MRI-based parameter inference for cerebral perfusion modelling in health and ischaemic stroke.

Cerebral perfusion modelling is a promising tool to predict the impact of acute ischaemic stroke treatments on the spatial distribution of cerebral blood flow (CBF) in the human brain. To estimate treatment efficacy based on CBF, perfusion simulations need to become suitable for group-level investigations and thus account for physiological variability between individuals. However, computational perfusion modelling to date has been restricted to a few patient-specific cases. This study set out to establish automated parameter inference for perfusion modelling based on neuroimaging data and thus enable CBF simulations of groups. Magnetic resonance imaging (MRI) data from 75 healthy senior adults were utilised. Brain geometries were computed from healthy reference subjects' T1-weighted MRI. Haemodynamic model parameters were determined from spatial CBF maps measured by arterial spin labelling (ASL) perfusion MRI. Thereafter, perfusion simulations were conducted in 75 healthy cases followed by 150 acute ischaemic stroke cases representing an occlusion and CBF cessation in the left and right middle cerebral arteries. The anatomical fitness of the brain geometries was evaluated by comparing the simulated grey (GM) and white matter (WM) volumes to measurements in healthy reference subjects. Strong positive correlations were found in both tissue types (GM: Pearson's r 0.74, P<0.001; WM: Pearson's r 0.84, P<0.001). Haemodynamic parameter tuning was verified by comparing the total volumetric blood flow rate to the brain in healthy reference subjects and simulations (Pearson's r 0.89, P<0.001). In acute ischaemic stroke cases, the simulated infarct volume using a perfusion-based estimate was 197±25 ml. Computational predictions were in agreement with anatomical and haemodynamic values from the literature concerning T1-weighted, T2-weighted, and phase-contrast MRI measurements in healthy scenarios and acute ischaemic stroke cases. The acute stroke simulations did not capture small infarcts (left tail of the distribution), which could be explained by neglected compensatory mechanisms, e.g. collaterals. The proposed parameter inference method provides a foundation for group-level CBF simulations and for in silico clinical stroke trials which could assist in medical device and drug development.

Arterial Spin-Labeling Parameters and Their Associations with Risk Factors, Cerebral Small-Vessel Disease, and Etiologic Subtypes of Cognitive Impairment and Dementia.

BACKGROUND AND PURPOSE: Cerebral small-vessel disease may alter cerebral blood flow (CBF) leading to brain changes and, hence, cognitive impairment and dementia. CBF and the spatial coefficient of variation can be measured quantitatively by arterial spin-labeling. We aimed to investigate the associations of demographics, vascular risk factors, location, and severity of cerebral small-vessel disease as well as the etiologic subtypes of cognitive impairment and dementia with CBF and the spatial coefficient of variation. MATERIALS AND METHODS: Three hundred ninety patients with a diagnosis of no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia were recruited from the memory clinic. Cerebral microbleeds and lacunes were categorized into strictly lobar, strictly deep, and mixed-location and enlarged perivascular spaces into the centrum semiovale and basal ganglia. Total and region-specific white matter hyperintensity volumes were segmented using FreeSurfer. CBF (n = 333) and the spatial coefficient of variation (n = 390) were analyzed with ExploreASL from 2D-EPI pseudocontinuous arterial spin-labeling images in white matter (WM) and gray matter (GM). To analyze the effect of demographic and vascular risk factors as well as the location and severity of cerebral small-vessel disease markers on arterial spin-labeling parameters, we constructed linear regression models, whereas logistic regression models were used to determine the association between arterial spin-labeling parameters and cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia. RESULTS: Increasing age, male sex, hypertension, hyperlipidemia, history of heart disease, and smoking were associated with lower CBF and a higher spatial coefficient of variation. Higher numbers of lacunes and cerebral microbleeds were associated with lower CBF and a higher spatial coefficient of variation. Location-specific analysis showed mixed-location lacunes and cerebral microbleeds were associated with lower CBF. Higher total, anterior, and posterior white matter hyperintensity volumes were associated with a higher spatial coefficient of variation. No association was observed between enlarged perivascular spaces and arterial spin-labeling parameters. A higher spatial coefficient of variation was associated with the diagnosis of vascular cognitive impairment no dementia, Alzheimer's disease, and vascular dementia. CONCLUSIONS: Reduced CBF and an increased spatial coefficient of variation were associated with cerebral small-vessel disease, and more specifically lacunes, whereas cerebral microbleeds and white matter hyperintensities were associated with WM-CBF and GM spatial coefficient of variation. The spatial coefficient of variation was associated with cognitive impairment and dementia, suggesting that hypoperfusion might be the key underlying mechanism for vascular brain damage.

Effects of Acquisition Parameter Modifications and Field Strength on the Reproducibility of Brain Perfusion Measurements Using Arterial Spin-Labeling.

BACKGROUND AND PURPOSE: Although the added diagnostic value of arterial spin-labeling is shown in various cerebral pathologies, its use in clinical practice is limited. To encourage clinical adoption of ASL, we investigated the reproducibility of CBF measurements and the effects of variations in acquisition parameters compared to the recommended ASL implementation. MATERIALS AND METHODS: Thirty-four volunteers (mean age, 57.8 ± 17.0 years; range, 22-80 years) underwent two separate sessions (1.5T and 3T scanners from a single vendor) using a 15-channel head coil. Both sessions contained repeated 3D and 2D pseudocontinuous arterial spin-labeling scans using vendor-recommended acquisition parameters (recommendation paper-based), followed by three 3D pseudocontinuous arterial spin-labeling scans, two with postlabeling delays of 1600 and 2000 ms and one with increased spatial resolution. All scans were single postlabeling delay. Intrasession (identical acquisitions, scanned five minutes apart) and intersession (first 2D and 3D acquisitions of two sessions) reproducibility was examined as well as the effect of parameter variations on CBF. RESULTS: Intrasession CBF reproducibility was similar across image readouts and field strengths (within-subject coefficient of variation between 4.0% and 6.7%). Intersession within-subject coefficient of variation ranged from 6.6% to 14.8%. At 3T, the 3D acquisition with a higher spatial resolution resulted in less mixing of GM and WM signal, thus decreasing the bias in GM CBF between the 2D and 3D acquisitions (ΔCBF = 2.49 mL/100g/min [P < .001]). Postlabeling delay variations caused a modest bias (ΔCBF between -3.78 [P < .001] and 2.83 [P < .001] mL/100g/min). CONCLUSIONS: Arterial spin-labeling imaging is reproducible at both field strengths, and the reproducibility is not significantly correlated with age. Furthermore, 3T tolerates more acquisition parameter variations and allows more extensive optimizations so that 3D and 2D acquisitions can be compared.

A visual quality control scale for clinical arterial spin labeling images.

BACKGROUND: Image-quality assessment is a fundamental step before clinical evaluation of magnetic resonance images. The aim of this study was to introduce a visual scoring system that provides a quality control standard for arterial spin labeling (ASL) and that can be applied to cerebral blood flow (CBF) maps, as well as to ancillary ASL images. METHODS: The proposed image quality control (QC) system had two components: (1) contrast-based QC (cQC), describing the visual contrast between anatomical structures; and (2) artifact-based QC (aQC), evaluating image quality of the CBF map for the presence of common types of artifacts. Three raters evaluated cQC and aQC for 158 quantitative signal targeting with alternating radiofrequency labelling of arterial regions (QUASAR) ASL scans (CBF, T1 relaxation rate, arterial blood volume, and arterial transient time). Spearman correlation coefficient (r), intraclass correlation coefficients (ICC), and receiver operating characteristic analysis were used. RESULTS: Intra/inter-rater agreement ranged from moderate to excellent; inter-rater ICC was 0.72 for cQC, 0.60 for aQC, and 0.74 for the combined QC (cQC + aQC). Intra-rater ICC was 0.90 for cQC; 0.80 for aQC, and 0.90 for the combined QC. Strong correlations were found between aQC and CBF maps quality (r = 0.75), and between aQC and cQC (r = 0.70). A QC score of 18 was optimal to discriminate between high and low quality clinical scans. CONCLUSIONS: The proposed QC system provided high reproducibility and a reliable threshold for discarding low quality scans. Future research should compare this visual QC system with an automatic QC system.

Cerebrovascular Reactivity during Prolonged Breath-Hold in Experienced Freedivers.

BACKGROUND AND PURPOSE: Experienced freedivers can endure prolonged breath-holds despite severe hypoxemia and are therefore ideal subjects to study apnea-induced cerebrovascular reactivity. This multiparametric study investigated CBF, the spatial coefficient of variation as a correlate of arterial transit time and brain metabolism, dynamics during prolonged apnea. MATERIALS AND METHODS: Fifteen male freedivers (age range, 20-64 years; cumulative previous prolonged breath-holds >2 minutes and 30 seconds: 4-79,200) underwent repetitive 3T pseudocontinuous arterial spin-labeling and 31P-/1H-MR spectroscopy before, during, and after a 5-minute breath-hold (split into early and late phases) and gave temporally matching venous blood gas samples. Correlation of temporal and regional cerebrovascular reactivity to blood gases and cumulative previous breath-holds of >2 minutes and 30 seconds in a lifetime was assessed. RESULTS: The spatial coefficient of variation of CBF (by arterial spin-labeling) decreased during the early breath-hold phase (-30.0%, P = .002), whereas CBF remained almost stable during this phase and increased in the late phase (+51.8%, P = .001). CBF differed between the anterior and the posterior circulation during all phases (eg, during late breath-hold: MCA, 57.3 ± 14.2 versus posterior cerebral artery, 42.7 ± 10.8 mL/100 g/min; P = .001). There was an association between breath-hold experience and lower CBF (1000 previous breath-holds reduced WM CBF by 0.6 mL/100 g/min; 95% CI, 0.15-1.1 mL/100 g/min; P = .01). While breath-hold caused peripheral lactate rise (+18.5%) and hypoxemia (oxygen saturation, -24.0%), cerebral lactate and adenosine diphosphate remained within physiologic ranges despite early signs of oxidative stress [-6.4% phosphocreatine / (adenosine triphosphate + adenosine diphosphate); P = .02]. CONCLUSIONS: This study revealed that the cerebral energy metabolism of trained freedivers withstands severe hypoxic hypercarbia in prolonged breath-hold due to a complex cerebrovascular hemodynamic response.

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling.

BACKGROUND AND PURPOSE: White matter hyperintensities of presumed vascular origin in elderly patients with hypertension may be part of a general cerebral perfusion deficit, involving not only the white matter hyperintensities but also the surrounding normal-appearing white matter and gray matter. We aimed to study the relation between white matter hyperintensity volume and CBF and assess whether white matter hyperintensities are related to a general perfusion deficit. MATERIALS AND METHODS: In 185 participants of the Prevention of Dementia by Intensive Vascular Care trial between 72 and 80 years of age with systolic hypertension, white matter hyperintensity volume and CBF were derived from 3D FLAIR and arterial spin-labeling MR imaging, respectively. We compared white matter hyperintensity CBF, normal-appearing white matter CBF, and GM CBF across quartiles of white matter hyperintensity volume and assessed the continuous relation between these CBF estimates and white matter hyperintensity volume by using linear regression. RESULTS: Mean white matter hyperintensity CBF was markedly lower in higher quartiles of white matter hyperintensity volume, and white matter hyperintensity volume and white matter hyperintensity CBF were negatively related (standardized ß = -0.248, P = .001) in linear regression. We found no difference in normal-appearing white matter or GM CBF across quartiles of white matter hyperintensity volume or any relation between white matter hyperintensity volume and normal-appearing white matter CBF (standardized ß = -0.065, P = .643) or GM CBF (standardized ß = -0.035, P = .382) in linear regression. CONCLUSIONS: Higher white matter hyperintensity volume in elderly individuals with hypertension was associated with lower perfusion within white matter hyperintensities, but not with lower perfusion in the surrounding normal-appearing white matter or GM. These findings suggest that white matter hyperintensities in elderly individuals with hypertension relate to local microvascular alterations rather than a general cerebral perfusion deficit.

In Vivo T1 of Blood Measurements in Children with Sickle Cell Disease Improve Cerebral Blood Flow Quantification from Arterial Spin-Labeling MRI.

BACKGROUND AND PURPOSE: Children with sickle cell disease have low hematocrit and elevated CBF, the latter of which can be assessed with arterial spin-labeling MR imaging. Quantitative CBF values are obtained by using an estimation of the longitudinal relaxation time of blood (T1blood). Because T1blood depends on hematocrit in healthy individuals, we investigated the importance of measuring T1blood in vivo with MR imaging versus calculating it from hematocrit or assuming an adult fixed value recommended by the literature, hypothesizing that measured T1blood would be the most suited for CBF quantification in children with sickle cell disease. MATERIALS AND METHODS: Four approaches for T1blood estimation were investigated in 39 patients with sickle cell disease and subsequently used in the CBF quantification from arterial spin-labeling MR imaging. First, we used 1650 ms as recommended by the literature (T1blood-fixed); second, T1blood calculated from hematocrit measured in patients (T1blood-hematocrit); third, T1blood measured in vivo with a Look-Locker MR imaging sequence (T1blood-measured); and finally, a mean value from T1blood measured in this study in children with sickle cell disease (T1blood-sickle cell disease). Quantitative flow measurements acquired with phase-contrast MR imaging served as reference values for CBF. RESULTS: T1blood-measured (1818 ± 107 ms) was higher than the literature recommended value of 1650 ms, was significantly lower than T1blood-hematocrit (2058 ± 123 ms, P < .001), and, most interesting, did not correlate with hematocrit measurements. Use of either T1blood-measured or T1blood-sickle cell disease provided the best agreement on CBF between arterial-spin labeling and phase-contrast MR imaging reference values. CONCLUSIONS: This work advocates the use of patient-specific measured T1blood or a standardized value (1818 ms) in the quantification of CBF from arterial spin-labeling in children with SCD.

Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies.

Cerebral Perfusion Measurements in Elderly with Hypertension Using Arterial Spin Labeling.

PURPOSE: The current study assesses the feasibility and value of crushed cerebral blood flow (CBFcrushed) and arterial transit time (ATT) estimations for large clinical imaging studies in elderly with hypertension. MATERIAL AND METHODS: Two pseudo-continuous arterial spin labeling (ASL) scans with (CBFcrushed) and without flow crushers (CBFnon-crushed) were performed in 186 elderly with hypertension, from which CBF and ATT maps were calculated. Standard flow territory maps were subdivided into proximal, intermediate and distal flow territories, based on the measured ATT. The coefficient of variation (CV) and physiological correlations with age and gender were compared between the three perfusion parameters. RESULTS: There was no difference in CV between CBFcrushed and CBFnon-crushed (15-24%, p>0.4) but the CV of ATT (4-9%) was much smaller. The total gray matter correlations with age and gender were most significant with ATT (p = .016 and p<.001 respectively), in between for CBFcrushed (p = .206 and p = .019) and least significant for CBFnon-crushed (p = .236 and p = .100). CONCLUSION: These data show the feasibility and added value of combined measurements of both crushed CBF and ATT for group analyses in elderly with hypertension. The obtained flow territories provide knowledge on vascular anatomy of elderly with hypertension and can be used in future studies to investigate regional vascular effects.

Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: a head-to-head comparison with ¹5O H2O positron emission tomography.

Measurements of the cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide useful information about cerebrovascular condition and regional metabolism. Pseudo-continuous arterial spin labeling (pCASL) is a promising non-invasive MRI technique to quantitatively measure the CBF, whereas additional hypercapnic pCASL measurements are currently showing great promise to quantitatively assess the CVR. However, the introduction of pCASL at a larger scale awaits further evaluation of the exact accuracy and precision compared to the gold standard. (15)O H2O positron emission tomography (PET) is currently regarded as the most accurate and precise method to quantitatively measure both CBF and CVR, though it is one of the more invasive methods as well. In this study we therefore assessed the accuracy and precision of quantitative pCASL-based CBF and CVR measurements by performing a head-to-head comparison with (15)O H2O PET, based on quantitative CBF measurements during baseline and hypercapnia. We demonstrate that pCASL CBF imaging is accurate during both baseline and hypercapnia with respect to (15)O H2O PET with a comparable precision. These results pave the way for quantitative usage of pCASL MRI in both clinical and research settings.