challenges that we have encountered in experimental implementations and finally present a fairly simple method that successfully generates non-deterministic maximally random sequences.

Random number generation plays an essential role in technology with important applications in areas ranging from cryptography to Monte Carlo methods, and other probabilistic algorithms. All such applications require high-quality sources of random numbers, yet effective methods for assessing whether a source produce truly random sequences are still missing. Current methods either do not rely on a formal description of randomness (NIST test suite) on the one hand, or are inapplicable in principle (the characterization derived from the Algorithmic Theory of Information), on the other, for they require testing all the possible computer programs that could produce the sequence to be analysed. Here we present a rigorous method that overcomes these problems based on Bayesian model selection. We derive analytic expressions for a model's likelihood which is then used to compute its posterior distribution. Our method proves to be more rigorous than NIST's suite and Borel-Normality criterion and its implementation is straightforward. We applied our method to an experimental device based on the process of spontaneous parametric downconversion to confirm it behaves as a genuine quantum random number generator. As our approach relies on Bayesian inference our scheme transcends individual sequence analysis, leading to a characterization of the source itself.

We present a method designed to efficiently extract optical signals from InGaAs avalanche photodiodes (APDs) operated in gated mode. In particular, our method permits an estimation of the fraction of counts that actually results from the signal being measured, as opposed to being produced by noise mechanisms, specifically by afterpulsing. Our method in principle allows the use of InGaAs APDs at high detection efficiencies, with the full operation bandwidth, either with or without resorting to the application of a dead-time. As we show below, our method can be used in configurations where afterpulsing exceeds the genuine signal by orders of magnitude, even near saturation. The algorithms that we have developed are suitable to be used either in real-time processing of raw detection probabilities or in post-processing applications, after a calibration step has been performed. The algorithms that we propose here can complement technologies designed for the reduction of afterpulsing.

The relation between the onset of chaos and critical phenomena, like quantum phase transitions (QPTs) and excited-state quantum phase transitions (ESQPTs), is analyzed for atom-field systems. While it has been speculated that the onset of hard chaos is associated with ESQPTs based in the resonant case, the off-resonant cases, and a close look at the vicinity of the QPTs in resonance, show clearly that both phenomena, ESQPTs and chaos, respond to different mechanisms. The results are supported in a detailed numerical study of the dynamics of the semiclassical Hamiltonian of the Dicke model. The appearance of chaos is quantified calculating the largest Lyapunov exponent for a wide sample of initial conditions in the whole available phase space for a given energy. The percentage of the available phase space with chaotic trajectories is evaluated as a function of energy and coupling between the qubit and bosonic part, allowing us to obtain maps in the space of coupling and energy, where ergodic properties are observed in the model. Different sets of Hamiltonian parameters are considered, including resonant and off-resonant cases.

Employing efficient diagonalization techniques, we perform a detailed quantitative study of the regular and chaotic regions in phase space in the simplest nonintegrable atom-field system, the Dicke model. A close correlation between the classical Lyapunov exponents and the quantum Participation Ratio of coherent states on the eigenenergy basis is exhibited for different points in the phase space. It is also shown that the Participation Ratio scales linearly with the number of atoms in chaotic regions and with its square root in the regular ones.

Purpose: To detail the rationale, design, and future perspective of implementing whole-body magnetic resonance (MR) imaging in the German National Cohort, a large multicentric population-based study., Materials and Methods: All institutional review boards approved the study, and informed consent is obtained before study enrollment. Participants are enrolled from a random sample of the general population at five dedicated imaging sites among 18 recruitment centers. MR imaging facilities are equipped with identical 3.0-T imager technology and use uniform MR protocols. Imager-specific hardware and software settings remained constant over the study period. On-site and centralized measures of image quality enable monitoring of completeness of the acquisitions and quality of each of the MR sequences. Certified radiologists read all MR imaging studies for presence of incidental findings according to predefined algorithms., Results: Over a 4-year period, six participants per day are examined at each center, totaling a final imaging cohort of approximately 30 000 participants. The MR imaging protocol is identical for each site and comprises a set of 12 native series to cover neurologic, cardiovascular, thoracoabdominal, and musculoskeletal imaging phenotypes totaling approximately 1 hour of imaging time. A dedicated analysis platform as part of a central imaging core incorporates a thin client-based integrative and modular data handling platform to enable multicentric off-site image reading for incidental findings. Scientific analysis will be pursued on a per-project hypothesis-driven basis., Conclusion: Population-based whole-body MR imaging as part of the German National Cohort will serve to compile a comprehensive image repository, will provide insight into physiologic variants and subclinical disease burden, and has the potential to enable identification of novel imaging biomarkers of risk., ((©) RSNA, 2015 Online supplemental material is available for this article.)

Different pathological processes like demyelination and axonal loss can alter the magnetisation transfer ratio (MTR) in brain tissue. The standard method to measure this effect is to scan the respective tissue twice, one with and one without a specific saturation pulse. A major drawback of this technique based on spoiled gradient echo (GRE) sequences relates to its long acquisition time due to the saturation pulses. Recently, an alternative concept for MT imaging based on balanced steady state free precession (bSSFP) has been proposed. Modification of the duration of the radiofrequency pulses for imaging allows scanning MT sensitive and non-sensitive images. The steady-state character of bSSFP with high intrinsic signal-to-noise ratio (SNR) allows three-dimensional (3D) whole brain MTR at high spatial resolution within short and thus clinically feasible acquisition times. In the present study, both bSSFP-MT and 2D GRE-MT imaging were used in a cohort of 31 patients with multiple sclerosis (MS) to characterize different normal appearing (NA) and pathological brain structures. Under the constraint of identical SNR and scan time, a 3.4 times higher voxel size could be achieved with bSSFP. This increased resolution allowed a more accurate delineation of the different brain structures, especially of cortex, hippocampus and MS lesions. In a multiple linear regression model, we found an association between MTR of cortical lesions and a clinical measure of disability (r= -0.407, p=0.035) in the bSSFP dataset only. The different relaxation weighting of the base images (T2/T1 in bSSFP, proton density in GRE) had no effects besides a larger spreading of the MTR values of the different NA structures. This was demonstrated by the nearly perfect linearity between the NA matter MTR of both techniques as well as in the absolute MTR differences between NA matter and the respective lesions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Mild cognitive impairment (MCI) is an intermediary state on the way to Alzheimer's disease (AD). Little is known about whole brain concentration of the neuronal marker, N-acetylaspartate (NAA) in MCI patients., Objective: To test the hypothesis that since MCI and AD are both neurodegenerative, quantification of the NAA in their whole brain (WBNAA) could differentiate them from cognitively-intact matched controls., Methods: Proton MR spectroscopy to quantify the WBNAA was applied to 197 subjects (86 females) 72.6 ± 8.4 years old (mean ± standard deviation). Of these, 102 were cognitively intact, 42 diagnosed as MCI, and 53 as probable AD. Their WBNAA amounts were converted into absolute concentration by dividing with the brain volume segmented from the MRI that also yielded the fractional brain volume (fBPV), an atrophy metric., Results: WBNAA concentration of MCI and AD patients (10.5 ± 3.0 and 10.1 ± 2.9 mM) were not significantly different (p = 0.85). They were, however, highly significantly 25-29% lower than the 14.1 ± 2.4 mM of normal matched controls (p < 10-4). The fBPV of MCI and AD patients (72.9 ± 4.9 and 69.9 ± 4.7%) differed significantly from each other (4%, p = 0.02) and both were significantly lower than the 74.6 ± 4.4% of normal elderly (2%, p = 0.003 for MCI; 6%, p < 10-4 for AD). ROC curve analysis has shown WBNAA to have 70.5% sensitivity and 84.3% specificity to differentiate MCI or AD patients from normal elderly versus just 68.4 and 65.7% for fBPV., Conclusion: Low WBNAA in MCI patients compared with cognitively normal contemporaries may indicate early neuronal damage accumulation and supports the notion of MCI as an early stage of AD. It also suggests WBNAA as a potential marker of early AD pathology.

Subcortical age-related white matter changes (ARWMC) are a frequent finding in healthy elderly people suggested to cause secondary tissue changes and possibly affecting cognitive processes. We aimed to determine the influence of the extent of ARWMC load on attention and working memory processes in healthy elderly individuals. Fourteen healthy elderly subjects (MMSE >26; age 55-80 years) performed three fMRI tasks with increasing difficulty assessing alertness, attention (0-back), and working memory (2-back). We compared activation patterns in those with only minimal ARWMC (Fazekas 0-1) to those with moderate to severe ARWMC (Fazekas 2-3). During the fMRI experiments, the study population showed activation in brain areas typically involved in attention and working memory with a recruitment of cortical areas with increasing task difficulty. Subjects with higher lesion load showed a higher activation at all task levels with only sparse increase of signal with increasing complexity. In the lower lesion load group, rising task difficulty lead to a significant and widely distributed increase of activation. Although the number of patients included in the study is small, these findings suggest that even clinically silent ARWMC may affect cognitive processing and lead to compensatory activation during cognitive tasks. This can be interpreted as a reduction of functional reserve and may pose a risk for cognitive decline in these patients.

Background: We hypothesized that in multiple sclerosis (MS) patients, reduced cortical perfusion is associated with chronic white matter injury., Objective: To investigate the influence of different clinical and magnetic resonance imaging characteristics on cortical perfusion., Methods: Cerebral blood flow (CBF) was assessed by applying a pulsed arterial spin labelling (ASL) technique combined with single-shot 3D-GRASE (gradient-spin echo) in a cohort of 165 MS patients with a relapsing-remitting (n=123) or secondary progressive disease course (n=42). Mean age was 45.4 years (20-68 years), mean disease duration was 14.2 years (1-48 years)., Results: Mean cortical CBF was 45.6 ml/100g per min (SD: 7.8 ml/100g per min). Stepwise multiple linear regression models were calculated to investigate the relationship between different factor sets and mean CBF. The model with the highest adjusted coefficient of determination included T2 lesion load, age, gender and disease duration as significant factors. Post-hoc Spearman rank correlation revealed significant correlation of adjusted CBF with T2 lesion load (ρ=-0.35, p=1*10(-6)), with age (ρ=-0.34, p=4*10(-6)), and with disease duration (ρ=0.16, p=0.03), while Expanded Disability Status Scale (EDSS) did not reach significance in either model., Conclusion: This study suggests that the amount of white matter lesions indicates a reduced metabolic demand and reduced perfusion at a cortical level.

Objective: To investigate the entire spinal cord (SC) of multiple sclerosis (MS) patients with biplanar MRI and to relate these MRI findings to clinical functional scores., Methods: Two hundred and two patients (140 women, 62 men 24-74 years, Expanded Disability Status Scale (EDSS) scores 0-7.5) were investigated clinically and with biplanar MRI. Sagittal and axial proton density weighted (PDw) and T2 weighted (T2w) images of the whole SC were obtained employing parallel imaging. Data were analyzed by consensus reading using a standardized reporting scheme. Different combinations of findings were compared to EDSS scores with Spearman's rank correlation coefficient (ρ)., Results: The combined analysis of sagittal and axial planes demonstrated slightly differing results in 97/202 (48%) patients. There were 9% additional lesions identified, leading to a higher lesion count in 28% of these patients, but also rejection of equivocal abnormality leading to a lower lesion count in 11% of patients. Considering both sagittal and axial images, SC abnormalities were found in 167/202 (83%) patients. When compared with EDSS scores, the combination of focal lesions, signs of atrophy and diffuse abnormalities showed a moderate correlation (ρ=0.52), that precludes its use for individual patient assessment., Conclusion: Biplanar MRI facilitates a comprehensive identification, localization, and grading of pathological SC findings in MS patients. This improves the confidence and utility of SC imaging.

Background: Epidural steroid injections (ESIs) are now increasing in popularity with regard to the management of chronic lumbar radiculopathy. While ESIs have been shown to be effective in relieving low back and radicular pain, adverse reactions have also been reported, notably abnormal vaginal bleeding., Objective: We present a case series of four women, both pre- and postmenopausal, with chronic lumbar radiculopathy and corresponding pathology who developed abnormal vaginal bleeding after receiving either ESIs or facet medial branch blocks (MBBs) for pain management. Setting.  University of California, Los Angeles., Patients: Four women, both pre- and postmenopausal., Conclusions: We discuss the potential effects of corticosteroids on the hypothalamic-pituitary-ovarian axis and highlight our patients' risk factors for abnormal vaginal bleeding, both exogenous and endogenous, as well as focus on the technical approaches to corticosteroid administration utilized in our patients' procedures. We acknowledge that because this is a small case series, further prospective investigation is warranted regarding the above topics. Until then, it may be beneficial to consider whether patients, both pre- and postmenopausal, have risk factors for abnormal uterine bleeding prior to undergoing interventional pain management strategies, specifically ESI and MBB, and to inform all women upon consent that abnormal vaginal bleeding is a potential risk following procedures with corticosteroids., (Wiley Periodicals, Inc.)

As attention, processing speed, and working memory seem to be fundamental for a broad range of cognitive performance, the present study on patients with mild forms of relapsing-remitting multiple sclerosis (RR-MS) focused on these domains. To explore subtle neuropsychological changes in either the clinical or fMRI domain, we applied a multistep experimental design with increasing task complexity to investigate global brain activity, functional adaptation, and behavioral responses to typical cognitive processes related to attention and working memory. Fifteen patients with RR-MS (mean age 38 years, 22-49 years, 9 females, mean disease duration 5.9 years (SD = 3.6 years), mean Expanded Disability Status Scale score, 2.3 (SD = 1.3) but without reported cognitive impairment), and 15 age-matched healthy controls (HC; mean age, 34 years, 23-50 years, 6 women) participated. After a comprehensive neuropsychological assessment, participants performed different fMRI experiments testing attention and working memory. In the neuropsychological assessment, patients showed only subtle reduction in learning and memory abilities. In the fMRI experiments, both groups activated the brain areas typically involved in attention and working memory. HC showed a linear in- or decrease in activation paralleling the changing task complexity. Patients showed stronger activation change at the level of the simple tasks and a subsequent saturation effect of (de-)activation at the highest task load. These group/task interaction differences were found in the right parahippocampal cortex and in the middle and medial frontal regions. Our results indicate that, in MS, functional adaptation patterns can be found which precede clinical evidence of apparent cognitive decline., (Copyright © 2010 Wiley-Liss, Inc.)

Purpose: To assess the effect on diffusion tensor (DT) magnetic resonance imaging (MRI) of acquiring data with different scanners., Materials and Methods: Forty-four healthy controls and 36 multiple sclerosis patients with low disability were studied using eight MR scanners with acquisition protocols that were as close to a standard protocol as possible. Between 7 and 13 subjects were studied in each center. Region-of-interest (ROI) and histogram-based analyses of fractional anisotropy (FA), axial (D(ax)), radial (D(rad)), and mean diffusivity (MD) were performed. The influence of variables such as the acquisition center and the control/patient group was determined with an analysis of variance (ANOVA) test., Results: The patient/control group explained approximately 25% of data variability of FA and D(rad) from midsagittal corpus callosum (CC) ROIs. Global FA, MD, and D(rad) in the white matter differentiated patients from controls, but with lower discriminatory power than for the CC. In the gray matter, MD discriminated patients from controls (30% of variability explained by group vs. 17% by center)., Conclusion: Significant variability of DT-MRI data can be attributed to the acquisition center, even when a standardized protocol is used. The use of appropriate segmentation methods and statistical models allows DT-derived metrics to differentiate patients from healthy controls.

To date, little data is available on the reproducibility of functional connectivity MRI (fcMRI) studies. Here, we tested the variability and reproducibility of both the functional connectivity itself and different statistical methods to analyze this phenomenon. In the main part of our study, we repeatedly examined two healthy subjects in 10 sessions over 6 months with fcMRI. Cortical areas involved in motor function were examined under two different cognitive states: during continuous performance (CP) of a flexion/extension task of the fingers of the right hand and while subjects were at rest. Connectivity to left primary motor cortex (lSM1) was calculated by correlation analysis. The resulting correlation coefficients were transformed to z-scores of the standard normal distribution. For each subject, multisession statistical analyses were carried out with the z-score maps of the resting state (RS) and the CP experiments. First, voxel based t tests between the two groups of fcMRI experiments were performed. Second, ROI analyses were carried out for contralateral right SM1 and for supplementary motor area (SMA). For both ROI, mean and maximum z-score were calculated for each experiment. Also, the fraction of significantly (P<.05) correlated voxels (FCV) in each ROI was calculated. To evaluate the differences between the RS and the CP condition, paired t tests were performed for the mean and maximum z-scores, and Wilcoxon signed ranks tests for matched pairs were carried out for the FCV. All statistical methods and connectivity measures under investigation yielded a distinct loss in left-right SM1 connectivity under the CP condition. For SMA, interindividual differences were apparent. We therefore repeated the fcMRI experiments and the ROI analyses in a group of seven healthy subjects (including the two subjects of the main study). In this substudy, we were able to verify the reduction of left-right SM1 connectivity during unilateral performance. Still, the direction of SMA to lSM1 connectivity change during the CP condition remained undefined as four subjects showed a connectivity increase and three showed a decrease. In summary, we were able to demonstrate a distinct reduction in left-right SM1 synchrony in the CP condition compared to the RS both in the longitudinal and in the multisubject study. This effect was reproducible with all statistical methods and all measures of connectivity under investigation. We conclude that despite intra- and interindividual variability, serial and cross-sectional assessment of functional connectivity reveals stable and reliable results.

Short-term adaptation indicates the attenuation of the functional MRI (fMRI) response during repeated task execution. It is considered to be a physiological process, but it is unknown whether short-term adaptation changes significantly in patients with brain disorders, such as multiple sclerosis (MS). In order to investigate short-term adaptation during a repeated right-hand tapping task in both controls and in patients with MS, we analyzed the fMRI data collected in a large cohort of controls and MS patients who were recruited into a multi-centre European fMRI study. Four fMRI runs were acquired for each of the 55 controls and 56 MS patients at baseline and 33 controls and 26 MS patients at 1-year follow-up. The externally cued (1 Hz) right hand tapping movement was limited to 3 cm amplitude by using at all sites (7 at baseline and 6 at follow-up) identically manufactured wooden frames. No significant differences in cerebral activation were found between sites. Furthermore, our results showed linear response adaptation (i.e. reduced activation) from run 1 to run 4 (over a 25 minute period) in the primary motor area (contralateral more than ipsilateral), in the supplementary motor area and in the primary sensory cortex, sensory-motor cortex and cerebellum, bilaterally. This linear activation decay was the same in both control and patient groups, did not change between baseline and 1-year follow-up and was not influenced by the modest disease progression observed over 1 year. These findings confirm that the short-term adaptation to a simple motor task is a physiological process which is preserved in MS.

In patients with multiple sclerosis (MS) non-communicating syringomyelia (NCS) has been described as an incidental finding in case studies and small case series. NCS in MS patients commonly leads to uncertainty particularly as the clinical picture of NCS is variable and surgical therapy may be considered. Up to date little is known about the prevalence and clinical importance of NCS in MS. We report the imaging and clinical characteristics of NCS formations in nine MS patients from a 1 year follow-up study in a representative group of 202 MS (4.5%) patients. Brain and spinal cord MRI was performed as part of a genetic study. NCS did commonly extend the central canal and the cord was slightly distended at the level of the syrinx. The cord and syrinx showed no tendency to change in size or shape over 1 year. Despite thorough search into the clinical history and current clinical status no definite but only minimal indications of symptoms potentially related to the NCS were found. We confirm that NCS may occur in MS patients with spinal cord pathology. It can be a subtle finding without clinical correlates. Syrinx formations are more likely to be a consequence of MS cord pathology than a coincidental finding.

Although cognitive side effects may occur after electroconvulsive therapy (ECT), no structural brain abnormalities have been detected after ECT with conventional magnetic resonance imaging (MRI). Transient disturbances of memory function are common findings after ECT indicating functional compromise. Diffusion weighted imaging (DWI) has been shown to be sensitive to focal tissue changes associated with compromise of energy metabolism in cerebral ischemia and after prolonged ictal activity. We used conventional MRI and DWI in an exploratory study examining ten patients after treatment with ECT, eight of whom experienced short-lasting memory disturbances. MRI and DWI showed no definite signal abnormalities on qualitative and quantitative analysis. In three patients, equivocal marginal DWI hyperintensity was noted in the hippocampal formation. These findings are in line with previous negative studies using conventional MRI. Higher resolution DWI and serial imaging may be necessary to visualize possible minimal signal changes after ECT.

Background: Brain imaging studies have revealed anatomical anomalies in the brains of individuals with Tourette syndrome (TS). Prefrontal regions have been found to be larger and the corpus callosum (CC) area smaller in children and young adults with TS compared with healthy control subjects, and these anatomical features have been understood to reflect neural plasticity that helps to attenuate the severity of tics., Method: CC white matter connectivity, as measured by the Fractional Anisotropy (FA) index from diffusion tensor images, was assessed in 20 clinically well-defined boys with Tourette syndrome and 20 age- and gender-matched controls., Results: The hypothesis that children with TS would show reduced measures of connectivity in CC fibers was confirmed for all subregions of the CC. There was no significant interaction of TS and region. Reductions in FA in CC regions may reflect either fewer interhemispheric fibers or reduced axonal myelination. FA values did not correlate significantly with the severity of tic symptoms. Group differences in measures of connectivity did not seem to be attributable to the presence of comorbid ADHD or OCD, to medication exposure, or group differences in IQ., Conclusion: Our findings of a reduced interhemispheral white matter connectivity add to the understanding of neural connectivity and plasticity in the brains of children who have TS.

The diffusion properties of water are sensitive to microscopic changes in the white matter of multiple sclerosis (MS) patients. Typical MRI measures of disease burden in MS demonstrate modest to poor correlation with disability. Functional MRI and DTI-based fiber tracking were used to define the interhemispheric white matter pathway connecting bilateral supplementary motor areas (SMA) in 16 MS patients sand 16 control subjects. Fractional anisotropy (FA), mean diffusivity (MD), longitudinal (lambda(1)) and transverse diffusivity (lambda(2)) were measured along this pathway in all subjects. Mean FA was 0.587 +/- 0.032 for patients and 0.608 +/- 0.020 for controls (P < 0.02). Mean MD was (0.821 +/- 0.055) x 10(-3) mm(2) s(-1) for patients and (0.770 +/- 0.020) x 10(-3) mm(2) s(-1) for controls (P < 0.004). Mean lambda(1) values were (1.462 +/- 0.099) x 10(-3) mm(2) s(-1) for patients and (1.400 +/- 0.034) x 10(-3) mm(2) s(-1) for controls (P < 0.02). Mean lambda(2) values were (0.500 +/- 0.047) x 10(-3) mm(2) s(-1) for patients and (0.454 +/- 0.027) x 10(-3) mm(2) s(-1) for controls (P < 0.001). In addition, the correlation between the Multiple Sclerosis Functional Composite (MSFC) and transverse diffusivity was -0.341 (P < 0.05). The component test of the MSFC most related to the SMA pathway studied with our MRI method (Nine-hole Peg Test) showed significant correlation with transverse diffusivity (r = 0.392, P < 0.02), indicating that probing functional pathways with MRI measures can lead to a better reflection of disease status.

Purpose: To prospectively evaluate incidence of clinically silent and clinically apparent embolic cerebral infarction following diagnostic and interventional coronary angiography and associated risk factors., Materials and Methods: Written informed consent was obtained from all patients, and the study was approved by the research ethics committee of University of Heidelberg, Germany. Fifty-two patients, including 37 men (mean age, 66.1 years +/- 11.9 [standard deviation]) and 15 women (mean age, 65.3 years +/- 10.3), undergoing elective cardiac catheterization were examined 3-26 hours (mean, 15.3 hours +/- 6) before and 12-48 hours (mean, 25.9 hours +/- 10.4) after cardiac catheterization. Magnetic resonance imaging protocol included isotropic and anisotropic diffusion-weighted single-shot echo-planar sequences. T2-weighted turbo spin-echo and T1-weighted spin-echo sequences also were performed. Apparent diffusion coefficient maps were calculated to exclude false-positive reading results on diffusion-weighted images because of T2 shine-through effect. Images were assessed by two experienced radiologists blinded to clinical data. Cardiac catheterization was performed by 11 experienced cardiologists to exclude operator-related risk. A neurologic examination according to the National Institutes of Health Stroke Scale and Barthel index was performed by a senior cardiologist before acquisition of each image. Sixteen clinical and angiographic variables were analyzed with univariate analysis for ability to predict occurrence of cerebral infarction., Results: No embolic cerebral lesions could be detected at diffusion-weighted imaging before catheterization. After coronary angiography, seven (15%) of 48 patients demonstrated nine focal cerebral infarcts affecting anterior and posterior circulation. Patients remained asymptomatic. Of all tested variables, only duration of the procedure was identified as an independent predictor of occurrence of cerebral infarction (P < .05)., Conclusion: In this prospective study, asymptomatic cerebral infarction following cardiac catheterization occurred in 15% of patients in whom duration of the procedure was significantly longer than in those without infarction (P = .017)., ((c) RSNA, 2005.)

It has been suggested that chaotic motion inside the nucleus may significantly limit the accuracy with which nuclear masses can be calculated. Using a power spectrum analysis we show that the inclusion of additional physical contributions in mass calculations, through many-body interactions or local information, removes the chaotic signal in the discrepancies between calculated and measured masses. Furthermore, a systematic application of global mass formulas and of a set of relationships among neighboring nuclei to more than 2000 nuclear masses allows one to set an unambiguous upper bound for the average errors in calculated masses, which turn out to be almost an order of magnitude smaller than estimated chaotic components.

Background: There is still limited knowledge on the location and etiology of transient global amnesia (TGA). MR studies including diffusion-weighted imaging (DWI) have been unable to demonstrate consistently the location and underlying pathology of TGA., Objective: To investigate patients with TGA using serial DWI performed from the day of symptom onset through days 1 and 2., Methods: After reporting negative DWI results in a previous study, the authors used a modified study design to investigate patients with TGA using serial DWI performed from the day of symptom onset through days 1 and 2., Results: Of 31 consecutive patients studied, 26 developed a small, punctate DWI lesion in the lateral aspect of the hippocampal formation (pes and fimbria hippocampi) on either side (left, n = 15; right, n = 6) or bilaterally (n = 5). Lesions were rarely noted in the hyperacute phase (n = 2), but all became visible regularly at 48 hours., Conclusions: The study confirms the involvement of hippocampal parenchyma in the pathophysiology of TGA. The delayed detectability of the lesions may explain the incongruence of previous MR DWI studies in TGA patients.

Background and Purpose: Although modern multisequence stroke MRI protocols are an emerging imaging routine for the diagnostic assessment of acute ischemic stroke, their sensitivity for intracerebral hemorrhage (ICH), the most important differential diagnosis, is still a matter of debate. We hypothesized that stroke MRI is accurate in the detection of ICH. To evaluate our hypotheses, we conducted a prospective multicenter trial., Methods: Stroke MRI protocols of 6 university hospitals were standardized. Images from 62 ICH patients and 62 nonhemorrhagic stroke patients, all imaged within the first 6 hours after symptom onset (mean, 3 hours 18 minutes), were analyzed. For diagnosis of hemorrhage, CT served as the "gold standard." Three readers experienced in stroke imaging and 3 final-year medical students, unaware of clinical details, separately evaluated sets of diffusion-, T2-, and T2*-weighted images. The extent and phenomenology of the hemorrhage on MRI were assessed separately., Results: Mean patient age was 65.5 years; median National Institutes of Health Stroke Scale score was 10. The experienced readers identified ICH with 100% sensitivity (confidence interval, 97.1 to 100) and 100% overall accuracy. Mean ICH size was 17.3 mL (range, 1 to 101.5 mL). The students reached a mean sensitivity of 95.16% (confidence interval, 90.32 to 98.39)., Conclusions: Hyperacute ICH causes a characteristic imaging pattern on stroke MRI and is detectable with excellent accuracy. Even raters with limited film-reading experience reached good accuracy. Stroke MRI alone can rule out ICH and demonstrate the underlying pathology in hyperacute stroke.

Unlabelled: Background- Small capsular strokes are difficult to assess with regard to the precise location and the extent of pyramidal tract damage with conventional brain imaging. Color-coded diffusion tensor imaging (CDTI) provides a means to visualize the course of the corticospinal tract within the white matter. In addition to T2-weighted MRI, diffusion-weighted MRI and CDTI were used to analyze the topographical patterns of small lacunar corticospinal tract strokes., Methods: We examined 15 patients with pyramidal tract strokes in the subacute phase (days 3 to 7). Lesions were identified on diffusion-weighted MRI and superimposed on CDTI images. The anatomic location and pattern of the lesion were visualized on CDTI with regard to the corticospinal tract and subsequently compared with the clinical presentation. In addition, infarct areas were evaluated with quantitative parameters: mean diffusivity and lattice anisotropy index of lesions were determined., Results: We identified 5 different patterns of corticospinal tract stroke falling into 2 clinical subgroups: (1) those with marked deficits and minor improvement (6/15) and (2) those with good recovery (9/15). Group 1 had long lesions centered in the pyramidal tract, involving the basal ganglia (anterior choroidal artery); group 2 lesions were very small and/or located anteriorly and medially (periventricular anterior choroidal artery territory; thalamogeniculate, tuberothalamic, and lateral striate branches). Lesions showed a significant increase of mean diffusivity and decrease of lattice anisotropy., Conclusions: CDTI allows in vivo differentiation of distinct subcortical stroke subtypes. Improved anatomic definition of lesion localization using CDTI may help in better establishing the prognosis for patients after subcortical stroke.

The standard diffusion tensor model is limited in its ability to provide detailed information about multidirectional fiber architecture in human white matter. Additional directional acquisition of diffusivity properties with high angular resolution diffusion-weighted imaging (HARDI) acquisition schemes may deliver more information on areas with fiber crossings than standard DTI. However, representation of the additional information and the rating and visualization of fiber complexity is challenging. We used projection 2D-plots in combination with a HARDI acquisition scheme of 129 diffusion directions and compared the spherical diffusion variance index (SDI) with the relative anisotropy index (RAI). In normal controls, white matter areas with unidirectional fiber arrangement and areas with more complex fiber composition were identified with this approach. HARDI confirms and can visualize deviations from the tensor-like representation, thereby providing information on fiber structure complexity, which may be of considerable interest for clinical studies.

Magnetic resonance imaging (MRI) of diffusion and magnetization transfer was combined with 1H-spectroscopic imaging (CSI) to evaluate the clinical potential of in-vivo profiles of various brain pathologies. Ten patients (multiple sclerosis, cerebrovascular disease, leukodystrophy, Alzheimer dementia) and five healthy volunteers were investigated with diffusion-weighted MRI, magnetization transfer imaging, and CSI. Proton spectra were analyzed as ratios of NAA/Cr and Cho/Cr calculated from the peak areas of N-acetylaspartate (NAA), (phospho)-creatine (Cr) and choline (Cho). The apparent diffusion coefficient (ADC) and the magnetization transfer ratio (MTR) were determined in identical voxels to ensure identical partial volume effects compared to CSI. Compared to MTR and ADC assessments, the lower spatial resolution of CSI clearly indicates a hindrance at 1.5 T. In most demyelinating lesions, NAA/Cr reduction paralleled attenuated MTRs and elevated ADCs. By contrast, in acute stroke and some acute MS lesions the ADC was reduced, while MTR and NAA/Cr were also decreased. In Alzheimer's dementia, ADC was increased, MTR unchanged and Cho/Cr increased. In a case of leukodystrophy, ADC was pronouncedly increased, MTR and NAA/Cr both reduced, and Cho/Cr normal. Combined measurements of ADC, MTR and CSI are feasible and provide differential in-vivo information on various brain pathologies.

Diffusion-weighted imaging (DWI) of the brain has become a valuable tool for the reliable detection and diagnosis of several neurological disorders. Although DWI is in wide use in daily practice, the underlying biophysical mechanisms that contribute to changes in the apparent diffusion coefficient (ADC) are still under discussion. Alterations in the apparent water diffusion rate reflect pathological changes in the brain tissue state, via changes in the diffusion characteristics of the intra- and extra-cellular water compartments including restricted diffusion, water exchange across permeable boundaries, the concept of the extra-cellular tortuosity and the intra- and extra-cellular volume fraction. A reduction of the ADC has been detected in acute neurological diseases, while disease states associated with dominant acute vasogenic edema formation or chronic tissue destruction usually show elevations of the ADC. Compromise of energy metabolism is likely to contribute to a reduction of the ADC while already minor structural disintegration may contribute to elevations of the ADC.

In psychiatric research, there is a growing interest in the microstructural and functional characteristics of brain networks, which often form the basis of current etiological concepts. As a result of novel magnetic resonance imaging techniques, the pathogenic characteristics of neuronal activity and connectivity can be examined in a noninvasive, safe, and repeatable manner. Functional magnetic resonance imaging (fMRI) uses blood oxygenation level-dependent (BOLD) measures for identifying the gray matter contribution to cognition. Diffusion tensor imaging (DTI) reveals the course and structural integrity of white matter projections. Because DTI does not require special motivation and performance, group differences in psychiatry are more easily interpreted in terms of underlying pathology. To date few studies have tried to investigate both, i.e. dynamic and microstructural data in the sense of a modern multi-dimensional investigation approach. The combination of both techniques, however, seems to offer a promising vehicle to further extent our current understanding of mental disorders and to identify populations at risk. In addition to addressing findings in psychiatric research, the present article presents a technical overview of DTI and examines the limitations and potential applications of both techniques.

Background and Purpose: Peri-infarct depolarizations (PIDs) have been demonstrated with diffusion-weighted MRI (DWI) in experimental stroke and are regarded as an important mechanism of ischemic injury. We tested the hypothesis that PIDs are of relevance for the early enlargement of human brain infarcts., Methods: Ten stroke patients were investigated by repetitive imaging of the apparent diffusion coefficient (ADC) in the acute phase (7 patients) or subacute phase (3 patients) of developing cortical infarction. In each patient, 20 ADC maps were obtained from serially measured echo-planar DWI (interval of 45 seconds). Data analysis focused on the potential spatial and temporal ADC changes, including structured qualitative analysis, calculation of subtraction images, serial analysis of regions of interest positioned in the infarct core and border, and calculation of hemispheric lesion areas, depending on various ADC thresholds ranging between 0 and 800 microm(2)/s., Results: Data analysis was unable to disclose any time-dependent changes in ADC that would resemble PID. In ischemic regions, the ADC reduction significantly progressed from the infarct border (555+/-96 microm(2)/s) to the infarct core (431+/-104 microm(2)/s, P:<0.01)., Conclusions: By using an MRI protocol with high temporal resolution and elaborated postprocessing, we were unable to demonstrate a pattern of diffusion changes that would be indicative of PID in human stroke. Experimental infarction and human stroke may differ in the detectability of PID.