Arterial Cerebral Blood Volume Research Articles

Quantitative analysis of similarity between cerebral arterial blood volume and intracranial pressure pulse waveforms during intracranial pressure plateau waves

IntroductionBoth intracranial pressure (ICP) and cerebral arterial blood volume (CaBV) have a pulsatile character related to the cardiac cycle. The evolution of the shape of ICP pulses under increasing ICP or decreasing intracranial compliance is well documented. Nevertheless, the exact origin of the alterations in the ICP morphology remains unclear. Research questionDoes ICP pulse waveform become similar to non-invasively estimated CaBV pulse during ICP plateau waves. Material and methodsA total of 15 plateau waves recorded in 15 traumatic brain injured patients were analyzed. CaBV pulse waveforms were calculated using global cerebral blood flow model from transcranial Doppler cerebral blood flow velocity (CBFV) signals. The difference index (DI) was used to quantify the similarity between ICP and CaBV waveforms. DI was calculated as the sum of absolute sample-by-sample differences between ICP and CaBV waveforms, representing the area between the pulses. ResultsICP increased (19.4 mm Hg [Q1–Q3: 18.2–23.4 mm Hg] vs. 42.7 mm Hg [Q1–Q3: 36.5–45.1 mm Hg], p < 0.001) while CBFV decreased (44.2 cm/s [Q1–Q3: 34.8–69.5 cm/s] vs. 32.9 cm/s [Q1–Q3: 24.7–68.2 cm/s], p = 0.002) during plateau waves. DI was smaller during the plateau waves (20.4 [Q1–Q3: 15.74–23.0]) compared to the baselines (26.3 [Q1–Q3: 24.2–34.7], p < 0.001). Discussion and conclusionThe area between corresponding ICP and CaBV pulse waveforms decreased during the plateau waves which suggests they became similar in shape. CaBV may play a significant role in determining the shape of ICP pulses during the plateau waves and might be a driving force in formulating ICP elevation.

On the optimization of 3D inflow-based vascular-space-occupancy (iVASO) MRI for the quantification of arterial cerebral blood volume (CBVa).

The inflow-based vascular-space-occupancy (iVASO) MRI was originally developed in a single-slice mode to measure arterial cerebral blood volume (CBVa). When vascular crushers are applied in iVASO, the signals can be sensitized predominantly to small pial arteries and arterioles. The purpose of this study is to perform a systematic optimization and evaluation of a 3D iVASO sequence on both 3 T and 7 T for the quantification of CBVa values in the human brain. Three sets of experiments were performed in three separate cohorts. (1) 3D iVASO MRI protocols were compared to single-slice iVASO, and the reproducibility of whole-brain 3D iVASO MRI was evaluated. (2) The effects from different vascular crushers in iVASO were assessed. (3) 3D iVASO MRI results were evaluated in arterial and venous blood vessels identified using ultrasmall-superparamagnetic-iron-oxides-enhanced MRI to validate its arterial origin. 3D iVASO scans showed signal-to-noise ratio (SNR) and CBVa measures consistent with single-slice iVASO with reasonable intrasubject reproducibility. Among the iVASO scans performed with different vascular crushers, the whole-brain 3D iVASO scan with a motion-sensitized-driven-equilibrium preparation with two binomial refocusing pulses and an effective TE of 50 ms showed the best suppression of macrovascular signals, with a relatively low specific absorption rate. When no vascular crusher was applied, the CBVa maps from 3D iVASO scans showed large CBVa values in arterial vessels but well-suppressed signals in venous vessels. A whole-brain 3D iVASO MRI scan was optimized for CBVa measurement in the human brain. When only microvascular signals are desired, a motion-sensitized-driven-equilibrium-based vascular crusher with binomial refocusing pulses can be applied in 3D iVASO.

Brain blood flow pulse analysis may help to recognize individuals who suffer from hydrocephalus

BackgroundNormal pressure hydrocephalus (NPH) is often associated with altered cerebral blood flow. Recent research with the use of the ultrasonic method suggests specific changes in the shape of cardiac-related cerebral arterial blood volume (CaBV) pulses in NPH patients. Our study aims to provide a quantitative analysis of the shape of CaBV pulses, estimated based on transcranial Doppler ultrasonography (TCD) in NPH patients and healthy individuals.MethodsThe CaBV pulses were estimated using TCD cerebral blood flow velocity signals recorded from probable NPH adults and age-matched healthy individuals at rest. The shape of the CaBV pulses was compared to a triangular shape with 27 similarity parameters calculated for every reliable CaBV pulse and compared between patients and volunteers. The diagnostic accuracy of the most prominent parameter for NPH classification was evaluated using the area under the receiver operating characteristic curve (AUC).ResultsThe similarity parameters were calculated for 31 probable NPH patients (age: 59 years (IQR: 47, 67 years), 14 females) and 23 healthy volunteers (age: 54 years (IQR: 43, 61 years), 18 females). Eighteen of 27 parameters were different between healthy individuals and NPH patients (p < 0.05). The most prominent differences were found for the ascending slope of the CaBV pulse with the AUC equal to 0.87 (95% confidence interval: 0.77, 0.97, p < 0.001).ConclusionsThe findings suggest that in NPH, the ascending slope of the CaBV pulse had a slower rise, was more like a straight line, and generally was less convex than in volunteers. Prospective research is required to verify the clinical utility of these findings.

Hyperperfusion of bilateral amygdala in patients with chronic migraine: an arterial spin-labeled magnetic resonance imaging study

BackgroundAmygdala, an essential element of the limbic system, has served as an important structure in pain modulation. There is still a lack of clarity about altered cerebral perfusion of amygdala in migraine. This study aimed to investigate the perfusion variances of bilateral amygdala in episodic migraine (EM) and chronic migraine (CM) using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI).MethodsTwenty-six patients with EM, 55 patients with CM (33 CM with medication overuse headache (MOH)), and 26 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL MR imaging to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The CBF and aCBV values in the bilateral amygdala were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed.ResultsCompared with HC participants, patients with CM were found to have increased CBF and aCBV values in the left amygdala, as well as increased CBF values in the right amygdala (all P < 0.05). There were no significant differences of CBF and aCBV values in the bilateral amygdala between the HC and EM groups, the EM and CM groups, as well as the CM without and with MOH groups (all P > 0.05). In patients with CM, the increased perfusion parameters of bilateral amygdala were positively correlated with MIDAS score after adjustments for age, sex, and body mass index (BMI).ConclusionHyperperfusion of bilateral amygdala might provide potential hemodynamics evidence in the neurolimbic pain network of CM.

Brain perfusion imaging by multi-delay arterial spin labeling: Impact of modeling dispersion and interaction with denoising strategies and pathology.

Arterial spin labeling (ASL) acquisitions at multiple post-labeling delays may provide more accurate quantification of cerebral blood flow (CBF), by fitting appropriate kinetic models and simultaneously estimating relevant parameters such as the arterial transit time (ATT) and arterial cerebral blood volume (aCBV). We evaluate the effects of denoising strategies on model fitting and parameter estimation when accounting for the dispersion of the label bolus through the vasculature in cerebrovascular disease. We analyzed multi-delay ASL data from 17 cerebral small vessel disease patients (50 ± 9 y) and 13 healthy controls (52 ± 8 y), by fitting an extended kinetic model with or without bolus dispersion. We considered two denoising strategies: removal of structured noise sources by independent component analysis (ICA) of the control-label image timeseries; and averaging the repetitions of the control-label images prior to model fitting. Modeling bolus dispersion improved estimation precision and impacted parameter values, but these effects strongly depended on whether repetitions were averaged before model fitting. In general, repetition averaging improved model fitting but adversely affected parameter values, particularly CBF and aCBV near arterial locations in patients. This suggests that using all repetitions allows better noise estimation at the earlier delays. In contrast, ICA denoising improved model fitting and estimation precision while leaving parameter values unaffected. Our results support the use of ICA denoising to improve model fitting to multi-delay ASL and suggest that using all control-label repetitions improves the estimation of macrovascular signal contributions and hence perfusion quantification near arterial locations. This is important when modeling flow dispersion in cerebrovascular pathology.

Diagnostic Value of Multi‐delay Multi‐parametric 3D pCASL in Early Alzheimer' Disease

AbstractBackgroundSingle post‐labeling delay (PLD) pseudo‐continuous arterial spin‐labeling (pCASL) measures cerebral blood Flow (CBF). The altered CBF is associated with cognitive decline in early Alzheimer’s disease (AD). However, multi‐delay pCASL that measures multi‐parametric measurements including CBF, arterial cerebral blood volume (aCBV) and arterial transit time (ATT) has rarely been applied to AD studies and its diagnostic performance to recognize AD in early stage remains unclear. The purpose of this study is to compare the diagnostic value between the CBF measured by single PLD pCASL and the CBF/aCBV/ATT measured by multi‐PLD pCASL for early‐stage AD.MethodBoth 1 PLD and 7 PLD 3D pCASL protocols on 3T GE scanner were performed within one MR session for 26 cognitively normal (CN), 37 mild cognitive impairment (MCI) and 39 AD subjects who were recruited in Chinese Imaging, Biomarkers, and Lifestyle Study of Ageing Project (CIBL) from April to October 2021. Comparisons on CBF/aCBV/ATT in 10 regions of interest (ROIs), including left and right regions of olfactory, post cingulate, hippocampus, cuneus and precuneus, were performed across different groups. The area under the curve (AUC) were assessed through receiver operating characteristic (ROC) analysis.ResultAll ROIs showed significant decrease in CBF and increase in ATT of AD groups compared with that of CN and MCI groups (P &lt; 0.05). There was no significant difference in aCBV between groups and CBF/ATT between CN and MCI (P &gt; 0.05). The area under the ROC curve (AUC) of CBF in ROIs for both3D pCASL protocols was similar for discriminating AD against HC (0.949 vs. 0.965 for 1 PLD vs. 7 PLD, respectively), AD against MCI (0.836 vs. 0.830), MCI against HC (0.686 vs. 0.786). However, the combination of CBF/aCBV/ATT in ROIs measured by 7 PLD 3D pCASL could significantly improve diagnostic performance, which AUC was 1.000, 0.967 and 0.918 for identifying AD against HC, AD against MCI and MCI against HC respectively.ConclusionMulti‐parametric perfusion data from multi‐delay pCASL can improve the diagnostic value of AD in early stage, which could be a promising imaging biomarker in AD patients.

Cerebral perfusion variance in new daily persistent headache and chronic migraine: an arterial spin-labeled MR imaging study.

New daily persistent headache (NDPH) and chronic migraine (CM) are two different types of headaches that might involve vascular dysregulation. There is still a lack of clarity about altered brain perfusion in NDPH and CM. This study aimed to investigate the cerebral perfusion variances of NDPH and CM using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI). Fifteen patients with NDPH, 18 patients with CM, and 15 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL-MRI to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The automated anatomical labeling atlas 3 (AAL3) was used to parcellate 170 brain regions. The CBF and aCBV values in each brain region were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed. Compared with HC participants, patients with NDPH were found to have decreased CBF and aCBV values in multiple regions in the right hemisphere, including the right posterior orbital gyrus (OFCpost.R), right middle occipital gyrus (MOG.R), and ventral anterior nucleus of right thalamus (tVA.R), while patients with CM showed increased CBF and aCBV values presenting in the ventral lateral nucleus of left thalamus (tVL.L) and right thalamus (tVL.R) compared with HCs (all p < 0.05). In patients with NDPH, after age and sex adjustment, the increased aCBV values of IFGorb. R were positively correlated with GAD-7 scores; and the increased CBF and aCBV values of tVA.R were positively correlated with disease duration. The multi-delay pCASL technique can detect cerebral perfusion variation in patients with NDPH and CM. The cerebral perfusion changes may suggest different variations between NDPH and CM, which might provide hemodynamic evidence of these two types of primary headaches.

Magnetization transfer weighted laminar fMRI with multi-echo FLASH

Laminar functional magnetic resonance imaging (fMRI) using the gradient echo (GRE) blood oxygenation level dependent (BOLD) contrast is prone to signal changes arising from large unspecific venous vessels. Alternatives based on changes of cerebral blood volume (CBV) become more popular since it is expected that this hemodynamic response is dominant in microvasculature. One approach to sensitize the signal toward changes in CBV, and to simultaneously reduce unwanted extravascular (EV) BOLD blurring, is to selectively reduce gray matter (GM) signal via magnetization transfer (MT). In this work, we use off-resonant MT-pulses with a 3D FLASH readout to perform MT-prepared (MT-prep) laminar fMRI of the primary visual cortex (V1) at multiple echo times at 7 T. With a GRE-BOLD contrast without additional MT-weighting as reference, we investigated the influence of the MT-preparation on the shape and the echo time dependency of laminar profiles. Through numerical simulations, we optimized the sequence parameters to increase the sensitivity toward signal changes induced by changes in arterial CBV and to delineate the contributions of different compartments to the signal. We show that at 7 T, GM signals can be reduced by 30 %. Our laminar fMRI responses exhibit an increased signal change in the parenchyma at very short TE compared to a BOLD-only reference as a result of reduced EV signal intensity. By varying echo times, we could show that MT-prep results in less sensitivity toward unwanted signal changes based on changes in T2*. We conclude that when accounting for nuclear overhauser enhancement effects in blood, off-resonant MT-prep combined with efficient short TE readouts can become a promising method to reduce unwanted EV venous contributions in GRE-BOLD and/or to allow scanning at much shorter echo times without incurring a sensitivity penalty in laminar fMRI.

Separating spin compartments in arterial spin labeling using delays alternating with nutation for tailored excitation (DANTE) pulse: A validation study using T2 -relaxometry and application to arterial cerebral blood volume imaging.

To clarify the type of spin compartment in arterial spin labeling (ASL) that is eliminated by delays alternating with nutation for tailored excitation (DANTE) pulse using T2 -relaxometry, and to demonstrate the feasibility of arterial cerebral blood volume (CBVa ) imaging using DANTE-ASL in combination with a simplified two-compartment model. The DANTE and T2 -preparation modules were combined into a single ASL sequence. T2 values under the application of DANTE were determined to evaluate changes in T2 , along with the post-labeling delay (PLD) and the relationship between transit time without DANTE (TTnoVS ) and T2 . The reference tissue T2 (T2_ref ) was also obtained. Subsequently, the DANTE module was embedded into the Hadamard-encoded ASL. Cerebral blood flow (CBF) and CBVa were computed using two Hadamard-encoding datasets (with and without DANTE) in a rest and breath-holding (BH) task. While T2 without DANTE (T2_noVS ) decreased as the PLD increased, T2 with DANTE (T2_DANTE ) was equivalent to T2_ref and did not change with the PLD. Although there was a significant positive correlation between TTnoVS and T2_noVS with short PLD, T2_DANTE was not correlated with TTnoVS nor PLD. Baseline CBVa values obtained at rest were 0.64 ± 0.12, 0.64 ± 0.11, and 0.58 ± 0.15 mL/100 g for anterior, middle, and posterior cerebral arteries, respectively. Significant CBF and CBVa elevations were observed in the BH task. Microvascular compartment signals were eliminated from the total ASL signals by DANTE. CBVa can be measured using Hadamard-encoded DANTE-ASL in combination with a simplified two-compartment model.

Analysis of cerebral perfusion of leptomeningeal branch and perforating branch of unilateral middle cerebral artery with severe stenosis or occlusion based on multi-delay arterial spin labeling

Objective: To compare the cerebral perfusion differences between the symptomatic patients and the asymptomatic patients with unilateral middle cerebral artery (MCA) severe stenosis or occlusion by using three post labeling delays (PLD) of the three-dimensional pseudo-continuous arterial spin labeling (pCASL) technique. Methods: The clinical characteristics and ASL data of the 27 patients with severe stenosis or occlusion of unilateral MCA (18 symptomatic, 9 asymptomatic) were prospectively enrolled from April 2018 to November 2019 in the Department of Radiology of China-Japan Friendship Hospital. There were 16 males and 11 females, age range from 29 to 85 (55±13) years. According to the symptoms, they were divided into symptomatic group (18 cases) and asymptomatic group (9 cases). The parameters of cerebral blood flow (CBF), mean cerebral blood flow (mCBF), arterial transit time (ATT) and arterial cerebral blood volume (aCBV) were obtained using the Cereflow software. One-way multivariate analysis of variance (one-way MANOVA) was used to compare the differences of cerebral perfusion parameters between symptomatic group and asymptomatic group, and between the affected side and the control side in the two groups. Two-way ANOVA was used to evaluate the effects of symptoms, hemisphere (affected and control side), PLD times (1.5, 2.0 and 2.5 s) and the interaction between the two factors. Results: The CBF of the affected leptomeningeal branch and perforating branch of MCA in symptomatic group was lower than that in asymptomatic group [(36.8±10.2) ml·100 g-1·min-1 versus (46.6±13.9) ml·100 g-1·min-1, F(1, 75)=13.279, P=0.000 49; (32.3±8.3) ml·100 g-1·min-1 versus (36.2±7.5) ml·100 g-1·min-1, F (1, 75)=4.065, P=0.047], and there was no interaction between the symptom and PLD [F(2, 75) =0.061, P=0.940]. In the symptomatic group, the CBF of the leptomeningeal branch and perforating branch of MCA in affected side was lower than that in control side [(36.8±10.2) ml·100 g-1·min-1 versus (43.7±10.0) ml·100 g-1·min-1, F(1, 102)=12.559, P=0.000 59; (32.3±8.3) ml·100 g-1·min-1 versus (36.4±8.0) ml·100 g-1·min-1, F(1, 102)=6.493, P=0.012]. In the symptomatic group, the CBF of leptomeningeal branch of MCA when PLD was 2.5 s was 7.34 ml·100 g-1·min-1, which were higher than that when PLD of 1.5 s (95%CI: 0.72-13.9, P=0.03). There was no interaction between PLD and hemisphere [F(2, 102) =0.307, P=0.736]. Conclusions: The collateral circulation in the blood supply area of MCA in asymptomatic patients with severe unilateral MCA stenosis or occlusion is more abundant than that in symptomatic patients. ASL can be an effective technique for evaluating the cerebral perfusion of collateral circulation in patients with severe stenosis or occlusion of MCA.

Three-dimensional gradient and spin-echo readout for time-encoded pseudo-continuous arterial spin labeling: Influence of segmentation factor and flow compensation.

PurposeTo monitor the complete passage of the labeled blood through the vascular tree into tissue and improve the quantification of ASL maps, we evaluated the effect of 3D gradient and spin‐echo (GRASE) readout segments on temporal SNR (tSNR) and image blurriness for time‐encoded pseudo‐continuous arterial spin labeling and the effect of flow‐compensation gradients on the presence of intravascular signal.MethodsFifteen volunteers were scanned using time‐encoded pCASL with 2D EPI and single‐segment, two‐segments, and three‐segments 3D‐GRASE readouts with first‐order flow compensation (FC) gradients. Two‐segments 3D‐GRASE scans were acquired with 25%, 50%, 75%, and 100% of full first‐order FC. Temporal SNR was assessed, and cerebral blood flow and arterial blood volume were quantified for all readout strategies.ResultsFor single‐segment 3D GRASE, tSNR was comparable to 2D EPI for perfusion signal but worse for the arterial signal. Two‐segments and three‐segments 3D GRASE resulted in higher tSNR than 2D EPI for perfusion and arterial signal. The arterial signal was not well visualized for 3D‐GRASE data without FC. Visualization of the intravascular signal at postlabeling delays of 660 ms and 1060 ms was restored with FC. Adequate visualization of the intravascular signal was achieved from 75% of FC gradient strength at a postlabeling delay of 660 ms. For a postlabeling delay of 1060 ms, full‐FC gradients were the best option to depict intravascular signal.ConclusionSegmented GRASE provided higher effective tSNR compared with 2D‐EPI and single‐segment GRASE. Flow compensation with GRASE readout should be carefully controlled when applying for time‐encoded pCASL to visualize intravascular signal.

Compliance of the cerebrospinal space: comparison of three methods

BackgroundCerebrospinal compliance describes the ability of the cerebrospinal space to buffer changes in volume. Diminished compliance is associated with increased risk of potentially threatening increases in intracranial pressure (ICP) when changes in cerebrospinal volume occur. However, despite various methods of estimation proposed so far, compliance is seldom used in clinical practice. This study aimed to compare three measures of cerebrospinal compliance.MethodsICP recordings from 36 normal-pressure hydrocephalus patients who underwent infusion tests with parallel recording of transcranial Doppler blood flow velocity were retrospectively analysed. Three methods were used to calculate compliance estimates during changes in the mean ICP induced by infusion of fluid into the cerebrospinal fluid space: (a) based on Marmarou’s model of cerebrospinal fluid dynamics (CCSF), (b) based on the evaluation of changes in cerebral arterial blood volume (CCaBV), and (c) based on the amplitudes of peaks P1 and P2 of ICP pulse waveform (CP1/P2).ResultsIncrease in ICP caused a significant decrease in all compliance estimates (p < 0.0001). Time courses of compliance estimators were strongly positively correlated with each other (group-averaged Spearman correlation coefficients: 0.94 [0.88–0.97] for CCSF vs. CCaBV, 0.77 [0.63–0.91] for CCSF vs. CP1/P2, and 0.68 [0.48–0.91] for CCaBV vs. CP1/P2).ConclusionsIndirect methods, CCaBV and CP1/P2, allow for the assessment of relative changes in cerebrospinal compliance and produce results exhibiting good correlation with the direct method of volumetric manipulation. This opens the possibility of monitoring relative changes in compliance continuously.

High-resolution magnetic resonance imaging-based atlases for the young and adolescent domesticated pig (Sus scrofa)

BackgroundNeurodevelopmental studies utilize the pig as a translational animal model due to anatomical and morphological similarities between the pig and human brain. However, neuroimaging resources are not as well developed for the pig as they are for humans and other animal models. We established a magnetic resonance imaging-based brain atlas at two different ages for biomedical studies utilizing the pig as a preclinical model. New MethodTwenty artificially-reared domesticated male pigs (Sus scrofa) and thirteen sow-reared adolescent domesticated male pigs (Sus scrofa) underwent a series of scans measuring brain macrostructure, microstructure, and arterial cerebral blood volume. ResultsAn atlas for the 4-week-old and 12-week-old pig were created along with twenty-six regions of interest. Normative data for brain measures were obtained and detailed descriptions of the data processing pipelines were provided. Comparison with Existing MethodAtlases at the two different ages were created for the pig utilizing newer imaging technology and software. This facilitates the performance of longitudinal studies and enables more precise volume measurements in pigs of various ages by appropriately representing the neuroanatomical features of younger and older pigs and accommodating the proportion differences of the brain over time. ConclusionTwo high-resolution MRI brain atlases specific to the domesticated young and adolescent pig were created using defined image acquisition and data processing methods to facilitate the generation of high-quality normative data for neurodevelopmental research.

Usability of Noninvasive Counterparts of Traditional Autoregulation Indices in Traumatic Brain Injury.

The pressure reactivity index (PRx) and the pulse amplitude index (PAx) are invasively determined parameters that are commonly used to describe autoregulation following traumatic brain injury (TBI). Using a transcranial Doppler ultrasound (TCD) technique, it is possible to approximate cerebral arterial blood volume (CaBV) solely from cerebral blood flow velocities, and further, to calculate non-invasive markers of autoregulation. In this brief study, we aimed to investigate whether the estimation of relative CaBV with different models could describe the cerebrovascular reactivity of TBI patients. PRx, PAx and their non-invasive counterparts (nPRx and nPAx) were calculated retrospectively from data collected during the monitoring of TBI patients. CaBV, an essential parameter for the calculation of nPRx and nPAx, was determined with both a continuous flow forward (CFF) model-considering a non-pulsatile blood outflow from the brain-and a pulsatile flow forward (PFF) model, presuming a pulsatile outflow. We found that the estimated CaBV demonstrates good coherence with ICP and that nPRx and nPAx can describe cerebrovascular reactivity similarly to PRx and PAx. Continuous monitoring with TCD is difficult, so the usability of PRx and PAx is limited. However, they might become useful for clinicians in the near future owing to rapid advances in these technologies.

Mathematical Modelling in Hydrocephalus.

Various studies highlight the significance of alterations in cerebrospinal fluid (CSF) and cerebral blood flow (CBF) dynamics in the pathogenesis of hydrocephalus and suggest the role of mathematical modeling in studying these complex interactions. This narrative review discusses mathematical models of CSF and CBF dynamics, including Marmarou's compartmental model of CSF spaces and a model of cardiac changes in cerebral arterial blood volume. The diagnostic utility of CSF compensatory parameters is described along with current information on secondary model-based indices of cerebral hemodynamics in hydrocephalus. Compensatory parameters derived from the model of CSF circulation have long been used in the diagnosis and management of hydrocephalus patients. However, recent studies using mathematical models of cerebral circulation also show alterations in CBF dynamics, and model-based indices of cerebral hemodynamics, which can be calculated non-invasively using transracranial Doppler ultrasonography, can be used as a complementary source of information about the state of the cerebrospinal space.

Validation of non-invasive cerebrovascular pressure reactivity and pulse amplitude reactivity indices in traumatic brain injury

BackgroundTwo transcranial Doppler (TCD) estimators of cerebral arterial blood volume (CaBV) coexist: continuous outflow of arterial blood outside the cranium through a low-pulsatile venous system (continuous flow forward, CFF) and pulsatile outflow through regulating arterioles (pulsatile flow forward, PFF). We calculated non-invasive equivalents of the pressure reactivity index (PRx) and the pulse amplitude index PAx with slow waves of mean CaBV and its pulse amplitude.MethodsAbout 273 individual TBI patients were retrospectively reviewed. PRx is the correlation coefficient between 30 samples of 10-second averages of ICP and mean ABP. PAx is the correlation coefficient between 30 samples of 10-second averages of the amplitude of ICP (AMP, derived from Fourier analysis of the raw full waveform ICP tracing) and mean ABP. nPRx is calculated with CaBV instead of ICP and nPAx with the pulse amplitude of CaBV instead of AMP (calculated using both the CFF and PFF models). All reactivity indices were additionally compared with Glasgow Outcome Score (GOS) to verify potential outcome-predictive strength.ResultsWhen correlated, slow waves of ICP demonstrated good coherence between slow waves in CaBV (>0.75); slow waves of AMP showed good coherence with slow waves of the pulse amplitude of CaBV (>0.67) in both the CFF and PFF models. nPRx was moderately correlated with PRx (R = 0.42 for CFF and R = 0.38 for PFF; p < 0.0001). nPAx correlated with PAx with slightly better strength (R = 0.56 for CFF and R = 0.41 for PFF; p < 0.0001). nPAx_CFF showed the strongest association with outcomes.ConclusionsNon-invasive estimators (nPRx and nPAx) are associated with their invasive counterparts and can provide meaningful associations with outcome after TBI. The CFF model is slightly superior to the PFF model.

Estimation of pulsatile cerebral arterial blood volume based on transcranial doppler signals

ObjectiveMathematical modeling of cerebral hemodynamics by descriptive equations can estimate the underlying pulsatile component of cerebral arterial blood volume (CaBV). This way, clinical monitoring of changes in cerebral compartmental compliances becomes possible. Our aim is to validate the most adequate method of CaBV estimation in neurocritical care. ApproachWe retrospectively reviewed patients with severe traumatic brain injury (TBI) [admitted from 1992–2012] and continuous transcranial Doppler (TCD) monitoring of cerebral blood flow velocity (FV) displaying either plateau waves of intracranial pressure (ICP), episodes of controlled, mild hypocapnia, or vasopressor-induced increases in arterial blood pressure (ABP). Each cohort was analyzed with continuous flow forward (CFF, pulsatile blood inflow and steady blood outflow) or pulsatile flow forward (PFF, both blood inflow and outflow are pulsatile) modeling approaches for estimating the pulse component of CaBV. Spectral pulsatility index (sPI, the first harmonic of the FV pulse/mean FV) can be estimated using the compliance of the vascular bed (Ca) and the cerebrovascular resistance (CVR – here, Ra). We compared three possible methods of assessing Ca (C1: the CFF model, C2 and C3: the PFF models based on ABP or cerebral perfusion pressure (CPP) pulsations, respectively) and combined them with three possible methods of assessing Ra (Ra1= ABP/FV, Ra2= the resistance area product, and Ra3= CPP/FV). Linear regression techniques were applied to describe the strength of each CaBV estimator (a combination of Ca and Ra) against sPI. Main ResultsThe combination of C1 and Ra3 (PI_C1Ra3) was the superior descriptor of CaBV as approximated by sPI for both the plateau waves and the hypocapnia cohorts (r = 0.915 and r = 0.955, respectively). The combination of C1 and Ra1 (PI_C1Ra1) was nearly as robust in the vasopressors cohort (r = 0.938 and r = 0.931, respectively). SignificanceTCD-based estimation of CaBV pulsations seems to be feasible when employing the CFF modeling approach.

Coupling between cerebral blood flow and cerebral blood volume: Contributions of different vascular compartments.

A better understanding of the coupling between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is vital for furthering our understanding of the BOLD response. The aim of this study was to measure CBF‐CBV coupling in different vascular compartments during neural activation. Three haemodynamic parameters were measured during a visual stimulus. Look‐Locker flow‐sensitive alternating inversion recovery was used to measure changes in CBF and arterial CBV (CBVa) using sequence parameters optimized for each contrast. Changes in total CBV (CBVtot) were measured using a gadolinium‐based contrast agent technique. Haemodynamic changes were extracted from a region of interest based on voxels that were activated in the CBF experiments. The CBF‐CBVtot coupling constant α tot was measured as 0.16 ± 0.14 and the CBF‐CBVa coupling constant α a was measured as 0.65 ± 0.24. Using a two‐compartment model of the vasculature (arterial and venous), the change in venous CBV (CBVv) was predicted for an assumed value of baseline arterial and venous blood volume. These results will enhance the accuracy and reliability of applications that rely on models of the BOLD response, such as calibrated BOLD.

Cerebral arterial time constant calculated from the middle and posterior cerebral arteries in healthy subjects.

The cerebral arterial blood volume changes (∆CaBV) during a single cardiac cycle can be estimated using transcranial Doppler ultrasonography (TCD) by assuming pulsatile blood inflow, constant, and pulsatile flow forward from large cerebral arteries to resistive arterioles [continuous flow forward (CFF) and pulsatile flow forward (PFF)]. In this way, two alternative methods of cerebral arterial compliance (Ca) estimation are possible. Recently, we proposed a TCD-derived index, named the time constant of the cerebral arterial bed (τ), which is a product of Ca and cerebrovascular resistance and is independent of the diameter of the insonated vessel. In this study, we aim to examine whether the τ estimated by either the CFF or the PFF model differs when calculated from the middle cerebral artery (MCA) and the posterior cerebral artery (PCA). The arterial blood pressure and TCD cerebral blood flow velocity (CBFVa) in the MCA and in the PCA were non-invasively measured in 32 young, healthy volunteers (median age: 24, minimum age: 18, maximum age: 31). The τ was calculated using both the PFF and CFF models from the MCA and the PCA and compared using anon-parametric Wilcoxon signed-rank test. Results are presented as medians (25th-75th percentiles). The cerebrovascular time constant estimated in both arteries using the PFF model was shorter than when using the CFF model (ms): [64.83 (41.22-104.93) vs. 178.60 (160.40-216.70), p < 0.001 in the MCA, and 44.04 (17.15-81.17) vs. 183.50 (153.65-204.10), p < 0.001 in the PCA, respectively]. The τ obtained using the PFF model was significantly longer from the MCA than from the PCA, p = 0.004. No difference was found in the τ when calculated using the CFF model. Longer τ from the MCA might be related to the higher Ca of the MCA than that of the PCA. Our results demonstrate MCA-PCAdifferences in the τ, but only when the PFF model was applied.

Assessment of cerebral hemodynamic parameters using pulsatile versus non-pulsatile cerebral blood outflow models.

Prior methods evaluating the changes in cerebral arterial blood volume (∆CaBV) assumed that brain blood transport distal to big cerebral arteries can be approximated with a non-pulsatile flow (CFF) model. In this study, a modified ∆CaBV calculation that accounts for pulsatile blood flow forward (PFF) from large cerebral arteries to resistive arterioles was investigated. The aim was to assess cerebral hemodynamic indices estimated by both CFF and PFF models while changing arterial blood carbon dioxide concentration (EtCO2) in healthy volunteers. Continuous recordings of non-invasive arterial blood pressure (ABP), transcranial Doppler blood flow velocity (CBFVa), and EtCO2 were performed in 53 young volunteers at baseline and during both hypo- and hypercapnia. The time constant of the cerebral arterial bed (τ) and critical closing pressure (CrCP) were estimated using mathematical transformations of the pulse waveforms of ABP and CBFVa, and with both pulsatile and non-pulsatile models of ∆CaBV estimation. Results are presented as median values ± interquartile range. Both CrCP and τ gave significantly lower values with the PFF model when compared with the CFF model (p ≪ 0.001 for both). In comparison to normocapnia, both CrCP and τ determined with the PFF model increased during hypocapnia [CrCPPFF (mmHg): 5.52 ± 8.78 vs. 14.36 ± 14.47, p = 0.00006; τPFF (ms): 47.4 ± 53.9 vs. 72.8 ± 45.7, p = 0.002] and decreased during hypercapnia [CrCPPFF (mmHg): 5.52 ± 8.78 vs. 2.36 ± 7.05, p = 0.0001; τPFF (ms): 47.4 ± 53.9 vs. 29.0 ± 31.3, p = 0.0003]. When the CFF model was applied, no changes were found for CrCP during hypercapnia or in τ during hypocapnia. Our results suggest that the pulsatile flow forward model better reflects changes in CrCP and in τ induced by controlled alterations in EtCO2.