The Brain/MINDS Marmoset Connectivity Resource: An open-access platform for cellular-level tracing and tractography in the primate brain.

The primate brain has unique anatomical characteristics, which translate into advanced cognitive, sensory, and motor abilities. Thus, it is important that we gain insight on its structure to provide a solid basis for models that will clarify function. Here, we report on the implementation and features of the Brain/MINDS Marmoset Connectivity Resource (BMCR), a new open-access platform that provides access to high-resolution anterograde neuronal tracer data in the marmoset brain, integrated to retrograde tracer and tractography data. Unlike other existing image explorers, the BMCR allows visualization of data from different individuals and modalities in a common reference space. This feature, allied to an unprecedented high resolution, enables analyses of features such as reciprocity, directionality, and spatial segregation of connections. The present release of the BMCR focuses on the prefrontal cortex (PFC), a uniquely developed region of the primate brain that is linked to advanced cognition, including the results of 52 anterograde and 164 retrograde tracer injections in the cortex of the marmoset. Moreover, the inclusion of tractography data from diffusion MRI allows systematic analyses of this noninvasive modality against gold-standard cellular connectivity data, enabling detection of false positives and negatives, which provide a basis for future development of tractography. This paper introduces the BMCR image preprocessing pipeline and resources, which include new tools for exploring and reviewing the data.

Inflammation-Triggered Enlargement of Choroid Plexus in Subacute COVID-19 Patients with Neurological Symptoms.

OBJECTIVE: To investigate whether choroid plexus volumes in subacute coronavirus disease 2019 (COVID-19) patients with neurological symptoms could indicate inflammatory activation or barrier dysfunction and assess their association with clinical data. METHODS: Choroid plexus volumes were measured in 28 subacute COVID-19 patients via cerebral magnetic resonance imaging (MRI), compared with those in infection-triggered non-COVID-19 encephalopathy patients (n = 25), asymptomatic individuals after COVID-19 (n = 21), and healthy controls (n = 21). Associations with inflammatory serum markers (peak counts of leukocytes, C-reactive protein [CRP], interleukin 6), an MRI-based marker of barrier dysfunction (CSF volume fraction [V-CSF]), and clinical parameters like olfactory performance and cognitive scores (Montreal Cognitive Assessment) were investigated. RESULTS: COVID-19 patients showed significantly larger choroid plexus volumes than control groups (p < 0.001, η2 = 0.172). These volumes correlated significantly with peak leukocyte levels (p = 0.001, Pearson's r = 0.621) and V-CSF (p = 0.009, Spearman's rho = 0.534), but neither with CRP nor interleukin 6. No significant correlations were found with clinical parameters. INTERPRETATION: In patients with subacute COVID-19, choroid plexus volume is a marker of central nervous system inflammation and barrier dysfunction in the presence of neurologic symptoms. The absence of plexus enlargement in infection-triggered non-COVID-19 encephalopathy suggests a specific severe acute respiratory syndrome coronavirus 2 effect. This study also documents an increase in choroid plexus volume for the first time as a parainfectious event. ANN NEUROL 2024.

Cerebellar, Not Nigrostriatal Degeneration Impairs Dexterity in Multiple System Atrophy.

BACKGROUND: Multiple system atrophy (MSA) clinically manifests with either predominant nigrostriatal or cerebellopontine degeneration. This corresponds to two different phenotypes, one with predominant Parkinson's symptoms (MSA-P [multiple system atrophy-parkinsonian subtype]) and one with predominant cerebellar deficits (MSA-C [multiple system atrophy-cerebellar subtype]). Both nigrostriatal and cerebellar degeneration can lead to impaired dexterity, which is a frequent cause of disability in MSA. OBJECTIVE: The aim was to disentangle the contribution of nigrostriatal and cerebellar degeneration to impaired dexterity in both subtypes of MSA. METHODS: We thus investigated nigrostriatal and cerebellopontine integrity using diffusion microstructure imaging in 47 patients with MSA-P and 17 patients with MSA-C compared to 31 healthy controls (HC). Dexterity was assessed using the 9-Hole Peg Board (9HPB) performance. RESULTS: Nigrostriatal degeneration, represented by the loss of cells and neurites, leading to a larger free-fluid compartment, was present in MSA-P and MSA-C when compared to HCs. Whereas no intergroup differences were observed between the MSAs in the substantia nigra, MSA-P showed more pronounced putaminal degeneration than MSA-C. In contrast, a cerebellopontine axonal degeneration was observed in MSA-P and MSA-C, with stronger effects in MSA-C. Interestingly, the degeneration of cerebellopontine fibers is associated with impaired dexterity in both subtypes, whereas no association was observed with nigrostriatal degeneration. CONCLUSION: Cerebellar dysfunction contributes to impaired dexterity not only in MSA-C but also in MSA-P and may be a promising biomarker for disease staging. In contrast, no significant association was observed with nigrostriatal dysfunction. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Accuracy of automated segmentation and volumetry of acute intracerebral hemorrhage following minimally invasive surgery using a patch-based convolutional neural network in a small dataset.

PURPOSE: In cases of acute intracerebral hemorrhage (ICH) volume estimation is of prognostic and therapeutic value following minimally invasive surgery (MIS). The ABC/2 method is widely used, but suffers from inaccuracies and is time consuming. Supervised machine learning using convolutional neural networks (CNN), trained on large datasets, is suitable for segmentation tasks in medical imaging. Our objective was to develop a CNN based machine learning model for the segmentation of ICH and of the drain and volumetry of ICH following MIS of acute supratentorial ICH on a relatively small dataset. METHODS: Ninety two scans were assigned to training (n = 29 scans), validation (n = 4 scans) and testing (n = 59 scans) datasets. The mean age (SD) was 70 (± 13.56) years. Male patients were 36. A hierarchical, patch-based CNN for segmentation of ICH and drain was trained. Volume of ICH was calculated from the segmentation mask. RESULTS: The best performing model achieved a Dice similarity coefficient of 0.86 and 0.91 for the ICH and drain respectively. Automated ICH volumetry yielded high agreement with ground truth (Intraclass correlation coefficient = 0.94 [95% CI: 0.91, 0.97]). Average difference in the ICH volume was 1.33 mL. CONCLUSION: Using a relatively small dataset, originating from different CT-scanners and with heterogeneous voxel dimensions, we applied a patch-based CNN framework and successfully developed a machine learning model, which accurately segments the intracerebral hemorrhage (ICH) and the drains. This provides automated and accurate volumetry of the bleeding in acute ICH treated with minimally invasive surgery.

Impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion in patients with suspected stroke.

PURPOSE: CT perfusion of the brain is a powerful tool in stroke imaging, though the radiation dose is rather high. Several strategies for dose reduction have been proposed, including increasing the intervals between the dynamic scans. We determined the impact of temporal resolution on perfusion metrics, therapy decision, and radiation dose reduction in brain CT perfusion from a large dataset of patients with suspected stroke. METHODS: We retrospectively included 3555 perfusion scans from our clinical routine dataset. All cases were processed using the perfusion software VEOcore with a standard sampling of 1.5 s, as well as simulated reduced temporal resolution of 3.0, 4.5, and 6.0 s by leaving out respective time points. The resulting perfusion maps and calculated volumes of infarct core and mismatch were compared quantitatively. Finally, hypothetical decisions for mechanical thrombectomy following the DEFUSE-3 criteria were compared. RESULTS: The agreement between calculated volumes for core (ICC = 0.99, 0.99, and 0.98) and hypoperfusion (ICC = 0.99, 0.99, and 0.97) was excellent for all temporal sampling schemes. Of the 1226 cases with vascular occlusion, 14 (1%) for 3.0 s sampling, 23 (2%) for 4.5 s sampling, and 63 (5%) for 6.0 s sampling would have been treated differently if the DEFUSE-3 criteria had been applied. Reduction of temporal resolution to 3.0 s, 4.5 s, and 6.0 s reduced the radiation dose by a factor of 2, 3, or 4. CONCLUSION: Reducing the temporal sampling of brain perfusion CT has only a minor impact on image quality and treatment decision, but significantly reduces the radiation dose to that of standard non-contrast CT.

Quantification of cervical spinal stenosis by automated 3D MRI segmentation of spinal cord and cerebrospinal fluid space.

DESIGN: Prospective diagnostic study. OBJECTIVES: Anatomical evaluation and graduation of the severity of spinal stenosis is essential in degenerative cervical spine disease. In clinical practice, this is subjectively categorized on cervical MRI lacking an objective and reliable classification. We implemented a fully-automated quantification of spinal canal compromise through 3D T2-weighted MRI segmentation. SETTING: Medical Center - University of Freiburg, Germany. METHODS: Evaluation of 202 participants receiving 3D T2-weighted MRI of the cervical spine. Segments C2/3 to C6/7 were analyzed for spinal cord and cerebrospinal fluid space volume through a fully-automated segmentation based on a trained deep convolutional neural network. Spinal canal narrowing was characterized by relative values, across sever segments as adapted Maximal Canal Compromise (aMCC), and within the index segment as adapted Spinal Cord Occupation Ratio (aSCOR). Additionally, all segments were subjectively categorized by three observers as "no", "relative" or "absolute" stenosis. Computed scores were applied on the subjective categorization. RESULTS: 798 (79.0%) segments were subjectively categorized as "no" stenosis, 85 (8.4%) as "relative" stenosis, and 127 (12.6%) as "absolute" stenosis. The calculated scores revealed significant differences between each category (p ≤ 0.001). Youden's Index analysis of ROC curves revealed optimal cut-offs to distinguish between "no" and "relative" stenosis for aMCC = 1.18 and aSCOR = 36.9%, and between "relative" and "absolute" stenosis for aMCC = 1.54 and aSCOR = 49.3%. CONCLUSION: The presented fully-automated segmentation algorithm provides high diagnostic accuracy and objective classification of cervical spinal stenosis. The calculated cut-offs can be used for convenient radiological quantification of the severity of spinal canal compromise in clinical routine.

Photon-counting detector computed tomography for metal artifact reduction: a comparative study of different artifact reduction techniques in patients with orthopedic implants.

PURPOSE: Artifacts caused by metallic implants remain a challenge in computed tomography (CT). We investigated the impact of photon-counting detector computed tomography (PCD-CT) for artifact reduction in patients with orthopedic implants with respect to image quality and diagnostic confidence using different artifact reduction approaches. MATERIAL AND METHODS: In this prospective study, consecutive patients with orthopedic implants underwent PCD-CT imaging of the implant area. Four series were reconstructed for each patient (clinical standard reconstruction [PCD-CTStd], monoenergetic images at 140 keV [PCD-CT140keV], iterative metal artifact reduction (iMAR) corrected [PCD-CTiMAR], combination of iMAR and 140 keV monoenergetic [PCD-CT140keV+iMAR]). Subsequently, three radiologists evaluated the reconstructions in a random and blinded manner for image quality, artifact severity, anatomy delineation (adjacent and distant), and diagnostic confidence using a 5-point Likert scale (5 = excellent). In addition, the coefficient of variation [CV] and the relative quantitative artifact reduction potential were obtained as objective measures. RESULTS: We enrolled 39 patients with a mean age of 67.3 ± 13.2 years (51%; n = 20 male) and a mean BMI of 26.1 ± 4 kg/m2. All image quality measures and diagnostic confidence were significantly higher for the iMAR vs. non-iMAR reconstructions (all p < 0.001). No significant effect of the different artifact reduction approaches on CV was observed (p = 0.26). The quantitative analysis indicated the most effective artifact reduction for the iMAR reconstructions, which was higher than PCD-CT140keV (p < 0.001). CONCLUSION: PCD-CT allows for effective metal artifact reduction in patients with orthopedic implants, resulting in superior image quality and diagnostic confidence with the potential to improve patient management and clinical decision making.

Speaking in gestures: Left dorsal and ventral frontotemporal brain systems underlie communication in conducting.

Conducting constitutes a well-structured system of signs anticipating information concerning the rhythm and dynamic of a musical piece. Conductors communicate the musical tempo to the orchestra, unifying the individual instrumental voices to form an expressive musical Gestalt. In a functional magnetic resonance imaging (fMRI) experiment, 12 professional conductors and 16 instrumentalists conducted real-time novel pieces with diverse complexity in orchestration and rhythm. For control, participants either listened to the stimuli or performed beat patterns, setting the time of a metronome or complex rhythms played by a drum. Activation of the left superior temporal gyrus (STG), supplementary and premotor cortex and Broca's pars opercularis (F3op) was shared in both musician groups and separated conducting from the other conditions. Compared to instrumentalists, conductors activated Broca's pars triangularis (F3tri) and the STG, which differentiated conducting from time beating and reflected the increase in complexity during conducting. In comparison to conductors, instrumentalists activated F3op and F3tri when distinguishing complex rhythm processing from simple rhythm processing. Fibre selection from a normative human connectome database, constructed using a global tractography approach, showed that the F3op and STG are connected via the arcuate fasciculus, whereas the F3tri and STG are connected via the extreme capsule. Like language, the anatomical framework characterising conducting gestures is located in the left dorsal system centred on F3op. This system reflected the sensorimotor mapping for structuring gestures to musical tempo. The ventral system centred on F3Tri may reflect the art of conductors to set this musical tempo to the individual orchestra's voices in a global, holistic way.

A Context-based Chatbot Surpasses Trained Radiologists and Generic ChatGPT in Following the ACR Appropriateness Guidelines.

Background Radiological imaging guidelines are crucial for accurate diagnosis and optimal patient care as they result in standardized decisions and thus reduce inappropriate imaging studies. Purpose In the present study, we investigated the potential to support clinical decision-making using an interactive chatbot designed to provide personalized imaging recommendations from American College of Radiology (ACR) appropriateness criteria documents using semantic similarity processing. Methods We utilized 209 ACR appropriateness criteria documents as specialized knowledge base and employed LlamaIndex, a framework that allows to connect large language models with external data, and the ChatGPT 3.5-Turbo to create an appropriateness criteria contexted chatbot (accGPT). Fifty clinical case files were used to compare the accGPT's performance against general radiologists at varying experience levels and to generic ChatGPT 3.5 and 4.0. Results All chatbots reached at least human performance level. For the 50 case files, the accGPT performed best in providing correct recommendations that were "usually appropriate" according to the ACR criteria and also did provide the highest proportion of consistently correct answers in comparison with generic chatbots and radiologists. Further, the chatbots provided substantial time and cost savings, with an average decision time of 5 minutes and a cost of 0.19 € for all cases, compared to 50 minutes and 29.99 € for radiologists (both p < 0.01). Conclusion ChatGPT-based algorithms have the potential to substantially improve the decision-making for clinical imaging studies in accordance with ACR guidelines. Specifically, a context-based algorithm performed superior to its generic counterpart, demonstrating the value of tailoring AI solutions to specific healthcare applications.

Spinal cord motion and CSF flow in the cervical spine of 70 healthy participants.

Pulsatile spinal cord and CSF velocities related to the cardiac cycle can be depicted by phase-contrast MRI. Among patients with spontaneous intracranial hypotension, we have recently described relevant differences compared with healthy controls in segment C2/C3. The method might be a promising tool to solve clinical and diagnostic ambiguities. Therefore, it is important to understand the physiological range and the effects of clinical and anatomical parameters in healthy volunteers. Within a prospective study, 3D T2 -weighted MRI for spinal canal anatomy and cardiac-gated phase-contrast MRI adapted to CSF flow and spinal cord motion for time-resolved velocity data and derivatives were performed in 70 participants (age 20-79 years) in segments C2/C3 and C5/C6. Correlations were analyzed by multiple linear regression models; p < 0.01 was required to assume a significant impact of clinical or anatomical data quantified by the regression coefficient B. Data showed that in C2/C3, the CSF and spinal cord craniocaudal velocity ranges were 4.5 ± 0.9 and 0.55 ± 0.15 cm/s; the total displacements were 1.1 ± 0.3 and 0.07 ± 0.02 cm, respectively. The craniocaudal range of the CSF flow rate was 8.6 ± 2.4 mL/s; the CSF stroke volume was 2.1 ± 0.7 mL. In C5/C5, physiological narrowing of the spinal canal caused higher CSF velocity ranges and lower stroke volume (C5/C6 B = +1.64 cm/s, p < 0.001; B = -0.4 mL, p = 0.002, respectively). Aging correlated to lower spinal cord motion (e.g., B = -0.01 cm per 10 years of aging, p < 0.001). Increased diastolic blood pressure was associated with lower spinal cord motion and CSF flow parameters (e.g., C2/C3 CSF stroke volume B = -0.3 mL per 10 mmHg, p < 0.001). Males showed higher CSF flow and spinal cord motion (e.g., CSF stroke volume B = +0.5 mL, p < 0.001; total displacement spinal cord B = +0.016 cm, p = 0.002). We therefore propose to stratify data for age and sex and to adjust for diastolic blood pressure and segmental narrowing in future clinical studies.

Biomechanical Effects of Chronic Ankle Instability on the Talar Cartilage Matrix: The Value of T1ρ Relaxation Mapping Without and With Mechanical Loading.

BACKGROUND: T1ρ mapping has been proposed for the detection of early cartilage degeneration associated with chronic ankle instability (CAI). However, there are limited data surrounding the influence of ankle loading on T1ρ relaxation. PURPOSE: To evaluate T1ρ relaxation times of talar cartilage, as an indicator of early degenerative changes, associated with CAI and to investigate the influence of acute axial in situ loading on T1ρ values in CAI patients and healthy controls. STUDY TYPE: Prospective. SUBJECTS: A total of 9 patients (age = 21.8 ± 2.5 years, male/female = 2/7) with chronic ankle instability and 18 healthy control subjects (age = 22.8 ± 3.6 years, male/female = 5/13). FIELD STRENGTH: 3 T. SEQUENCE: 3D gradient echo fast low-angle shot (FLASH) sequence augmented with a variable spin-lock preparation period. ASSESSMENT: Ankle T1ρ mapping was performed without and with axial loading of 500 N. The talar cartilage was segmented in five coronal slices covering the central talocrural joint. Median talar T1ρ values were separately calculated for the medial and lateral facets. STATISTICAL TESTS: Mann-Whitney U and Wilcoxon signed-rank tests, significance level: P < 0.05. RESULTS: For the combined cohorts, the statistical analysis yielded significantly lower T1ρ values with loading compared to the no-load measurement for both the lateral (no load: [51.0 ± 4.0] msec, load: [49.5 ± 5.4] msec) as well as the medial compartment (no load: [50.0 ± 5.4] msec, load: [47.8 ± 6.8] msec). In the unloaded scans, the CAI patients showed significantly increased talar T1ρ values ([53.0 ± 7.4] mse ) compared to the healthy control subjects ([48.8 ± 4.1] msec) in the medial compartment. DATA CONCLUSION: Increased talar T1ρ relaxation times in CAI patients compared to healthy controls suggest that T1ρ relaxation is a sensitive biomarker for CAI-induced early-stage cartilage degeneration. However, the load-induced T1ρ change did not prove to be a viable marker for the altered biomechanical properties of the hyaline talar cartilage. LEVEL OF EVIDENCE: 2 LEVEL OF EFFICACY: Stage 2.

Impact of different metal artifact reduction techniques in photon-counting computed tomography head and neck scans in patients with dental hardware.

OBJECTIVES: Metal artifacts remain a challenge in computed tomography. We investigated the potential of photon-counting computed tomography (PCD-CT) for metal artifact reduction using an iterative metal artifact reduction (iMAR) algorithm alone and in combination with high keV monoenergetic images (140 keV) in patients with dental hardware. MATERIAL AND METHODS: Consecutive patients with dental implants were prospectively included in this study and received PCD-CT imaging of the craniofacial area. Four series were reconstructed (standard [PCD-CTstd], monoenergetic at 140 keV [PCD-CT140keV], iMAR corrected [PCD-CTiMAR], combination of iMAR and 140 keV monoenergetic [PCD-CTiMAR+140keV]). All reconstructions were assessed qualitatively by four radiologists (independent and blinded reading on a 5-point Likert scale [5 = excellent; no artifact]) regarding overall image quality, artifact severity, and delineation of adjacent and distant anatomy. To assess signal homogeneity and evaluate the magnitude of artifact reduction, we performed quantitative measures of coefficient of variation (CV) and a region of interest (ROI)-based relative change in artifact reduction [PCD-CT/PCD-CTstd]. RESULTS: We enrolled 48 patients (mean age 66.5 ± 11.2 years, 50% (n = 24) males; mean BMI 25.2 ± 4.7 kg/m2; mean CTDIvol 6.2 ± 6 mGy). We found improved overall image quality, reduced artifacts and superior delineation of both adjacent and distant anatomy for the iMAR vs. non-iMAR reconstructions (all p < 0.001). No significant effect of the different artifact reduction approaches on CV was observed (p = 0.42). The ROI-based analysis indicated the most effective artifact reduction for the iMAR reconstructions, which was significantly higher compared to PCD-CT140keV (p < 0.001). CONCLUSION: PCD-CT offers highly effective approaches for metal artifact reduction with the potential to overcome current diagnostic challenges in patients with dental implants. CLINICAL RELEVANCE STATEMENT: Metallic artifacts pose a significant challenge in CT imaging, potentially leading to missed findings. Our study shows that PCD-CT with iMAR post-processing reduces artifacts, improves image quality, and can possibly reveal pathologies previously obscured by artifacts, without additional dose application. KEY POINTS: • Photon-counting detector CT (PCD-CT) offers highly effective approaches for metal artifact reduction in patients with dental fillings/implants. • Iterative metal artifact reduction (iMAR) is superior to high keV monoenergetic reconstructions at 140 keV for artifact reduction and provides higher image quality. • Signal homogeneity of the reconstructed images is not affected by the different artifact reduction techniques.

Application of diffusion microstructure imaging in musculoskeletal radiology - translation from head to shoulders.

OBJECTIVES: Quantitative MRI techniques, such as diffusion microstructure imaging (DMI), are increasingly applied for advanced tissue characterization. We determined its value in rotator cuff (RC) muscle imaging by studying the association of DMI parameters to isometric strength and fat fraction (FF). METHODS: Healthy individuals prospectively underwent 3T-MRI of the shoulder using DMI and chemical shift encoding-based water-fat imaging. RC muscles were segmented and quantitative MRI metrics (V-ISO, free fluid; V-intra, compartment inside of muscle fibers; V-extra, compartment outside of muscle fibers, and FF) were extracted. Isometric shoulder strength was quantified using specific clinical tests. Sex-related differences were assessed with Student's t. Association of DMI-metrics, FF, and strength was tested. A factorial two-way ANOVA was performed to compare the main effects of sex and external/internal strength-ratio and their interaction effects on quantitative imaging parameters ratios of infraspinatus/subscapularis. RESULTS: Among 22 participants (mean age: 26.7 ± 3.1 years, 50% female, mean BMI: 22.6 ± 1.9 kg/m2), FF of the individual RC muscles did not correlate with strength or DMI parameters (all p > 0.05). Subjects with higher V-intra (r = 0.57 to 0.87, p < 0.01) and lower V-ISO (r = -0.6 to -0.88, p < 0.01) had higher internal and external rotation strength. Moreover, V-intra was higher and V-ISO was lower in all RC muscles in males compared to female subjects (all p < 0.01). There was a sex-independent association of external/internal strength-ratio with the ratio of V-extra of infraspinatus/subscapularis (p = 0.02). CONCLUSIONS: Quantitative DMI parameters may provide incremental information about muscular function and microstructure in young athletes and may serve as a potential biomarker. KEY POINTS: • Diffusion microstructure imaging was successfully applied to non-invasively assess the microstructure of rotator cuff muscles in healthy volunteers. • Sex-related differences in the microstructural composition of the rotator cuff were observed. • Muscular microstructural metrics correlated with rotator cuff strength and may serve as an imaging biomarker of muscular integrity and function.

Deep learning segmentation results in precise delineation of the putamen in multiple system atrophy.

OBJECTIVES: The precise segmentation of atrophic structures remains challenging in neurodegenerative diseases. We determined the performance of a Deep Neural Patchwork (DNP) in comparison to established segmentation algorithms regarding the ability to delineate the putamen in multiple system atrophy (MSA), Parkinson's disease (PD), and healthy controls. METHODS: We retrospectively included patients with MSA and PD as well as healthy controls. A DNP was trained on manual segmentations of the putamen as ground truth. For this, the cohort was randomly split into a training (N = 131) and test set (N = 120). The DNP's performance was compared with putaminal segmentations as derived by Automatic Anatomic Labelling, Freesurfer and Fastsurfer. For validation, we assessed the diagnostic accuracy of the resulting segmentations in the delineation of MSA vs. PD and healthy controls. RESULTS: A total of 251 subjects (61 patients with MSA, 158 patients with PD, and 32 healthy controls; mean age of 61.5 ± 8.8 years) were included. Compared to the dice-coefficient of the DNP (0.96), we noted significantly weaker performance for AAL3 (0.72; p < .001), Freesurfer (0.82; p < .001), and Fastsurfer (0.84, p < .001). This was corroborated by the superior diagnostic performance of MSA vs. PD and HC of the DNP (AUC 0.93) versus the AUC of 0.88 for AAL3 (p = 0.02), 0.86 for Freesurfer (p = 0.048), and 0.85 for Fastsurfer (p = 0.04). CONCLUSION: By utilization of a DNP, accurate segmentations of the putamen can be obtained even if substantial atrophy is present. This allows for more precise extraction of imaging parameters or shape features from the putamen in relevant patient cohorts. CLINICAL RELEVANCE STATEMENT: Deep learning-based segmentation of the putamen was superior to currently available algorithms and is beneficial for the diagnosis of multiple system atrophy. KEY POINTS: • A Deep Neural Patchwork precisely delineates the putamen and performs equal to human labeling in multiple system atrophy, even when pronounced putaminal volume loss is present. • The Deep Neural Patchwork-based segmentation was more capable to differentiate between multiple system atrophy and Parkinson's disease than the AAL3 atlas, Freesurfer, or Fastsurfer.

Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms.

While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value <26/30 points) underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n = 35) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r = -0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response. In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase. In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.

Automated signal intensity analysis of the spinal cord for detection of degenerative cervical myelopathy - a matched-pair MRI study.

PURPOSE: Detection of T2 hyperintensities in suspected degenerative cervical myelopathy (DCM) is done subjectively in clinical practice. To gain objective quantification for dedicated treatment, signal intensity analysis of the spinal cord is purposeful. We investigated fully automated quantification of the T2 signal intensity (T2-SI) of the spinal cord using a high-resolution MRI segmentation. METHODS: Matched-pair analysis of prospective acquired cervical 3D T2-weighted sequences of 114 symptomatic patients and 88 healthy volunteers. Cervical spinal cord was segmented automatically through a trained convolutional neuronal network with subsequent T2-SI registration slice-by-slice. Received T2-SI curves were subdivided for each cervical level from C2 to C7. Additionally, all levels were subjectively classified concerning a present T2 hyperintensity. For T2-positive levels, corresponding T2-SI curves were compared to curves of age-matched volunteers at the identical level. RESULTS: Forty-nine patients showed subjective T2 hyperintensities at any level. The corresponding T2-SI curves showed higher signal variabilities reflected by standard deviation (18.51 vs. 7.47 a.u.; p < 0.001) and range (56.09 vs. 24.34 a.u.; p < 0.001) compared to matched controls. Percentage of the range from the mean absolute T2-SI per cervical level, introduced as "T2 myelopathy index" (T2-MI), was correspondingly significantly higher in T2-positive segments (23.99% vs. 10.85%; p < 0.001). ROC analysis indicated excellent differentiation for all three parameters (AUC 0.865-0.920). CONCLUSION: This fully automated T2-SI quantification of the spinal cord revealed significantly increased signal variability for DCM patients compared to healthy volunteers. This innovative procedure and the applied parameters showed sufficient diagnostic accuracy, potentially diagnosing radiological DCM more objective to optimize treatment recommendation. TRIAL REGISTRATION: DRKS00012962 (17.01.2018) and DRKS00017351 (28.05.2019).

Diffusion microstructure imaging in progressive supranuclear palsy: reduced axonal volumes in the superior cerebellar peduncles, dentato-rubro-thalamic tracts, ventromedial thalami, and frontomesial white matter.

Differentiating between Parkinson's disease (PD) and atypical Parkinson syndromes such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration is challenging. Diffusion microstructure imaging (DMI) was analyzed in patients with clinically suspected atypical Parkinson syndromes and healthy controls. In an exploration cohort, the spatial distribution of PSP-related changes of DMI parameters were evaluated in a voxel-wise analysis and a region-of-interest (ROI)-based approach was established. The diagnostic performance was subsequently tested in an independent validation cohort. In the exploration cohort, 53 PSP patients were compared to a pooled comparison group of 19 patients with PD, 26 patients with MSA, 7 patients with corticobasal syndrome, and 25 healthy controls. PSP patients showed widespread axonal loss in the superior cerebellar peduncles, the dentato-rubro-thalamic tracts, the thalami and the frontal white matter (each P < 0.001). In the validation cohort consisting of 12 patients with PSP vs. 13 patients with other movement disorders, the accuracy of this ROI-based approach for identifying the PSP was highest in the thalamus and the frontal white matter (accuracy 0.96 each). This DMI approach can identify PSP patients on an individual level in a collective with suspected atypical Parkinson syndromes and allows further insight on microstructural alterations in vivo.

Where Position Matters-Deep-Learning-Driven Normalization and Coregistration of Computed Tomography in the Postoperative Analysis of Deep Brain Stimulation.

INTRODUCTION: Recent developments in the postoperative evaluation of deep brain stimulation surgery on the group level warrant the detection of achieved electrode positions based on postoperative imaging. Computed tomography (CT) is a frequently used imaging modality, but because of its idiosyncrasies (high spatial accuracy at low soft tissue resolution), it has not been sufficient for the parallel determination of electrode position and details of the surrounding brain anatomy (nuclei). The common solution is rigid fusion of CT images and magnetic resonance (MR) images, which have much better soft tissue contrast and allow accurate normalization into template spaces. Here, we explored a deep-learning approach to directly relate positions (usually the lead position) in postoperative CT images to the native anatomy of the midbrain and group space. MATERIALS AND METHODS: Deep learning is used to create derived tissue contrasts (white matter, gray matter, cerebrospinal fluid, brainstem nuclei) based on the CT image; that is, a convolution neural network (CNN) takes solely the raw CT image as input and outputs several tissue probability maps. The ground truth is based on coregistrations with MR contrasts. The tissue probability maps are then used to either rigidly coregister or normalize the CT image in a deformable way to group space. The CNN was trained in 220 patients and tested in a set of 80 patients. RESULTS: Rigorous validation of such an approach is difficult because of the lack of ground truth. We examined the agreements between the classical and proposed approaches and considered the spread of implantation locations across a group of identically implanted subjects, which serves as an indicator of the accuracy of the lead localization procedure. The proposed procedure agrees well with current magnetic resonance imaging-based techniques, and the spread is comparable or even lower. CONCLUSIONS: Postoperative CT imaging alone is sufficient for accurate localization of the midbrain nuclei and normalization to the group space. In the context of group analysis, it seems sufficient to have a single postoperative CT image of good quality for inclusion. The proposed approach will allow researchers and clinicians to include cases that were not previously suitable for analysis.

The dual-loop model for combining external and internal worlds in our brain.

Intelligible communication with others as well as covert conscious thought requires us to combine a representation of the external world with inner abstract concepts. Interaction with the external world through sensory perception and motor execution is arranged as sequences in time and space, whereas abstract thought and invariant categories are independent of the moment. Using advanced MRI-based fibre tracking on high resolution data from 183 participants in the Human Connectome Project, we identified two large supramodal systems comprising specific cortical regions and their connecting fibre tracts; a dorsal one for processing of sequences in time and space, and a ventral one for concepts and categories. We found that two hub regions exist in the executive front and the perceptive back of the brain where these two cognitive processes converge, constituting a dual-loop model. The hubs are located in the onto- and phylogenetically youngest regions of the cortex. We propose that this hub feature serves as the neural substrate for the more abstract sense of syntax in humans, i.e. for the system populating sequences with content in all cognitive domains. The hubs bring together two separate systems (dorsal and ventral) at the front and the back of the brain and create a closed-loop. The closed-loop facilitates recursivity and forethought, which we use twice; namely, for communication with others about things that are not there and for covert thought.

What does FEXI measure?

Filter-exchange imaging (FEXI) has already been utilized in several biomedical studies for evaluating the permeability of cell membranes. The method relies on suppressing the extracellular signal using strong diffusion weighting (the mobility filter causing a reduction in the overall diffusivity) and monitoring the subsequent diffusivity recovery. Using Monte Carlo simulations, we demonstrate that FEXI is sensitive not uniquely to the transcytolemmal exchange but also to the geometry of involved compartments: complex geometry offers locations where spins remain unaffected by the mobility filter; moving to other locations afterwards, such spins contribute to the diffusivity recovery without actually permeating any membrane. This exchange mechanism is a warning for those who aim to use FEXI in complex media such as brain gray matter and opens wide scope for investigation towards crystallizing the genuine membrane permeation and characterizing the compartment geometry.