Data-based modeling of cerebral hemodynamics quantifies impairment of cerebral blood flow regulation in type-2 diabetes.

We studied the regulation dynamics of cerebral blood velocity (CBv) at middle cerebral arteries (MCA) in response to spontaneous changes of arterial blood pressure (ABP), termed dynamic cerebral autoregulation (dCA), and end-tidal CO as proxy for blood CO tension, termed dynamic vasomotor reactivity (DVR), by analyzing time-series data collected at supine rest from 36 patients with Type-2 Diabetes Mellitus (T2DM) and 22 age/sex-matched non-diabetic controls without arterial hypertension. Our analysis employed a robust dynamic modeling methodology that utilizes Principal Dynamic Modes (PDM) to estimate subject-specific dynamic transformations of spontaneous changes in ABP and end-tidal CO (viewed as two "inputs") into changes of CBv at MCA measured via Transcranial Doppler ultrasound (viewed as the "output"). The quantitative results of PDM analysis indicate significant alterations in T2DM of both DVR and dCA in terms of two specific PDM contributions that rise to significance (p < 0.

Impaired dynamic cerebral autoregulation measured in the middle cerebral artery in patients with vertebrobasilar ischemia is associated with autonomic failure.

Objectives: To assess whether vertebrobasilar artery ischemia (VBI) affects cortical cerebral blood flow (CBF) regulation.

Material And Methods: 107 consecutive patients (mean age 65 ± 15 years; women 21) with VBI underwent structured stroke care with assessment of dynamic cerebral autoregulation (dCA) in both middle cerebral arteries (MCAs) by transfer function analysis using spontaneous oscillations of blood pressure (BP) and CBF velocity that yields by extraction of phase and gain information in the very low (0.02-0.

Dynamic effects of cholinergic blockade upon cerebral blood flow autoregulation in healthy adults.

Cerebral flow autoregulation (CFA) is a homeostatic mechanism critical for survival. The autonomic nervous system (ANS) plays a key role in maintaining proper CFA function. More quantitative studies of how the ANS influences CFA are desirable.

The Dynamic Relationship Between Cortical Oxygenation and End-Tidal Transient Changes Is Impaired in Mild Cognitive Impairment Patients.

Recent studies have utilized data-based dynamic modeling to establish strong association between dysregulation of cerebral perfusion and Mild Cognitive Impairment (MCI), expressed in terms of impaired CO dynamic vasomotor reactivity in the cerebral vasculature. This raises the question of whether this is due to dysregulation of central mechanisms (baroreflex and chemoreflex) or mechanisms of cortical tissue oxygenation (CTO) in MCI patients. We seek to answer this question using data-based input-output predictive dynamic models.

Dysregulation of CO2-Driven Heart-Rate Chemoreflex Is Related Closely to Impaired CO2 Dynamic Vasomotor Reactivity in Mild Cognitive Impairment Patients.

Background: Significant reduction of dynamic vasomotor reactivity (DVR) was recently reported in patients with amnestic mild cognitive impairment (MCI) relative to age-matched controls. These results were obtained via a novel approach that utilizes data-based predictive dynamic models to quantify DVR.

Objective: Using the same methodological approach, we seek to quantify the dynamic effects of the CO2-driven chemoreflex and baroreflex upon heart-rate in order to examine their possible correlation with the observed DVR impairment in each MCI patient.

Closed-loop modeling of the heart-rate reflex for improved diagnosis and monitoring of Mild Cognitive Impairment.

Analysis of beat-to-beat spontaneous cerebral hemodynamic data has yielded predictive dynamic models of cerebral hemodynamics and has shown previously that patients with Mild Cognitive Impairment (MCI) exhibit significantly reduced cerebral vasomotor reactivity to CO relative to cognitively normal control subjects [1]. The present work examines the heart-rate reflex (HRR) dynamics of 46 MCI patients compared to 20 control subjects, using closed-loop modeling of HRR under resting conditions of spontaneous variations of arterial blood pressure (baroreflex) and end-tidal CO (chemoreflex). These subject-specific predictive dynamic models are obtained via the methodology of Principal Dynamic Modes [2] and allow the computation of model-based markers of baroreflex and chemoreflex function.

Assessment of dynamic cerebral autoregulation in humans: Is reproducibility dependent on blood pressure variability?

We tested the influence of blood pressure variability on the reproducibility of dynamic cerebral autoregulation (DCA) estimates. Data were analyzed from the 2nd CARNet bootstrap initiative, where mean arterial blood pressure (MABP), cerebral blood flow velocity (CBFV) and end tidal CO2 were measured twice in 75 healthy subjects. DCA was analyzed by 14 different centers with a variety of different analysis methods.

Quantification of dynamic cerebral autoregulation and CO dynamic vasomotor reactivity impairment in essential hypertension.

The study of dynamic cerebral autoregulation (DCA) in essential hypertension has received considerable attention because of its clinical importance. Several studies have examined the dynamic relationship between spontaneous beat-to-beat arterial blood pressure data and contemporaneous cerebral blood flow velocity measurements (obtained via transcranial Doppler at the middle cerebral arteries) in the form of a linear input-output model using transfer function analysis. This analysis is more reliable when the contemporaneous effects of changes in blood CO tension are also taken into account, because of the significant effects of CO dynamic vasomotor reactivity (DVR) upon cerebral flow.

Dynamic Cerebral Autoregulation Reproducibility Is Affected by Physiological Variability.

Parameters describing dynamic cerebral autoregulation (DCA) have limited reproducibility. In an international, multi-center study, we evaluated the influence of multiple analytical methods on the reproducibility of DCA. Fourteen participating centers analyzed repeated measurements from 75 healthy subjects, consisting of 5 min of spontaneous fluctuations in blood pressure and cerebral blood flow velocity signals, based on their usual methods of analysis.

Comparing model-based cerebrovascular physiomarkers with DTI biomarkers in MCI patients.

Objective: To compare the novel model-based hemodynamic physiomarker of Dynamic Vasomotor Reactivity (DVR) with biomarkers based on Diffusion Tensor Imaging (DTI) and some widely used neurocognitive scores in terms of their ability to delineate patients with amnestic Mild Cognitive Impairment (MCI) from age-matched cognitively normal controls.

Materials & Methods: The model-based DVR and MRI-based DTI markers were obtained from 36 patients with amnestic MCI and 16 age-matched controls without cognitive impairment, for whom widely used neurocognitive scores were available. These markers and scores were subsequently compared in terms of statistical delineation between patients and controls.

Multi-Input, Multi-Output Neuronal Mode Network Approach to Modeling the Encoding Dynamics and Functional Connectivity of Neural Systems.

This letter proposes a novel method, multi-input, multi-output neuronal mode network (MIMO-NMN), for modeling encoding dynamics and functional connectivity in neural ensembles such as the hippocampus. Compared with conventional approaches such as the Volterra-Wiener model, linear-nonlinear-cascade (LNC) model, and generalized linear model (GLM), the NMN has several advantages in terms of estimation accuracy, model interpretation, and functional connectivity analysis. We point out the limitations of current neural spike modeling methods, especially the estimation biases caused by the imbalanced class problem when the number of zeros is significantly larger than ones in the spike data.

Reproducibility of dynamic cerebral autoregulation parameters: a multi-centre, multi-method study.

Objective: Different methods to calculate dynamic cerebral autoregulation (dCA) parameters are available. However, most of these methods demonstrate poor reproducibility that limit their reliability for clinical use. Inter-centre differences in study protocols, modelling approaches and default parameter settings have all led to a lack of standardisation and comparability between studies.

Mechanism-Based and Input-Output Modeling of the Key Neuronal Connections and Signal Transformations in the CA3-CA1 Regions of the Hippocampus.

This letter examines the results of input-output (nonparametric) modeling based on the analysis of data generated by a mechanism-based (parametric) model of CA3-CA1 neuronal connections in the hippocampus. The motivation is to obtain biological insight into the interpretation of such input-output (Volterra-equivalent) models estimated from synthetic data. The insights obtained may be subsequently used to interpretat input-output models extracted from actual experimental data.

Comparison of Model-Based Indices of Cerebral Autoregulation and Vasomotor Reactivity Using Transcranial Doppler versus Near-Infrared Spectroscopy in Patients with Amnestic Mild Cognitive Impairment.

We recently introduced model-based "physiomarkers" of dynamic cerebral autoregulation and CO2 vasomotor reactivity as an aid for diagnosis of early-stage Alzheimer's disease (AD) [1], where significant impairment of dynamic vasomotor reactivity (DVR) was observed in early-stage AD patients relative to age-matched controls. Milder impairment of DVR was shown in patients with amnestic mild cognitive impairment (MCI) using the same approach in a subsequent study [2]. The advocated approach utilizes subject-specific data-based models of cerebral hemodynamics to quantify the dynamic effects of resting-state changes in arterial blood pressure and end-tidal CO2 (the putative inputs) upon cerebral blood flow velocity (the putative output) measured at the middle cerebral artery via transcranial Doppler (TCD).

Compartmental and Data-Based Modeling of Cerebral Hemodynamics: Nonlinear Analysis.

Objective: As an extension to our study comparing a putative compartmental and data-based model of linear dynamic cerebral autoregulation (CA) and CO-vasomotor reactivity (VR), we study the CA-VR process in a nonlinear context.

Methods: We use the concept of principal dynamic modes (PDM) in order to obtain a compact and more easily interpretable input-output model. This in silico study permits the use of input data with a dynamic range large enough to simulate the classic homeostatic CA and VR curves using a putative structural model of the regulatory control of the cerebral circulation.

Assessment of cerebrovascular reactivity during resting state breathing and its correlation with cognitive function in hypertension.

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.

Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing.

Objective: Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer's, ageing and dementia resulting from impaired hippocampal function in the medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states.

Approach: NHPs trained to perform a short-term delayed match-to-sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3.

Time-varying modeling of cerebral hemodynamics.

The scientific and clinical importance of cerebral hemodynamics has generated considerable interest in their quantitative understanding via computational modeling. In particular, two aspects of cerebral hemodynamics, cerebral flow autoregulation (CFA) and CO2 vasomotor reactivity (CVR), have attracted much attention because they are implicated in many important clinical conditions and pathologies (orthostatic intolerance, syncope, hypertension, stroke, vascular dementia, mild cognitive impairment, Alzheimer's disease, and other neurodegenerative diseases with cerebrovascular components). Both CFA and CVR are dynamic physiological processes by which cerebral blood flow is regulated in response to fluctuations in cerebral perfusion pressure and blood CO2 tension.

Analysis of intravenous glucose tolerance test data using parametric and nonparametric modeling: application to a population at risk for diabetes.

Background: Modeling studies of the insulin-glucose relationship have mainly utilized parametric models, most notably the minimal model (MM) of glucose disappearance. This article presents results from the comparative analysis of the parametric MM and a nonparametric Laguerre based Volterra Model (LVM) applied to the analysis of insulin modified (IM) intravenous glucose tolerance test (IVGTT) data from a clinical study of gestational diabetes mellitus (GDM).

Methods: An IM IVGTT study was performed 8 to 10 weeks postpartum in 125 women who were diagnosed with GDM during their pregnancy [population at risk of developing diabetes (PRD)] and in 39 control women with normal pregnancies (control subjects).

Nonlinear modeling of dynamic interactions within neuronal ensembles using Principal Dynamic Modes.

A methodology for nonlinear modeling of multi-input multi-output (MIMO) neuronal systems is presented that utilizes the concept of Principal Dynamic Modes (PDM). The efficacy of this new methodology is demonstrated in the study of the dynamic interactions between neuronal ensembles in the Pre-Frontal Cortex (PFC) of a behaving non-human primate (NHP) performing a Delayed Match-to-Sample task. Recorded spike trains from Layer-2 and Layer-5 neurons were viewed as the "inputs" and "outputs", respectively, of a putative MIMO system/model that quantifies the dynamic transformation of multi-unit neuronal activity between Layer-2 and Layer-5 of the PFC.

A nonlinear model for hippocampal cognitive prosthesis: memory facilitation by hippocampal ensemble stimulation.

Collaborative investigations have characterized how multineuron hippocampal ensembles encode memory necessary for subsequent successful performance by rodents in a delayed nonmatch to sample (DNMS) task and utilized that information to provide the basis for a memory prosthesis to enhance performance. By employing a unique nonlinear dynamic multi-input/multi-output (MIMO) model, developed and adapted to hippocampal neural ensemble firing patterns derived from simultaneous recorded CA1 and CA3 activity, it was possible to extract information encoded in the sample phase necessary for successful performance in the nonmatch phase of the task. The extension of this MIMO model to online delivery of electrical stimulation delivered to the same recording loci that mimicked successful CA1 firing patterns, provided the means to increase levels of performance on a trial-by-trial basis.

Differentiation of cancerous lesions in excised human breast specimens using multiband attenuation profiles from ultrasonic transmission tomography.

Objective: This study examines the tissue differentiation capability of the recently developed high-resolution ultrasonic transmission tomography (HUTT) system in the context of differentiating between benign and malignant tissue types in mastectomy specimens.

Methods: Eight mastectomy patients provided breast specimens with benign and malignant lesions. The specimens were scanned by the HUTT system with a pair of either 8- or 4-MHz transducers.

Segmentation methodology for automated classification and differentiation of soft tissues in multiband images of high-resolution ultrasonic transmission tomography.

This paper presents a novel segmentation methodology for automated classification and differentiation of soft tissues using multiband data obtained with the newly developed system of high-resolution ultrasonic transmission tomography (HUTT) for imaging biological organs. This methodology extends and combines two existing approaches: the L-level set active contour (AC) segmentation approach and the agglomerative hierarchical kappa-means approach for unsupervised clustering (UC). To prevent the trapping of the current iterative minimization AC algorithm in a local minimum, we introduce a multiresolution approach that applies the level set functions at successively increasing resolutions of the image data.

Soft tissue differentiation using multiband signatures of high resolution ultrasonic transmission tomography.

In this paper, we are interested in soft tissue differentiation by multiband images obtained from the High-Resolution Ultrasonic Transmission Tomography (HUTT) system using a spectral target detection method based on constrained energy minimization (CEM). We have developed a new tissue differentiation method (called "CEM filter bank") consisting of multiple CEM filters specially designed for detecting multiple types of tissues. Statistical inference on the output of the CEM filter bank is used to make a decision based on the maximum statistical significance rather than the magnitude of each CEM filter output.