Estimating Flow Direction of Circle of Willis Using Dynamic Arterial Spin Labeling Magnetic Resonance Angiography.

BACKGROUND AND PURPOSE: The Circle of Willis (COW) is a crucial mechanism for cerebral collateral circulation. This proof-ofconcept study aims to develop and assess an analysis method to characterize the hemodynamics of the arterial segments in COW using arterial spin labeling (ASL) based non-contrast enhanced dynamic magnetic resonance angiography (dMRA). MATERIALS AND METHODS: The developed analysis method uses a graph model, bootstrap strategy, and ensemble learning methodologies to determine the time-curve shift from ASL dMRA to estimate the flow direction within the COW. The performance of the method was assessed on 52 subjects, using the flow direction, either antegrade or retrograde, derived from 3D phase contrast (PC) MRI as the reference. RESULTS: A total of 340 arterial segments in COW were evaluated, among which 30 (8.8%) had retrograde flow according to 3D PC. The ASL dMRA-based flow direction estimation has an accuracy, sensitivity, and specificity of 95.47%, 80%, and 96.34%, respectively. CONCLUSIONS: Using ASL dMRA and the developed image analysis method to estimate the flow direction in COW is feasible. This study provides a new method to assess the hemodynamics of the COW, which could be useful for the diagnosis and study of cerebrovascular diseases. ABBREVIATIONS: COW = Circle of Willis; ASL = arterial spin labeling; dMRA =dynamic magnetic resonance angiography; PC = phase contrast.

Alterations in cerebral distal vascular features and effect on cognition in a high cardiovascular risk population: A prospective longitudinal study.

BACKGROUND: Alterations in cerebral vasculature are instrumental in affecting cognition. Current studies mainly focus on proximal large arteries and small vessels, while disregarding morphology and blood flow of the arteries between them (medium-to-large arteries). METHODS: In this prospective study, two types of non-contrast enhanced magnetic resonance angiography (NCE-MRA) techniques, simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) and 3D Time-of-flight (TOF), were used to measure vascular morphologic features in medium-to-large intracranial arteries. Grey matter (GM) tissue level perfusion was assessed with arterial spin labeling (ASL) MRI. Twenty-seven subjects at high cardiovascular risk underwent baseline and 12-month follow-up MRI to compare the relationship between morphological features measured by NCE MRA, GM CBF by ASL MRI, and cognitive function measured by the Montreal Cognitive Assessment (MoCA). RESULTS: Changes in both global medium-to-large arteries and posterior cerebral (PCA) distal artery length and branch numbers, measured on SNAP MRA, were significantly associated with alterations in MoCA scores (P < 0.01), after adjusting for clinical confounding factors, total brain volume, and total white matter lesion (WML) volume. There were no associations between MoCA scores and vascular features on TOF MRA or ASL GM CBF. CONCLUSIONS: Alterations in vascular features of distal medium-to-large arteries may be more sensitive for detecting potential changes in cognition than cerebral blood flow alterations at the parenchymal level captured by perfusion ASL. Hemodynamic information from distal medium-to-large arteries provides an additional tool to advance understanding of the vascular contributions to cognitive function.

Characterization of non-stenotic plaques in intracranial arteries with multi-contrast, multi-planar vessel wall image analysis.

OBJECTIVES: Non-stenotic plaques have been observed in intracranial arteries but are less understood compared to those in coronary and carotid arteries. We sought to compare plaque distribution and morphology between stenotic and non-stenotic intracranial plaques with MR vessel wall imaging (VWI) and quantitative image analysis. MATERIALS AND METHODS: Twenty-four patients with intracranial arterial stenosis or luminal irregularity on clinical imaging were scanned with a multi-contrast VWI protocol. Plaques were detected as focal wall thickening on co-registered multiplanar reformats of multi-contrast VWI, with assessment of the location and morphology. TOF-MRA was independently reviewed for any appreciable stenosis using the WAISD criteria. RESULTS: Across 504 arterial segments, a total of 80 plaques were detected, including 23 (29%) with stenosis on TOF-MRA, 56 (70%) without, and 1 (1%) not covered by TOF-MRA. Plaques involving the ICA were more likely to be non-stenotic than those involving other segments (80% versus 55%, p = 0.030) whereas the basilar artery (40%) and PCA (33%) had the lowest proportions of non-stenotic plaques. Maximum wall thickness, indicative of plaque burden, correlated poorly with degree of stenosis (p = 0.10) and overlapped substantially between stenotic and non-stenotic plaques (1.9 [1.5, 2.4] versus 2.0 [1.5, 2.2] mm, p = 0.074). CONCLUSIONS: Intracranial plaques without appreciable stenosis on TOF-MRA represent a large proportion of lesions throughout arterial segments but disproportionately affect the ICA. Morphological characterization of plaques with and without stenosis shows that luminal stenosis is a poor indicator of the underlying burden of intracranial atherosclerosis.

Associations of intracranial artery length and branch number on non-contrast enhanced MRA with cognitive impairment in individuals with carotid atherosclerosis.

Developing novel risk markers for vascular contributions to cognitive impairment and dementia is important. This study aimed to extract total length, branch number and average tortuosity of intracranial distal arteries (A2, M2, P2 and more distal) from non-contrast enhanced magnetic resonance angiography (NCE-MRA) images, and explore their associations with global cognition. In 29 subjects (aged 40-90 years) with carotid atherosclerotic disease, the 3 intracranial vascular features on two NCE-MRA techniques (i.e. time of flight, TOF and simultaneous non-contrast angiography and intraplaque hemorrhage, SNAP) were extracted using a custom-developed software named iCafe. Arterial spin labeling (ASL) and phase contrast (PC) cerebral blood flow (CBF) were measured as references. Linear regression was performed to study their associations with global cognition, measured with the Montreal Cognitive Assessment (MoCA). Intracranial artery length and number of branches on NCE-MRA, ASL CBF and PC CBF were found to be positively associated with MoCA scores (P < 0.01). The associations remained significant for artery length and number of branches on NCE-MRA after adjusting for clinical covariates and white matter hyperintensity volume. Further adjustment of confounding factors of ASL CBF or PC CBF did not abolish the significant association for artery length and number of branches on TOF. Our findings suggest that intracranial vascular features, including artery length and number of branches, on NCE-MRA may be useful markers of cerebrovascular health and provide added information over conventional brain blood flow measurements in individuals with cognitive impairment.

Vessel length on SNAP MRA and TOF MRA is a potential imaging biomarker for brain blood flow.

PURPOSE: To explore feasibility of using the vessel length on time-of-flight (TOF) or simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) MRA as an imaging biomarker for brain blood flow, by using arterial spin labeling (ASL) perfusion imaging and 3D phase contrast (PC) quantitative flow imaging as references. METHODS: In a population of thirty subjects with carotid atherosclerotic disease, the visible intracranial arteries on TOF and SNAP were semi-automatically traced and the total length of the distal segments was calculated with a dedicated software named iCafe. ASL blood flow was calculated automatically using the recommended hemodynamic model. PC blood flow was obtained by generating cross-sectional arterial images and semi-automatically drawing the lumen contours. Pearson correlation coefficients were used to assess the associations between the different whole-brain or hemispheric blood flow measurements. RESULTS: Under the imaging protocol used in this study, TOF vessel length was larger than SNAP vessel length (P < 0.001). Both whole-brain TOF and SNAP vessel length showed a correlation with whole brain ASL and 3D PC blood flow measurements, and the correlation coefficients were higher for SNAP vessel length (TOF vs ASL: R = 0.554, P = 0.002; SNAP vs ASL: R = 0.711, P < 0.001; TOF vs 3D PC: R = 0.358, P = 0.052; SNAP vs 3D PC: R = 0.425, P = 0.019). Similar correlation results were observed for the hemispheric measurements. Hemispheric asymmetry index of SNAP vessel length also showed a significant correlation with hemispheric asymmetry index of ASL cerebral blood flow (R = 0.770, P < 0.001). CONCLUSION: The results suggest that length of the visible intracranial arteries on TOF or SNAP MRA can serve as a potential imaging marker for brain blood flow.

A novel algorithm for refining cerebral vascular measurements in infants and adults.

BACKGROUND: Comprehensive quantification of intracranial vascular characteristics by vascular tracing provides an objective clinical assessment of vascular structure. However, weak signal or low contrast in small distal arteries, artifacts due to volitional motion, and vascular pulsation are challenges for accurate vessel tracing from 3D time-of-flight (3D-TOF) magnetic resonance angiography (MRA) images. NEW METHOD: A vascular measurement refinement algorithm is developed and validated for robust quantification of intracranial vasculature from 3D-TOF MRA. After automated vascular tracing, centerline positions, lumen radii and centerline deviations are jointly optimized to restrict traces to within vascular regions in the straightened curved planar reformation (CPR) views. The algorithm is validated on simulated vascular images and on repeat 3D-TOF MRA acquired from infants and adults. RESULTS: The refinement algorithm can reliably estimate vascular radius and correct deviated centerlines. For the simulated vascular image with noise level of 1 and deviation of centerline of 3, the mean radius difference is below 15.3 % for scan-rescan reliability. Vascular features from repeated clinical scans show significantly improved measurement agreement, with intra-class correlation coefficient (ICC) improvement from 0.55 to 0.7 for infants and from 0.59 to 0.92 for adults. COMPARISON WITH EXISTING METHODS: The refinement algorithm is novel because it utilizes straightened CPR views that incorporate information from the entire artery. In addition, the optimization corrects centerline positions, lumen radii and centerline deviations simultaneously. CONCLUSIONS: Intracranial vasculature quantification using a novel refinement algorithm for vascular tracing improves the reliability of vascular feature measurements in both infants and adults.

Quantification of morphometry and intensity features of intracranial arteries from 3D TOF MRA using the intracranial artery feature extraction (iCafe): A reproducibility study.

BACKGROUND: Accurate and reliable vascular features extracted from 3D time-of-flight (TOF) magnetic resonance angiography (MRA) can help evaluate cerebral vascular diseases and conditions. The goal of this study was to evaluate the reproducibility of an intracranial artery feature extraction (iCafe) algorithm for quantitative analysis of intracranial arteries from TOF MRA. METHODS: Twenty-four patients with known intracranial artery stenosis were recruited and underwent two separate MRA scans within 2 weeks of each other. Each dataset was blinded to associated imaging and clinical data and then processed independently using iCafe. Inter-scan reproducibility analysis was performed on the 24 pairs of scans while intra-/inter-operator reproducibility and stenosis detection were assessed on 8 individual MRA scans. After tracing the vessels visualized on TOF MRA, iCafe was used to automatically extract the locations with stenosis and eight other vascular features. The vascular features included the following six morphometry and two signal intensity features: artery length (total, distal, and proximal), volume, number of branches, average radius of the M1 segment of the middle cerebral artery, and average normalized intensity of all arteries and large vertical arteries. A neuroradiologist independently reviewed the images to identify locations of stenosis for the reference standard. Reproducibility of stenosis detection and vascular features was assessed using Cohen's kappa, the intra-class correlation coefficient (ICC), and within-subject coefficient of variation (CV). RESULTS: The segment-based sensitivity of iCafe for stenosis detection ranged from 83.3-91.7% while specificity was 97.4%. Kappa values for inter-scan and intra-operator reproducibility were 0.73 and 0.77, respectively. All vascular features demonstrated excellent inter-scan and intra-operator reproducibility (ICC = 0.91-1.00, and CV = 1.21-8.78% for all markers), and good to excellent inter-operator reproducibility (ICC = 0.76-0.99, and CV = 3.27-15.79% for all markers). CONCLUSION: Intracranial artery features can be reliably quantified from TOF MRA using iCafe to provide both clinical diagnostic assistance and facilitate future investigative quantitative analyses.

Development of a quantitative intracranial vascular features extraction tool on 3D MRA using semiautomated open-curve active contour vessel tracing.

PURPOSE: To develop a quantitative intracranial artery measurement technique to extract comprehensive artery features from time-of-flight MR angiography (MRA). METHODS: By semiautomatically tracing arteries based on an open-curve active contour model in a graphical user interface, 12 basic morphometric features and 16 basic intensity features for each artery were identified. Arteries were then classified as one of 24 types using prediction from a probability model. Based on the anatomical structures, features were integrated within 34 vascular groups for regional features of vascular trees. Eight 3D MRA acquisitions with intracranial atherosclerosis were assessed to validate this technique. RESULTS: Arterial tracings were validated by an experienced neuroradiologist who checked agreement at bifurcation and stenosis locations. This technique achieved 94% sensitivity and 85% positive predictive values (PPV) for bifurcations, and 85% sensitivity and PPV for stenosis. Up to 1,456 features, such as length, volume, and averaged signal intensity for each artery, as well as vascular group in each of the MRA images, could be extracted to comprehensively reflect characteristics, distribution, and connectivity of arteries. Length for the M1 segment of the middle cerebral artery extracted by this technique was compared with reviewer-measured results, and the intraclass correlation coefficient was 0.97. CONCLUSION: A semiautomated quantitative method to trace, label, and measure intracranial arteries from 3D-MRA was developed and validated. This technique can be used to facilitate quantitative intracranial vascular research, such as studying cerebrovascular adaptation to aging and disease conditions. Magn Reson Med 79:3229-3238, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A vascular image registration method based on network structure and circuit simulation.

BACKGROUND: Image registration is an important research topic in the field of image processing. Applying image registration to vascular image allows multiple images to be strengthened and fused, which has practical value in disease detection, clinical assisted therapy, etc. However, it is hard to register vascular structures with high noise and large difference in an efficient and effective method. RESULTS: Different from common image registration methods based on area or features, which were sensitive to distortion and uncertainty in vascular structure, we proposed a novel registration method based on network structure and circuit simulation. Vessel images were transformed to graph networks and segmented to branches to reduce the calculation complexity. Weighted graph networks were then converted to circuits, in which node voltages of the circuit reflecting the vessel structures were used for node registration. The experiments in the two-dimensional and three-dimensional simulation and clinical image sets showed the success of our proposed method in registration. CONCLUSIONS: The proposed vascular image registration method based on network structure and circuit simulation is stable, fault tolerant and efficient, which is a useful complement to the current mainstream image registration methods.

High resolution FDG-microPET of carotid atherosclerosis: plaque components underlying enhanced FDG uptake.

This study sought to discover which atherosclerotic plaque components co-localize with enhanced [(18)F]-fluorodeoxyglucose (FDG) uptake in carotid positron emission tomography (PET) images. Although in vivo PET currently lacks the resolution, high-resolution ex vivo FDG-microPET with histology validation of excised carotid plaque might accomplish this goal. Thirteen patients were injected with FDG before carotid endarterectomy. After excision, the plaque specimens were scanned by microPET and magnetic resonance imaging, and then serially sectioned for histological analysis. Two analyses were performed using generalized linear mixed models: (1) a PET-driven analysis which sampled high and low FDG uptake areas from PET images to identify their components in matched histology specimens; and (2) a histology-driven analysis where specific plaque components were selected and matched to corresponding PET images. In the PET-driven analysis, regions of high FDG uptake were more likely to contain inflammatory cells (p < 0.001) and neovasculature (p = 0.008) than regions of low FDG uptake. In the histology-driven analysis, regions with inflammatory cells (p = 0.001) and regions with loose extracellular matrix (p = 0.001) were associated with enhanced FDG uptake. Furthermore, areas of complex inflammatory cell infiltrate (co-localized macrophages, lymphocytes and foam cells) had the highest FDG uptake among inflammatory subgroups (p < 0.001). In conclusion, in carotid plaque, regions of inflammatory cell infiltrate, particularly complex one, co-localized with enhanced FDG uptake in high-resolution FDG-microPET images. Loose extracellular matrix and areas containing neovasculature also produced FDG signal. This study points to the potential ability of FDG-PET to detect the cellular components of the vulnerable plaque.

Many infants prenatally exposed to high levels of alcohol show one particular anomaly of the corpus callosum.

INTRODUCTION: Effects of prenatal alcohol exposure on the brain are seen at every age. The earlier they can be quantified, the better the prognosis for the affected child. Here we show measurable alcohol effects at birth on a structure currently used for nosology only much later in life. METHODS: Midline shape of the corpus callosum was imaged in infants via averaged unwarped transfontanelle ultrasound. We compared measures of these shapes among 23 infants prenatally exposed to high levels of alcohol and 21 infants unexposed to alcohol or only lightly exposed. RESULTS: A particular feature of the corpus callosum, the appearance of a "hook" (obtuse angle) between the splenium and the long diameter of the arch in this plane, is strongly associated with prenatal alcohol exposure. In half of the high-exposed infants, the splenium angle is larger than in any of the unexposed brains. Simply characterizing this angle as less than or greater than 90 degrees detects 12 of the 23 exposed infants as anomalous with only 1 false positive among the unexposed. This apparently direct effect of prenatal ethanol exposure on the details of the callosum in about half the at-risk subjects cannot be attributed to any of several plausible competing exposures or other confounding factors applying during or after gestation. CONCLUSION: An average of the images for the unexposed subjects has the geometry of textbook images of normal babies; but the average for the subgroup of high-angle subjects may serve as a template or guide to this regional damage parallel to the familiar photographic exemplars that help to assess facial signs.