Default mode network activity in schizophrenia studied at resting state using probabilistic ICA.

Alterations in brain function in schizophrenia and other neuropsychiatric disorders are evident not only during specific cognitive challenges, but also from functional MRI data obtained during a resting state. Here we apply probabilistic independent component analysis (pICA) to resting state fMRI series in 25 schizophrenia patients and 25 matched healthy controls. We use an automated algorithm to extract the ICA component representing the default mode network (DMN) as defined by a DMN-specific set of 14 brain regions, resulting in z-scores for each voxel of the (whole-brain) statistical map. While goodness of fit was found to be similar between the groups, the region of interest (ROI) as well as voxel-wise analysis of the DMN showed significant differences between groups. Healthy controls revealed stronger effects of pICA-derived connectivity measures in right and left dorsolateral prefrontal cortices, bilateral medial frontal cortex, left precuneus and left posterior lateral parietal cortex, while stronger effects in schizophrenia patients were found in the right amygdala, left orbitofrontal cortex, right anterior cingulate and bilateral inferior temporal cortices. In patients, we also found an inverse correlation of negative symptoms with right anterior prefrontal cortex activity at rest and negative symptoms. These findings suggest that aberrant default mode network connectivity contributes to regional functional pathology in schizophrenia and bears significance for core symptoms.

Computer assisted analysis of MR-mammography reveals association between contrast enhancement and occurrence of distant metastasis.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is able to detect breast cancer with high sensitivity. Furthermore, this method provides functional information on tissue composition and vascularization. This study aims to identify the potential of DCE-MRI to predict distant metastasis in breast cancer patients using computer assisted interpretation of dynamic enhancement data. For this purpose, 59 consecutive patients with newly diagnosed invasive breast cancer received pretherapeutic DCE-MRI at 1.5 Tesla according to international recommendations. In all patients, follow up interval and occurrence of distant metastasis was documented. For DCE-MRI analysis dedicated software was used (Brevis, Siemens Healthcare, Erlangen, Germany). It allows semiautomatic identification of the most suspect curve in a lesion analyzed. Enhancement parameters assessed were "Initial Enhancement", "Washout", "Peak-Enhancement", and "Time to Peak Enhancement". Cox proportional hazards regression (CPHR) was used to analyze the effect of these parameters on the probability of metachronous distant metastasis. Median follow up period was 52.0 months. 6 patients developed distant metastases between 11 and 35 months after breast cancer diagnosis. In CPHR, Washout could be identified as significant and independent predictor for occurrence of distant metastasis (P = 0.0134). Our initial data demonstrate an association between computer measured enhancement parameters in DCE-MRI and occurrence of distant metastasis by quantification of Washout.

Antipsychotic drug effects on left prefrontal phospholipid metabolism: a follow-up 31P-2D-CSI study of haloperidol and risperidone in acutely ill chronic schizophrenia patients.

INTRODUCTION: ³¹Phosphorous magnetic resonance spectroscopy (2D chemical shift imaging, CSI) allows multiregional study of membrane phospholipids and high-energy phosphates in vivo. Increased membrane lipid turnover and impaired energy supply have repeatedly been shown in first-episode schizophrenia patients, and might be a target of drug actions other than dopamine receptors. Here, we explored differential metabolic effects of a typical vs. an atypical antipsychotic on brain phospholipids. METHODS: We applied 2D-CSI MR spectroscopy in 17 recurrent-episode schizophrenia patients off antipsychotics at baseline and at follow-up after 6 weeks, during which 7 patients were treated with haloperidol (10-16 mg/d) and 10 with risperidone (4-6 mg/d). Psychopathology changes were assessed using PANSS, BPRS and CGI scores. RESULTS: Follow-up analysis using repeated measure ANOVA revealed different effects of both antipsychotic agents: while risperidone generally increased metabolite levels, haloperidol showed a tendency to decrease them. This diverging effect was significant for ATP levels in the left lateral frontal cortex. Furthermore, risperidone increased ATP in the left dorsolateral prefrontal cortex, left anterior temporal cortex and left insular cortex, basal ganglia, and anterior cerebellum, along with left frontal and prefrontal increase of PCr, PDE and PME in these brain regions. CONCLUSION: Risperidone seems to stimulate neuronal and synaptic phospholipid remodeling in left frontal and prefrontal regions, and to a lesser extent also in temporal and insular cortices. We discuss these effects with respect to clinical effects on negative and cognitive symptoms, as well as interaction of phospholipid metabolism with glutamatergic neurotransmission.

Imaging of lamination patterns of the adult human olfactory bulb and tract: in vitro comparison of standard- and high-resolution 3T MRI, and MR microscopy at 9.4 T.

PURPOSE: Neurological and smelling disorders (e.g. Alzheimer's disease, sinonasal disease) negatively affect the microstructural integrity of the olfactory bulb's (OB) cortical layers. Recovery processes depend on active restoration of this microstructural integrity enabled by neuroneogenesis in the OB. The aim of this study was to evaluate lamination patterns of the OB and adjacent tract (OT) using high resolution MRI at 3 Tesla (T) as well as MR microscopy at 9.4 T in comparison with histological sections. MATERIAL AND METHODS: Twenty-four human OBs were imaged in vitro using standard (2mm slice thickness) and high resolution (0.2mm slice thickness) T1w and T2w MR imaging at 3T. Based on signal intensity differences, the number of OB layers and the OB lamination patterns were assessed by two observers in consensus. Results were compared using Wilcoxon test. Signal intensity profiles were compared to reference Nissl stained histological sections and imaging results of MR microscopy. OT lamination patterns were assessed and different configurations of cross sectional areas were compared to macroscopic results and OB/OT lamination patterns. RESULTS: Standard resolution at 3T identified three layers in 8.3%, two layers in 83.3%, and one layer in 8.3%. High resolution at 3T (4 layers in 91.7%, 3 layers in 8.3%) significantly performed better (P<0.001). Signal intensity profile analysis at 3T and 9.4 T (yielding up to 6 different signal intensities) correlated with histological sections and enabled quantitative evaluation of OB lamination patterns. 3T MRI of the OT revealed two separate signal intensities in T2w in 73%, a hyperintense core and a hypointense sheath, and the number of OT signal intensities positively correlated (ρ=0.541, P=0.006) with the increasing complexity of the OTs' cross sectional area configurations. Additionally, cross sectional area configurations correlated with macroscopic results (ρ=0.558, P=0.002) and OB lamination patterns (ρ=0.446, P=0.022). CONCLUSIONS: 3T MRI and MR-microscopy indicate the possibility to identify the lamination pattern of the human OB/OT and to reflect the histological status. If further development will be able to provide technical equipment that complies with the condition of human in vivo high resolution imaging achieving a good enough signal noise ratio, the method of signal intensity profile analysis could prospectively enable scientists to assess the OB's microstructural status in neurological and smelling disorders.

Artificial Neural Networks for differential diagnosis of breast lesions in MR-Mammography: a systematic approach addressing the influence of network architecture on diagnostic performance using a large clinical database.

RATIONALE AND OBJECTIVES: Differential diagnosis of lesions in MR-Mammography (MRM) remains a complex task. The aim of this MRM study was to design and to test robustness of Artificial Neural Network architectures to predict malignancy using a large clinical database. MATERIALS AND METHODS: For this IRB-approved investigation standardized protocols and study design were applied (T1w-FLASH; 0.1 mmol/kgBW Gd-DTPA; T2w-TSE; histological verification after MRM). All lesions were evaluated by two experienced (>500 MRM) radiologists in consensus. In every lesion, 18 previously published descriptors were assessed and documented in the database. An Artificial Neural Network (ANN) was developed to process this database (The-MathWorks/Inc., feed-forward-architecture/resilient back-propagation-algorithm). All 18 descriptors were set as input variables, whereas histological results (malignant vs. benign) was defined as classification variable. Initially, the ANN was optimized in terms of "Training Epochs" (TE), "Hidden Layers" (HL), "Learning Rate" (LR) and "Neurons" (N). Robustness of the ANN was addressed by repeated evaluation cycles (n: 9) with receiver operating characteristics (ROC) analysis of the results applying 4-fold Cross Validation. The best network architecture was identified comparing the corresponding Area under the ROC curve (AUC). RESULTS: Histopathology revealed 436 benign and 648 malignant lesions. Enhancing the level of complexity could not increase diagnostic accuracy of the network (P: n.s.). The optimized ANN architecture (TE: 20, HL: 1, N: 5, LR: 1.2) was accurate (mean-AUC 0.888; P: <0.001) and robust (CI: 0.885-0.892; range: 0.880-0.898). CONCLUSION: The optimized neural network showed robust performance and high diagnostic accuracy for prediction of malignancy on unknown data.

Time course of cortical plasticity after facial nerve palsy: a single-case study.

BACKGROUND: Functional connectivity is defined as the temporal correlation between spatially remote neurophysiological events. This method has become particularly useful for studying neuroplasticity to detect changes in the collaboration of brain areas during cortical reorganization. METHODS: In this article, the authors longitudinally studied voxel-based morphometry and resting state functional magnetic resonance imaging 10 times in 1 patient during the course of Bell palsy (idiopathic facial nerve palsy) up to complete clinical recovery. RESULTS: Morphometric analysis revealed a significant alteration in the face area of the primary motor cortex (M1) contralateral to the paretic face, with an initial increase in gray matter concentration. Functional connectivity analysis between the M1 and other parts of the facial motor network revealed acutely disrupted intrahemispheric connectivity but unaltered interhemispheric connectivity. The disrupted functional connectivity was most pronounced on the day of the onset of symptoms, with a subsequent return toward normal during the course of recovery. This time course was found to differ between the selected parts of the facial motor network. However, the increase in functional connectivity strength preceded clinical recovery in all areas and reached a stable level before the patient fully recovered. CONCLUSION: These results demonstrate that recovery from facial nerve palsy is complemented by cortical reorganization, with pronounced changes of functional connectivity that precede clinical recovery.

Cortical reorganization in Bell's palsy.

PURPOSE: Bell's palsy, a unilateral, idiopathic facial nerve palsy, is a common disorder that is generally followed by a good recovery of function. The aim of this study was to investigate the impact of such a transiently decreased motor control (without deafferentation) on the functional reorganization of the brain. METHODS: To address this issue, functional MRI was applied to 10 patients in the acute state of Bell's palsy and after their complete clinical recovery. The functional paradigm consisted of unilateral facial movements with the affected as well as the non-affected side. RESULTS: We found an overactivity of several brain areas contralateral to the palsy that are related to error detection and sensory-motor integration in the acute stage and motor integration and control in the follow-up. Functional connectivity was disrupted in the affected cortical motor system during the acute stage of Bell's palsy compared to the follow-up. This altered connectivity was found mostly between motor areas in the hemisphere contralateral to the paretic side, whereas the interhemispherical connectivity remained largely stable. CONCLUSION: Our results indicate that a transient peripheral deefferentation causes functional reorganization in the brain that partly persists even after an apparently complete clinical recovery.

Application of MR mammography beyond local staging: is there a potential to accurately assess axillary lymph nodes? evaluation of an extended protocol in an initial prospective study.

OBJECTIVE: The purpose of our study was to clinically test an extended MR mammography (MRM) protocol for combined local staging (T-staging) and locoregional staging (N-staging) of breast cancer within one single examination using a dedicated whole-body scanner. SUBJECTS AND METHODS: Fifty-six consecutive primary breast cancer patients without prior treatment underwent MRM and surgicopathological N-staging. The MRM protocol (10 minutes; axial T1-weighted gradient-recalled echo; dynamic contrast-enhanced; T2-weighted; turbo spin-echo) was extended to evaluate axillary lymph nodes (90 seconds; coronal T2-weighted HASTE; T1-weighted volumetric breath-hold examination; field of view, both axillae, supraclavicular nodes, and cervical nodes). A dedicated whole-body scanner was used. First, two experienced radiologists independently rated the presence of lymph node metastasis (present or absent, weighted kappa). Second, predefined descriptors were applied by both readers to differentiate lymph node status. These were statistically analyzed using univariate chi-square statistics, sensitivity and specificity, positive likelihood ratio, diagnostic odds ratio (OR), and multivariate statistics (binary logistic-regression, receiver operating characteristics, and chi-squared automatic interaction detection [CHAID] tree). RESULTS: Most significant predictors (p < 0.001) of present metastasis were "irregular margin" (diagnostic OR, 14.0), "inhomogeneous cortex" (diagnostic OR, 8.4), "perifocal edema" (positive likelihood ratio, 100) and "asymmetry" (diagnostic OR, 19.5). CHAID tree identified "asymmetry" and "irregular margin" as significant predictors (adjusted-p < 0.05) for present metastasis (PPV: 100%), whereas absence of "asymmetry" and "homogeneous internal structure" were highly predictive of absent metastasis (negative predictive value, 94.3%). Combination of significant descriptors using binary logistic regression revealed an area under the receiver operating characteristic curve of 0.93 (p < 0.001). Interrater agreement was "almost-perfect" (κ = 0.95). CONCLUSION: Combined T-staging and locoregional staging (N-staging) was possible within one imaging session using the proposed protocol. Despite a minimal increase in examination time, high diagnostic accuracy and excellent interrater reliability were achieved.