Reduced cerebrospinal fluid motion in patients with Parkinson's disease revealed by magnetic resonance imaging with low b-value diffusion weighted imaging.

BACKGROUND: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation of α-synuclein protofibrils. New diagnostic methods assess α-synuclein aggregation characteristics from cerebrospinal fluid (CSF) and recent pathophysiologic mechanisms suggest that CSF circulation disruptions may precipitate α-synuclein retention. Here, diffusion-weighted MRI with low-to-intermediate diffusion-weightings was applied to test the hypothesis that CSF motion is reduced in Parkinson's disease relative to healthy participants. METHODS: Multi-shell diffusion weighted MRI (spatial resolution = 1.8 × 1.8 × 4.0 mm) with low-to-intermediate diffusion weightings (b-values = 0, 50, 100, 200, 300, 700, and 1000 s/mm2) was applied over the approximate kinetic range of suprasellar cistern fluid motion at 3 Tesla in Parkinson's disease (n = 27; age = 66 ± 6.7 years) and non-Parkinson's control (n = 32; age = 68 ± 8.9 years) participants. Wilcoxon rank-sum tests were applied to test the primary hypothesis that the noise floor-corrected decay rate of CSF signal as a function of b-value, which reflects increasing fluid motion, is reduced within the suprasellar cistern of persons with versus without Parkinson's disease and inversely relates to choroid plexus activity assessed from perfusion-weighted MRI (significance-criteria: p < 0.05). RESULTS: Consistent with the primary hypothesis, CSF decay rates were higher in healthy (D = 0.00673 ± 0.00213 mm2/s) relative to Parkinson's disease (D = 0.00517 ± 0.00110 mm2/s) participants. This finding was preserved after controlling for age and sex and was observed in the posterior region of the suprasellar cistern (p < 0.001). An inverse correlation between choroid plexus perfusion and decay rate in the voxels within the suprasellar cistern (Spearman's-r=-0.312; p = 0.019) was observed. CONCLUSIONS: Multi-shell diffusion MRI was applied to identify reduced CSF motion at the level of the suprasellar cistern in adults with versus without Parkinson's disease; the strengths and limitations of this methodology are discussed in the context of the growing literature on CSF flow.

Cerebrovascular reactivity dispersion as a new biomarker of recent stroke symptomatology in moyamoya.

Background: Moyamoya disease (MMD) is a non-atherosclerotic intracranial steno-occlusive condition placing patients at high risk for ischemic stroke. Direct and indirect surgical revascularization can improve blood flow in MMD; however, randomized trials demonstrating efficacy have not been performed and biomarkers of parenchymal hemodynamic impairment are needed to triage patients for interventions and evaluate post-surgical efficacy. We test the hypothesis that hypercapnia-induced maximum cerebrovascular reactivity (CVR MAX ) and the more novel indicator cerebrovascular reactivity (CVR) response time (CVR DELAY ), both assessed from time-regression analyses of non-invasive hypercapnic imaging, correlate with recent focal ischemic symptoms. Methods: Hypercapnic reactivity medical resonance imaging (blood oxygenation level-dependent; echo time=35ms; spatial resolution=3.5×3.5×3.5mm) and catheter angiography assessments of cortical reserve capacity and vascular patency, respectively, in MMD participants (n=73) were performed in sequence. Time regression analyses were applied to quantify CVR MAX and CVR DELAY . Symptomatology information for each hemisphere (n=109) was categorized into symptomatic (ischemic symptoms within six months) or asymptomatic (no history of ischemic symptoms) and logistic regression analysis assessed the association of CVR metrics with ischemic symptoms after controlling for age and sex. Results: Symptomatic hemispheres displayed lengthened CVR DELAY (p<0.001), which was more discriminatory between hemispheres than CVR MAX (p=0.037). CVR DELAY (p<0.001), but not CVR MAX (p=0.127), was found to be sensitively related to age in asymptomatic tissue (0.33-unit increase/year); age-dependent normative ranges are presented to enable quantitative assessment of patient-specific impairment. Furthermore, the area under the receiver operating characteristic curves shows that CVR DELAY predicts ischemic symptoms (p<0.001), whereas CVR MAX does not (p=0.056). Conclusion: Findings support that CVR metrics are uniquely altered in hemispheres with recent ischemic symptoms, motivating the investigation of CVR as a surrogate of ischemic symptomatology and treatment efficacy.

Deep learning segmentation of the choroid plexus from structural magnetic resonance imaging (MRI): validation and normative ranges across the adult lifespan.

BACKGROUND: The choroid plexus functions as the blood-cerebrospinal fluid (CSF) barrier, plays an important role in CSF production and circulation, and has gained increased attention in light of the recent elucidation of CSF circulation dysfunction in neurodegenerative conditions. However, methods for routinely quantifying choroid plexus volume are suboptimal and require technical improvements and validation. Here, we propose three deep learning models that can segment the choroid plexus from commonly-acquired anatomical MRI data and report performance metrics and changes across the adult lifespan. METHODS: Fully convolutional neural networks were trained from 3D T1-weighted, 3D T2-weighted, and 2D T2-weighted FLAIR MRI using gold-standard manual segmentations in control and neurodegenerative participants across the lifespan (n = 50; age = 21-85 years). Dice coefficients, 95% Hausdorff distances, and area-under-curve (AUCs) were calculated for each model and compared to segmentations from FreeSurfer using two-tailed Wilcoxon tests (significance criteria: p < 0.05 after false discovery rate multiple comparisons correction). Metrics were regressed against lateral ventricular volume using generalized linear models to assess model performance for varying levels of atrophy. Finally, models were applied to an expanded cohort of adult controls (n = 98; age = 21-89 years) to provide an exemplar of choroid plexus volumetry values across the lifespan. RESULTS: Deep learning results yielded Dice coefficient = 0.72, Hausdorff distance = 1.97 mm, AUC = 0.87 for T1-weighted MRI, Dice coefficient = 0.72, Hausdorff distance = 2.22 mm, AUC = 0.87 for T2-weighted MRI, and Dice coefficient = 0.74, Hausdorff distance = 1.69 mm, AUC = 0.87 for T2-weighted FLAIR MRI; values did not differ significantly between MRI sequences and were statistically improved compared to current commercially-available algorithms (p < 0.001). The intraclass coefficients were 0.95, 0.95, and 0.96 between T1-weighted and T2-weighted FLAIR, T1-weighted and T2-weighted, and T2-weighted and T2-weighted FLAIR models, respectively. Mean lateral ventricle choroid plexus volume across all participants was 3.20 ± 1.4 cm3; a significant, positive relationship (R2 = 0.54-0.60) was observed between participant age and choroid plexus volume for all MRI sequences (p < 0.001). CONCLUSIONS: Findings support comparable performance in choroid plexus delineation between standard, clinically available, non-contrasted anatomical MRI sequences. The software embedding the evaluated models is freely available online and should provide a useful tool for the growing number of studies that desire to quantitatively evaluate choroid plexus structure and function ( https://github.com/hettk/chp_seg ).

Choroid plexus vascular reactivity in moyamoya: Implications for choroid plexus regulation in ischemic stress.

BACKGROUND AND PURPOSE: Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy. METHODS: We performed hypercapnic reactivity (blood oxygenation level-dependent; echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm, repetition time = 2000 ms) and catheter angiography assessments of ChP reserve capacity and vascular patency in moyamoya patients (n = 53) with and without prior surgical revascularization. Time regression analyses quantified maximum cerebrovascular reactivity and reactivity delay time in ChP and cortical flow territories of major intracranial vessels with steno-occlusion graded as <70%, 70%-99%, and occlusion using Warfarin-Aspirin-Symptomatic-Intracranial-Disease stenosis grading criteria. Analysis of variance (significance: two-sided Bonferroni-corrected p < .05) was applied to evaluate cortical and ChP reactivity, after accounting for end-tidal carbon dioxide change, for differing vasculopathy categories. RESULTS: In patients without prior revascularization, arterial vasculopathy was associated with reduced cortical reactivity and lengthened reactivity delay (p ≤ .01), as expected. Regardless of surgical history, the ChP reactivity metrics were not significantly related to the degree of proximal stenosis, consistent with ChP reactivity being largely preserved in this population. CONCLUSIONS: Findings are consistent with ChP reactivity in moyamoya not being dependent on observed vasculopathy. Future work may investigate the extent to which ChP hyperemia in chronic ischemia reflects circulating markers of glial or ischemic stress.

Reduced suprasellar cistern cerebrospinal fluid motion in patients with Parkinson's disease revealed by magnetic resonance imaging with dynamic cycling of diffusion weightings.

BACKGROUND: Parkinson's disease is characterized by dopamine-responsive symptoms as well as aggregation and accumulation of a-synuclein protofibrils. New diagnostic methods assess a-synuclein aggregation characteristics from cerebrospinal fluid and recent pathophysiologic mechanisms suggest that cerebrospinal fluid circulation disruptions may precipitate a-synuclein retention. Here, we test the hypothesis that cerebrospinal fluid motion at the level of the suprasellar cistern is reduced in Parkinson's disease relative to healthy participants and this reduction relates to choroid plexus perfusion. METHODS: Diffusion weighted imaging (spatial resolution=1.8×1.8×4 mm) magnetic resonance imaging with cycling of diffusion weightings (b-values=0, 50, 100, 200, 300, 700, and 1000 s/mm2) over the approximate kinetic range of suprasellar cistern neurofluid motion was applied at 3-Tesla in Parkinson's disease (n=27; age=66±6.7 years) and healthy (n=32; age=68±8.9 years) participants. Wilcoxon rank-sum tests were applied to test the primary hypothesis that the decay rate of cerebrospinal fluid signal as a function of b-value, which reflects increasing fluid motion, is reduced in persons with versus without Parkinson's disease and inversely relates to choroid plexus activity assessed from perfusion-weighted magnetic resonance imaging (Spearman rank-order correlation; significance-criteria: p<0.05). RESULTS: Consistent with the primary hypothesis, decay rates were higher in healthy (D=0.00328±0.00123mm2/s) relative to Parkinson's disease (D=0.00256±0.0094mm2/s) participants (p=0.016). This finding was preserved after controlling for age and sex. An inverse correlation between choroid plexus perfusion and decay rate (p=0.011) was observed in Parkinson's disease participants. CONCLUSIONS: Cerebrospinal fluid motion at the level of the suprasellar cistern is often reduced in adults with versus without Parkinson's disease and this reduction correlates on average with choroid plexus perfusion.

The critical role of job embeddedness: The impact of psychological empowerment and learning orientation on organizational commitment.

Job embeddedness (JE) has been recognized as a key factor to address the issue of employee turnover and employee attitudes. This study explores underlying mechanisms of job embeddedness that link the organizational environment and the individuals' perceptions of the job. Particularly, the effects of psychological empowerment and learning orientation on organizational commitment were examined. This study hypothesizes that psychological empowerment (PE) and learning orientation (LO) should influence organizational commitment (OC) and job embeddedness plays a significant mediating role in these relationships. Data were collected from 27 offices of Human Resource Development Service of Korea (governmental agency) located in major cities in South Korea. Results indicate that all hypothesized relationships (PE and JE, LO and JE, LO and OC, JE and OC, and the mediating role of JE) are supported, except for psychological empowerment and organizational commitment. While the impact of psychological empowerment was not significantly related to organizational commitment, it is notable that through job embeddedness, psychological empowerment had indirect effects on organizational commitment. Further, learning orientation had significant effects on job embeddedness and organizational commitment. Lastly, the most compelling finding is a full mediation of job embeddedness in the relationship between psychological empowerment and organization commitment. Implications for research and practice are discussed.

Chemokine-Driven Migration of Pro-Inflammatory CD4+ T Cells in CNS Autoimmune Disease.

Pro-inflammatory CD4+ T helper (Th) cells drive the pathogenesis of many autoimmune conditions. Recent advances have modified views of the phenotype of pro-inflammatory Th cells in autoimmunity, extending the breadth of known Th cell subsets that operate as drivers of these responses. Heterogeneity and plasticity within Th1 and Th17 cells, and the discovery of subsets of Th cells dedicated to production of other pro-inflammatory cytokines such as GM-CSF have led to these advances. Here, we review recent progress in this area and focus specifically upon evidence for chemokine receptors that drive recruitment of these various pro-inflammatory Th cell subsets to sites of autoimmune inflammation in the CNS. We discuss expression of specific chemokine receptors by subsets of pro-inflammatory Th cells and highlight which receptors may be tractable targets of therapeutic interventions to limit pathogenic Th cell recruitment in autoimmunity.