Armin Biller

Grey matter abnormalities within cortico-limbic-striatal circuits in acute and weight-restored anorexia nervosa patients.

Functional disturbances within cortico-striatal control systems have been implicated in the psychobiology (i.e. impaired cognitive-behavioral flexibility, perfectionist personality) of anorexia nervosa. The aim of the present study was to investigate the morphometry of brain regions within cortico-striatal networks in acute anorexia nervosa (AN) as well as long-term weight-restored anorexia nervosa (AN-WR) patients. A total of 39 participants: 12 AN, 13 AN-WR patients, and 14 healthy controls (HC) underwent high-resolution, T1-weighted magnetic resonance imaging (MRI), a cognitive-behavioral flexibility task, and a psychometric assessment. Group differences in local grey matter volume (GMV) were analyzed using whole brain voxel-based morphometry (VBM) and brain-atlas based automatic volumetry computation (IBASPM). Individual differences in total GMV were considered as a covariate in all analyses. In the regional brain morphometry, AN patients, as compared to HC, showed decreased GMVs (VBM and volumetry) in the anterior cingulate cortex (ACC), the supplementary motor area (SMA), and in subcortical regions (amygdala, putamen: VBM only). AN-WR compared to HC showed decreased GMV (VBM and volumetry) in the ACC and SMA, whereas GMV of the subcortical region showed no differences. The findings of the study suggest that structural abnormalities of the ACC and SMA were independent of the disease stage, whereas subcortical limbic-striatal changes were state dependent.

The potential of relaxation-weighted sodium magnetic resonance imaging as demonstrated on brain tumors

Objectives:Total tissue sodium (23Na) content is associated with the viability of cells and can be assessed by 23Na magnetic resonance imaging. However, the resulting total sodium signal (23NaT) represents a volume-weighted average of different sodium compartments assigned to the intra- and extracellular space. In addition to the spin-density weighted contrast of 23NaT imaging, relaxation-weighted (23NaR) sequences were applied. The aim of this study was to evaluate the potential of 23NaR imaging for tissue characterization and putative additional benefits to 23NaT imaging. Materials and Methods:For 23NaT and 23NaR imaging, novel magnetic resonance imaging sequences were established and applied in 16 patients suffering from brain tumors (14 WHO grade I–IV and 2 metastases). All 23Na sequences were based on density-adapted three-dimensional radial projection reconstruction to obtain short echo times and high signal-to-noise ratio efficiency. Results:23NaT imaging revealed increased signal intensities in 15 of 16 brain tumors before therapy. In addition, 23NaR imaging enabled further differentiation of these lesions; all glioblastomas demonstrated higher 23NaR signal intensities as compared with WHO grade I–III tumors. Thus, 23NaR imaging allowed for correct separation between WHO grade I–III and WHO grade IV gliomas. In contrast to the 23NaT signal, the 23NaR signal correlated with the MIB-1 proliferation rate of tumor cells. Conclusions:These results serve as a proof of concept that 23NaR imaging reveals important physiological tissue characteristics different from 23NaT imaging. Furthermore, they indicate that the combined use of 23NaT and 23NaR imaging might add valuable information for the functional in vivo characterization of brain tissue.

Deep MRI brain extraction: A 3D convolutional neural network for skull stripping

Brain extraction from magnetic resonance imaging (MRI) is crucial for many neuroimaging workflows. Current methods demonstrate good results on non-enhanced T1-weighted images, but struggle when confronted with other modalities and pathologically altered tissue. In this paper we present a 3D convolutional deep learning architecture to address these shortcomings. In contrast to existing methods, we are not limited to non-enhanced T1w images. When trained appropriately, our approach handles an arbitrary number of modalities including contrast-enhanced scans. Its applicability to MRI data, comprising four channels: non-enhanced and contrast-enhanced T1w, T2w and FLAIR contrasts, is demonstrated on a challenging clinical data set containing brain tumors (N=53), where our approach significantly outperforms six commonly used tools with a mean Dice score of 95.19. Further, the proposed method at least matches state-of-the-art performance as demonstrated on three publicly available data sets: IBSR, LPBA40 and OASIS, totaling N=135 volumes. For the IBSR (96.32) and LPBA40 (96.96) data set the convolutional neuronal network (CNN) obtains the highest average Dice scores, albeit not being significantly different from the second best performing method. For the OASIS data the second best Dice (95.02) results are achieved, with no statistical difference in comparison to the best performing tool. For all data sets the highest average specificity measures are evaluated, whereas the sensitivity displays about average results. Adjusting the cut-off threshold for generating the binary masks from the CNNs probability output can be used to increase the sensitivity of the method. Of course, this comes at the cost of a decreased specificity and has to be decided application specific. Using an optimized GPU implementation predictions can be achieved in less than one minute. The proposed method may prove useful for large-scale studies and clinical trials.

Immune reconstitution inflammatory syndrome after withdrawal of natalizumab

Natalizumab, a humanized monoclonal antibody directed against the very late activating antigen-4, prevents lymphocyte transmigration across endothelium in multiple sclerosis (MS).1 It is undefined whether cessation of treatment carries the risk of disease exacerbation. A postwithdrawal rebound in T2-weighted lesional activity has been described after short-term exposure, whereas another study reported stable findings up to 14 months after discontinuation of natalizumab.2 We report a patient who developed dramatic clinical and radiologic worsening as a consequence of natalizumab withdrawal after prolonged therapy. Several features were reminiscent of an immune reconstitution inflammatory syndrome (IRIS). ### Case report. A 30-year-old woman had been diagnosed with relapsing-remitting MS in 1999 and had received glatiramer acetate and interferon-β as disease-modifying agents before natalizumab was started as escalating therapy because of continuing relapses (3–4/year; Expanded Disability Status Scale score [EDSS] 5). Natalizumab effectively reduced disease activity to 3 mild clinical events within a treatment period of almost 2 years (22 infusions). A cranial MRI 4 months after institution of therapy showed no new or active lesions (figure, A and B). In November 2008, natalizumab was discontinued because of a wish to have children. At that time, the disease was clinically stable. The patient was able to manage her everyday life with mild support and was employed half-time as an office clerk (EDSS 5). Within 9 weeks after natalizumab withdrawal, she progressively developed high-grade tetraparesis despite repeated IV steroid pulses (methylprednisolone 8.5 g in total). This coincided with multiple new T2-weighted and gadolinium-enhancing lesions in …

Diagnostic functional MRI: Illustrated clinical applications and decision-making

Functional magnetic resonance imaging (fMRI) has become a popular research tool, yet its use for diagnostic purposes and actual treatment planning has remained less widespread. The literature yields rather sparse evidence‐based data on clinical fMRI applications and accordant decision‐making. Notwithstanding, blood oxygenation level dependent (BOLD)‐ and arterial spin labeling (ASL)‐fMRI can be judiciously combined with perfusion measurements, electroencephalographic (EEG) recordings, diffusion‐weighted imaging (DWI), and fiber tractographies to assist clinical decisions. In this article we provide an overview of clinical fMRI applications based on illustrative examples. Assessment of cochlear implant candidates by fMRI is covered in some detail, and distinct reference is made to particular challenges imposed by brain tumors, other space‐occupying lesions, cortical dysplasias, seizure disorders, and vascular malformations. Specific strategies, merits, and pitfalls of analyzing and interpreting diagnostic fMRI studies in individual patients are highlighted. J. Magn. Reson. Imaging 2006.

Rapid-onset central motor plasticity in multiple sclerosis.

Objective: To study rapid-onset central motor plasticity, and its relationship to motor impairment and CNS injury in patients with multiple sclerosis (MS). Methods: In this cross-sectional observational study, motor plasticity was examined neurophysiologically and behaviorally in 22 patients with moderately severe (median Expanded Disability Status Scale score 2.5 [0–6]) stable MS and matched healthy controls. First, plasticity was assessed using paired associative stimulation (PAS), a protocol modeling long-term synaptic potentiation in human cortex. PAS combines repetitive electric nerve stimulation with transcranial magnetic stimulation (TMS) of the contralateral motor cortex. Second, motor learning was tested by a force production task. Motor impairment was assessed by functional tests. CNS injury was evaluated by obtaining normalized N-acetyl-aspartate (NAA/Cr) spectra using magnetic resonance spectroscopy and by the corticomuscular latency (CML) to the abductor pollicis brevis muscle as tested by TMS. Results: Patients with MS performed worse than controls in functional motor tests, CMLs were prolonged, and NAA/Cr was decreased. PAS-induced enhancement of corticospinal excitability and training-induced increments of motor performance were comparable between patients with MS and controls. Neither PAS-induced plasticity nor motor learning performance correlated with motor impairment or measures of CNS injury. Patients with high CNS injury and good motor performance did not differ significantly from those with high CNS injury and poor motor performance with respect to PAS-induced plasticity and motor learning success. Conclusions: Despite motor impairment and CNS injury in patients with multiple sclerosis (MS), rapid-onset motor plasticity is comparable to that in healthy subjects. Compensation of MS-related CNS injury is unlikely to be constrained by insufficient rapid-onset neuroplasticity.

The effect of ethanol on human brain metabolites longitudinally characterized by proton MR spectroscopy

The effect ethanol exerts on the human brain has not yet been addressed by longitudinal magnetic resonance (MR) spectroscopic experiments. Therefore, we longitudinally characterized cerebral metabolite changes in 15 healthy individuals by proton magnetic resonance spectroscopy (1H-MRS) subsequent to the ingestion of a standard beverage (mean peak blood alcohol concentration (BAC): 51.43 ± 10.27 mg/dL). Each participant was examined before, over 93.71 ± 11.17 mins immediately after and 726.36 ± 94.96 mins (12.11 ± 1.58 h) past per os alcohol exposure. Fronto-mesial and cerebellar ethanol concentrations over time were similar as determined by the LCModel analysis of spectral data. Alcohol-induced changes of fronto-mesial creatine, choline, glucose, inositol and aspartate levels for 5.79 ± 2.94 mins upon ingestion as well as cerebellar choline and inositol levels for 8.64 ± 2.98 mins past exposure. Closely associated with ethanol concentrations, supratentorial creatine, choline, inositol and aspartate levels decreased after ethanol administration, whereas glucose levels increased. Similarly, infratentorial choline and inositol concentrations were negatively correlated with ethanol levels over time. There were no changes in N-acetyl-aspartate levels upon alcohol exposure. Furthermore, no influence of ethanol on brain water integrals was detected. Ethanol consumption may directly increase oxidative stress and the neuronal vulnerability to it. In addition, our results are compatible with ethanol-induced cell membrane modifications and alternative energy substrate usage upon alcohol exposure.

Improved Brain Tumor Classification by Sodium MR Imaging: Prediction of IDH Mutation Status and Tumor Progression.

BACKGROUND AND PURPOSE: MR imaging in neuro-oncology is challenging due to inherent ambiguities in proton signal behavior. Sodium-MR imaging may substantially contribute to the characterization of tumors because it reflects the functional status of the sodium-potassium pump and sodium channels. MATERIALS AND METHODS: Sodium-MR imaging data of patients with treatment-naïve glioma WHO grades I–IV (n = 34; mean age, 51.29 ± 17.77 years) were acquired by using a 7T MR system. For acquisition of sodium-MR images, we applied density-adapted 3D radial projection reconstruction pulse sequences. Proton-MR imaging data were acquired by using a 3T whole-body system. RESULTS: We demonstrated that the initial sodium signal of a treatment-naïve brain tumor is a significant predictor of isocitrate dehydrogenase (IDH) mutation status (P < .001). Moreover, independent of this correlation, the Cox proportional hazards model confirmed the sodium signal of treatment-naïve brain tumors as a predictor of progression (P = .003). Compared with the molecular signature of IDH mutation status, information criteria of model comparison revealed that the sodium signal is even superior to IDH in progression prediction. In addition, sodium-MR imaging provides a new approach to noninvasive tumor classification. The sodium signal of contrast-enhancing tumor portions facilitates differentiation among most glioma types (P < .001). CONCLUSIONS: The information of sodium-MR imaging may help to classify neoplasias at an early stage, to reduce invasive tissue characterization such as stereotactic biopsy specimens, and overall to promote improved and individualized patient management in neuro-oncology by novel imaging signatures of brain tumors.

Responses of the Human Brain to Mild Dehydration and Rehydration Explored In Vivo by 1H-MR Imaging and Spectroscopy

Serial T1WI and 1H-MR spectroscopy data were acquired in 15 healthy individuals at normohydration, at 12 hours of dehydration, and during 1 hour of oral rehydration. Osmotic challenges were monitored by serum measures, including osmolality and hematocrit. With dehydration, serum osmolality increased by 0.67% and brain tissue fluid decreased by 1.63%. MR imaging morphometry demonstrated corresponding decreases of cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus. These changes reversed during rehydration. The authors conclude that it is essential to control for hydration levels in studies on brain morphometry and metabolism in order to avoid confounding the findings. BACKGROUND AND PURPOSE: As yet, there are no in vivo data on tissue water changes and associated morphometric changes involved in the osmo-adaptation of normal brains. Our aim was to evaluate osmoadaptive responses of the healthy human brain to osmotic challenges of de- and rehydration by serial measurements of brain volume, tissue fluid, and metabolites. MATERIALS AND METHODS: Serial T1-weighted and 1H-MR spectroscopy data were acquired in 15 healthy individuals at normohydration, on 12 hours of dehydration, and during 1 hour of oral rehydration. Osmotic challenges were monitored by serum measures, including osmolality and hematocrit. MR imaging data were analyzed by using FreeSurfer and LCModel. RESULTS: On dehydration, serum osmolality increased by 0.67% and brain tissue fluid decreased by 1.63%, on average. MR imaging morphometry demonstrated corresponding decreases of cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus. These changes reversed during rehydration. Continuous fluid ingestion of 1 L of water for 1 hour within the scanner lowered serum osmolality by 0.96% and increased brain tissue fluid by 0.43%, on average. Concomitantly, cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus increased. Changes in brain tissue fluid were related to volume changes of the whole brain, the white matter, and hypothalamus/thalamus. Only volume changes of the hypothalamus/thalamus significantly correlated with serum osmolality. CONCLUSIONS: This is the first study simultaneously evaluating changes in brain tissue fluid, metabolites, volume, and cortical thickness. Our results reflect cellular volume regulatory mechanisms at a macroscopic level and emphasize that it is essential to control for hydration levels in studies on brain morphometry and metabolism in order to avoid confounding the findings.

Scanning for the scanner: FMRI of audition by read-out omissions from echo-planar imaging.

Echo-planar imaging (EPI) generates considerable acoustic noise by rapidly oscillating gradients. In functional magnetic resonance imaging (FMRI), unshielded EPI sounds activate the auditory system inasmuch as it is responsive. Instead of attenuating EPI noise, our goal was to utilize it for auditory FMRI by omitting read-outs from the pulse sequences gradient train. Read-out gradient pulses are the primary noise determinant of EPI introducing its peak sound level and fundamental frequency peak which inversely relates to twice the echo spacing. Using model-driven analyses, we demonstrate that withholding read-outs from EPI is suited to reliably evoke hemodynamic blood oxygenation level-dependent (BOLD) signal modulations bilaterally in the auditory cortex of normal hearing subjects (n=60). To investigate the utility of EPI read-out omissions for auditory FMRI at an individual subjects level, we compare traditional Family-Wise-Error-Rate (FWER)-corrected maximum height thresholding to spatial mixture modeling (SMM). With the latter, appropriate bilateral auditory activations were confirmed in 95% of the individuals, whereas FWER-based voxel thresholding detected such activations in up to 72%. We illustrate the applicability of this novel EPI modification for clinical diagnostic purposes and report on a patient with bilateral large vestibular aqueducts (LVAs) and severe binaural sensorineural hearing loss (SNHL). In this particular case, read-out omissions from EPI were used to assert residual audition prior to cochlear implantation (CI). Requiring no specific task compliance or sophisticated stimulation equipment other than the scanner on its own, FMRI by read-out omissions lends itself to auditory investigations and to quickly probe audition.