Cerebral Perfusion Maps Research Articles

Cerebral perfusion software: comparative evaluation

IntroductionPerfusion CT (CTP) is crucial in defining the best treatment strategy for patients with acute ischemic stroke. Several software is available for assessing cerebral perfusion maps, which may show some variability in results. We aim to investigate the agreement between CT perfusion values in acute ischemic stroke of 2 different software (Syngo.via and Icobrain) in estimating ischemic core, ischemic penumbra, and mismatch ratio.Methods17 patients (10 women, mean age = 79.5 years) with acute stroke with large vessel occlusion (LVO) were enrolled in our study between August 2022 and March 2023. All patients underwent a CTP scan to determine the best treatment approach: endovascular treatment or systemic fibrinolysis according to DAWN/DEFUSE-3 criteria. All CTP examinations were analyzed using 2 different dedicated software (Syngo.via, Icobrain) and the perfusion values obtained (core, penumbra, mismatch ratio) were compared with each other. A basal CT scan 24 h after treatment was acquired to assess the final infarct volume (FIV) and possible hemorrhagic infarction. Then we compared the true FIV, manually assessed, with the predicted FIV calculated by the two software.ResultsThe values obtained showed that the mean core volumes calculated by Syngo.via and Icobrain did not exhibit any statistically significant differences with a p-value of 0.09. There is no statistically significant difference between the mean penumbra volumes calculated by the two software (p-value = 0.29). There is no statistically significant difference between the mean values of core and penumbra calculated by both software. Furthermore, both Icobrain and Syngo.via gave the same therapeutic indication. Correlation analysis indicated a slightly stronger correlation between the core volume calculated by Icobrain and the FIV (r = 0.98 vs r = 0.94). Both correlations were statistically significant (p = < 0.001).ConclusionThe evaluation of perfusion indices by automated systems may present a certain degree of variability between different software, although they agree on the final therapeutic stratification.

A dynamic simulation framework for CT perfusion in stroke assessment built from first principles.

Physicians utilize cerebral perfusion maps (e.g., cerebral blood flow, cerebral blood volume, transit time) to prescribe the plan of care for stroke patients. Variability in scanning techniques and post-processing software can result in differences between these perfusion maps. To determine which techniques are acceptable for clinical care, it is important to validate the accuracy and reproducibility of the perfusion maps. Validation using clinical data is challenging due to the lack of a gold standard to assess cerebral perfusion and the impracticality of scanning patients multiple times with different scanning techniques. In contrast, simulated data from a realistic digital phantom of the cerebral perfusion in acute stroke patients would enable studies to optimize and validate the scanning and post-processing techniques. We describe a complete framework to simulate CT perfusion studies for stroke assessment. We begin by expanding the XCAT brain phantom to enable spatially varying contrast agent dynamics and incorporate a realistic model of the dynamics in the cerebral vasculature derived from first principles. A dynamic CT simulator utilizes the time-concentration curves to define the contrast agent concentration in the object at each time point and generates CT perfusion images compatible with commercially available post-processing software. We also generate ground truth perfusion maps to which the maps generated by post-processing software can be compared. We demonstrate a dynamic CT perfusion study of a simulated patient with an ischemic stroke and the resulting perfusion maps generated by post-processing software. We include a visual comparison between the computer-generated perfusion maps and the ground truth perfusion maps. The framework is highly tunable; users can modify the perfusion properties (e.g., occlusion location, CBF, CBV, and MTT), scanner specifications (e.g., focal spot size and detector configuration), scanning protocol (e.g., kVp and mAs), and reconstruction parameters (e.g., slice thickness and reconstruction filter). This framework provides realistic test data with the underlying ground truth that enables a robust assessment of CT perfusion techniques and post-processing methods for stroke assessment.

On the ability to exploit signal fluctuations in pseudocontinuous arterial spin labeling for inferring the major flow territories from a traditional perfusion scan

In arterial spin labeling (ASL) a magnetic label is applied to the flowing blood in feeding arteries allowing depiction of cerebral perfusion maps. The labeling efficiency depends, however, on blood velocity and local field inhomogeneities and is, therefore, not constant over time. In this work, we investigate the ability of statistical methods used in functional connectivity research to infer flow territory information from traditional pseudo-continuous ASL (pCASL) scans by exploiting artery-specific signal fluctuations. By applying an additional gradient during labeling the minimum amount of signal fluctuation that allows discrimination of the main flow territories is determined. The following three approaches were tested for their performance on inferring the large vessel flow territories of the brain: a general linear model (GLM), an independent component analysis (ICA) and t-stochastic neighbor embedding. Furthermore, to investigate the effect of large vessel pathology, standard ASL scans of three patients with a unilateral stenosis (>70%) of one of the internal carotid arteries were retrospectively analyzed using ICA and t-SNE. Our results suggest that the amount of natural-occurring variation in labeling efficiency is insufficient to determine large vessel flow territories. When applying additional vessel-encoded gradients these methods are able to distinguish flow territories from one another, but this would result in approximately 8.5% lower perfusion signal and thus also a reduction in SNR of the same magnitude.

Brain areas with normatively greater cerebral perfusion in early life may be more susceptible to beta amyloid deposition in late life.

Background:The amyloid cascade hypothesis characterizes the stereotyped progression of pathological changes in Alzheimer’s disease (AD) beginning with beta amyloid deposition, but does not address the reasons for amyloid deposition. Brain areas with relatively higher neuronal activity, metabolic demand, and production of reactive oxygen species in earlier life may have higher beta amyloid deposition in later life. The aim of this study was to investigate early life patterns of perfusion and late life patterns of amyloid deposition to determine the extent to which normative cerebral perfusion predisposes specific regions to future beta amyloid deposition.Materials and Methods:One hundred twenty-eight healthy, older human subjects (age: 56–87 years old; 44% women) underwent positron emission tomography (PET) imaging with [11C]PiB for measures of amyloid burden. Cerebral perfusion maps derived from 47 healthy younger adults (age: 22–49; 47%) who had undergone single photon emission computed tomography (SPECT) imaging, were averaged to create a normative template, representative of young, healthy adults. Perfusion and amyloid measures were investigated in 31 cortical regions from the Hammers atlas. We examined the spatial relationship between normative perfusion patterns and amyloid pathophysiology.Results:The pattern of increasing perfusion (temporal lobe < parietal lobe < frontal lobe < insula/cingulate gyrus < occipital lobe; F(4,26) = 7.8, p = 0.0003) in young, healthy adults was not exactly identical to but approximated the pattern of increasing amyloid burden (temporal lobe < occipital lobe < frontal lobe < parietal lobe < insula/cingulate gyrus; F(4,26) = 5.0, p = 0.004) in older adults. However, investigating subregions within cortical lobes provided consistent agreement between ranked normative perfusion patterns and expected Thal staging of amyloid progression in AD (Spearman r = 0.39, p = 0.03).Conclusion:Our findings suggest that brain areas with normatively greater perfusion may be more susceptible to amyloid deposition in later life, possibly due to higher metabolic demand, and associated levels of oxidative stress and inflammation.

Multi-modal MRI Reveals the Neurovascular Coupling Dysfunction in Chronic Migraine

Previous studies reported that long-term nociceptive stimulation could result in neurovascular coupling (NVC) dysfunction in brain, but these studies were based mainly on unimodal imaging biomarkers, thus could not comprehensively reflect NVC dysfunction. We investigated the potential NVC dysfunction in chronic migraine by exploring the relationship between neuronal activity and cerebral perfusion maps. The Pearson correlation coefficients between these 2 maps were defined as the NVC biomarkers. NVC biomarkers in migraineurs were significantly lower in left inferior parietal gyrus (IPG), left superior marginal gyrus (SMG) and left angular gyrus (AG), but significantly higher in right superior occipital gyrus (SOG), right superior parietal gyrus (SPG), and precuneus. These brain regions were located mainly in parietal or occipital lobes and were related to visual or sensory information processing. ALFF-CBF in right SPG was positively correlated with disease history and that in right precuneus was negatively correlated with migraine persisting time. fALFF-CBF in left SMG and AG were negatively related to headache frequency and positively related to health condition and disease history. In conclusion, multi-modal MRI could be used to detect NVC dysfunction in chronic migraine patients, which is a new method to assess the impact of chronic pain on the brain.

Cerebral perfusion mapping during retrieval of spatial memory in rats

Studies of brain functional activation during spatial navigation using electrophysiology and immediate-early gene responses have typically targeted a limited number of brain regions. Our study provides the first whole brain analysis of cerebral activation during retrieval of spatial memory in the freely-moving rat. Rats (LEARNERS) were trained in the Barnes maze, an allocentric spatial navigation task, while CONTROLS received passive exposure. After 19 days, functional brain mapping was performed during recall by bolus intravenous injection of [14C]-iodoantipyrine using a novel subcutaneous minipump triggered by remote activation. Regional cerebral blood flow (rCBF)-related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of the three-dimensionally reconstructed brains. Functional connectivity was examined between regions of the spatial navigation circuit through interregional correlation analysis.Significant rCBF increases were noted in LEARNERS compared to CONTROLS broadly across the spatial navigation circuit, including the hippocampus (anterior dorsal CA1, posterior ventral CA1-3), subiculum, thalamus, striatum, medial septum, cerebral cortex, with decreases noted in the mammillary nucleus, amygdala and insula. LEARNERS showed a significantly greater positive correlation of rCBF of the ventral hippocampus with retrosplenial, lateral orbital, parietal and primary visual cortex, and a significantly more negative correlation with the mammillary nucleus, amygdala, posterior entorhinal cortex, and anterior thalamic nucleus. The complex sensory component of the spatial navigation task was underscored by broad activation across visual, somatosensory, olfactory, auditory and vestibular circuits which was enhanced in LEARNERS. Brain mapping facilitated by an implantable minipump represents a powerful tool for evaluation of mammalian behaviors dependent on locomotion.

Evidence of functional brain reorganization on the basis of blood flow changes in the CAG140 knock-in mouse model of Huntington's disease.

Neuroimaging, especially functional brain mapping, may provide insights into the distributed involvement of multiple brain regions and loops in disorders classically associated with pathology of a localized region. One example is Huntington's disease (HD), typically classified as a basal ganglia disorder. Here, we report genotypic differences in cerebral perfusion mapping in an HD mouse model characterized by a gene knock-in (KI) of a human exon 1 CAG140 expansion repeat (CAG140 KI mice). Animals were examined at 6 months and compared with wild-type littermates. Regional cerebral blood flow (rCBF) was mapped in the awake, nonrestrained, male mouse at rest using [C]-iodoantipyrine autoradiography and analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. Our results showed significant changes in rCBF between CAG140 KI and WT mice, such that CAG140 KI animals showed hypoperfusion of the basal ganglia motor circuit and hyperperfusion of cerebellar-thalamic and somatosensory regions. Significant hypoperfusion was also noted in CAG140 KI mice in the prelimbic and cingulate cortex (medial prefrontal area) and the hippocampus - areas associated with cognitive processing and mood. Changes in rCBF were apparent in the absence of motor deficits (rotarod test) or atrophy in the striatum (caudate-putamen) or hemispheric volume. Our results suggest a functional reorganization of whole-brain networks at a presymptomatic stage in the life of the CAG140 KI mouse. Functional brain mapping in animals may, in the future, serve as a translational biomarker for identifying sites of early synaptic change in the HD brain and for directing targeted preclinical molecular studies and clinical therapies.

Sinogram restoration for low-dose cerebral perfusion CT images

In clinical cerebral perfusion CT examination, repeated scanning the region of interest in the cine mode increases the radiation dose of the patients, while decreasing the radiation dose by lowering the scanning current results in poor image quality and affects the clinical diagnosis. We propose a penalized weighted least-square (PWLS) method for recovering the projection data to improve the quality of low-dose cerebral perfusion CT imaged. This method incorporates the statistical distribution characteristics of brain perfusion CT projection data and uses the statistical properties of the projection data for modeling. The PWLS method was used to recover the data, and the Gauss-Seidel (GS) method was employed for iterative solving. Adaptive weighting is introduced between the original projection data and the projection data after PWLS restoration. The experimental results on the clinical data demonstrated that the PWLS-based sinogram restoration method improved noise reduction and artifact suppression as compared with the conventional noise reduction methods, and better retained the edges and details to generate better cerebral perfusion maps.

Remote Brain Network Changes after Unilateral Cortical Impact Injury and Their Modulation by Acetylcholinesterase Inhibition

We explored whether cerebral cortical impact injury (CCI) effects extend beyond direct lesion sites to affect remote brain networks, and whether acetylcholinesterase (AChE) inhibition elicits discrete changes in functional activation of motor circuits following CCI. Adult male rats underwent unilateral motor-sensory CCI or sham injury. Physostigmine (AChE inhibitor) or saline were administered subcutaneously continuously via implanted minipumps (1.6 micromoles/kg/day) for 3 weeks, followed by cerebral perfusion mapping during treadmill walking using [(14)C]-iodoantipyrine. Quantitative autoradiographs were analyzed by statistical parametric mapping and functional connectivity (FC) analysis. CCI resulted in functional deficits in the ipsilesional basal ganglia, with increased activation contralesionally. Recruitment was also observed, especially contralesionally, of the red nucleus, superior colliculus, pedunculopontine tegmental nucleus, thalamus (ventrolateral n., central medial n.), cerebellum, and sensory cortex. FC decreased significantly within ipsi- and contralesional motor circuits and between hemispheres, but increased between midline cerebellum and select regions of the basal ganglia within each hemisphere. Physostigmine significantly increased functional brain activation in the cerebellar thalamocortical pathway (midline cerebellum→ventrolateral thalamus→motor cortex), subthalamic nucleus/zona incerta, and red nucleus and bilateral sensory cortex. In conclusion, CCI resulted in increased functional recruitment of contralesional motor cortex and bilateral subcortical motor regions, as well as recruitment of the cerebellar-thalamocortical circuit and contralesional sensory cortex. This phenomenon, augmented by physostigmine, may partially compensate motor deficits. FC decreased inter-hemispherically and in negative, but not positive, intra-hemispherical FC, and it was not affected by physostigmine. Circuit-based approaches into functional brain reorganization may inform future behavioral or molecular strategies to augment targeted neurorehabilitation.

Feasibility study of exploring a T1‐weighted dynamic contrast‐enhanced MR approach for brain perfusion imaging

To investigate the feasibility of T(1) -weighted dynamic contrast-enhanced (DCE) MRI for the measurement of brain perfusion. Dynamic imaging was performed on a 3.0 Tesla (T) MR scanner by using a rapid spoiled-GRE protocol. T(1) measurement with driven equilibrium single pulse observation of T(1) (DESPOT1) was used to convert the MR signal to tracer concentration. Cerebral perfusion maps were obtained by using an improved gamma-variate model in 10 subjects and compared with those with arterial spin label (ASL) approach. The cerebral blood volume (CBV) values were calculated as 4.74 ± 1.09 and 2.29 ± 0.58 mL/100 g in gray matter (GM) and whiter matter (WM), respectively. Mean transit time (MTT) values were 6.15 ± 0.59 s in GM and 6.96 ± 0.79 s in WM. The DCE values for GM/WM cerebral blood flow (CBF) were measured as 53.41 ± 9.23 / 25.78 ± 8.91 mL/100 g/min, versus ASL values of 49.05 ± 10.81 / 23.00 ± 5.89 mL/100 g/min for GW/WM. Bland-Altman plot revealed a small difference of CBF between two approaches (mean bias = 3.83 mL/100 g/min, SD = 11.29). There were 6 pairs of samples (5%, 6/120) beyond the 95% limits of agreement. The correlation plots showed that the slop of Y (CBF_(_DCE)) versus X intercept (CBF_(_ASL)) is 0.95 with the intercept of 4.53 mL/100 g/min (r = 0.74; P < 0.05). It is feasible to evaluate the cerebral perfusion by using T(1)-weighted DCE-MRI with the improved kinetic model.

High‐sensitivity cerebral perfusion mapping in mice by kbGRASE‐FAIR at 9.4 T

The combination of flow-sensitive alternating inversion recovery (FAIR) and single-shot k-space-banded gradient- and spin-echo (kbGRASE) is proposed here to measure perfusion in the mouse brain with high sensitivity and stability. Signal-to-noise ratio (SNR) analysis showed that kbGRASE-FAIR boosts image and temporal SNRs by 2.01 ± 0.08 and 2.50 ± 0.07 times, respectively, when compared with standard single-shot echo planar imaging (EPI)-FAIR implemented in our experimental systems, although the practically achievable spatial resolution was slightly reduced. The effects of varying physiological parameters on the precision and reproducibility of cerebral blood flow (CBF) measurements were studied following changes in anesthesia regime, capnia and body temperature. The functional MRI time courses with kbGRASE-FAIR showed a more stable response to 5% CO(2) than did those with EPI-FAIR. The results establish kbGRASE-FAIR as a practical and robust protocol for quantitative CBF measurements in mice at 9.4 T.

Dynamic contrast‐enhanced quantitative perfusion measurement of the brain using T1‐weighted MRI at 3T

To develop a method for the measurement of brain perfusion based on dynamic contrast-enhanced T(1)-weighted MR imaging. Dynamic imaging of the first pass of a bolus of a paramagnetic contrast agent was performed using a 3T whole-body magnet and a T(1)-weighted fast field echo sequence. The input function was obtained from the internal carotid artery. An initial T(1) measurement was performed in order to convert the MR signal to concentration of the contrast agent. Pixelwise and region of interest (ROI)-based calculation of cerebral perfusion (CBF) was performed using Tikhonov's procedure of deconvolution. Seven patients with acute optic neuritis and two patients with acute stroke were investigated. The mean perfusion value for ROIs in gray matter was 62 mL/100g/min and 21 mL/100g/min in white matter in patients with acute optic neuritis. The perfusion inside the infarct core was 9 mL/100g/min in one of the stroke patients. The other stroke patient had postischemic hyperperfusion and CBF was 140 mL/100g/min. Absolute values of brain perfusion can be obtained using dynamic contrast-enhanced MRI. These values correspond to expected values from established PET methods. Furthermore, at 3T pixelwise calculation can be performed, allowing construction of CBF maps.

Perfusion CT and catheter delivered thrombolytics in management of acute stroke

Stroke is an abrupt onset injury due to a vascular insult resulting in damage to brain by ischemia or hemorrhage. In recent times, perfusion computed tomography (CT) and catheter based delivery of thrombolytics have redefined the management of acute cerebral ischaemia [1]. Perfusion CT is multislice CT based imaging tool utilised for qualifying and quantifying early ischaemic brain changes by generating cerebral perfusion maps. Advances in endovascular therapy have allowed access to intracranial vasculature and intra arterial thrombolysis.

Cerebral perfusion mapping using a robust and efficient method for deconvolution analysis of dynamic contrast-enhanced images

Dynamic contrast-enhanced (DCE) imaging using MRI or CT is emerging as a promising tool for diagnostic imaging of cerebral disorders and the monitoring of tumor response to treatment. In this study, we present a robust and efficient deconvolution method based on a linearized model of the impulse residue function, which allows for the mapping of functional cerebral parameters such as cerebral blood flow, volume, mean transit time, and permeability. Monte Carlo simulation studies were performed to study the accuracy and stability of the proposed method, before applying it to clinical study cases of patients with cerebral tumors imaged using DCE CT. Functional parameter maps generated using the proposed method revealed the locations of the cerebral tumors and were found to be of sufficiently good clarity for marked regional differences in tissue vascularity and permeability to be assessed. In particular, tumor visualization and delineation were found to be better on the parameter maps that were indicative of the breakdown of the blood–brain barrier.

An evaluation of the time dependence of the anisotropy of the water diffusion tensor in acute human ischemia

We have performed MRI examinations to determine the water diffusion tensor in the brain of six patients who were admitted to the hospital within 12 h after the onset of cerebral ischemic symptoms. The examinations have been carried out immediately after admission, and thereafter at varying intervals up to 90 days post admission. Maps of the trace of the diffusion tensor, the fractional anisotropy and the lattice index, as well as maps of cerebral blood perfusion parameters, were generated to quantitatively assess the character of the water diffusion tensor in the infarcted area. In patients with significant perfusion deficits and substantial lesion volume changes, four of six cases, our measurements show a monotonic and significant decrease in the diffusion anisotropy within the ischemic lesion as a function of time. We propose that retrospective analysis of this quantity, in combination with brain tissue segmentation and cerebral perfusion maps, may be used in future studies to assess the severity of the ischemic event.

Cerebral Perfusion Mapping with Ultrasound Contrast

Cerebral Perfusion Mapping with Ultrasound Contrast