Performance evaluation of automated white matter hyperintensity segmentation algorithms in a multicenter cohort on cognitive impairment and dementia

Background: White matter hyperintensities (WMH), a biomarker of small vessel disease, are often found in Alzheimer’s disease (AD) and their advanced detection and quantification can be beneficial for research and clinical applications. To investigate WMH in large-scale multicenter studies on cognitive impairment and AD, appropriate automated WMH segmentation algorithms are required. This study aimed to compare the performance of segmentation tools and provide information on their application in multicenter research. Methods: We used a pseudo-randomly selected dataset (n = 50) from the DZNE-multicenter observational Longitudinal Cognitive Impairment and Dementia Study (DELCODE) that included 3D fluid-attenuated inversion recovery (FLAIR) images from participants across the cognitive continuum. Performances of top-rated algorithms for automated WMH segmentation [Brain Intensity Abnormality Classification Algorithm (BIANCA), lesion segmentation toolbox (LST), lesion growth algorithm (LGA), LST lesion prediction algorithm (LPA), pgs, and sysu_media] were compared to manual reference segmentation (RS). Results: Across tools, segmentation performance was moderate for global WMH volume and number of detected lesions. After retraining on a DELCODE subset, the deep learning algorithm sysu_media showed the highest performances with an average Dice’s coefficient of 0.702 (±0.109 SD) for volume and a mean F1-score of 0.642 (±0.109 SD) for the number of lesions. The intra-class correlation was excellent for all algorithms (>0.9) but BIANCA (0.835). Performance improved with high WMH burden and varied across brain regions. Conclusion: To conclude, the deep learning algorithm, when retrained, performed well in the multicenter context. Nevertheless, the performance was close to traditional methods. We provide methodological recommendations for future studies using automated WMH segmentation to quantify and assess WMH along the continuum of cognitive impairment and AD dementia

Selective engraftment of donor-derived myeloid cells in the lesioned facial nucleus after HI.

<p><b>A</b>) Identification of GFP⁺ myeloid cells in the lesioned facial nucleus of HI chimeras at 7 and 14 days after BMT. Note the increase in F4/80 immunoreactivity at day 14 compared with day 7, indicating increased inflammation. The contralateral unlesioned facial nucleus is devoid of donor-derived GFP⁺ cells and shows minimal F4/80 immunoreactivity. Laser confocal microscopic images of areas of interest (white squares) are shown at increasing magnifications (scale bars: 100 µm – 25 µm). Seven days after BMT, amoeboid GFP⁺F4/80⁺ and GFP⁺Iba-1⁺ cells were detected in the lesioned facial nucleus. At 14 days after BMT, GFP⁺F4/80⁺ and GFP⁺Iba-1⁺ cells in the lesioned facial nucleus were highly ramified. All donor-derived GFP⁺ cells expressed the macrophage markers, F4/80 and Iba-1. Nuclei were counterstained with DAPI. <b>B</b>) Quantification of myeloid cell engraftment in the lesioned facial nucleus at 7 and 14 days after BMT in FNA, HI, HI + FNA and busulfan + FNA animals. Note that donor-derived GFP⁺ cells were only detected in HI + FNA mice. Data are means + SEM from 3-5 animals per group. n.d. = none detected. <b>C</b>) Quantitative real-time PCR of CXCL10 and CCL2 mRNA expression in the facial nucleus of animals with FNA (white bars), HI (grey bars) and HI + FNA (black bars) at 14 days after BMT. The mRNA expression levels were normalized to GAPDH mRNA and compared to naïve mice (fold induction). Increased chemokine mRNA levels were observed in the facial nucleus of HI + FNA mice compared to HI animals. Data are means + SEM from 3-5 animals per group. Statistical significance is indicated by asterisks (*p<0.05).</p

Blood chimerism in HI- and busulfan-conditioned mice with FNA.

<p><b>A</b>) Overview of the experimental protocol. <i>HI</i>, <i>FNA</i> and <i>Tx</i> denote focal head irradiation, facial nerve axotomy and bone marrow transplantation, respectively. <b>B</b>) Flow cytometry of GFP expression in peripheral blood CD45⁺ cells at 2 weeks after BMT. The level of chimerism was significantly higher in the busulfan + FNA group compared with the HI + FNA group. FNA had no impact on blood chimerism. Data are means + SEM from 3-5 animals per group. Statistical significance is indicated by asterisks (****p<0.0001). <b>C</b>) Flow cytometric characterization of GFP-expressing cells in peripheral blood at 2 weeks after BMT. The vast majority of GFP⁺CD45⁺ cells express CD11b (>90%). Gating of this cell population reveals predominantly CD115⁺Ly6C^hiLy6G^- monocytes and CD115^-Ly6C⁺Ly6G⁺ neutrophils. Data are means + SEM from 3-5 animals per group. n.d. = none detected. No statistical differences were observed between the groups.</p

Gene expression profiles of cytokines and chemokines in the brain after HI and TBI.

<p><b>A</b>) Overview of the experimental protocol. <i>HI</i>, <i>TBI</i> and <i>Tx</i> denote focal head irradiation, total body irradiation and bone marrow transplantation, respectively. <b>B</b>) Quantitative real-time PCR of CCL2, CXCL10, CCL5 and TNF-α mRNA expression in brains of HI (grey columns) and TBI (white columns) animals at 1, 2, 4 and 16 weeks after irradiation and BMT. The mRNA expression levels were normalized to GAPDH mRNA and compared to naïve mice (fold induction). Reduced cytokine/chemokine mRNA levels were observed in HI brains compared to the TBI paradigm. Data are means + SEM from 3-5 animals per group. Statistical significance is indicated by asterisks (*p<0.05; **p<0.01; ***p<0.001).</p

No change of apathy, irritability, cognition or function after 10 weeks of treatment with bupropion.

<p>No change of apathy, irritability, cognition or function after 10 weeks of treatment with bupropion.</p

Demographic data and neuropsychiatric profiles (full analysis set).

<p>Demographic data and neuropsychiatric profiles (full analysis set).</p

Change of apathy after the first treatment period suggests activation through trial participation.

<p>Change of apathy after the first treatment period suggests activation through trial participation.</p

CONSORT flow diagram.

<p>CONSORT flow diagram.</p

DataSheet_1_Lower hypothalamus subunit volumes link with impaired long-term body weight gain after preterm birth.docx

IntroductionPreterm birth is associated with an increased risk for impaired body weight gain. While it is known that in prematurity several somatic and environmental factors (e.g., endocrine factors, nutrition) modulate short- and long-term body weight gain, the contribution of potentially impaired body weight control in the brain remains elusive. We hypothesized that the structure of hypothalamic nuclei involved in body weight control is altered after preterm birth, with these alterations being associated with aberrant body weight development into adulthood.Materials and methodsWe assessed 101 very preterm (i.e., ResultsVolumes of the whole hypothalamus and hypothalamus subunits relevant for body weight control were reduced in VP/VLBW adults and associated with birth variables (i.e., gestational age and intensity of neonatal treatment), body weight (i.e., weight at birth and adulthood), and body weight trajectories (i.e., trajectory slopes and cluster/types such as long-term catch-up growth). Particularly, VP/VLBW subgroups, whose individuals showed catch-up growth and/or were small for gestational age, were mostly associated with volumes of distinct hypothalamus subunits such as lateral or infundibular/ventromedial hypothalamus.ConclusionResults demonstrate lower volumes of body weight control-related hypothalamus subunits after preterm birth that link with long-term body weight gain. Data suggest postnatal development of body weight -related hypothalamic nuclei in VP/VLBW individuals that corresponds with distinct body weight trajectories into adulthood.</p

Resulting clusters of the seed-to-voxel connectivity analysis for the DMN seed.

Resulting clusters of the seed-to-voxel connectivity analysis for the DMN seed.</p