[Aphasia associated with lacunar infarctions]. / Aphasien bei lakunären Hirninfarkten.

BACKGROUND: Typical lacunar syndromes do not include aphasia but aphasia has been reported in rare atypical lacunar syndromes. OBJECTIVE: Description of the phenomenology and of affected fiber tracts. MATERIAL AND METHODS: Case series of three patients with lacunar stroke as evidenced by magnetic resonance imaging. Identification of affected fiber tracts via fiber tracking from coregistered lesion sites in brains of two healthy participants. RESULTS: The lacunar strokes that produced aphasia were located in the very lateral territory of perforating branches of the middle cerebral artery and extended along the external capsule into its most rostrodorsal aspect. Even though the cortex, thalamus and most parts of the basal ganglia were unaffected, patients exhibited a mild to moderate nonfluent aphasia with syntactic deficits. Fiber tracking revealed that in contrast to the nonaphasic control patient with a neighboring lacunar stroke, the aphasic patient strokes involved particularly fibers of the left arcuate fascicle as well as fibers of the frontostriatal and frontal aslant tracts. CONCLUSION: Left lateral lacunar stroke can cause clinically relevant aphasia through disruption of speech-relevant fiber tracts.

A pilot study of magnetic resonance fingerprinting in Parkinson's disease.

Parkinson's disease (PD) affects more than six million people, but reliable MRI biomarkers with which to diagnose patients have not been established. Magnetic resonance fingerprinting (MRF) is a recent quantitative technique that can provide relaxometric maps from a single sequence. The purpose of this study is to assess the potential of MRF to identify PD in patients and their disease severity, as well as to evaluate comfort during MRF. Twenty-five PD patients and 25 matching controls underwent 3 T MRI, including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 maps were generated by voxel-wise matching the measured MRF signal to a precomputed dictionary. All participants also received standard inversion recovery T1 and multi-echo T2 mapping. An ROI-based analysis of relaxation times was performed. Differences between patients and controls as well as techniques were determined by logistic regression, Spearman correlation and t-test. Patients were asked to estimate the subjective comfort of the MRF sequence. Both MRF-based T1 and T2 mapping discriminated patients from controls: T1 relaxation times differed most in cortical grey matter (PD 1337 ± 38 vs. control 1386 ± 37 ms; mean ± SD; P = .0001) and, in combination with normal-appearing white matter, enabled correct discrimination in 85.7% of cases (sensitivity 83.3%; specificity 88.0%; receiver-operating characteristic [ROC]) area under the curve [AUC] 0.87), while for T2 mapping the left putamen was the strongest classifier (40.54 ± 6.28 vs. 34.17 ± 4.96 ms; P = .0001), enabling differentiation of groups in 84.0% of all cases (sensitivity 80.0%; specificity 88.0%; ROC AUC 0.87). Relaxation time differences were not associated with disease severity. Standard mapping techniques generated significantly different relaxation time values and identified other structures as different between groups other than MRF. Twenty-three out of 25 PD patients preferred the MRF examination instead of a standard MRI. MRF-based mapping can identify PD patients with good comfort but needs further assessment regarding disease severity identification and its potential for comparability with standard mapping technique results.

MR fingerprinting as a diagnostic tool in patients with frontotemporal lobe degeneration: A pilot study.

Several very rare forms of dementia are associated with characteristic focal atrophy predominantly of the frontal and/or temporal lobes and currently lack imaging solutions to monitor disease. Magnetic resonance fingerprinting (MRF) is a recently developed technique providing quantitative relaxivity maps and images with various tissue contrasts out of a single sequence acquisition. This pilot study explores the utility of MRF-based T1 and T2 mapping to discover focal differences in relaxation times between patients with frontotemporal lobe degenerative dementia and healthy controls. 8 patients and 30 healthy controls underwent a 3 T MRI including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 relaxation maps were generated based on an extended phase graphs algorithm-founded dictionary involving inner product pattern matching. A region of interest (ROI)-based analysis of T1 and T2 relaxation times was performed with FSL and ITK-SNAP. Depending on the brain region analyzed, T1 relaxation times were up to 10.28% longer in patients than in controls reaching significant differences in cortical gray matter (P = .047) and global white matter (P = .023) as well as in both hippocampi (P = .001 left; P = .027 right). T2 relaxation times were similarly longer in the hippocampus by up to 19.18% in patients compared with controls. The clinically most affected patient had the most control-deviant relaxation times. There was a strong correlation of T1 relaxation time in the amygdala with duration of the clinically manifest disease (Spearman Rho = .94; P = .001) and of T1 relaxation times in the left hippocampus with disease severity (Rho = .90, P = .002). In conclusion, MRF-based relaxometry is a promising and time-saving new MRI tool to study focal cerebral alterations and identify patients with frontotemporal lobe degeneration. To validate the results of this pilot study, MRF is worth further exploration as a diagnostic tool in neurodegenerative diseases.

Automated quantitative evaluation of brain MRI may be more accurate for discriminating preterm born adults.

OBJECTIVE: To investigate the structural brain abnormalities and their diagnostic accuracy through qualitative and quantitative analysis in term born and very preterm birth or with very low birth weight (VP/VLBW) adults. METHODS: We analyzed 3-T MRIs acquired in 2011-2013 from 67 adults (27 term born controls, mean age 26.4 years, 8 females; 40 VP/VLBWs, mean age 26.6 years, 16 females). We compared automatic segmentations of the white matter, deep gray matter and cortical gray matter, manual corpus callosum measurements and visual ratings of the ventricles and white matter with t tests, logistic regression, and receiver operator characteristic (ROC) curves. RESULTS: Automatic segmentation correctly classified 84% of cases; visual ratings correctly classified 63%. Quantitative volumetry based on automatic segmentation revealed higher ventricular volume, lower posterior corpus callosum, and deep gray matter volumes in VP/VLBW subjects compared to controls (p < 0.01). Visual rating and manual measurement revealed a thinner corpus callosum in VP/VLBW adults (p = 0.04) and deformed lateral ventricles (p = 0.03) and tendency towards more "dirty" white matter (p = 0.06). Automatic/manual measures combined with visual ratings correctly classified 87% of cases. Stepwise logistic regression identified three independent features that correctly classify 81% of cases: ventricular volume, deep gray matter volume, and white matter aspect. CONCLUSION: Enlarged and deformed lateral ventricles, thinner corpus callosum, and "dirty" white matter are prevalent in preterm born adults. Their visual evaluation has low diagnostic accuracy. Automatic volume quantification is more accurate but time consuming. It may be useful to ask for prematurity before initiating further diagnostics in subjects with these alterations. KEY POINTS: • Our study confirms prior reports showing that structural brain abnormalities related to preterm birth persist into adulthood. • In the clinical practice, if large and deformed lateral ventricles, small and thin corpus callosum, and "dirty" white matter are visible on MRI, ask for prematurity before considering other diagnoses. • Although prevalent, visual findings have low accuracy; adding automatic segmentation of lateral ventricles and deep gray matter nuclei improves the diagnostic accuracy.

Limbic Encephalitis in Patients with Epilepsy-is Quantitative MRI Diagnostic?

PURPOSE: Limbic encephalitis (LE) is an immune-related disease with limbic symptoms, variable and asymmetric magnetic resonance imaging (MRI) aspects and antibody profiles. This study investigated the diagnostic value of quantitative relaxation times T2 (qT2) and MRI signal intensities (SI) in LE. METHODS: The prospective 3T-MRI study included 39 epilepsy patients with initially suspected LE and 20 healthy controls. Values and asymmetry indices of qT2, T2-weighted (T2-w) and proton density (PD)-w SI of manually delineated and automatically segmented amygdala and hippocampus were measured. Additionally, two raters made a blinded visual analysis on FLAIR (fluid attenuation inversion recovery) and T2-w images. RESULTS: According to diagnostic guidelines, 22 patients had probable LE and 17 patients had possible LE. The qT2 was higher (p < 0.01) in patients than in controls (mean ± SD, amygdala 98 ± 7 ms vs. 90 ± 5 ms, hippocampus 101 ± 7 ms vs. 92 ± 3 ms), but was not different between probable and possible LE or between sides (left and right). The PD-w SI and T2-w SI were lower in patients than in controls but were not different between patient subgroups or between sides. Diagnostic performance of visual analysis was relatively poor. CONCLUSIONS: Epilepsy patients with suspected LE had elevated qT2 in amygdala and hippocampus, whereas the expected T2-w SI increase was not found; however, the diagnostic value of qT2 remains questionable since it did not discriminate probable from possible LE.

The ERICA Score: An MR Imaging-based Visual Scoring System for the Assessment of Entorhinal Cortex Atrophy in Alzheimer Disease.

Purpose To establish and evaluate a visual score focused on entorhinal cortex atrophy (ERICA), as the entorhinal cortex is one of the first brain structures affected in Alzheimer disease (AD). Materials and Methods In this retrospective study, ERICA was visually evaluated with magnetic resonance imaging (2009-2016). First, a four-point ERICA score was developed by using data in 48 consecutive subjects (20 patients with AD and 28 control subjects). Then, in the main analysis, ERICA and the standard medial temporal lobe atrophy (MTA) scores were determined in an independent cohort of 60 patients suspected of having AD (mean age, 69.4 years; range, 46-86 years) and in 60 age-matched patients with subjective cognitive decline (SCD) (mean age, 72.4 years; range 50-87 years). Score performances were evaluated with κ statistics, receiver operating characteristic analysis, t tests, and analysis of variance according to the Standards for Reporting of Diagnostic Accuracy Studies. Results Patients with AD had higher MTA scores (mean, 2.13) and ERICA scores (mean, 2.05) than patients with SCD (P < .001). An ERICA score of 2 or greater achieved a higher diagnostic accuracy (91%) than the MTA score (74%), with a sensitivity of 83% versus 57% and a specificity of 98% versus 92% in discriminating dementia caused by AD from SCD (P < .001). The ERICA score was correlated with amyloid ß 42/40 ratio (ρ = -0.54, P < .001) and with cerebrospinal fluid tau (ρ = 0.35, P = .001) and p-tau (ρ = 0.31, P = .004). In multivariable linear regression analysis, ERICA was associated with verbal learning and recall (ß = -.40 and -.41), nonverbal recall (ß = -.28), and cued recall (ß = -.41, P ≤ .002 for all). Conclusion An ERICA score of 2 or greater indicates probable AD with high diagnostic accuracy. © RSNA, 2018 Online supplemental material is available for this article.

Hippocampal "gliosis only" on MR imaging represents a distinct entity in epilepsy patients.

PURPOSE: The purpose of this study is to evaluate whether patients with drug-resistant mesial temporal lobe epilepsy (TLE) due to hippocampal "gliosis only" have different MRI features than those with hippocampal sclerosis (HS). Most TLE patients have HS corresponding to severe neuronal loss and gliosis, but a few have "gliosis only" without significant reduction of neuronal density. METHODS: We analyzed the morphology of cerebral 3 T MRIs (T1, T2, and FLAIR) of 103 patients with HS and 20 with "gliosis only" concerning hippocampal and amygdala aspect, volumes, and signal intensity (SI) using Fisher's exact test, Student's t test, and principal component analysis. RESULTS: Visually, the ipsilateral hippocampus was hyperintense in both groups, but SI was markedly increased in 74% of HS and in 25% of "gliosis only" patients; the ipsilateral hippocampus was smaller in 92% of HS and in 50% of "gliosis only" patients, and its internal architecture was lost in 57% of HS and 5% of "gliosis only" patients; the contralateral hippocampal SI was altered in 25% of HS and in 70% of "gliosis only" patients (all p < 0.001). Ipsilateral hippocampus of HS patients had lower volume (mean ± SD 2.86 ± 0.87 ml) compared with that of "gliosis only" patients (3.4 ± 1.02 ml) and had higher SI than the contralateral hippocampus of HS patients and then the hippocampus of "gliosis only" patients (all p < 0.01). CONCLUSION: "Gliosis only" has different MRI hippocampal characteristics than HS: less volume loss, less increase of the T2-w signal intensity, preservation of internal architecture, and more contralateral affection.

Value of quantitative magnetic resonance imaging T1-relaxometry in predicting contrast-enhancement in glioblastoma patients.

SUMMARIZING THE IMPORTANCE OF THE STUDY: The repetitive usage of gadolinium-based contrast agents (GBCA) is critical for magnetic resonance imaging (MRI) evaluation of tumor burden in glioblastoma patients. It is also a crucial tool for determination of radiographical response to treatment. GBCA injection, however, comes with a 2.4% rate of adverse events including life-threatening conditions such as nephrogenic systemic fibrosis (NSF). Moreover, GBCA have been shown to be deposited in brain tissue of patients even with an intact blood-brain barrier (BBB). The present study explores quantitative T1 relaxometry as an alternative non-invasive imaging technique detection of tumor burden and determination of radiographical response. This technique exploits specific properties of brain tissue with impaired BBB. With a sensitivity and specificity as high as 86% and 80%, respectively, quantitative T1-relaxometry allows for detecting contrast-enhancing areas without the use of GBCA. This method could make it unnecessary to subject patients to the risk of adverse events associated with the use of GBCA. Nonetheless, a large-scale analysis is needed to confirm our findings. BACKGROUND: Gadolinium-based contrast agents (GBCA) are crucial for magnetic resonance imaging (MRI)-based evaluation of tumor burden in glioblastoma (GBM). Serious adverse events of GBCA, even though uncommon, and gadolinium deposition in brain tissue could be avoided by novel imaging techniques not requiring GBCA. Altered tissue composition in areas with impaired blood-brain-barrier also alters the quantified T1 relaxation time (qT1), so that qT1 analysis could replace GBCA-based MRI for the analysis of tumor burden and response. METHODS: As a part of a prospective pilot MRI-relaxometry trial, patients with newly-diagnosed GBM who relapsed under standard radiochemotherapy were selected for this study. At recurrence, subtraction of qT1 maps pre and post-GBCA application (ΔqT1 maps) was used to determine areas of contrast-enhancement. With the contrast-enhancement on ΔqT1 maps as reference, ROC analysis served to detect an optimal qT1 cut-off on qT1 maps prior to GBCA to distinguish between contrast-enhancing tissue and its surroundings. RESULTS: Ten patients were included. A qT1 value >2051ms predicted contrast-enhancing tumor tissue with a sensitivity of 86% and specificity of 80% (AUC, 0.92; p<0.0001). Interestingly, qT1 prolongation >2051 ms that did not overlap with contrast-enhancing area transformed into contrast-enhancement later on (n=4). CONCLUSION: T1-relaxometry may be a useful technique to assess tissue properties equivalent to contrast-enhancement without the need for GBCA application. It may also provide information on sites with future tumor progression. Nonetheless, large-scale studies are needed to confirm these findings.

Brain relaxometry after macrocyclic Gd-based contrast agent.

PURPOSE: To assess if ratios of T1-weighted (T1w) signal intensity (SI) and quantitative T1 relaxometry (qT1) change on serial administration of macrocyclic gadobutrol. METHODS: A total of 17 glioblastoma patients were scanned at 3.0 T magnetic resonance imaging (MRI) every 6 weeks after tumor resection with standard MRI and T1 and T2 relaxometry before and after gadobutrol administration. On co-registered images T1w SI was measured and relaxation times T1 (qT1) and quantitative T2 (qT2) were quantified in several deep grey matter nuclei as ratios relative to frontal white matter and to the pons. Ratio changes were evaluated over time with a paired t­test and multiple regression. RESULTS: An average of 8 (range 5-14) scans per patient were completed. Ratios of T1w SI, qT1 and qT2 remained unchanged for all target regions from the first to the last time point (p > 0.05) and did not correlate with the number of gadobutrol administrations. Multivariate regression showed no significant impact of gadobutrol on qT1 or qT2 ratios, but a significant negative effect on T1w SI ratios. Gender also had no impact on the ratios but age had a significant negative influence on the qT1 ratio. CONCLUSION: Multiple administrations of a macrocyclic contrast agent did not change relaxation time T1 ratios in any deep grey matter structure.

Neuroimaging Findings Related to Behavioral Disturbances in Alzheimer's Disease: A Systematic Review.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) associated with Alzheimer's Disease (AD) have been linked to structural and functional alterations in fronto-temporal circuits and cortical abnormalities. However, little is known on how specific volumetric and functional brain changes may be associated with the frequency, severity and pattern of BPSD. METHODS: A systematic review of the literature regarding neuroimaging and BPSD changes in AD was performed through Pubmed/Medline, ISI, and EMBASE electronic databases from January 2000 to May 2015. Eligible references (n=40) included clinical studies in which structural or functional neuroimaging assessment was performed in AD subjects presenting BPSD features. RESULTS: BPSD symptoms, particularly apathy and psychosis have been associated in most of studies with either volume reductions or decreased metabolism in the prefrontal cortex (orbital and dorsolateral portions), anterior cingulate, insula and temporal lobes (middle portion). WM lacunes associated with AD progression have been associated with depressive symptoms. CONCLUSION: The sum of evidence highlights the importance of BPSD-related imaging findings for the understanding of the non-cognitive symptom spectrum in AD. Results suggest that structural and functional changes in fronto-limbic areas may lead to emotional deregulation and symptom unawareness. As these findings may be present early on the AD clinical course, they may have a relevance for the development of imaging markers that could be used in diagnosis, disease monitoring and prediction of therapeutic response.

Quantitative T1-mapping detects cloudy-enhancing tumor compartments predicting outcome of patients with glioblastoma.

Contrast enhancement of glioblastomas (GBM) is caused by the decrease in relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1 (qT1) discovers a subtle enhancement in GBM patients that is invisible in standard MRI. We assessed the volume change of this "cloudy" enhancement during radio-chemotherapy and its impact on patients' progression-free survival (PFS). We enrolled 18 GBM patients in this observational, prospective cohort study and measured 3T-MRI pre- and post contrast agent with standard T1-weighted (T1w) and with sequences to quantify T1 before radiation, and at 6-week intervals during radio-chemotherapy. We measured contrast enhancement by subtracting pre from post contrast contrast images, yielding relative signal increase ∆T1w and relative T1 shortening ∆qT1. On ∆qT1, we identified a solid and a cloudy-enhancing compartment and evaluated the impact of their therapy-related volume change upon PFS. In ∆qT1 maps cloudy-enhancing compartments were found in all but two patients at baseline and in all patients during therapy. The qT1 decrease in the cloudy-enhancing compartment post contrast was 21.64% versus 1.96% in the contralateral control tissue (P < 0.001). It was located at the margin of solid enhancement which was also seen on T1w. In contrast, the cloudy-enhancing compartment was visually undetectable on ∆T1w. A volume decrease of more than 21.4% of the cloudy-enhancing compartment at first follow-up predicted longer PFS (P = 0.038). Cloudy-enhancing compartment outside the solid contrast-enhancing area of GBM is a new observation which is only visually detectable with qT1-mapping and may represent tumor infiltration. Its early volume decrease predicts a longer PFS in GBM patients during standard radio-chemotherapy.

The Relationship between Gray Matter Quantitative MRI and Disability in Secondary Progressive Multiple Sclerosis.

PURPOSE: In secondary progressive Multiple Sclerosis (SPMS), global neurodegeneration as a driver of disability gains importance in comparison to focal inflammatory processes. However, clinical MRI does not visualize changes of tissue composition outside MS lesions. This quantitative MRI (qMRI) study investigated cortical and deep gray matter (GM) proton density (PD) values and T1 relaxation times to explore their potential to assess neuronal damage and its relationship to clinical disability in SPMS. MATERIALS AND METHODS: 11 SPMS patients underwent quantitative T1 and PD mapping. Parameter values across the cerebral cortex and deep GM structures were compared with 11 healthy controls, and correlation with disability was investigated for regions exhibiting significant group differences. RESULTS: PD was increased in the whole GM, cerebral cortex, thalamus, putamen and pallidum. PD correlated with disability in the whole GM, cerebral cortex, putamen and pallidum. T1 relaxation time was prolonged and correlated with disability in the whole GM and cerebral cortex. CONCLUSION: Our study suggests that the qMRI parameters GM PD (which likely indicates replacement of neural tissue with water) and cortical T1 (which reflects cortical damage including and beyond increased water content) are promising qMRI candidates for the assessment of disease status, and are related to disability in SPMS.

Multimodal quantitative MRI assessment of cortical damage in relapsing-remitting multiple sclerosis.

PURPOSE: To investigate magnetization transfer ratio (MTR), T1 relaxation time, and proton density (PD) as indicators of gray matter damage in relapsing-remitting multiple sclerosis (RRMS), reflecting different aspects of microstructural damage and as imaging correlates of clinical disability. We aimed to determine which of these parameters may optimally quantify cortical damage, and serve as an imaging surrogate of clinical disability. In this study, cortical values of MTR, a surrogate for demyelination in MS, of PD, reflecting replacement of neural tissue by water, and of T1 , indicating a complex array of microstructural changes, were assessed in a group of RRMS patients in comparison to healthy controls (HC). MATERIALS AND METHODS: 22 RRMS patients with varying disease duration (4.0 ± 6.54 years) and 10 HC received quantitative 3T magnetic resonance imaging (MRI) with MTR, T1 , and PD mapping. We tested for differences in cortical measurements between patients and HC. Additionally, correlation with disability as quantified by the Expanded Disability Status Scale was investigated. RESULTS: Cortical parameter values were significantly altered in the RRMS group, with increased values of T1 (P = 0.008) and PD (P = 0.028) and reduced values of MTR (P = 0.043). Only cortical T1 was correlated with clinical disability measurements (P = 0.001, r = 0.65). Receiver operating characteristic analysis demonstrated the best discriminatory power for T1 (area under the curve 0.79, PD: 0.75, MTR 0.73). CONCLUSION: Out of the parameters studied, cortical T1 is best suited to detect cortical damage as an imaging surrogate of clinical disability in RRMS. J. Magn. Reson. Imaging 2016;44:1600-1607.

Misleading FLAIR imaging pattern after glioma surgery with intraoperative MRI.

Intraoperative MRI (iMRI) allows a more detailed appreciation of the extent of resection than does conventional neurosurgery and results in longer overall survival in patients with malignant glioma. However, it is unknown whether the intraoperative application of contrast agent influences the early postsurgical MRI. The preceding iMRI could alter the signals of MR sequences in the early postsurgical MRI, especially in sequences influenced by T1 contrast. Hereby, we investigate such iMRI-induced influences on the fluid-attenuated inversion recovery (FLAIR) sequence. We retrospectively analyzed postsurgical T2w, T1w, and FLAIR images by visual inspection and by signal measurements in 46 patients with malignant gliomas after tumor resection. Of these, n = 25 patients were operated with conventional microsurgery, and n = 21 patients were operated with contrast-enhanced iMRI-guided microsurgery. We measured signal intensity in the resection cavity, in the cerebrospinal fluid (CSF) of the ventricles, and in the normal brain tissue contralateral to the tumor-bearing hemisphere on axial FLAIR images and T1-weighted and T2-weighted images. In 18 patients, the FLAIR sequence revealed hyperintense signal changes of the CSF in the subarachnoid or ventricular spaces. Seventeen of these 18 patients had received intraoperative MRI. In both FLAIR and T1-weighted images, the signal of the CSF in the ventricles was significantly higher in patients with iMRI than in patients without iMRI. The intraoperative application of contrast agent that is used for iMRI significantly influences postsurgical MRI within the first 72 h. We found hyperintense signal changes of the CSF in the FLAIR sequence in the subarachnoid and intraventricular spaces mimicking subarachnoid hemorrhage. The findings may result in a misdiagnosis of subarachnoid hemorrhage (SAH) in these patients.

Perfusion MRI in the Evaluation of Suspected Glioblastoma Recurrence.

PURPOSE: Treatment-related changes (TRC) often imitate tumor progression in glioblastomas. Increased regional cerebral blood volume (rCBV) can differentiate tumor progression from TRC after the standardized first-line radiochemotherapy, but information about diagnostic accuracy of rCBV for patients without any clinical selection criteria is limited. Therefore, we aimed to evaluate if rCBV can differentiate between TRC and tumor progression irrespective of preceding therapies and number of tumor progressions. METHODS: We analyzed mean and maximum rCBV from the enhancing areas normalized to the contralateral white matter in 44 pretreated glioblastomas with MR-morphological tumor progression. The diagnosis (real progression vs. TRC) was determined by histopathology or by clinical/MRI-follow-up. We performed nonparametric tests, receiver operating characteristics (ROC), and Kaplan-Meier analysis. RESULTS: Significant differences between tumor progression (N = 37) and TRC (N = 7) were found for rCBVmean (2.44 ± 1.05 vs. 1.69 ± .56, P < .03) and rCBVmax (3.40 ± 1.25 vs. 2.21 ± .62, P < .0007). A rCBVmax of 2.6 had 78% sensitivity and 86% specificity to detect tumor progression. Neither rCBVmean nor rCBVmax was predictive for the patient overall survival (OS). There were no statistically different rCBVmean and rCBVmax between the first and further tumor progressions. CONCLUSIONS: The rCBVmax differentiates tumor progression from TRC in unselected recurrent glioblastomas, but it is not predictive for the OS.

White matter alterations of the corticospinal tract in adults born very preterm and/or with very low birth weight.

White matter (WM) injury, either visible on conventional magnetic resonance images (MRI) or measurable by diffusion tensor imaging (DTI), is frequent in preterm born individuals and often affects the corticospinal tract (CST). The relation between visible and invisible white mater alterations in the reconstructed CST of preterm subjects has so far been studied in infants, children and up to adolescence. Therefore, we probabilistically tracked the CST in 53 term-born and 56 very preterm and/or low birth weight (VP/VLBW, < 32 weeks of gestation and/or birth weight < 1,500 g) adults (mean age 26 years) and compared their DTI parameters (axial, radial, mean diffusivity--AD, RD, MD, fractional anisotropy--FA) in the whole CST and slice-wise along the CST. Additionally, we used the automatic, tract-based-spatial-statistics (TBSS) as an alternative to tractography. We compared control and VP/VLBW and subgroups with and without CST WM lesions visible on conventional MRI. Compared to controls, VP/VLBW subjects had significantly higher diffusivity (AD, RD, MD) in the whole CST, slice-wise along the CST, and in multiple regions along the TBSS skeleton. VP/VLBW subjects also had significantly lower (TBSS) and higher (tractography) FA in regions along the CST, but no different mean FA in the tracked CST as a whole. Diffusion changes were weaker, but remained significant for both, tractography and TBSS, when excluding subjects with visible CST lesions. Chronic CST injury persists in VP/VLBW adults even in the absence of visible WM lesions, indicating long-term structural WM changes induced by premature birth.

Neural correlates of executive attention in adults born very preterm.

Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing.

Central nervous system imaging in childhood Langerhans cell histiocytosis - a reference center analysis.

BACKGROUND: The aim of our study was (1) to describe central nervous system (CNS) manifestations in children with Langerhans cell histiocytosis (LCH) based on images sent to a reference center and meeting minimum requirements and (2) to assess the inter-rater agreement of CNS-MRI results, which represents the overall reproducibility of this investigation. METHODS: We retrospectively reviewed brain MRI examinations in children with LCH, for which MRI minimum requirements were met. Abnormalities were rated by two experienced neuroradiologists, and the inter-rater agreement was assessed. RESULTS: Out of a total of 94 imaging studies, only 31 MRIs met the minimum criteria, which included T2w, FLAIR, T1w images before/after contrast in at least two different section planes, and thin post contrast sagittal slices T1w through the sella. The most common changes were osseous abnormalities, followed by solid enlargement of the pineal gland, thickened enhancing stalk and signal changes of the dentate nucleus. Whereas inter-rater agreement in assessing most of the CNS lesions was relatively high (κ > 0.61), the application of minimum criteria often did not allow to evaluate the posterior pituitary. CONCLUSIONS: The diversity of radiological protocols from different institutions leads to difficulties in the diagnosis of CNS abnormalities in children with LCH. Although the inter-rater agreement between neuroradiologists was high, not all the LCH manifestations could be completely ruled out when using the minimum criteria. Brain MRIs should therefore follow LCH guideline protocols and include T1 pre-gadolinium sagittal images, and be centrally reviewed in order to improve the comparison of clinical trials.

Quantitative T2, T2*, and T2' MR imaging in patients with ischemic leukoaraiosis might detect microstructural changes and cortical hypoxia.

INTRODUCTION: Quantitative MRI with T2, T2*, and T2' mapping has been shown to non-invasively depict microstructural changes (T2) and oxygenation status (T2* and T2') that are invisible on conventional MRI. Therefore, we aimed to assess whether T2 and T2' quantification detects cerebral (micro-)structural damage and chronic hypoxia in lesions and in normal appearing white matter (WM) and gray matter (GM) of patients with ischemic leukoaraiosis (IL). Measurements were complemented by the assessment of the cerebral blood flow (CBF) and the degree of GM and WM atrophy. METHODS: Eighteen patients with IL and 18 age-matched healthy controls were included. High-resolution, motion-corrected T2, T2*, and T2' mapping, CBF mapping (pulsed arterial spin labeling, PASL), and segmentation of GM and WM were used to depict specific changes in both groups. All parameters were compared between patients and healthy controls, using t testing. Values of p < 0.05 were accepted as statistically significant. RESULTS: Patients showed significantly increased T2 in lesions (p < 0.01) and in unaffected WM (p = 0.045) as well as significantly increased T2* in lesions (p = 0.003). A significant decrease of T2' was detected in patients in unaffected WM (p = 0.027), while no T2' changes were observed in GM (p = 0.13). Both unaffected WM and GM were significantly decreased in volume in the patient-group (p < 0.01). No differences of PASL-based CBF could be shown. CONCLUSION: Non-invasive quantitative MRI with T2, T2*, and T2' mapping might be used to detect subtle structural and metabolic changes in IL. Assessing the grade of microstructural damage and hypoxia might be helpful to monitor disease progression and to perform risk assessment.

Schizophrenia risk variants modulate white matter volume across the psychosis spectrum: evidence from two independent cohorts.

Polygenic risk scores, based on risk variants identified in genome-wide-association-studies (GWAS), explain a considerable portion of the heritability for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about the combined effects of these variants, although polygenic neuroimaging has developed into a powerful tool of translational neuroscience. In this study, we used genome wide significant SZ risk variants to test the predictive capacity of the polygenic model and explored potential associations with white matter volume, a key candidate in imaging phenotype for psychotic disorders. By calculating the combined additive schizophrenia risk of seven SNPs (significant hits from a recent schizophrenia GWAS study), we show that increased additive genetic risk for SZ was associated with reduced white matter volume in a group of participants (n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ patients and BD patients. This effect was also seen in a second independent sample of healthy individuals (n = 89). We suggest that a moderate portion of variance (~4%) of white matter volume can be explained by the seven hits from the recent schizophrenia GWAS. These results provide evidence for associations between cumulative genetic risk for schizophrenia and intermediate neuroimaging phenotypes in models of psychosis. Our work contributes to a growing body of literature suggesting that polygenic risk may help to explain white matter alterations associated with familial risk for psychosis.