Non-conscious processing of fear faces: a function of the implicit self-concept of anxiety.

BACKGROUND: Trait anxiety refers to a stable tendency to experience fears and worries across many situations. High trait anxiety is a vulnerability factor for the development of psychopathologies. Self-reported trait anxiety appears to be associated with an automatic processing advantage for threat-related information. Self-report measures assess aspects of the explicit self-concept of anxiety. Indirect measures can tap into the implicit self-concept of anxiety. METHODS: We examined automatic brain responsiveness to non-conscious threat as a function of trait anxiety using functional magnetic resonance imaging. Besides a self-report instrument, we administered the Implicit Association Test (IAT) to assess anxiety. We used a gender-decision paradigm presenting brief (17 ms) and backward-masked facial expressions depicting disgust and fear. RESULTS: Explicit trait anxiety was not associated with brain responsiveness to non-conscious threat. However, a relation of the implicit self-concept of anxiety with masked fear processing in the thalamus, precentral gyrus, and lateral prefrontal cortex was observed. CONCLUSIONS: We provide evidence that a measure of the implicit self-concept of anxiety is a valuable predictor of automatic neural responses to threat in cortical and subcortical areas. Hence, implicit anxiety measures could be a useful addition to explicit instruments. Our data support the notion that the thalamus may constitute an important neural substrate in biased non-conscious processing in anxiety.

Spectrum of qualitative and quantitative imaging of pilomyxoid, intermediate pilomyxoid and pilocytic astrocytomas in relation to their genetic alterations.

PURPOSE: Pilomyxoid astrocytomas (PMA) are pediatric brain tumors predominantly located in the suprasellar region, third ventricle and posterior fossa, which are considered to be more clinically aggressive than pilocytic astrocytomas (PA). Another entity, intermediate pilomyxoid tumors (IPT), exists within the spectrum of pilocytic/pilomyxoid astrocytomas. The 2021 WHO CNS classification refrained from assigning grade 1 or 2 status to PMA, thereby reflecting the need to further elucidate their clinical and imaging characteristics. METHODS: We included a total of 15 patients with PMA, IPT and suprasellar PA. We retrospectively evaluated immunohistochemistry, imaging findings and diffusion characteristics within these tumors as well as whole exome sequencing for three of the cases. RESULTS: 87% of the tumors were supratentorial with 11 cases suprasellar in location, 1 case located in the frontal white matter and 1 in the hippocampus. 6 cases demonstrated intraventricular extension. ADC values were higher in PMA and IPT than PA. 3 cases demonstrated KIAA1549-BRAF-fusion, 2 had BRAF[Formula: see text]-mutation and 6 were BRAF-wildtype. All cases had recurrence/progression on follow-up. CONCLUSION: PMA and IPT do not demonstrate aggressive imaging characteristics in respect to their diffusion imaging with ADC values being higher than PA. Lack of BRAF-alteration in PMA corresponded to atypical location of tumors with atypical driver mutations and mechanisms.

How tissue fluidity influences brain tumor progression.

Mechanical properties of biological tissues and, above all, their solid or fluid behavior influence the spread of malignant tumors. While it is known that solid tumors tend to have higher mechanical rigidity, allowing them to aggressively invade and spread in solid surrounding healthy tissue, it is unknown how softer tumors can grow within a more rigid environment such as the brain. Here, we use in vivo magnetic resonance elastography (MRE) to elucidate the role of anomalous fluidity for the invasive growth of soft brain tumors, showing that aggressive glioblastomas (GBMs) have higher water content while behaving like solids. Conversely, our data show that benign meningiomas (MENs), which contain less water than brain tissue, are characterized by fluid-like behavior. The fact that the 2 tumor entities do not differ in their soft properties suggests that fluidity plays an important role for a tumor's aggressiveness and infiltrative potential. Using tissue-mimicking phantoms, we show that the anomalous fluidity of neurotumors physically enables GBMs to penetrate surrounding tissue, a phenomenon similar to Saffman-Taylor viscous-fingering instabilities, which occur at moving interfaces between fluids of different viscosity. Thus, targeting tissue fluidity of malignant tumors might open horizons for the diagnosis and treatment of cancer.

Association of Lesion Location and Depressive Symptoms Poststroke.

BACKGROUND: Depressive symptoms are a common stroke sequela, yet their neurobiological substrates are still unclear. We sought to determine if they are associated with specific lesion locations. METHODS: In a prospective observational study, 270 patients with stroke were tested twice with the Hospital Anxiety and Depression Scale around day 6 and again 6 months poststroke and voxel-based lesion behavior mapping was performed. RESULTS: Frequency of depressive symptoms (depression subscale of the Hospital Anxiety and Depression Scale >7) after 6 months was 19.6 %. Higher Hospital Anxiety and Depression Scale scores for depression around day 6 were the only variable associated with depressive symptoms after 6 months in a multiple logistic regression. Lesions in the right putamen were significantly associated with depressive symptoms after 6 months in the voxel-based lesion behavior mapping. CONCLUSIONS: Lesions in the right basal ganglia might increase the risk of depressive symptoms 6 months poststroke.

White Matter Integrity of the Corticospinal Tract for Estimation of Individual Patient Risk for Postoperative Neurological Deterioration after Glioma Surgery.

BACKGROUND: Tractography has become a standard tool for planning neurosurgical operations and has been proven to be useful for risk stratification. In various conditions, tractography-derived white matter integrity has been shown to be associated with neurological outcome. Postoperative performance has been shown to be a prognostic marker in glioma. We aimed to assess the relation of preoperative corticospinal tract (CST) integrity with postoperative neurological deterioration in patients with malignant glioma. METHODS: We retrospectively analyzed a cohort of 24 right-handed patients (41.7% female) for perioperative neurological performance score (NPS) and applied our anatomical tractography workflow to extract the median fractional anisotropy (FA) of the CST in preoperative magnetic resonance imaging (MRI). RESULTS: Median FA of the CST ipsilateral to the tumor correlated significantly with preoperative NPS (p = 0.025). After rank order correlation and multivariate linear regression, we found that the preoperative median FA of the right CST correlates with preoperative NPS, independently from epidemiological data (p = 0.019). In patients with lesions of the right hemisphere, median FA of the right CST was associated with a declining NPS in multivariate linear regression (p = 0.024). Receiver operating characteristic (ROC) analysis revealed an optimal FA cutoff at 0.3946 in this subgroup (area under the curve 0.83). Patients below that cutoff suffered from a decline in neurological performance significantly more often (p = 0.020). CONCLUSIONS: Assessment of preoperative white matter integrity may be a promising biomarker for risk estimation of patients undergoing craniotomy for resection of malignant glioma.

Diagnostic benefit of high b-value computed diffusion-weighted imaging in acute brainstem infarction.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) is a cornerstone in diagnostic of ischemic stroke. The aim of this study was to investigate the usefulness of high-b-value computed DWI (c-DWI) in comparison to standard DWI in patients with acute brainstem infarction. MATERIALS AND METHODS: 56 patients with acute brainstem infarction were retrospectively analysed by two readers. DWI was obtained with the b-values 0, 500 and 1000 s/mm² on either a 1.5 or 3 T magnetic resonance imaging (MRI) scanner. c-DWI was calculated with a monoexponential model with high b-values 2000, 3000, 4000 and 5000 s/mm². All c-DWI series with high-b-values were compared to the standard DWI sequence at b-value of 1000 s/mm² in terms of image artifacts, lesion extent and contrast. RESULTS: There was no statistically significant difference between 1.5 and 3 T MRI regarding the measured ischemic lesion size. There were no statistically significant differences between the ischemic lesion sizes on DWI at b-values of 1000 s/mm² and on c-DWI at higher b-values. Overall, the contrast between the lesion and the surrounding normal areas improved with increasing b-value on the isotropic DWIs: maximum at b = 5000, followed by that at b 2000 and b 1000 s/mm², in order. The best relation between artifacts and lesion contrast was identified for b 2000 s/mm². CONCLUSION: High b-value DWI derived from c-DWI has a higher visibility for ischemic brainstem lesions compared to standard DWI without additional time cost. The b-2000 image is recommended to use in clinical routine, higher b-value images lead to more imaging artifacts, which might result in misdiagnosis.

Association of Lesion Location and Depressive Symptoms Poststroke.

BACKGROUND AND PURPOSE: Poststroke depression is a common stroke sequel, yet its neurobiological substrates are still unclear. We sought to determine whether specific lesion locations are associated with depressive symptoms after stroke. METHODS: In a prospective study, 270 patients with first ever stroke were repeatedly tested with the depression subscale of the Hospital Anxiety and Depression Scale within the first 4 weeks and 6 months after stroke. Voxel-based lesion behavior mapping based on clinical imaging was performed to test for associations between symptoms of depression and lesion locations. RESULTS: Frequency of poststroke depression (Hospital Anxiety and Depression Scale-D score >7) after 6 months was 19.6%. Higher Hospital Anxiety and Depression Scale-D scores for depression within the first 4 weeks were the only independent predictor for poststroke depression after 6 months in a multiple logistic regression also including age, sex, lesion volume, stroke severity, Barthel-Index, and the anxiety subscale of the Hospital Anxiety and Depression Scale. Nonparametric permutation-test based voxel-based lesion behavior mapping identified a cluster of voxels mostly within the left ventrolateral prefrontal cortex where lesions were significantly associated with more depressive symptoms after 6 months. No such association was observed within the right hemisphere despite better lesion coverage. CONCLUSIONS: Lesions in the left ventrolateral prefrontal cortex increase the risk of depressive symptoms 6 months poststroke. Lesions within the right hemisphere are unrelated to depressive symptoms. Recognition of left frontal lesions as a risk factor should help in the early diagnosis of poststroke depression through better risk stratification. The results are in line with evidence from functional imaging and noninvasive brain stimulation in patients without focal brain damage indicating that dysfunction in the left lateral prefrontal cortex contributes to depressive disorders.

Whole tissue and single cell mechanics are correlated in human brain tumors.

Biomechanical changes are critical for cancer progression. However, the relationship between the rheology of single cells measured ex-vivo and the living tumor is not yet understood. Here, we combined single-cell rheology of cells isolated from primary tumors with in vivo bulk tumor rheology in patients with brain tumors. Eight brain tumors (3 glioblastoma, 3 meningioma, 1 astrocytoma, 1 metastasis) were investigated in vivo by magnetic resonance elastography (MRE), and after surgery by the optical stretcher (OS). MRE was performed in a 3-Tesla clinical MRI scanner and magnitude modulus |G*|, loss angle φ, storage modulus G', and loss modulus G'' were derived. OS experiments measured cellular creep deformation in response to laser-induced step stresses. We used a Kelvin-Voigt model to deduce two parameters related to cellular stiffness (µKV) and cellular viscosity (ηKV) from OS measurements in a time regimen that overlaps with that of MRE. We found that single-cell µKV was correlated with |G*| (R = 0.962, p < 0.001) and G'' (R = 0.883, p = 0.004) but not G' of the bulk tissue. These results suggest that single-cell stiffness affects tissue viscosity in brain tumors. The observation that viscosity parameters of individual cells and bulk tissue were not correlated suggests that collective mechanical interactions (i.e. emergent effects or cellular unjamming) of many cancer cells, which depend on cellular stiffness, influence the mechanical dissipation behavior of the bulk tissue. Our results are important to understand the emergent rheology of active multiscale compound materials such as brain tumors and its role in disease progression.

Clinical suspicion of spondylodiscitis with equivocal MRI findings: does diffusion-weighted imaging prove helpful here?

BACKGROUND: Despite the high sensitivity of magnetic resonance imaging (MRI), early detection of spondylodiscitis (SpD) remains challenging due to its low specificity. PURPOSE: To assess the diagnostic value of diffusion-weighted imaging (DWI) in suspected cases of SpD with ambiguous early MRI findings in the differentiation of degenerative disorders (DD). MATERIAL AND METHODS: In this prospective study, 52 patients suspected of having SpD underwent a whole-spine 3-T MRI scan comprising sagittal DWI. Of 58 conspicuous, T2-weighted, signal increased discs, 39 were successfully evaluated using DWI. Apparent diffusion coefficient (ADC) values and ADC maps were blindly analyzed using the region of interest of the conspicuous disc and a normal adjacent reference disc. Intraindividual ratios (conspicuous disc: reference disc) were calculated. RESULTS: All conspicuous discs showed increased absolute ADC values, which did not differ significantly between SpD (n = 22) and DD (n = 17). However, ADC ratio was significantly higher in SpD vs. DD (P < 0.05). In receiver operating characteristic curve analysis, an ADC ratio threshold of 1.6 resulted in 45% sensitivity and 88% specificity (area under the curve = 0.69) for SpD diagnosis. CONCLUSION: The absolute ADC value does not provide a reliable diagnosis of SpD. Increased diffusivity can be an indication of infection but should always be discussed in the context of existing disc degeneration.

Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors.

BACKGROUND: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. METHODS: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. RESULTS: Significant MRI site and vendor effects (p â€‹< â€‹.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p â€‹< â€‹1.39E-36). In particular, volumes larger than 200 â€‹mm3 (for amygdalar nuclei) and 300 â€‹mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε â€‹< â€‹5% and DICE â€‹> â€‹0.80). CONCLUSION: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Generalization of deep learning models for ultra-low-count amyloid PET/MRI using transfer learning.

PURPOSE: We aimed to evaluate the performance of deep learning-based generalization of ultra-low-count amyloid PET/MRI enhancement when applied to studies acquired with different scanning hardware and protocols. METHODS: Eighty simultaneous [18F]florbetaben PET/MRI studies were acquired, split equally between two sites (site 1: Signa PET/MRI, GE Healthcare, 39 participants, 67 ± 8 years, 23 females; site 2: mMR, Siemens Healthineers, 64 ± 11 years, 23 females) with different MRI protocols. Twenty minutes of list-mode PET data (90-110 min post-injection) were reconstructed as ground-truth. Ultra-low-count data obtained from undersampling by a factor of 100 (site 1) or the first minute of PET acquisition (site 2) were reconstructed for ultra-low-dose/ultra-short-time (1% dose and 5% time, respectively) PET images. A deep convolution neural network was pre-trained with site 1 data and either (A) directly applied or (B) trained further on site 2 data using transfer learning. Networks were also trained from scratch based on (C) site 2 data or (D) all data. Certified physicians determined amyloid uptake (+/-) status for accuracy and scored the image quality. The peak signal-to-noise ratio, structural similarity, and root-mean-squared error were calculated between images and their ground-truth counterparts. Mean regional standardized uptake value ratios (SUVR, reference region: cerebellar cortex) from 37 successful site 2 FreeSurfer segmentations were analyzed. RESULTS: All network-synthesized images had reduced noise than their ultra-low-count reconstructions. Quantitatively, image metrics improved the most using method B, where SUVRs had the least variability from the ground-truth and the highest effect size to differentiate between positive and negative images. Method A images had lower accuracy and image quality than other methods; images synthesized from methods B-D scored similarly or better than the ground-truth images. CONCLUSIONS: Deep learning can successfully produce diagnostic amyloid PET images from short frame reconstructions. Data bias should be considered when applying pre-trained deep ultra-low-count amyloid PET/MRI networks for generalization.

Subthalamic nucleus volumes are highly consistent but decrease age-dependently-a combined magnetic resonance imaging and stereology approach in humans.

The subthalamic nucleus (STN) is a main target structure of deep brain stimulation (DBS) in idiopathic Parkinson's disease. Nevertheless, there is an ongoing discussion regarding human STN volumes and neuron count, which could potentially have an impact on STN-DBS. Moreover, a suspected functional subdivision forms the basis of the tripartite hypothesis, which has not yet been morphologically substantiated. In this study, it was aimed to investigate the human STN by means of combined magnetic resonance imaging (MRI) and stereology. STN volumes were obtained from 14 individuals (ranging from 65 to 96 years, 25 hemispheres) in 3 T MRI and in luxol-stained histology slices. Neuron number and cell densities were investigated stereologically over the entire STN and in pre-defined subregions in anti-human neuronal protein HuC/D-stained slices. STN volumes measured with MRI were smaller than in stereology but appeared to be highly consistent, measuring on average 99 ± 6 mm3 (MRI) and 132 ± 20 mm3 (stereology). The neuron count was 431,088 ± 72,172. Both STN volumes and cell count decreased age-dependently. Neuron density was different for the dorsal, medial and ventral subregion with significantly higher values ventrally than dorsally. Small variations in STN volumes in both MRI and stereology contradict previous findings of large variations in STN size. Age-dependent decreases in STN volumes and neuron numbers might influence the efficacy of STN-DBS in a geriatric population. Though the study is limited in sample size, site-dependent differences for the STN subregions form a morphological basis for the tripartite theory. Hum Brain Mapp 38:909-922, 2017. © 2016 Wiley Periodicals, Inc.

Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in Thyroid Cancer.

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm². Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. CONCLUSIONS: histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted.

Longitudinal reproducibility of default-mode network connectivity in healthy elderly participants: A multicentric resting-state fMRI study.

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

Test-retest reliability of the default mode network in a multi-centric fMRI study of healthy elderly: Effects of data-driven physiological noise correction techniques.

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

Early [(18)F]florbetaben and [(11)C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer's disease.

PURPOSE: [(18)F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aß tracer [(11)C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [(18)F]FDG uptake. Uptake data for (18)F-labelled Aß PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aß tracer [(18)F]FBB in the diagnosis of Alzhimers disease (AD). METHODS: This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [(11)C]PiB (11 patients) or [(18)F]FBB (11 patients) in routine clinical practice. Images were acquired 1 - 9 min after administration of both tracers and 40 - 70 min and 90 - 110 min after administration of [(11)C]PiB and [(18)F]FBB, respectively. The patients also underwent [(18)F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aß tracer uptake and dementia as well as brain atrophy were investigated. RESULTS: Regional visual scores of early Aß tracer and [(18)F]FDG PET images were significantly correlated (Spearman's ρ = 0.780, P < 0.001). Global brain visual analysis revealed identical results between early Aß tracer and [(18)F]FDG PET images. In a VOI-based analysis, the early Aß tracer data correlated significantly with the [(18)F]FDG data (r = 0.779, P < 0.001), but there were no differences between [(18)F]FBB and [(11)C]PiB. Cortical SUVRs in regions typically affected in AD on early Aß tracer and [(18)F]FDG PET images were correlated with MMSE scores (ρ = 0.458, P = 0.032, and ρ = 0.456, P = 0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aß tracer PET images compared with [(18)F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison. CONCLUSION: Early [(18)F]FBB and [(11)C]PiB PET brain images are similar to [(18)F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [(18)F]FDG. Thus, Aß tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.

Feasibility and acceptance of simultaneous amyloid PET/MRI.

PURPOSE: Established Alzheimer's disease (AD) biomarker concepts classify into amyloid pathology and neuronal injury biomarkers, while recent alternative concepts classify into diagnostic and progression AD biomarkers. However, combined amyloid positron emission tomography/magnetic resonance imaging (PET/MRI) offers the chance to obtain both biomarker category read-outs within one imaging session, with increased patient as well as referrer convenience. The aim of this pilot study was to investigate this matter for the first time. METHODS: 100 subjects (age 70 ± 10 yrs, 46 female), n = 51 with clinically defined mild cognitive impairment (MCI), n = 44 with possible/probable AD dementia, and n = 5 with frontotemporal lobe degeneration, underwent simultaneous [18F]florbetaben or [11C]PIB PET/MRI (3 Tesla Siemens mMR). Brain amyloid load, mesial temporal lobe atrophy (MTLA) by means of the Scheltens scale, and other morphological brain pathologies were scored by respective experts. The patients/caregivers as well as the referrers were asked to assess on a five-point scale the convenience related to the one-stop-shop PET and MRI approach. RESULTS: In three subjects, MRI revealed temporal lobe abnormalities other than MTLA. According to the National Institute on Aging-Alzheimer's Association classification, the combined amyloid-beta PET/MRI evaluation resulted in 31 %, 45 %, and 24 % of the MCI subjects being categorized as "MCI-unlikely due to AD", "MCI due to AD-intermediate likelihood", and "MCI due to AD-high likelihood", respectively. 50 % of the probable AD dementia patients were categorized as "High level of evidence of AD pathophysiological process", and 56 % of the possible AD dementia patients as "Possible AD dementia - with evidence of AD pathophysiological process". With regard to the International Working Group 2 classification, 36 subjects had both positive diagnostic and progression biomarkers. The patient/caregiver survey revealed a gain of convenience in 88 % of responders as compared to a theoretically separate PET and MR imaging. In the referrer survey, an influence of the combined amyloid-beta PET/MRI on the final diagnosis was reported by 82 % of responders, with a referrer acceptance score of 3.7 ± 1.0 on a 5-point scale. CONCLUSION: Simultaneous amyloid PET/MRI is feasible and provides imaging biomarkers of all categories which are able to supplement the clinical diagnosis of MCI due to AD and that of AD dementia. Further, patient and referrer convenience is improved by this one-stop-shop imaging approach.

White matter lesions reduce number of brain metastases in different cancers: a high-resolution MRI study.

Brain metastases are major complications of common cancers. Tumor type and proneness to the CNS are thought to define the number and size of brain metastases. It is not known if intrinsic vascular factors can also have an effect. Restricted perfusion due to cerebral small vessel disease is frequent in elderly patients and causes white matter lesions (WML). The aim of this analysis was to evaluate a possible negative effect of WML and patient age on the number and size of brain metastases (BM) of different tumor entities. Pre-therapeutic 3 T brain magnetic resonance imaging (MRI) of 200 patients with BM were analyzed. Location, size and number of BM (NoM) were determined. T2 hyperintensive WML were scored according to Fazekas-Score (grade I-III). Patients with WML grade 1 (NoM: 5.59; p = 0.009) and grade 2 (NoM: 3.68; p = 0.002) had significantly less BM than patients without WML (NoM: 6.99). This effect was present in subgroups of different tumors: NSCLC (p = 0.05), other tumors than NSCLC (p = 0.048). Age (≤65 or >65 years) was positively correlated with the degree of WML but not with number (pNoM = 0.832) or mean diameter (pmDM = 0.662) of brain metastases. While patient age did not appear to be relevant, increasing WML were associated with lower number of brain metastases in different tumor types.

Distance to Thrombus in Acute Middle Cerebral Artery Occlusion Predicts Target Mismatch and Ischemic Penumbra.

BACKGROUND AND PURPOSE: In patients with occlusion of the middle cerebral artery (MCA) treated by intravenous thrombolysis (IVT), the distance to thrombus (DT) has been proposed as a predictor of outcome. The purpose of the present study was to investigate how DT relates to dynamic susceptibility contrast perfusion metrics. METHODS: Retrospective analysis was undertaken of patients who were diagnosed with acute MCA occlusion by magnetic resonance imaging and treated with IVT. Volumes of time-to-maximum (Tmax) perfusion deficits and diffusion-weighted imaging (DWI) lesions, diffusion-perfusion mismatch volumes, and the presence of target mismatch were determined. Correlations between the above stoke measures and DT were then calculated. RESULTS: Fifty-five patients were included. DT showed significant inverse correlations with Tmax greater than 4, 6, 8, and 10 seconds, respectively, and mismatch volumes. Using the DT group median (14 mm) as a separator, significant intergroup differences were observed for Tmax greater than 4, 6, and 8 seconds, respectively, and for mismatch volumes. Grouping DT into quartiles showed significant intergroup differences regarding mismatch volumes and Tmax values greater than 4 and 6 seconds. Binary logistic regression identified DT (odds ratio [OR] = .89; 95% confidence interval [CI], .81-.99) and DWI lesion volumes (OR = .92; 95% CI, .86-.97) as independent predictors of target mismatch. A low DT predicted target mismatch with an area under the curve of .69. CONCLUSIONS: DT correlates inversely with Tmax perfusion deficits and mismatch volumes and acts as an independent predictor of target mismatch.

Distance to thrombus in acute middle cerebral artery occlusion: a predictor of outcome after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: In patients with acute middle cerebral artery (MCA) stroke, therapeutic decisions are influenced by the location of the occlusion. This study aimed to analyze clinical outcomes in patients with acute ischemic MCA stroke treated with systemic intravenous thrombolysis (IVT) using recombinant tissue plasminogen activator, according to the location of the occlusion. METHODS: Of 621 patients screened, 136 with acute stroke and MCA occlusion confirmed by CT angiography were retrospectively included in this study. The distance from the carotid T to the thrombus (DT) on coronal maximum intensity projection images and the thrombus length were measured. The correlation between DT and the modified Rankin Scale score at 90 days was analyzed. RESULTS: DT was an independent predictor of clinical outcome in stroke patients treated with IVT. A long DT was significantly correlated with a good clinical outcome (modified Rankin Scale score at 90 days ≤2). A poor clinical outcome was exponentially more likely than a good outcome when the DT was <16 mm (P<0.001). The thrombus length was not correlated with the modified Rankin Scale score at 90 days. A long thrombus (>8 mm) occurred significantly more often in the proximal MCA than the distal MCA (P<0.001). CONCLUSION: DT is an independent predictor of clinical outcome in patients with acute MCA occlusion treated with IVT. In acute stroke with MCA occlusion confirmed by CT angiography and DT <16 mm, the likelihood of a good clinical outcome after treatment with IVT was exponentially <50%. This might warrant the evaluation of other therapy forms than IVT in patients with proximal MCA occlusion.