Closed-Loop Dynamic Modeling of Cerebral Hemodynamics

Marmarelis, Vasilis Z.; Shin, Dong-Joon; Orme, Melissa; Zhang, R.

doi:10.1007/s10439-012-0736-8

Cited by 25 publications

(49 citation statements)

References 20 publications

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“…We briefly outline below the proposed PDM-based modeling approach, which is also summarized in Appendix I. For the many mathematical and technical details of Volterra-type modeling and related issues, the reader is referred to the monograph [38] and to our recent publications presenting its application to cerebral hemodynamics in the input-output open-loop context [34] and in the closed-loop context [35]. In short, the output of the PDM-based open-loop model is formed by additive signal components that are generated by cascaded operations of convolutions of the input signal with each PDM and nonlinear transformations by the respective Associated Nonlinear Function (ANFs).…”

Section: Methodsmentioning

confidence: 99%

“…A block-diagram for the closed-loop model is shown in Figure 3 and indicates the presence of two putative external (systemic) "disturbances" which are the residuals for each open-loop model prediction. The key mathematical operations and the concepts involved in the closed-loop modeling approach are summarized in Appendix II and expounded in a recent publication [35]. …”

Section: Methodsmentioning

confidence: 99%

“…To advance the study of these processes, a modeling methodology has been introduced and tested with beat-to-beat hemodynamic data using open-loop analysis [34] and closed-loop analysis [35]. These modeling studies of cerebral hemodynamics explored the potential of model-based "physiomarkers" for improved diagnosis of early-stage AD and discovered that a subject-specific CVMR index attained significantly lower values in AD patients (relative to the normative population of control subjects), suggesting potential diagnostic utility for such indices [36].…”

Section: Introductionmentioning

confidence: 99%

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Model-based physiomarkers of cerebral hemodynamics in patients with mild cognitive impairment

Marmarelis

Shin

Orme³

et al. 2014

Medical Engineering & Physics

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In our previous studies, we have introduced model-based "unctional biomarkers"or "hysiomarkers"of cerebral hemodynamics that hold promise for improved diagnosis of early-stage Alzheimer’s disease (AD). The advocated methodology utilizes subject-specific data-based dynamic nonlinear models of cerebral hemodynamics to compute indices (serving as possible diagnostic physiomarkers) that quantify the state of cerebral blood flow autoregulation to pressure-changes (CFAP) and cerebral CO2 vasomotor reactivity (CVMR) in each subject. The model is estimated from beat-to-beat measurements of mean arterial blood pressure, mean cerebral blood flow velocity and end18 tidal CO2, which can be made reliably and non-invasively under resting conditions. In a previous study, it was found that a CVMR index quantifying the impairment in CO2 vasomotor reactivity correlates with clinical indications of early AD, offering the prospect of a potentially useful diagnostic tool. In this paper, we explore the use of the same model-based indices for patients with amnestic Mild Cognitive Impairment (MCI), a preclinical stage of AD, relative to a control subjects and clinical cognitive assessments. It was found that the model-based CVMR values were lower for MCI patients relative to the control subjects.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Model-based physiomarkers of cerebral hemodynamics in patients with mild cognitive impairment

Marmarelis

Shin

Orme³

et al. 2014

Medical Engineering & Physics

Self Cite

View full text Add to dashboard Cite

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“…[21,22] PDM constitute an efficient basis of reference functions for the representation of the system's kernels that can describe the dynamic relationship between input variables (e.g. blood pressure and end-tidal CO 2 ) and output variables (e.g.…”

Section: Methodsmentioning

confidence: 99%

“…[24] A full mathematical description of this method was described elsewhere. [25] The PDM-based models are not ad hoc models, but rather they are canonical representations of cerebral hemodynamics, yielding indices of physiological meaning. Specifically, the resulting PDM-based CO 2 vasoreactivity index represents the time-average of BFV increase over 30 sec per unit of imposed of %change in end-tidal CO 2 (cm/sec/%mmHg).…”

Section: Methodsmentioning

confidence: 99%

Assessment of Cerebrovascular Reactivity during Resting State Breathing and Its Correlation with Cognitive Function in Hypertension

Hajjar

Marmerelis²,

Shin³

et al. 2014

Cerebrovasc Dis

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Background: Hypertension is associated with cognitive deficits, particularly executive function, and decreased cerebral microvascular responsiveness to CO₂ (CO₂ vasoreactivity). The relation between CO₂ vasoreactivity and executive function is not known. Protocols to assess CO₂ vasoreactivity are cumbersome and require inhaling a CO₂-enriched gas. We explored the ability to measure CO₂ vasoreactivity using end-tidal CO₂ fluctuations during normal breathing and the association of this measure with cognitive function in hypertension. Methods: Executive function (Trail-Making Test parts A/B), memory, attention and blood flow velocity (BFV) in the middle cerebral artery using transcranial Doppler were measured in hypertensive subjects who were tapered off their treatment for 3 weeks. BFV was measured while sitting and normally breathing for 5 min, followed by breathing 5% CO₂ gas and hyperventilation for 2 min each. We calculated CO₂ vasoreactivity as the rate of BFV change from hypoventilation to hyperventilation, and as a model-derived measure using the normal breathing data. The latter was derived using nonlinear principal dynamic modes (PDM), which modelled the dynamic effect of fluctuations in end-tidal CO₂ and blood pressure upon BFV during normal room-air respiration. Multiple regression analyses were used to correlate cerebral hemodynamics with cognitive measures. Results: Data were collected from 41 individuals with hypertension (mean age 71 years, 24% African Americans, 61% women, off antihypertensive therapy). Lower CO₂ vasoreactivity was associated with a worse executive function test score using both calculation methods: p value using the hyper/hypoventilation data was 0.04 and from the PDM analysis was 0.009. PDM calculations showed a stronger correlation with executive function (0.41 vs. 0.21 using the hyper/hypoventilation data). There were no associations with memory or attention measures. There was a weak but statistically significant correlation between the two calculation methods of CO₂ vasoreactivity (R² = 14%, p = 0.02). Conclusion: This study suggests that the decrease in CO₂ vasoreactivity in hypertension is associated with lower executive function. This may offer new insight into the vascular underpinning of cognitive decline in hypertension. We demonstrate that calculating CO₂ vasoreactivity is possible during normal breathing. If replicated in future studies, this may offer a more convenient clinical way to assess CO₂ vasoreactivity in hypertension and cognitive disorders.

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Regulation of the Cerebral Circulation by Arterial Carbon Dioxide

Hoiland

Fisher

Ainslie

2019

Comprehensive Physiology

170

189

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Intact, coordinated, and precisely regulated cerebrovascular responses are required for the maintenance of cerebral metabolic homeostasis, adequate perfusion, oxygen delivery, and acid‐base balance during deviations from homeostasis. Increases and decreases in the partial pressure of arterial carbon dioxide (PaCO 2 ) lead to robust and rapid increases and decreases in cerebral blood flow (CBF). In awake and healthy humans, PaCO 2 is the most potent regulator of CBF, and even small fluctuations can result in large changes in CBF. Alterations in the responsiveness of the cerebral vasculature can be detected with carefully controlled stimulus‐response paradigms and hold relevance for cerebrovascular risk in steno‐occlusive disease. As changes in PaCO 2 do not typically occur in isolation, the integrative influence of physiological factors such as intracranial pressure, arterial oxygen content, cerebral perfusion pressure, and sympathetic nervous activity must be considered. Further, age and sex, as well as vascular pathologies are also important to consider. Following a brief summary of key historical events in the development of our understanding of cerebrovascular physiology and an overview of the measurement techniques to index CBF this review provides an in‐depth description of CBF regulation in response to alterations in PaCO 2 . Cerebrovascular reactivity and regional flow distribution are described, with further consideration of how differences in reactivity of parallel networks can lead to the “steal” phenomenon. Factors that influence cerebrovascular reactivity are discussed and the mechanisms and regulatory pathways mediating the exquisite sensitivity of the cerebral vasculature to changes in PaCO 2 are outlined. Finally, topical avenues for future research are proposed. © 2019 American Physiological Society. Compr Physiol 9:1101‐1154, 2019.

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Closed-Loop Dynamic Modeling of Cerebral Hemodynamics

Cited by 25 publications

References 20 publications

Model-based physiomarkers of cerebral hemodynamics in patients with mild cognitive impairment

Model-based physiomarkers of cerebral hemodynamics in patients with mild cognitive impairment

Assessment of Cerebrovascular Reactivity during Resting State Breathing and Its Correlation with Cognitive Function in Hypertension

Regulation of the Cerebral Circulation by Arterial Carbon Dioxide

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