Search

Purpose To date, there is no consensus on how to semi-quantitatively assess brain amyloid PET. Some approaches use late acquisition alone (e.g., ELBA, based on radiomic features), others integrate the early scan (e.g., TDr, which targets the area of maximum perfusion) and structural imaging (e.g., WMR, that compares kinetic behaviour of white and grey matter, or SI based on the kinetic characteristics of the grey matter alone). In this study SUVr, ELBA, TDr, WMR, and SI were compared. The latter — the most complete one — provided the reference measure for amyloid burden allowing to assess the efficacy and feasibility in clinical setting of the other approaches. Methods We used data from 85 patients (aged 44–87) who underwent dual time-point PET/MRI acquisitions. The correlations with SI were computed and the methods compared with the visual assessment. Assuming SUVr, ELBA, TDr, and WMR to be independent measures, we linearly combined them to obtain more robust indices. Finally, we investigated possible associations between each quantifier and age in amyloid-negative patients. Results Each quantifier exhibited excellent agreement with visual assessment and strong correlation with SI (average AUC = 0.99, ρ = 0.91). Exceptions to this were observed for subcortical regions with ELBA and WMR (ρELBA = 0.44, ρWMR = 0.70). The linear combinations showed better performances than the individual methods. Significant associations were observed between TDr, WMR, SI, and age in amyloid-negative patients (p Conclusion Among the other methods, TDr came closest to the reference with less implementation complexity. Moreover, this study suggests that combining independent approaches gives better results than the individual procedure, so efforts should focus on multi-classifier systems for amyloid PET. Finally, the ability of techniques integrating blood perfusion to depict age-related variations in amyloid load in amyloid-negative subjects demonstrates the goodness of the estimate.

No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS‐related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty‐seven relapse‐onset MS (RMS) patients having mean age of 35.6 ± 8.5 (18–56) years and mean disease duration of 1.1 ± 1.5 (0–5) years, and 36 age‐ and sex‐matched healthy controls (HC) were studied. Cerebellar and RN lesions and volumes were analyzed on 3 T‐MRI images. RMS did not differ from HC in cerebellar lobe volumes but significantly differed in both right (107.84 ± 13.95 mm3 vs. 99.37 ± 11.53 mm3, p = .019) and left (109.71 ± 14.94 mm3 vs. 100.47 ± 15.78 mm3, p = .020) RN volumes. Cerebellar white matter lesion volume (WMLV) inversely correlated with both right and left RN volumes (r = −.333, p = .004 and r = −.298, p = .010, respectively), while no correlation was detected between RN volumes and mean cortical thickness, cerebellar gray matter lesion volume, and supratentorial WMLV (right RN: r = −.147, p = .216; left RN: r = −.153, p = .196). Right, but not left, RN volume inversely correlated with midbrain WMLV (r = −.310, p = .008), while no correlation was observed between whole brainstem WMLV and either RN volumes (right RN: r = −.164, p = .164; left RN: r = −.64, p = .588). Finally, left RN volume correlated with vermis VIIb (r = .297, p = .011) and right interposed nucleus (r = .249, p = .034) volumes. We observed RN atrophy in early RMS, likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS., The cerebellum and the brainstem are major sites of pathology in multiple sclerosis (MS) and their involvement, although frequently asymptomatic, is known to be associated with a more severe prognosis. We explored RN atrophy in early MS phases and its association with cerebellar damage and physical disability. We observed RN atrophy in early relapse‐onset (RMS), likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS.

To analyze multimodal three-dimensional medical images, interpolation is required for resampling which—unavoidably—introduces an interpolation error. In this work we describe the interpolation method used for imaging and neuroimaging and we characterize the Gibbs effect occurring when using such methods. In the experimental section we consider three segmented three-dimensional images resampled with three different neuroimaging software tools for comparing undersampling and oversampling strategies and to identify where the oversampling error lies. The experimental results indicate that undersampling to the lowest image size is advantageous in terms of mean value per segment errors and that the oversampling error is larger where the gradient is steeper, showing a Gibbs effect.

Accurately reconstructing functions with discontinuities is the key tool in many bio-imaging applications as, for instance, in Magnetic Particle Imaging (MPI). In this paper, we apply a method for scattered data interpolation, named mapped bases or Fake Nodes approach, which incorporates discontinuities via a suitable mapping function. This technique naturally mitigates the Gibbs phenomenon, as numerical evidence for reconstructing MPI images confirms.

Background Progressive brain atrophy is a major feature of multiple sclerosis (MS) pathology and is actually considered a major determinant of the progressive accumulation of physical and cognitive disability in MS patients. Although brain atrophy may have different pathological substrates, several lines of evidence suggest that in disease modifying drug (DMD)-treated MS patients, the higher is the anti-inflammatory effect of the DMD the lower is the progression of brain volume loss, grey matter atrophy and the accumulation of disability. Areas covered Magnetic resonance imaging (MRI)-based measurements of inflammation (focal white matter and grey matter lesions) and neurodegeneration (decrease in brain volume, cortical and deep grey matter atrophy) are currently included among the primary or secondary end-points of Phase II and III randomized clinical trials (RCT). This review summarizes literature data on the effects of DMDs on either whole brain or grey matter atrophy emerged from RCT and from post-marketing studies. Commentary Taken all together, literature data show that DMDs are capable to reduce significantly brain inflammation and, although with different degrees of effectiveness, to slow down global brain and/or grey matter atrophy progression. Moreover, the comparison between early and delayed treatments clearly points out that the most relevant effects on brain and grey matter atrophy are observed when DMDs are initiated in the very early disease phases.

Cerebellar dysfunctions have been associated to depressive disorders and cognitive impairment in neurodegenerative diseases. The objective is to analyze the associations between cerebellar atrophy, depression, and fatigue in the early phases of relapse-onset multiple sclerosis (RRMS). Sixty-one RRMS patients and 50 healthy controls (HC) were enrolled and clinically evaluated by means of expanded disability status scale (EDSS), Rao’s brief repeatable battery of neuropsychological tests (BRB-NT), Delis-Kaplan executive function system sorting test, beck depression inventory II (BDI-II), and fatigue severity scale (FSS). The relationships between MRI variables and clinical scores were assessed. Depressed RRMS (dRRMS) had significantly lower Vermis Crus I volume compared with not depressed RRMS (ndRRMS) (p = 0.009). Vermis Crus I volume was lower in dRRMS suffering from fatigue than in ndRRMS without fatigue (p = 0.01). The hierarchical regression models which included demographic and clinical data (age, sex, and disease duration, FSS or BDI-II) and cerebellar volumes disclosed that cerebellar lobule right V atrophy explained an increase of 4% of the variability in FSS (p = 0.25) and Vermis Crus I atrophy explained an increase of 6% of variability in BDI-II (p = 0.049). Since clinical onset, atrophy of specific cerebellar lobules associates with important clinical aspects of RRMS. Cerebellar pathology may be one of the determinants of fatigue and depression that contribute to worsen disability in RRMS.

No data are available on the occurrence of gray matter lesions (GML) in the cerebellum of pediatric multiple sclerosis (pedMS). We analyzed frequency, number and topography of GML, and their correlation with cerebellar-related disability in pedMS at clinical onset. Fifteen adolescents with pedMS (12F/3M; mean age 14.9 ± 2.2, range 11–17) were studied. Neurological and cognitive evaluations were done by means of EDSS, Trail Making Test—Part B (TMT-B) and Symbol Digit Modalities Test—oral version (SDMT). Cerebellar GML were investigated with double inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) sequences obtained with a 3 T-MRI scan. All patients had white matter lesions (WML) and/or GML in the cerebellum. A significantly higher GML number was observed on PSIR compared to DIR (mean 2.3 ± 2.3 vs 1.1 ± 1.6; median 2.0 (IQR 1.0–2.0) vs 1.0 (IQR 0.0–1.5); p = 0.004). GML were observed in 14/15 (93.3%) patients and were more frequent in the posterior than in the anterior lobe (mean 1.8 ± 2.2 vs 0.47 ± 0.74; median 2.0 (IQR 0.5–2.0) vs 0.0 (IQR 0.0–1.0); p = 0.044). No correlation was found between lesion number or topography and EDSS (r = 0.12, p = 0.69), TMT-B and SDMT. At clinical onset, cerebellar GML are common in pedMS, are very often asymptomatic, do not correlate with physical and cognitive disability, and more frequently affect the posterior lobe.

In this work we propose a new method for univariate polynomial interpolation based on what we call mapped bases. As theoretically shown, constructing the interpolating function via the mapped bases, i.e. in the mapped space, turns out to be equivalent to map the nodes and then construct the approximant in the classical form without the need of resampling. In view of this, we also refer to such mapped points as “fake” nodes. Numerical evidence confirms that such scheme can be applied to mitigate Runge and Gibbs phenomena.

Across scientific disciplines, there is a rapidly growing recognition of the need for more statistically robust, transparent approaches to data visualization. Complementary to this, many scientists have called for plotting tools that accurately and transparently convey key aspects of statistical effects and raw data with minimal distortion. Previously common approaches, such as plotting conditional mean or median barplots together with error-bars have been criticized for distorting effect size, hiding underlying patterns in the raw data, and obscuring the assumptions upon which the most commonly used statistical tests are based. Here we describe a data visualization approach which overcomes these issues, providing maximal statistical information while preserving the desired 'inference at a glance' nature of barplots and other similar visualization devices. These "raincloud plots" can visualize raw data, probability density, and key summary statistics such as median, mean, and relevant confidence intervals in an appealing and flexible format with minimal redundancy. In this tutorial paper, we provide basic demonstrations of the strength of raincloud plots and similar approaches, outline potential modifications for their optimal use, and provide open-source code for their streamlined implementation in R, Python and Matlab ( https://github.com/RainCloudPlots/RainCloudPlots). Readers can investigate the R and Python tutorials interactively in the browser using Binder by Project Jupyter., MA is supported by a Lundbeckfonden Fellowship (R272-2017-4345), the AIAS-COFUND II fellowship programme that is supported by the Marie Skłodowska-Curie actions under the European Union’s Horizon 2020 (Grant agreement no 754513), and the Aarhus University Research Foundation, and thanks Lincoln Colling for insightful statistical discussions. KW is funded by the Alan Turing Institute under the EPSRC grant EP/N510129/1. RAK is supported by the Wellcome Trust (grant number 107392/Z/15/Z).

Available online 30 April 2021. Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress. The present manuscript is part of a growing community effort to collate Brainhack-related insights and expertise into a Jupyter Book (http://brainhack.org/brainhack_jupyter_book/) that will serve as a centralized set of resources for the community; we acknowledge all the individuals who contributed and will make ongoing contributions to these resources. A pre-print version of the present manuscript is available as part of the Jupyter Book. Moreover, we would like to acknowledge all Brainhack organizers, supporters, presenters, and participants for their contribution to growing and maintaining this community. The benefits described in this manuscript would not be possible without them. We also thank all institutions, labs, and organizations who have helped this community grow, meet in stimulating environments, and add an excellent educational resource pool and agenda. With an expanding community, Brainhack’s support network keeps growing, and we thank all labs and individual researchers for their dedication and expertise offered to this community (see http://brainhack.org/brainhack_jupyter_book/acknowledgments.html for a full list of individual acknowledgments; an updated list will be maintained in the Jupyter Book). Grants and funding bodies: This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 867458 awarded to Julia M. Huntenburg; from ANR-19-DATA-0025 NeuroWebLab for Katja Heuer, Roberto Toro, and Nicholas Traut; and from NIH K00MH122372 for Stephanie Noble. The Brainhack Community member list and contributions of the different authors are detailed at http://brainhack.org/brainhack_jupyter_book/contributors.html. Our crediting system is described here: http://brainhack.org/brainhack_jupyter_book/neuroview_authorship-agreement.html.

The pathological significance and the diagnostic usefulness of intrathecal κ and λ free light chain (FLC) synthesis in Multiple Sclerosis (MS) are debated.Paired cerebrospinal fluid (CSF) and serum specimens from 70 relapsing remitting MS (RRMS), 40 with and 30 without CSF restricted IgG Oligoclonal Band (IgGOB), and 37 from healthy controls (HC) were analyzed. IgG, IgM, κFLC and λFLC concentrations and indexes were evaluated. All RRMS performed MRI to estimate white and grey matter (WM) pathology.In HC, no intrathecal κ or λ FLC synthesis was found, and κFLC and λFLC Indexes were reciprocally correlated (r = 0.67, p 0.001). In RRMS, intrathecal κFLC or λFLC synthesis was demonstrated in respectively 66% and 43% of the cases, the QThe demonstration of intrathecal κFLC synthesis may further improve the diagnostic usefulness of CSF examination in RRMS. The marked increased in Q

Objective Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our study was to investigate the relationship between inflammation and neurodegeneration and to achieve evidence of trans-synaptic degeneration in the optic pathway in MS at clinical onset. Methods 50 clinically isolated syndromes/early relapse-onset MS (CIS/eRRMS) with mean disease duration of 4.0±3.5 months, 28 MRI healthy controls (HC) and 31 OCT-HC were studied. Ten patients had optic neuritis at presentation (MSON+), 40 presented with other symptoms (MSON-). MRI examination included 3D-T1, 3D-FLAIR and 3D-DIR sequences. Global cortical thickness (gCTh), pericalcarin CTh (pCTh) and white matter volume (WMV) were analysed by means of Freesurfer on 3D-T1 scans. Optic radiation morphology (OR) and volume (ORV) were reconstructed on the base of the Julich’s Atlas. White matter lesion volume (WMLV), OR-WMLV and percent WM damage (WMLV/WMV = WMLV% and OR-WMLV/ORV = ORWMLV%) were obtained by 3D-FLAIR image segmentation. 3D-DIR sequences were applied to identify inflammatory lesions of the optic nerve. Optic coherence tomography (OCT) protocol included the analysis of global peripapillary retinal nerve fiber layer (g-RNFL) and the 6 fundus oculi’s sectors (temporal, T-RNFL; temporal superior, TS-RNFL; nasal superior, NS-RNFL; nasal, N-RNFL; nasal inferior, NI-RNFL, temporal inferior, TI-RNFL). The retina of both eyes was analyzed. The eyes of ON+ were further divided into affected (aON+) or not (naON+). Results No difference in CTh was found between CIS/eRRMS and HC, and between MSON+ and MSON-. Moreover, MSON+ and MSON- did not differ for any WM lesion load parameter. The most significant correlations between RNFL thickness and optic radiation WM pathology were found in MSON+. In these patients, the temporal RNFL inversely correlated to ipsilateral optic radiation WM lesion load (T-RNFL: r -0.7, p

In the initial evaluation of patients with suspected dementia and Alzheimer’s disease, there is no consensus on how to perform semiquantification of amyloid in such a way that it: (1) facilitates visual qualitative interpretation, (2) takes the kinetic behaviour of the tracer into consideration particularly with regard to at least partially correcting for blood flow dependence, (3) analyses the amyloid load based on accurate parcellation of cortical and subcortical areas, (4) includes partial volume effect correction (PVEC), (5) includes MRI-derived topographical indexes, (6) enables application to PET/MRI images and PET/CT images with separately acquired MR images, and (7) allows automation. A method with all of these characteristics was retrospectively tested in 86 subjects who underwent amyloid (18F-florbetaben) PET/MRI in a clinical setting (using images acquired 90–110 min after injection, 53 were classified visually as amyloid-negative and 33 as amyloid-positive). Early images after tracer administration were acquired between 0 and 10 min after injection, and later images were acquired between 90 and 110 min after injection. PVEC of the PET data was carried out using the geometric transfer matrix method. Parametric images and some regional output parameters, including two innovative “dual time-point” indexes, were obtained. Subjects classified visually as amyloid-positive showed a sparse tracer uptake in the primary sensory, motor and visual areas in accordance with the isocortical stage of the topographic distribution of the amyloid plaque (Braak stages V/VI). In patients classified visually as amyloid-negative, the method revealed detectable levels of tracer uptake in the basal portions of the frontal and temporal lobes, areas that are known to be sites of early deposition of amyloid plaques that probably represented early accumulation (Braak stage A) that is typical of normal ageing. There was a strong correlation between age and the indexes of the new dual time-point amyloid imaging method in amyloid-negative patients. The method can be considered a valuable tool in both routine clinical practice and in the research setting as it will standardize data regarding amyloid deposition. It could potentially also be used to identify early amyloid plaque deposition in younger subjects in whom treatment could theoretically be more effective.

Background: The demonstration of cortical lesions (CL) in the cerebellum by magnetic resonance imaging (MRI) is hampered by technical and anatomical constraints. Objective: To investigate the occurrence of cerebellar CL and their correlation with cerebellar-related disability by combining Double Inversion Recovery (DIR) and Phase Sensitive Inversion Recovery (PSIR) MRI images in multiple sclerosis (MS) patients. Material and methods: 40 MS patients (10 CIS/eRRMS, 24 RRMS, 6 SPMS), having a wide range of disability and disease duration, were enrolled. DIR and PSIR images were obtained with a 3T-MRI. Results: Cerebellar white matter lesions (WML) and/or CL were observed in 33/40 patients (82.5%) among which 14/40 had only CL. CL were demonstrated in 26/40 patients by DIR and in 31/40 by PSIR, and their number increased from CIS/eRRMS to SPMS. PSIR disclosed a significantly higher number of CL compared to DIR (RRMS: p=0.0008; SPMS: p=0.002). CL number correlates with the cerebellar Expanded Disability Status Score (EDSS) score ( r=0.72, pConclusions: CL are detected by PSIR in the cerebellum of the majority of MS patients, are more than WML, increase with disease progression and strongly correlate with the cerebellar EDSS. Thus, the observation of CL in the cerebellum of MS at clinical onset might be useful for prognostic and therapeutic aims.

Background Double inversion recovery (DIR) detects only a minority (

Introduction. It is well known that resolution on a gamma camera varies as a function of distance, scatter and the camera’s characteristics (collimator type, crystal thickness, intrinsic resolution etc). Manufacturers frequently provide only a few pre-calculated resolution values (using a line source in air, 10–15 cm from the collimator surface and without scattering). However, these are typically not obtained in situations resembling a clinical setting. From a diagnostic point of view, it is useful to know the expected resolution of a gamma camera at a given distance from the collimator surface for a particular setting in order to decide whether it is worth scanning patients with “small lesion” or not. When dealing with absolute quantification it is also mandatory to know precisely the expected resolution and its uncertainty in order to make appropriate corrections. Aim. Our aims are: to test a novel mathematical approach, the cubic spline interpolation, for the extraction of the full width at half maximum (FWHM) from the acquisition of a line source (experimental resolution) also considering measurement uncertainty; to compare it with the usually adopted methods such as the gaussian approach; to compare it with the theoretical resolution (analytical resolution) of a gamma camera at different distances; to create a web-based educational program with which to test these theories. Methods. Three mathematical methods (direct calculation, global interpolation using gaussian and local interpolation using splines) for calculating FWHM from a line source (planar scintigraphy) were tested and compared. A NEMA Triple Line Source Phantom was used to obtain static images both in air and with different scattering levels. An advanced, open-source software (MATLAB/Octave and PHP based) was created “ad hoc” to obtain and compare FWHM values and relative uncertainty. Results and Conclusion. Local interpolation using splines proved faster and more reliable than the usually-adopted Gaussian interpolation. The proposed freely available software proved effective in assessing both FWHM and its uncertainty.

Background B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS. Methods Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh). Results Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes (p 0.5 and p