Hemodynamic Failure Staging With Blood Oxygenation Level-Dependent Cerebrovascular Reactivity and Acetazolamide-Challenged (15O-)H2O-Positron Emission Tomography Across Individual Cerebrovascular Territories.

BACKGROUND: Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF. METHODS AND RESULTS: Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge (15O-)H2O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative (15O-)H2O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2. CONCLUSIONS: Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease.

Determining the effects of elevated partial pressure of oxygen on hypercapnia-induced cerebrovascular reactivity.

Evaluation of cerebrovascular reactivity (CVR) to hypo- and hypercapnia is a valuable test for the assessment of vasodilatory reserve. While hypercapnia-induced CVR testing is usually performed at normoxia, mild hyperoxia may increase tolerability of hypercapnia by reducing the ventilatory distress. However, the effects of mild hyperoxia on CVR was unknown. We therefore recruited 21 patients with a range of steno-occlusive diseases and 12 healthy participants who underwent a standardized 13-minute step plus ramp CVR test with a carbon dioxide gas challenge at the subject's resting end-tidal partial pressure of oxygen or at mild hyperoxia (PetO2 = 150 mmHg) depending on to which group they were assigned. In 11 patients, the second CVR test was at normoxia to examine test-retest differences. CVR was defined as % Δ Signal/ΔPetCO2. We found that there was no significant difference between CVR test results conducted at normoxia and at mild hyperoxia for participants in Groups 1 and 2 for the step and ramp portion. We also found no difference between test and retest CVR at normoxia for patients with cerebrovascular pathology (Group 3) for step and ramp portion. We concluded normoxic CVR is repeatable, and that mild hyperoxia does not affect CVR.

Voxel-based morphometry and a deep learning model for the diagnosis of early Alzheimer's disease based on cerebral gray matter changes.

This study aimed to analyse cerebral grey matter changes in mild cognitive impairment (MCI) using voxel-based morphometry and to diagnose early Alzheimer's disease using deep learning methods based on convolutional neural networks (CNNs) evaluating these changes. Participants (111 MCI, 73 normal cognition) underwent 3-T structural magnetic resonance imaging. The obtained images were assessed using voxel-based morphometry, including extraction of cerebral grey matter, analyses of statistical differences, and correlation analyses between cerebral grey matter and clinical cognitive scores in MCI. The CNN-based deep learning method was used to extract features of cerebral grey matter images. Compared to subjects with normal cognition, participants with MCI had grey matter atrophy mainly in the entorhinal cortex, frontal cortex, and bilateral frontotemporal lobes (p < 0.0001). This atrophy was significantly correlated with the decline in cognitive scores (p < 0.01). The accuracy, sensitivity, and specificity of the CNN model for identifying participants with MCI were 80.9%, 88.9%, and 75%, respectively. The area under the curve of the model was 0.891. These findings demonstrate that research based on brain morphology can provide an effective way for the clinical, non-invasive, objective evaluation and identification of early Alzheimer's disease.

Glymphatic System Visualized by Chemical-Exchange-Saturation-Transfer Magnetic Resonance Imaging.

Dysfunction of the glymphatic system may play a significant role in the development of neurodegenerative diseases. However, in vivo imaging of the glymphatic system is challenging. In this study, we describe an unconventional MRI method for imaging the glymphatic system based on chemical exchange saturation transfer, which we tested in an in vivo porcine model of impaired glymphatic function. The blood, lymph, and cerebrospinal fluid (CSF) from one pig were used for testing the MRI effect in vitro at 7 Tesla (T). Unilateral deep cervical lymph node ligation models were then performed in 20 adult male Sprague-Dawley rats. The brains were scanned in vivo dynamically after surgery using the new MRI method. Behavioral tests were performed after each scanning session and the results were tested for correlations with the MRI signal intensity. Finally, the pathological assessment was conducted in the same brain slices. The special MRI effect in the lymph was evident at about 1.0 ppm in water and was distinguishable from those of blood and CSF. In the model group, the intensity of this MRI signal was significantly higher in the ipsilateral than in the contralateral hippocampus. The correlation between the signal abnormality and the behavioral score was significant (Pearson's, R2 = 0.9154, p < 0.005). We conclude that the novel MRI method can visualize the glymphatic system in vivo.

Is Rest Really Rest? Resting-State Functional Connectivity During Rest and Motor Task Paradigms.

Numerous studies have identified several large-scale networks within the brain of healthy individuals, some of which have been attributed to ongoing mental activity during the wakeful resting state. While engaged during specific resting-state functional magnetic resonance imaging (fMRI) paradigms, it remains unclear as to whether traditional block-design simple movement fMRI experiments significantly influence these mode networks or other areas. Using blood-oxygen level-dependent fMRI, we characterized the pattern of functional connectivity in healthy subjects during a resting-state paradigm and compared this with the same resting-state analysis performed on motor task data residual time courses after regressing out the task paradigm. Using seed-voxel analysis to define the default mode network, the executive control network (ECN), and sensorimotor, auditory, and visual networks, the resting-state analysis of the residual time courses demonstrated reduced functional connectivity in the motor network and reduced connectivity between the insula and the ECN compared with the standard resting-state data sets. Overall, performance of simple self-directed motor tasks does little to change the resting-state functional connectivity across the brain, especially in nonmotor areas. This would suggest that previously acquired fMRI studies incorporating simple block-design motor tasks could be mined retrospectively for assessment of the resting-state connectivity.

Reduced contralateral cerebrovascular reserve in patients with unilateral steno-occlusive disease.

UNLABELLED: The purpose of this study was to evaluate cerebrovascular reactivity (CVR) of major arterial vascular territories, particularly in the contralateral hemodynamically unaffected hemisphere, in patients with unilateral internal carotid artery (ICA) steno-occlusive disease compared to control subjects with risk factors for cerebrovascular disease. METHODS: In this retrospective observational study, twenty-seven patients with right-sided unilateral ICA steno-occlusive disease (age range, 25 to 91 years; 17 males) and twenty-one patients with left-sided unilateral ICA steno-occlusive disease (age range, 24 to 83 years; 14 males) and 41 control subjects were studied. CVR was quantitated as the change in blood oxygen level dependent (BOLD) MRI signal (as a surrogate of cerebral blood flow), in response to a consistently applied step change in the arterial partial pressure of carbon dioxide (PaCO2). The CVR of each major arterial vascular territory was assessed in the ipsilateral hemodynamically affected hemisphere and compared to the corresponding territory in the contralateral hemisphere. RESULTS: In patients, a significant reduction in CVR was observed in the ipsilateral anterior circulation compared to that of the corresponding territory on the contralateral side (0.027 ± 0.083 vs. 0.109 ± 0.066% BOLD change/​mm Hg, p < 0.0001) and to controls (0.195 ± 0.054% BOLD change/mm Hg, p < 0.0001). The CVR of the contralateral anterior circulation was reduced on average by 50% compared to controls (p < 0.0001). CONCLUSIONS: The implication of these findings is that unilateral carotid stenosis affects the vascular reserve of both sides of the brain compared to control subjects. This indicates that the collateral blood flow support from the contralateral to the ipsilateral hemisphere comes at a cost of reduced reserve capacity in the contralateral hemisphere. The findings suggest that there may be a reduction in functional hyperemia associated with neuronal activation, not only affecting the hemisphere ipsilateral to an occlusion, but also the hemisphere contralateral to an occlusion. It remains to be determined if 'stealing' from the 'rich' to support the 'poor' has clinical consequences over the long term.

Vascular steal explains early paradoxical blood oxygen level-dependent cerebrovascular response in brain regions with delayed arterial transit times.

INTRODUCTION: Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) during manipulation of inhaled carbon dioxide (CO2) can be used to measure cerebrovascular reactivity (CVR) and map regions of exhausted cerebrovascular reserve. These regions exhibit a reduced or negative BOLD response to inhaled CO2. In this study, we sought to clarify the mechanism behind the negative BOLD response by investigating its time delay (TD). Dynamic susceptibility contrast (DSC) MRI with the injection of a contrast agent was used as the gold standard in order to provide measurement of the blood arrival time to which CVR TD could be compared. We hypothesize that if negative BOLD responses are the result of a steal phenomenon, they should be synchronized with positive BOLD responses from healthy brain tissue, even though the blood arrival time would be delayed. METHODS: On a 3-tesla MRI system, BOLD CVR and DSC images were collected in a group of 19 patients with steno-occlusive cerebrovascular disease. For each patient, we generated a CVR magnitude map by regressing the BOLD signal with the end-tidal partial pressure of CO2 (PETCO2), and a CVR TD map by extracting the time of maximum cross-correlation between the BOLD signal and PETCO2. In addition, a blood arrival time map was generated by fitting the DSC signal with a gamma variate function. ROI masks corresponding to varying degrees of reactivity were constructed. Within these masks, the mean CVR magnitude, CVR TD and DSC blood arrival time were extracted and averaged over the 19 patients. CVR magnitude and CVR TD were then plotted against DSC blood arrival time. RESULTS: The results show that CVR magnitude is highly correlated to DSC blood arrival time. As expected, the most compromised tissues with the longest blood arrival time have the lowest (most negative) CVR magnitude. However, CVR TD shows a noncontinuous relationship with DSC blood arrival time. CVR TD is well correlated to DSC blood arrival time (p < 0.0001) for tissue of positive reactivity, but fails to maintain this trend for tissue of negative reactivity. Regions with negative reactivity have similar CVR TD than healthy regions. CONCLUSION: These results support the hypothesis that negative reactivity is the result of a steal phenomenon, lowering the BOLD signal as soon as healthier parts of the brain start to react and augment their blood flow. BOLD CVR MRI is capable of identifying this steal distribution, which has particular diagnostic significance as it represents an actual reduction in flow to already compromised tissue.

Steal physiology is spatially associated with cortical thinning.

BACKGROUND: The physiological impact of severely impaired cerebral autoregulatory vascular reactivity on cortical integrity is unknown. The purpose of this study is to determine the relationship between severe impairment of autoregulatory flow control associated with steal phenomenon and its impact on cortical thickness. METHODS: 250 blood oxygen level dependent (BOLD) MRI cerebrovascular reactivity (CVR) studies were reviewed in order to identify subjects with severe unilateral exhausted cerebrovascular reserve demonstrating steal physiology but with normal appearing cortex on fluid attenuated inversion recovery imaging. 17 patients meeting the inclusion criteria were identified. A reconstructed inflated cortical surface map was created for every subject using Freesurfer software (http://surfer.nmr.mgh.harvard.edu/). The region of interest (ROI) reflecting the steal physiology was determined by overlaying the subject's CVR map on to the cortical surface map. This ROI was compared with the corresponding area in the healthy hemisphere which provided control cortical thickness measurement in each subject. RESULTS: The hemisphere with steal physiology showed an 8% thinner cortex (2.23+/-0.28 mm) than the corresponding healthy hemisphere (2.42+/-0.23 mm) (p=0.0005). CONCLUSIONS: Our findings indicate that a spatial correspondence exists between impairment of autoregulatory capacity with steal physiology and cortical thinning.

Absence of localized grey matter volume changes in the motor cortex following spinal cord injury.

The consequences of spinal cord injury (SCI) have considerable effects on motor function, typically resulting in functional impairment. Pathological changes have been studied at the site of trauma, rostrocaudally within the cord, and in the periphery. Few studies, however, have investigated the consequences of SCI at the cortical level. Magnetic resonance imaging (MRI) was used to explore the morphological changes in the grey and white matter within the primary motor (M1) cortex of individuals with cervical SCI. The "precentral knob," a landmark of M1 cortex dedicated to hand function, was selected for regionally specific measurements of change. Thirty-one hemispheres of SCI subjects and 28 hemispheres of control subjects were compared using a manual measurement after the images were segmented into grey matter, white matter, and cerebral spinal fluid (CSF). No significant differences in grey matter area measured at the precentral knob were found with the manual approach. An automated voxel-based morphometric analysis was also performed and demonstrated no significant differences in grey or white matter volume within an M1 region of interest. These data suggest that there is no gross anatomical change within M1 following cervical SCI. Our previously reported findings of reorganization of cortical motor output maps following SCI therefore likely result from changes in functional organization rather than anatomical changes.