The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during Hemodialysis.

BACKGROUND: Patients with kidney failure treated with hemodialysis (HD) may be at risk for cerebral hypoperfusion due to HD-induced BP decline in the setting of impaired cerebral autoregulation. Cerebrovascular reactivity (CVR), the cerebrovascular response to vasoactive stimuli, may be a useful indicator of cerebral autoregulation in the HD population and identify those at risk for cerebral hypoperfusion. We hypothesize that CVR combined with intradialytic BP changes will be associated with declines in cerebral oxygenation saturation (ScO2) during HD. METHODS: Participants completed the MRI scans on a non-HD day and cerebral oximetry during HD. We measured CVR with resting-state fMRI (rs-fMRI) without a gas challenge and ScO2 saturation with near-infrared spectroscopy. Regression analysis was used to examine the relationship between intradialytic cerebral oxygen desaturation, intradialytic BP, and CVR in different gray matter regions. RESULTS: Twenty-six patients on HD had complete data for analysis. Sixteen patients were men, 18 had diabetes, and 20 had hypertension. Mean±SD age was 65.3±7.2 years, and mean±SD duration on HD was 11.5±9.4 months. CVR in the anterior cingulate gyrus (ACG; P=0.03, r2 =0.19) and insular cortex (IC; P=0.03, r2 =0.19) regions negatively correlated with decline in intradialytic ScO2. Model prediction of intradialytic ScO2 improved when including intradialytic BP change and ultrafiltration rate to the ACG rsCVR (P<0.01, r2 =0.48) and IC rsCVR (P=0.02, r2 =0.35) models, respectively. CONCLUSIONS: We found significant relationships between regional rsCVR measured in the brain and decline in intradialytic ScO2. Our results warrant further exploration of using CVR in determining a patient's risk of cerebral ischemic injury during HD.

Longitudinal changes in diffusion tensor imaging in hemodialysis patients.

INTRODUCTION: Hemodialysis patients have increased white matter and gray matter pathology in the brain relative to controls based on MRI. Diffusion tensor imaging is useful in detecting differences between hemodialysis and controls but has not identified the expected longitudinal decline in hemodialysis patients. In this study we implemented specialized post-processing techniques to reduce noise to detect longitudinal changes in diffusion tensor imaging parameters and evaluated for any association with changes in cognition. METHODS: We collected anatomical and diffusion MRIs as well as cognitive testing from in-center hemodialysis patients at baseline and 1 year later. Gray matter thickness, white matter volume, and white matter diffusion tensor imaging parameters were measured to identify longitudinal changes. We analyzed the diffusion tensor imaging parameters by averaging the whole white matter and using a pothole analysis. Eighteen hemodialysis patients were included in the longitudinal analysis and 15 controls were used for the pothole analysis. We used the NIH Toolbox Cognition Battery to assess cognitive performance over the same time frame. FINDINGS: Over the course of a year on hemodialysis, we found a decrease in white matter fractional anisotropy across the entire white matter (p < 0.01), and an increase in the number of white matter fractional anisotropy voxels below pothole threshold (p = 0.03). We did not find any relationship between changes in whole brain structural parameters and cognitive performance. DISCUSSION: By employing noise reducing techniques, we were able to detect longitudinal changes in diffusion tensor imaging parameters in hemodialysis patients. The fractional anisotropy declines over the year indicate significant decreases in white matter health. However, we did not find that declines in fractional anisotropy was associated with declines in cognitive performance.

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.

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.

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.

Characterization of diffusion MRI using the mean apparent propagator model in hemodialysis patients: A pilot study.

To better understand documented cognitive decline in hemodialysis (HD) patients, diffusion MRI (dMRI) has been used to characterize brain anatomical deficits relative to controls. Studies to this point have primarily used diffusion tensor imaging (DTI) to model the three-dimensional diffusion of water in HD patients, with DTI parameters reflecting underlying microstructural changes of brain tissue. Since DTI has some limitations in characterizing tissue microstructure, some of which may be complicated by HD, we explored the use of the mean apparent propagator (MAP) model to describe diffusion in HD patients. We collected anatomical T1 and T2 FLAIR MRIs as well as multi-shell dMRI in ten HD participants and ten age-matched controls. The T1 and T2 FLAIR MRIs were used for tissue segmentation and identification of white matter hyperintensity, respectively. Multi-shell dMRI data were used to estimate MAP and DTI diffusion models. Each model was then used to characterize the differences between the HD cohort and the age-matched controls in normal appearing white matter, subcortical gray matter, corpus callosum (CC) and bilateral radiata (Rad). As expected, parameters of both DTI and MAP models of dMRI were significantly different in HD participants compared to controls. However, some MAP parameters suggested additional tissue microstructural changes in HD participants, such as increased axonal diameter. Measurements of non-Gaussianity indicated that MAP provided better a diffusion estimate than DTI, and MAP appeared to provide a more accurate measure of anisotropy in Rad, based on measures of the Rad/CC ratio. In conclusion, parameters of the MAP and DTI models were both sensitive to changes in diffusivity in HD participants compared to controls; however, the MAP model appeared to provide additional detailed information about changes in brain tissue microstructure.

Changes in Cerebral Volume and White Matter Integrity in Adults on Hemodialysis and Relationship to Cognitive Function.

INTRODUCTION: Patients on hemodialysis (HD) have a significant burden of cognitive impairment. Characterizing the cerebral structural changes in HD patients compared to healthy controls and evaluating the relationship of cerebral structural integrity with cognitive performance in HD patients can help clarify the pathophysiology of the cognitive impairment in HD patients. METHODS: In this cross-sectional study, in-center HD patients ≥50 years of age underwent brain structural and diffusion MRIs and cognitive assessment using the NIH Toolbox cognition battery. The cerebral imaging measures of the HD participants were compared to imaging from age-matched controls. Gray matter volume, white matter volume, and white matter integrity determined by diffusion tensor imaging parameters (including fractional anisotropy [FA]) were measured in both cohorts to determine differences in the cerebral structure between HD participants and healthy controls. The association between cognitive performance on the NIH Toolbox cognition battery and cerebral structural integrity was evaluated using multiple linear regression models. RESULTS: We compared imaging measures form 23 HD participants and 15 age-matched controls. The HD participants had decreased gray matter volumes (526.8 vs. 589.5 cm3, p < 0.01) and worsened white matter integrity overall (FA values of 0.2864 vs. 0.3441, p < 0.01) within major white matter tracts compared to healthy controls. Decreases in white matter integrity in the left superior longitudinal fasciculus was associated with lower executive function scores (r2 = 0.24, p = 0.02) and inferior longitudinal fasciculus with lower memory scores (r = 0.25 and p = 0.03 for left and r2 = 0.21 and p = 0.03 for right). CONCLUSIONS: HD patients have a pattern of decreased white matter integrity and gray matter atrophy compared to controls. Decreases in white matter integrity were associated with decreased cognitive performance in the HD population.