Magnetic Resonance Imaging-based biomechanical simulation of cartilage: A systematic review.

MRI-based mathematical and computational modeling studies can contribute to a better understanding of the mechanisms governing cartilage's mechanical performance and cartilage disease. In addition, distinct modeling of cartilage is needed to optimize artificial cartilage production. These studies have opened up the prospect of further deepening our understanding of cartilage function. Furthermore, these studies reveal the initiation of an engineering-level approach to how cartilage disease affects material properties and cartilage function. Aimed at researchers in the field of MRI-based cartilage simulation, research articles pertinent to MRI-based cartilage modeling were identified, reviewed, and summarized systematically. Various MRI applications for cartilage modeling are highlighted, and the limitations of different constitutive models used are addressed. In addition, the clinical application of simulations and studied diseases are discussed. The paper's quality, based on the developed questionnaire, was assessed, and out of 79 reviewed papers, 34 papers were determined as high-quality. Due to the lack of the best constitutive models for various clinical conditions, researchers may consider the effect of constitutive material models on the cartilage disease simulation. In the future, research groups may incorporate various aspects of machine learning into constitutive models and MRI data extraction to further refine the study methodology. Moreover, researchers should strive for further reproducibility and rigorous model validation and verification, such as gait analysis.

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

T1 and T2* mapping of the human quadriceps and patellar tendons using ultra-short echo-time (UTE) imaging and bivariate relaxation parameter-based volumetric visualization.

Quantification of magnetic resonance (MR)-based relaxation parameters of tendons and ligaments is challenging due to their very short transverse relaxation times, requiring application of ultra-short echo-time (UTE) imaging sequences. We quantify both T1 and T2* in the quadriceps and patellar tendons of healthy volunteers at a field strength of 3 T and visualize the results based on 3D segmentation by using bivariate histogram analysis. We applied a 3D ultra-short echo-time imaging sequence with either variable repetition times (VTR) or variable flip angles (VFA) for T1 quantification in combination with multi-echo acquisition for extracting T2*. The values of both relaxation parameters were subsequently binned for bivariate histogram analysis and corresponding cluster identification, which were subsequently visualized. Based on manually-drawn regions of interest in the tendons on the relaxation parameter maps, T1 and T2* boundaries were selected in the bivariate histogram to segment the quadriceps and patellar tendons and visualize the relaxation times by 3D volumetric rendering. Segmentation of bone marrow, fat, muscle and tendons was successfully performed based on the bivariate histogram analysis. Based on the segmentation results mean T2* relaxation times, over the entire tendon volumes averaged over all subjects, were 1.8 ms ±â€¯0.1 ms and 1.4 ms ±â€¯0.2 ms for the patellar and quadriceps tendons, respectively. The mean T1 value of the patellar tendon, averaged over all subjects, was 527 ms ±â€¯42 ms and 476 ms ±â€¯40 ms for the VFA and VTR acquisitions, respectively. The quadriceps tendon had higher mean T1 values of 662 ms ±â€¯97 ms (VFA method) and 637 ms ±â€¯40 ms (VTR method) compared to the patellar tendon. 3D volumetric visualization of the relaxation times revealed that T1 values are not constant over the volume of both tendons, but vary locally. This work provided additional data to build upon the scarce literature available on relaxation times in the quadriceps and patellar tendons. We were able to segment both tendons and to visualize the relaxation parameter distributions over the entire tendon volumes.

Disturbed glutathione antioxidative defense is associated with structural brain changes in neuroleptic-naïve first-episode psychosis patients.

BACKGROUND: Oxidative stress and impaired antioxidant defense are reported in schizophrenia and are thought to be associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, negative symptomatology, and cognitive impairment. To test some of these assumptions we investigated the glutathione (GSH) antioxidant defense system (AODS) and brain structural abnormalities in drug-naïve individuals with first acute episode of psychosis (FEP). METHOD: The study involved 27 drug-naïve FEP patients and 31 healthy controls (HC). GSH AODS markers and TBARS (thiobarbituric acid reactive substances) were measured in blood plasma and erythrocytes. High-resolution T1-weighted 3T MRI were acquired from all subjects. To investigate brain structural abnormalities and effects of illness on interactions between GSH metabolites or enzyme activities and local grey matter density, voxel-based morphometry (VBM) with the computational anatomy toolbox (CAT12) was used. Symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Symptom Checklist 1990 revised (SCL-90-R). RESULTS: (i) In FEP patients, glutathione reductase activity (GSR) was lower than in the HC group. GSR activity in plasma was inversely correlated with SCL-90-R scores of depression and PANSS scores of the negative symptom subscale. (ii) A reduction of GM was observed in left inferior frontal, bilateral temporal, as well as parietal cortices of FEP patients. (iii) Interaction analyses revealed an influence of illness on GSR/GM associations in the left orbitofrontal cortex (BA 47). CONCLUSION: Our findings support the notion of altered GSH antioxidative defense in untreated acute psychosis as a potential pathomechanism for localized brain structural abnormalities. This pathology relates to a key brain region of social cognition, affective motivation control and decision making, and is clinically accompanied by depressive and negative symptoms.

Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging.

BACKGROUND: Time resolved 4D phase contrast (PC) cardiovascular magnetic resonance (CMR) in mice is challenging due to long scan times, small animal ECG-gating and the rapid blood flow and cardiac motion of small rodents. To overcome several of these technical challenges we implemented a retrospectively self-gated 4D PC radial ultra-short echo-time (UTE) acquisition scheme and assessed its performance in healthy mice by comparing the results with those obtained with an ECG-triggered 4D PC fast low angle shot (FLASH) sequence. METHODS: Cardiac 4D PC CMR images were acquired at 9.4 T in healthy mice using the proposed self-gated radial center-out UTE acquisition scheme (TE/TR of 0.5 ms/3.1 ms) and a standard Cartesian 4D PC imaging sequence (TE/TR of 2.1 ms/5.0 ms) with a four-point Hadamard flow encoding scheme. To validate the proposed UTE flow imaging technique, experiments on a flow phantom with variable pump rates were performed. RESULTS: The anatomical images and flow velocity maps of the proposed 4D PC UTE technique showed reduced artifacts and an improved SNR (left ventricular cavity (LV): 8.9 ± 2.5, myocardium (MC): 15.7 ± 1.9) compared to those obtained using a typical Cartesian FLASH sequence (LV: 5.6 ± 1.2, MC: 10.1 ± 1.4) that was used as a reference. With both sequences comparable flow velocities were obtained in the flow phantom as well as in the ascending aorta (UTE: 132.8 ± 18.3 cm/s, FLASH: 134.7 ± 13.4 cm/s) and pulmonary artery (UTE: 78.5 ± 15.4 cm/s, FLASH: 86.6 ± 6.2 cm/s) of the animals. Self-gated navigator signals derived from information of the oversampled k-space center were successfully extracted for all animals with a higher gating efficiency of time spent on acquiring gated data versus total measurement time (UTE: 61.8 ± 11.5%, FLASH: 48.5 ± 4.9%). CONCLUSIONS: The proposed self-gated 4D PC UTE sequence enables robust and accurate flow velocity mapping of the mouse heart in vivo at high magnetic fields. At the same time SNR, gating efficiency, flow artifacts and image quality all improved compared to the images obtained using the well-established, ECG-triggered, 4D PC FLASH sequence.

Combined spiroergometry and 31 P-MRS of human calf muscle during high-intensity exercise.

Simultaneous measurements of pulmonary oxygen consumption (VO2 ), carbon dioxide exhalation (VCO2 ) and phosphorus magnetic resonance spectroscopy (31 P-MRS) are valuable in physiological studies to evaluate muscle metabolism during specific loads. Therefore, the aim of this study was to adapt a commercially available spirometric device to enable measurements of VO2 and VCO2 whilst simultaneously performing 31 P-MRS at 3 T. Volunteers performed intense plantar flexion of their right calf muscle inside the MR scanner against a pneumatic MR-compatible pedal ergometer. The use of a non-magnetic pneumotachograph and extension of the sampling line from 3 m to 5 m to place the spirometric device outside the MR scanner room did not affect adversely the measurements of VO2 and VCO2 . Response and delay times increased, on average, by at most 0.05 s and 0.79 s, respectively. Overall, we were able to demonstrate a feasible ventilation response (VO2 = 1.05 ± 0.31 L/min; VCO2 = 1.11 ± 0.33 L/min) during the exercise of a single calf muscle, as well as a good correlation between local energy metabolism and muscular acidification (τPCr fast and pH; R2 = 0.73, p < 0.005) and global respiration (τPCr fast and VO2 ; R2  = 0.55, p = 0.01). This provides improved insights into aerobic and anaerobic energy supply during strong muscular performances.

[Cerebral metabolic changes and chronic back pain: Study taking into consideration clinical and psychological parameters]. / Hirnmetabolische Veränderungen bei chronischem Rückenschmerz : Studie unter Berücksichtigung von klinischen und psychischen Parametern.

BACKGROUND: The manifestation of chronic pain and psychological impairments are related to alterations of neurotransmitter metabolism in cerebral pain processing regions, e.g., anterior cingular cortex (ACC), insula. Magnetic resonance spectroscopy ((1)H-MRS) enables in vivo quantification of neurotransmitters in the brain and was applied in this study to examine the hypothesized chronic pain-related imbalance between excitatory (glutamatergic) and inhibitory (GABA-ergic) neurotransmitter turnovers in the brain of patients with nonspecific chronic pain. MATERIALS AND METHODS: A total of 19 patients with nonspecific chronic (> 3 months) back pain and 19 age- and gender-matched healthy subjects participated in this study. Glutamate and GABA as well as glutamate/GABA ratios were determined in the ACC and insula using (1)H-MRS. Sociodemographic, psychological, and pain-related features were measured with standardized questionnaires. RESULTS: There was a strong variance of glutamate/GABA ratios for both patients and healthy subjects with no significant difference between the two groups. Regression analysis revealed certain significant predictors, such as anxiety as causal variable for reduced glutamate and depression and age as predictors for reduced GABA in ACC. In the patient group, intensity of pain was a significant predictor for glutamate and GABA levels in the insula. CONCLUSIONS: Despite the uniform diagnosis of nonspecific chronic back pain, we observed a strong variance of neurotransmitters in cerebral pain processing regions. It is necessary to include psychological as well as clinical parameters (e.g., intensity of pain or depression) for a proper interpretation of neurotransmitter turnovers.

Quantitative Susceptibility Mapping: Concepts and Applications.

PURPOSE: To review the fundamental principles of susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM), and to discuss recent clinical developments. METHODS: SWI is a magnetic resonance imaging method that takes advantage of magnitude signal loss and phase information to reveal anatomic and physiologic information about tissue and venous vasculature. The method enhances image contrast qualitatively, relying on phase shifts due to differences in magnetic susceptibility between tissues. QSM, extending SWI in an elegant way, is a new sophisticated postprocessing technique that numerically solves the inverse source-effect problem to derive local tissue magnetic susceptibility (source) from the measured magnetic field distribution (effect) as it is reflected in the phase images of gradient-echo sequences. RESULTS: SWI has meanwhile been established in numerous clinical as well as basic biomedical applications due to its ability to highlight tissue structures and compounds that are difficult to detect by conventional magnetic resonance imaging (MRI), including iron, calcifications, small veins, blood, and bones. The field of QSM has also progressed rapidly, both in terms of optimizing the post-processing strategies and algorithms as well as in gaining ground for new clinical applications that take advantage of its quantitative nature and improved specificity to identify the magnetic signature of lesions. CONCLUSIONS: Though magnetic susceptibility may be a major nuisance producing image artifacts in MRI, recent work has transformed it into a useful source of image contrast. Both SWI and QSM are gaining increasing acceptance in clinical practice. In particular, QSM provides new insights into tissue composition and organization due to its more direct relation to the actual physical tissue magnetic properties.

Intrinsic correction of system delays for radial magnetic resonance imaging.

INTRODUCTION: When using radial MR image acquisition techniques gradient or sampling delays due to hardware imperfections can cause mismatch between the expected and the actual k-space trajectory along the readout direction. To provide a robust and simple correction of such system delays we developed a new calibration method which is independent of using any reference data or applying sequence modifications. MATERIAL AND METHODS: Radial data obtained with 180°, 360° and golden-angle radial ordering schemes were deliberately shifted along the readout direction for a discrete range of gradient delays. Following 2D regridding, images were reconstructed and analyzed in image space for all applied shifts to estimate the optimal system delay. Phantom and in vivo measurements were performed to test the robustness of the algorithm. RESULTS: Using the 360° and golden-angle radial ordering schemes system delays in the range of 3.3µs to 6.3µs were estimated and corrected for several imaging applications and different conditions, including cardiac and real-time MRI as well as multiple acquisitions using different imaging parameters and slice orientations. When using the standard 180° radial acquisition scheme no automated correction was possible. With a mean computation time of 23.2±14.0s for the delay estimation computational demands were moderate allowing implementation of the algorithm on the image reconstruction system of any modern MR system. CONCLUSION: We have demonstrated that radial data acquired with a 360° or golden-angle ordering scheme can be used for reliable intrinsic correction of system delays. The proposed technique enables a per-scan correction of system delays without the need for additional calibration data or modifications of the radial imaging sequence.

ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and healthy subjects.

BACKGROUND: Genetic variation in the gene encoding ZNF804A, a risk gene for schizophrenia, has been shown to affect brain functional endophenotypes of the disorder, while studies of white matter structure have been inconclusive. METHOD: We analysed effects of ZNF804A single nucleotide polymorphism rs1344706 on grey and white matter using voxel-based morphometry (VBM) in high-resolution T1-weighted magnetic resonance imaging scans of 62 schizophrenia patients and 54 matched healthy controls. RESULTS: We found a significant (p < 0.05, family-wise error corrected for multiple comparisons) interaction effect of diagnostic group x genotype for local grey matter in the left orbitofrontal and right and left lateral temporal cortices, where patients and controls showed diverging effects of genotype. Analysing the groups separately (at p < 0.001, uncorrected), variation in rs1344706 showed effects on brain structure within the schizophrenia patients in several areas including the left and right inferior temporal, right supramarginal/superior temporal, right and left inferior frontal, left frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and the right thalamus, as well as effects within the healthy controls in left lateral temporal, right anterior insula and left orbitofrontal cortical areas. We did not find effects of genotype of regional white matter in either of the two cohorts. CONCLUSIONS: Our findings demonstrate effects of ZNF804A genetic variation on brain structure, with diverging regional effects in schizophrenia patients and healthy controls in frontal and temporal brain areas. These effects, however, might be dependent on the impact of other (genetic or non-genetic) disease factors.

Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia.

BACKGROUND: Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls. METHOD: Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer). RESULTS: In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls. CONCLUSIONS: This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.

Effect of age on MRI phase behavior in the subcortical deep gray matter of healthy individuals.

BACKGROUND AND PURPOSE: It has been demonstrated that increased levels of iron in the brain occur with aging. In this study we investigated the nature of the association between age and SWI-filtered phase values, indicative of iron content, in the subcortical deep gray matter of healthy individuals. MATERIALS AND METHODS: A total of 210 healthy individuals (men: n = 89, women: n = 121), mean age, 39.8 years (standard deviation = 15.5; range = 6-76 years), were imaged on a 3T scanner. Mean MRI phase, mean phase of low-phase voxels, and normalized volumes were determined for total subcortical deep gray matter, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus, hippocampus, amygdala, nucleus accumbens, red nucleus, and substantia nigra. Linear and nonlinear regression models were used to explore the relationship between phase and volume measures, and aging. RESULTS: Mean phase values of subcortical deep gray matter structures showed a quadratic relationship, with individuals in late middle age (40-59 years) having the lowest mean phase values, followed by a reversal of this trend in the elderly. In contrast, mean phase of low-phase voxel measurements showed strong negative linear relationships with aging. Significantly lower phase values were detected in women compared with men (P < .001), whereas no sex differences were observed for mean phase of low-phase voxels. Normalized volume measurements were also linearly related to aging, and women showed smaller normalized volumes of subcortical deep gray matter structures than men (P < .001). Lower mean phase of low-phase voxels was related to decreased volume measures. CONCLUSIONS: A strong association between phase (quadratic effect; phase decreases are followed by increases), mean phase of low-phase voxels (linear effect), volume (linear effect), and age was observed. Low phase was related to brain atrophy.

Determination of three-dimensional muscle architectures: validation of the DTI-based fiber tractography method by manual digitization.

In the last decade, diffusion tensor imaging (DTI) has been used increasingly to investigate three-dimensional (3D) muscle architectures. So far there is no study that has proved the validity of this method to determine fascicle lengths and pennation angles within a whole muscle. To verify the DTI method, fascicle lengths of m. soleus as well as their pennation angles have been measured using two different methods. First, the 3D muscle architecture was analyzed in vivo applying the DTI method with subsequent deterministic fiber tractography. In a second step, the muscle architecture of the same muscle was analyzed using a standard manual digitization system (MicroScribe MLX). Comparing both methods, we found differences for the median pennation angles (P < 0.001) but not for the median fascicle lengths (P = 0.216). Despite the statistical results, we conclude that the DTI method is appropriate to determine the global fiber orientation. The difference in median pennation angles determined with both methods is only about 1.2° (median pennation angle of MicroScribe: 9.7°; DTI: 8.5°) and probably has no practical relevance for muscle simulation studies. Determining fascicle lengths requires additional restriction and further development of the DTI method.

Structure-function relationships in the context of reinforcement-related learning: a combined diffusion tensor imaging-functional magnetic resonance imaging study.

In the context of probabilistic learning, previous functional magnetic resonance imaging studies have shown decreasing uncertainty accompanying decreasing neuronal activation in task-relevant networks. Moreover, initial evidence points to a relationship between white matter structure and cognitive performance. Little is known, however, about the structural correlates underlying individual differences in activation and performance in the context of probabilistic learning. This combined functional magnetic resonance imaging-diffusion tensor imaging study aimed at investigating the individual ability to reduce processing resources with decreasing uncertainty in direct relation to individual characteristics in white matter brain structure. Results showed that more successful learners, as compared with less successful learners, exhibited stronger activation decreases with decreasing uncertainty. An increased mean and axial diffusivity in, among others, the inferior and superior longitudinal fasciculus, the posterior part of the cingulum bundle, and the corpus callosum were detectable in less successful learners compared with more successful learners. Most importantly, there was a negative correlation between uncertainty-related activation and diffusivity in a fronto-parieto-striatal network in less successful learners only, indicating a direct relation between diffusivity and the ability to reduce processing resources with decreasing uncertainty. These findings indicate that interindividual variations in white matter characteristics within the normal population might be linked to neuronal activation and critically influence individual learning performance.

Attenuation of cerebral venous contrast in susceptibility-weighted imaging of spontaneously breathing pediatric patients sedated with propofol.

BACKGROUND AND PURPOSE: SWI is known for its detailed visualization of the cerebral venous system and seems to be a promising tool for early detection of cerebrovascular pathologies in children, who are frequently sedated for MR imaging. Because sedation influences cerebral hemodynamics, we hypothesized that it would affect cerebral venous contrast in SWI. MATERIALS AND METHODS: SWI (125 examinations) of 26 patients (age, 2-16 years) was reviewed in this study. Images were acquired of patients sedated with propofol. Reviewers classified the images by weak or strong venous contrast. Physiologic data, such as etCO(2), BP, age, and CBF by arterial spin-labeling, were monitored and collected during MR imaging. A generalized estimating equation approach was used to model associations of these parameters with venous contrast. RESULTS: EtCO(2) and CBF were found to correlate with venous contrast, suggesting that patients with high etCO(2) and CBF have weak contrast and patients with low etCO(2) and CBF have strong contrast. BP was also found to correlate with the venous contrast of SWI, suggesting that patients with high BP have strong venous contrast. No significant correlations were found for any other physiologic parameters. CONCLUSIONS: We found that the venous contrast in SWI is affected by propofol sedation in spontaneously breathing patients. We also found that low etCO(2), low CBF, and high BP are associated with strong venous contrast. Reviewing SWI data in light of physiologic measures may therefore help prevent potential misinterpretations of weak venous contrast in SWI examinations under propofol sedation.

Intensive practice of a cognitive task is associated with enhanced functional integration in schizophrenia.

BACKGROUND: There is increasing evidence that the frequently reported working memory impairments in schizophrenia might be partly due to an alteration in the functional connectivity between task-relevant areas. However, little is known about the functional connectivity patterns in schizophrenia patients during learning processes. In a previous study, Koch et al. [Neuroscience (2007) 146, 1474-1483] have demonstrated stronger exponential activation decreases in schizophrenia patients during overlearning of short-term memory material. The question arises whether these differential temporal patterns of activation in schizophrenia patients and controls are going along with changes in task-related functional connectivity. METHOD: Therefore, in the current study, 13 patients with schizophrenia and 13 controls were studied while performing a short-term memory task associated with increasing overlearning of verbal stimulus material. Functional connectivity was investigated by analyses of psychophysiological interactions (PPI). RESULTS: Results revealed significant task-related modulation of functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and a network including the right DLPFC, left ventrolateral prefrontal cortex, premotor cortex, right inferior parietal cortex, left and right cerebellum as well as the left occipital lobe in patients during the course of overlearning and practice. No significant PPI results were detectable in controls. CONCLUSIONS: Activation changes with practice were associated with high functional connectivity between task-relevant areas in schizophrenia patients. This could be interpreted as a compensatory resource allocation and network integration in the context of cortical inefficiency and may be a specific neurophysiological signature underlying the pathophysiology of schizophrenia.

Diffusion-weighted imaging (DWI) in MR mammography (MRM): clinical comparison of echo planar imaging (EPI) and half-Fourier single-shot turbo spin echo (HASTE) diffusion techniques.

Diffusion-weighted imaging (DWI) techniques have shown potential to differentiate between benign and malignant neoplasms. However, the diagnostic significance of using DWI under routine conditions remains unclear. This study investigated the use of echo planar imaging (EPI) and half-Fourier acquired single-shot turbo spin echo (HASTE)-DWI with respect to the three parameters: lesion visibility, apparent diffusion coefficient (ADC) measurements, and size estimation. Following MRM (1.5 T), EPI- and HASTE-DWI were applied in 65 patients. Lesion visibility on DWI was compared with lesion visibility on subtracted contrast-enhanced T1w images (CE-T1w). Statistical tests were applied to diameter, visibility, and ADC value measurements. Seventy-four lesions were identified. ADC value measurements did not differ significantly between the two DWI sequences. The sensitivity and specificity of routine diagnostics (97.4% and 85.7%) were superior to EPI-DWI (87.2% and 82.9%) and HASTE-DWI (76.9% and 88.6%). Selecting only nonmass lesions, DWI did not prove to be of diagnostic value. Lesion demarcation by DWI was significantly lower compared with that by CE-T1w, with EPI-DWI showing the better performance (p < 0.001). No significant differences were found for size measurements between CE-T1w and DWI. Although clearly inferior compared with CE-T1w imaging, both DWI techniques are applicable for lesion assessment and size measurements.

Modelling and analysis of time-variant directed interrelations between brain regions based on BOLD-signals.

Time-variant Granger Causality Index (tvGCI) was applied to simulated and measured BOLD signals to investigate the reliability of time-variant analysis approaches for the identification of directed interrelations between brain areas on the basis of fMRI data. Single-shot fMRI data of a single image slice with short repetition times (200 ms, 16000 frames/subject, 64x64 voxels) were acquired from 5 healthy subjects during an externally-driven, self-paced finger-tapping paradigm (57-59 single taps for each subject). BOLD signals were derived from the pre-supplementary motor area (preSMA), the supplementary motor area (SMA), and the primary motor cortex (M1). The simulations were carried out by means of a Dynamic Causal Modelling (DCM) approach. The tvGCI as well as time-variant Partial Directed Coherence (tvPDC) were used to identify the modelled connectivity network (connectivity structure - CS - of the DCM). Different CSs were applied by using dynamic systems (Generalized Dynamic Neural Network - GDNN) and trivariate autoregressive (AR) processes. The influence of the low-pass characteristics of the simulated hemodynamic response (Balloon model) and of the measuring noise was tested. Additionally, our modelling strategy considered "spontaneous" BOLD fluctuations before, during, and after the appearance of the event-related BOLD component. Couplings which were extracted from the simulated signals were statistically evaluated (tvGCI for shuffled data, confidence tubes for tvGCI courses). We demonstrate that connections of our CS models can be correctly identified during the event-related BOLD component and with signal-to-noise-ratios corresponding to those of the measured data. The results based on simulations can be used to examine the reliability of connectivity identification based on BOLD signals by means of time-variant as well as time-invariant connectivity measures and enable a better interpretation of the analysis results using fMRI data. A readiness-BOLD response was only detected in one subject. However, in two subjects a strong time-variant connection (tvGCI) from preSMA to SMA was observed 3 s before the tapping was executed. This connection was accompanied by a weaker rise of the tvGCI from preSMA to M1. These preceding interrelations were confirmed in the other subjects by the dynamics of tvGCI courses. Based on the results of tvGCI analysis, the time-evolution of an individual connectivity network is shown for each subject.

[Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus]. / Familiäre Alzheimer-Variante mit Amyloidangiopathie als Ausdruck einer APP-Gen-Duplikation.

We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.

Fronto-cingulate effective connectivity in major depression: a study with fMRI and dynamic causal modeling.

Functional imaging studies are indicating disrupted error monitoring and executive control in a fronto-cingulate network in major depression. However, univariate statistical analyses allow only for a limited assessment of directed neuronal interactions. Therefore, the present study used dynamic causal modeling (DCM) of a fronto-cingulate network to re-analyze the data from a preceding fMRI study in 16 drug-free patients with major depression and 16 healthy controls using the Stroop Color-Word Test (Wagner et al., 2006). In both groups, a significant reciprocal interregional connectivity was found in a cognitive control network including prefrontal cortex (PFC) and dorsal anterior cingulate cortex (ACC). With regard to intrinsic connections we detected a significant difference for dorsal to rostral ACC connectivity between depressive patients and controls in terms of higher connectivity in patients. Additionally, a task by group interaction was observed for the bilinear interaction signaling enhanced task-related input from the dorsal to rostral ACC in subjects with depression. This could be related to the inability of patients to down-regulate rostral ACC activation as observed in the previous univariate analysis. The correlation between interference scores and intrinsic connections from dorsal ACC to dorsolateral PFC (DLPFC) was significant for both groups together, but no significant group differences in correlations could be detected. Thus, the observed relationship between control functions of the dorsal ACC exerted over DLPFC and interference scores appears to be valid in both patients with depression and controls. The findings are consistent with current models of a differential involvement of the fronto-cingulate system in the pathophysiology of major depression.