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Abstract Diffusion-MRI (dMRI) measures molecular diffusion, which allows to characterize microstructural properties of the human brain. Gliomas strongly alter these microstructural properties. Delineation of brain tumors currently mainly relies on conventional MRI-techniques, which are, however, known to underestimate tumor volumes in diffusely infiltrating glioma. We hypothesized that dMRI is well suited for tumor delineation, and developed two different deep-learning approaches. The first diffusion-anomaly detection architecture is a denoising autoencoder, the second consists of a reconstruction and a discrimination network. Each model was exclusively trained on non-annotated dMRI of healthy subjects, and then applied on glioma patients’ data. To validate these models, a state-of-the-art supervised tumor segmentation network was modified to generate groundtruth tumor volumes based on structural MRI. Compared to groundtruth segmentations, a dice score of 0.67 ± 0.2 was obtained. Further inspecting mismatches between diffusion-anomalous regions and groundtruth segmentations revealed, that these colocalized with lesions delineated only later on in structural MRI follow-up data, which were not visible at the initial time of recording. Anomaly-detection methods are suitable for tumor delineation in dMRI acquisitions, and may further enhance brain-imaging analysis by detection of occult tumor infiltration in glioma patients, which could improve prognostication of disease evolution and tumor treatment strategies.

Abstract The pathophysiology of degenerative cervical myelopathy (DCM) is characterized by chronic compression-induced damage to the spinal cord leading to secondary harm such as disruption of the blood spinal cord barrier (BSCB). It is therefore the purpose of this study to analyze BSCB disruption in pre- and postoperative DCM patients and to correlate those with the clinical status and postoperative outcome. This prospectively controlled cohort included 50 DCM patients (21 female; 29 male; mean age: 62.9 ± 11.2 years). As neurological healthy controls, 52 (17 female; 35 male; mean age 61.8 ± 17.3 years) patients with thoracic abdominal aortic aneurysm (TAAA) and indication for open surgery were included. All patients underwent a neurological examination and DCM-associated scores (Neck Disability Index, modified Japanese Orthopaedic Association Score) were assessed. To evaluate the BSCB status, blood and cerebrospinal fluid (CSF) samples (lumbar puncture or CSF drainage) were taken preoperatively and in 15 DCM patients postoperatively (4 female; 11 male; mean age: 64.7 ± 11.1 years). Regarding BSCB disruption, CSF and blood serum were examined for albumin, immunoglobulin (Ig) G, IgA and IgM. Quotients for CSF/serum were standardized and calculated according to Reiber diagnostic criteria. Significantly increased preoperative CSF/serum quotients were found in DCM patients as compared to control patients: AlbuminQ (p

Abstract With diffuse infiltrative glioma being increasingly recognized as a systemic brain disorder, the macroscopically apparent tumor lesion is suggested to impact on cerebral functional and structural integrity beyond the apparent lesion site. We investigated resting-state functional connectivity (FC) and diffusion-MRI-based structural connectivity (SC) (comprising edge-weight (EW) and fractional anisotropy (FA)) in isodehydrogenase mutated (IDHmut) and wildtype (IDHwt) patients and healthy controls. SC and FC were determined for whole-brain and the Default-Mode Network (DMN), mean intra- and interhemispheric SC and FC were compared across groups, and partial correlations were analyzed intra- and intermodally. With interhemispheric EW being reduced in both patient groups, IDHwt patients showed FA decreases in the ipsi- and contralesional hemisphere, whereas IDHmut patients revealed FA increases in the contralesional hemisphere. Healthy controls showed strong intramodal connectivity, each within the structural and functional connectome. Patients however showed a loss in structural and reductions in functional connectomic coherence, which appeared to be more pronounced in IDHwt glioma patients. Findings suggest a relative dissociation of structural and functional connectomic coherence in glioma patients at the time of diagnosis, with more structural connectomic aberrations being encountered in IDHwt glioma patients. Connectomic profiling may aid in phenotyping and monitoring prognostically differing tumor types.

Metacognition has only scarcely been investigated in brain tumor patients. It is unclear if and how the tumor-lesioned brain might be able to maintain an adequate sense-of-self. As cortical midline structures (CMS) are regarded as essential for self-referential mental activity, we investigated resting-state fMRI connectivity (FC) of CMS to the default-mode network (DMN) and to the whole brain, comparing glioma patients and matched controls. Subjects furthermore performed a trait judgement (TJ), a trait recall task (TR), and neuropsychological testing. In the TJ, adjectives had to be ascribed as self- or non-self-describing, assessing the self-serving effect (SSE), a normally observed bias for positive traits. In the TR, the mnemic neglect effect (MNE), a memory advantage for positive traits, was tested. The groups were compared and partial correlations between FC and test metrics were analyzed. Although patients were significantly impaired in terms of verbal memory, groups did not differ in the SSE or the MNE results, showing preserved metacognitive abilities in patients. FC of CMS to the DMN was maintained, but was significantly decreased to whole brain in the patients. FC of the dorsomedial prefrontal cortex (DMPFC) to whole brain was correlated with the MNE in patients. Preserving the DMPFC in therapeutic interventions might be relevant for maintaining self-related verbal information processing in the memory domain in glioma patients.

This study investigated supra- and infratentorial structural gray and white matter (GM, WM) alterations in patients with degenerative cervical myelopathy (DCM) as an indicator of secondary harm due to chronic cervical cord compression and micro trauma. With MRI-based anatomical assessment and subsequent voxel-based morphometry analyses, pre- and postoperative volume alterations in the primary motor cortex (MI), the primary somatosensory cortex (SI), the supplementary motor area (SMA), and the cerebellum were analyzed in 43 DCM patients and 20 controls. We assessed disease-related symptom severity by the modified Japanese Orthopaedic Association scale (mJOA). The study also explored symptom severity-based brain volume alterations as well as their association with clinical status. Patients had lower mJOA scores (p = .000) and lower GM volume than controls in SI (p = .016) and cerebellar regions (p = .001). Symptom severity-based subgroup analyses revealed volume reductions in almost all investigated GM ROIs (MI: p = .001; CB: p = .040; SMA: p = .007) in patients with severe clinical symptoms as well as atrophy already present in patients with moderate symptom severity. Clinical symptoms in DCM were associated with cortical and cerebellar volume reduction. GM volume alterations may serve as an indicator of both disease severity and ongoing disease progression in DCM, and should be considered in further patient care and treatment monitoring.

Diffusion-weighted MRI makes it possible to quantify subvoxel brain microstructure and to reconstruct white matter fiber trajectories with which structural connectomes can be created. However, at the border between cerebrospinal fluid and white matter, or in the presence of edema, the obtained MRI signal originates from both the cerebrospinal fluid as well as from the white matter partial volume. Diffusion tractography can be strongly influenced by these free water partial volume effects. Thus, including a free water model can improve diffusion tractography in glioma patients. Here, we analyze how including a free water model influences structural connectivity estimates in healthy subjects as well as in brain tumor patients. During a clinical study, we acquired diffusion MRI data of 35 glioma patients and 28 age- and sex-matched controls, on which we applied an open-source deep learning based free water model. We performed deterministic as well as probabilistic tractography before and after free water modeling, and utilized the tractograms to create structural connectomes. Finally, we performed a quantitative analysis of the connectivity matrices. In our experiments, the number of tracked diffusion streamlines increased by 13% for high grade glioma patients, 9.25% for low grade glioma, and 7.65% for healthy controls. Intra-subject similarity of hemispheres increased significantly for the patient as well as for the control group, with larger effects observed in the patient group. Furthermore, inter-subject differences in connectivity between brain tumor patients and healthy subjects were reduced when including free water modeling. Our results indicate that free water modeling increases the similarity of connectivity matrices in brain tumor patients, while the observed effects are less pronounced in healthy subjects. As the similarity between brain tumor patients and healthy controls also increased, connectivity changes in brain tumor patients may have been overestimated in studies that did not perform free water modeling.

Immunohistochemical data based on isocitrate–dehydrogenase (IDH) mutation status have redefined glioma as a whole-brain disease, while occult tumor cell invasion along white matter fibers is inapparent in conventional magnetic resonance imaging (MRI). The functional and prognostic impact of focal glioma may however relate to the extent of white matter involvement. We used diffusion tensor imaging (DTI) to investigate microstructural characteristics of whole-brain normal-appearing white matter (NAWM) in relation to cognitive functions as potential surrogates for occult white matter involvement in glioma. Twenty patients (12 IDH-mutated) and 20 individually matched controls were preoperatively examined using DTI combined with a standardized neuropsychological examination. Tumor lesions including perifocal edema were masked, and fractional anisotropy (FA) as well as mean, radial, and axial diffusivity (MD, RD, and AD, respectively) of the remaining whole-brain NAWM were determined by using Tract-Based Spatial Statistics and histogram analyses. The relationship between extratumoral white matter integrity and cognitive performance was examined using partial correlation analyses controlling for age, education, and lesion volumes. In patients, mean FA and AD were decreased as compared to controls, which agrees with the notion of microstructural impairment of NAWM in glioma patients. Patients performed worse in all cognitive domains tested, and higher anisotropy and lower MD and RD values of NAWM were associated with better cognitive performance. In additional analyses, IDH-mutated and IDH-wildtype patients were compared. Patients with IDH-mutation showed higher FA, but lower MD, AD, and RD values as compared to IDH-wildtype patients, suggesting a better preserved microstructural integrity of NAWM, which may relate to a less infiltrative nature of IDH-mutated gliomas. Diffusion-based phenotyping and monitoring microstructural integrity of extratumoral whole-brain NAWM may aid in estimating occult white matter involvement and should be considered as a complementary biomarker in glioma.

BACKGROUND: Corticobasal Syndrome (CBS) is a rare neurodegenerative syndrome characterized by unilaterally beginning frontoparietal and basal ganglia atrophy. The study aimed to prove the hypothesis that there are differences in hemispheric susceptibility to disease-related changes. METHODS: Two groups of CBS patients with symptoms starting either on the left or right body side were investigated. Groups consisted of four patients each and were matched for sex, age and disease duration. Patient groups and a group of eight healthy age-matched controls were analyzed using deformation field morphometry and neuropsychological testing. To further characterize individual disease progression regarding brain atrophy and neuropsychological performance, two female, disease duration-matched patients differing in initially impaired body side were followed over six months. RESULTS: A distinct pattern of neural atrophy and neuropsychological performance was revealed for both CBS: Patients with initial right-sided impairment (r-CBS) revealed atrophy predominantly in frontoparietal areas and showed, except from apraxia, no other cognitive deficits. In contrast, patients with impairment of the left body side (l-CBS) revealed more widespread atrophy, extending from frontoparietal to orbitofrontal and temporal regions; and apraxia, perceptional and memory deficits could be found. A similar pattern of morphological and neuropsychological differences was found for the individual disease progression in l-CBS and r-CBS single cases. CONCLUSIONS: For similar durations of disease, volumetric grey matter loss related to CBS pathology appeared earlier and progressed faster in l-CBS than in r-CBS. Cognitive impairment in r-CBS was characterized by apraxia, and additional memory and perceptional deficits for l-CBS.