Simultaneous 3D-TOF angiography and 4D-flow MRI with enhanced flow signal using multiple overlapping thin slab acquisition and magnetization transfer.

PURPOSE: To investigate the fusion of 3D time-of-flight principles into 4D-flow MRI to enhance vessel contrast and signal without an exogenous contrast agent, enabling simultaneous in-flow based angiograms. METHODS: A 4D-flow MRI technique was developed consisting of multiple overlapping slabs with intermittent magnetization transfer preparation. The scan time penalty associated with multiple slab acquisitions was mitigated by using undersampled distributed spiral trajectories and compressed sensing reconstruction. A flow phantom was used to characterize in-flow enhancement, velocity noise improvement, and flow rate measurements against the single-slab 4D-flow MRI. In a patient-volunteer cohort (n = 15), magnitude-based angiograms were radiologically evaluated against 3D time-of-flight, and velocity measurements were compared pixel-wise against single-slab and contrast-enhanced 4D-flow MRI. RESULTS: Multiple-slab acquisitions, together with magnetization transfer preparation, substantially improved vessel signal, contrast, and vessel conspicuity in magnitude angiograms. Both clinical 3D time-of-flight and the proposed technique produced equivalent vessel depictions with no statistically significant difference (p < .1). Both techniques also produced clear depictions of brain aneurysms in all patients; however, very small vessels tended to show reduced conspicuity in the proposed technique. Velocity measurements agreed with contrast-enhanced and single-slab scans with high correlations (R2 = 0.941-0.974) and agreements (slopes = 0.994-1.071). Slab boundary and magnetization transfer-related artifacts were not observed in velocity measurements, and velocity noise was reduced with in-flow enhancement over single-slab scans (phantom). CONCLUSION: The vessel signal and contrast can be improved in 4D-flow MRI without exogenous contrast agents by utilizing in-flow enhancement, efficient sampling, and compressed sensing. The in-flow enhancement also enables simultaneous 3D time-of-flight angiograms useful for flow quantification and diagnosis.

Virtual injections using 4D flow MRI with displacement corrections and constrained probabilistic streamlines.

PURPOSE: Streamlines from 4D-flow MRI have been used clinically for intracranial blood-flow tracking. However, deterministic and stochastic errors degrade streamline quality. The purpose of this study is to integrate displacement corrections, probabilistic streamlines, and novel fluid constraints to improve selective blood-flow tracking and emulate "virtual bolus injections." METHODS: Both displacement artifacts (deterministic) and velocity noise (stochastic) inherently occur during phase-contrast MRI acquisitions. Here, two displacement correction methods, single-step and iterative, were tested in silico with simulated displacements and were compared with ground-truth velocity fields. Next, the effects of combining displacement corrections and constrained probabilistic streamlines were performed in 10 healthy volunteers using time-averaged 4D-flow data. Measures of streamline length and depth into vasculature were then compared with streamlines generated with no corrections and displacement correction alone using one-way repeated-measures analysis of variance and Friedman's tests. Finally, virtual injections with improved streamlines were generated for three intracranial pathology cases. RESULTS: Iterative displacement correction outperformed the single-step method in silico. In volunteers, the combination of displacement corrections and constrained probabilistic streamlines allowed for significant improvements in streamline length and increased the number of streamlines entering the circle of Willis relative to streamlines with no corrections and displacement correction alone. In the pathology cases, virtual injections with improved streamlines were qualitatively similar to dynamic arterial spin labeling images and allowed for forward/reverse selective flow tracking to characterize cerebrovascular malformations. CONCLUSION: Virtual injections with improved streamlines from 4D-flow MRI allow for flexible, robust, intracranial flow tracking.

Spatial dependency and the role of local susceptibility for velocity selective arterial spin labeling (VS-ASL) relative tagging efficiency using accelerated 3D radial sampling with a BIR-8 preparation.

PURPOSE: Velocity selective arterial spin labeling (VS-ASL) is a promising approach for non-contrast perfusion imaging that provides robustness to vascular geometry and transit times; however, VS-ASL assumes spatially uniform tagging efficiency. This work presents a mapping approach to investigate VS-ASL relative tagging efficiency including the impact of local susceptibility effects on a BIR-8 preparation. METHODS: Numerical simulations of tagging efficiency were performed to evaluate sensitivity to regionally varying local susceptibility gradients and blood velocity. Tagging efficiency mapping was performed in susceptibility phantoms and healthy human subjects (N = 7) using a VS-ASL preparation module followed by a short, high spatial resolution 3D radial-based image acquisition. Tagging efficiency maps were compared to 4D-flow, B1 , and B0 maps acquired in the same imaging session for six of the seven subjects. RESULTS: Numerical simulations were found to predict reduced tagging efficiency with the combination of high blood velocity and local gradient fields. Phantom experiments corroborated numerical results. Relative efficiency mapping in normal volunteers showed unique efficiency patterns depending on individual subject anatomy and physiology. Uniform tagging efficiency was generally observed in vivo, but reduced efficiency was noted in regions of high blood velocity and local susceptibility gradients. CONCLUSION: We demonstrate an approach to map the relative tagging efficiency and show application of this methodology to a novel BIR-8 preparation recently proposed in the literature. We present results showing rapid flow in the presence of local susceptibility gradients can lead to complicated signal modulations in both tag and control images and reduced tagging efficiency.

Cardiorespiratory Fitness Associates with Cerebral Vessel Pulsatility in a Cohort Enriched with Risk for Alzheimer's Disease.

BACKGROUND: There is increasing evidence that vascular disease risk factors contribute to evolution of the dementia syndrome of Alzheimer's disease (AD). One important measure of cerebrovascular health is pulsatility index (PI) which is thought to represent distal vascular resistance, and has previously been reported to be elevated in AD clinical syndrome. Physical inactivity has emerged as an independent risk factor for cardiovascular disease. OBJECTIVE: This study aims to examine the relationship between a measure of habitual physical activity, cardiorespiratory fitness (CRF), and PI in the large cerebral vessels. METHODS: Ninety-two cognitively-healthy adults (age = 65.34±5.95, 72% female) enrolled in the Wisconsin Registry for Alzheimer's Prevention participated in this study. Participants underwent 4D flow brain MRI to measure PI in the internal carotid artery (ICA), basilar artery, middle cerebral artery (MCA), and superior sagittal sinus. Participants also completed a self-report physical activity questionnaire. CRF was calculated using a previously-validated equation that incorporates sex, age, body-mass index, resting heart rate, and self-reported physical activity. A series of linear regression models adjusted for age, sex, APOE4 status, and 10-year atherosclerotic cardiovascular disease risk were used to analyze the relationship between CRF and PI. RESULTS: Inverse associations were found between CRF and mean PI in the inferior ICA (p = .001), superior ICA (p = .035), and basilar artery (p = .040). No other cerebral vessels revealed significant associations between CRF and PI (p≥.228). CONCLUSIONS: Higher CRF was associated with lower PI in several large cerebral vessels. Since increased pulsatility has been associated with poor brain health and reported in persons with AD, this suggests that aerobic fitness might provide protection against cerebrovascular changes related to the progression of AD clinical syndrome.

Composite MRA: statistical approach to generate an MR angiogram from multiple contrasts.

PURPOSE: To develop a method to use information from multiple MRI contrasts to produce a composite angiogram with reduced sequence-specific artifacts and improved vessel depiction. METHODS: Bayesian posterior vessel probability was determined as a function of black blood (BB), contrast enhanced angiography (CE-MRA), and phase-contrast MRA (PC-MRA) intensities from training subjects (N = 4). To generate composite angiogram in evaluation subjects (N = 12), the voxel-wise vessel probabilities were weighted with a confidence measure and combined as a weighted product to yield angiogram intensity. For 23 internal carotid artery (ICA) segments (N = 23) from evaluation subjects, segmentation accuracy of composite MRA was evaluated and compared against CE-MRA using dice similarity coefficient (DSC). RESULTS: The composite MRA suppressed venous contaminations in CE-MRA, reduced flow artifacts, and velocity aliasing seen in PC-MRA and removed signal ambiguities in BB images. For ICA segmentations, the composite MRA improved segmentation over CE-MRA per DSC (0.908 ± 0.037 vs. 0.765 ± 0.079). Compared with CE-MRA, the composite MRA showed conservative changes in vessel appearance to small threshold changes. However, small vessels that are sensitive to registration errors or visible only weakly in CE-MRA were susceptible to poor depiction in composite MRA. CONCLUSION: By dynamically weighting vessel information from multiple contrasts and extracting their complementary information, the composite MRA produces reduced sequence-specific artifacts and improved vessel contrast. It is a promising technique for semi-automatic segmentation of vessels that are hard to segment because of artifacts.

Association of Cardiovascular and Alzheimer's Disease Risk Factors with Intracranial Arterial Blood Flow in Whites and African Americans.

BACKGROUND: Alzheimer's disease (AD) has a higher prevalence among African Americans. Targeting cardiovascular and metabolic risk factors may be potential mechanisms to modify AD risk and address racial/ethnic disparities in AD dementia. OBJECTIVE: This study investigated relationships among cardiovascular and metabolic risk factors, APOE genotype, AD biomarkers, and intracranial arterial blood flow in Whites and African Americans enriched for AD risk. METHODS: 399 cognitively unimpaired adults from the Wisconsin Alzheimer's Disease Research Center completed physical and neuroimaging examinations. A 4D Flow MRI sequence (phase-contrast vastly under sampled isotropic projection imaging) measured intracranial arterial flow in the Circle of Willis. Linear mixed-effects regression models estimated relationships between risk factors and intracranial arterial flow and tested interactions with racial group, APOE genotype, and AD biomarkers, with separate models per risk factor. RESULTS: Higher fasting glucose was associated with lower intracranial arterial flow; no additional relationships between flow and risk factors were observed. Main effects of racial group were observed, without an interaction, indicating lower flow in African Americans compared to Whites. In race-stratified analyses, higher glucose and triglycerides were associated with lower flow for African Americans, but not for Whites. No main effects or interactions among risk factors, APOE, or AD biomarkers, and flow were observed. CONCLUSION: Elevated fasting glucose and triglycerides were associated with lower intracranial arterial flow; these relationships were more prominent in African Americans. Targeting metabolic risk factors may impact intracranial arterial health. Additional research is needed to determine if this will impact disparities in dementia prevalence.

Serial Quantitative and Qualitative Measurements of Flow in Vein of Galen Malformations Using 4-Dimensional Flow Magnetic Resonance Imaging (Phase Contrast Vastly undersampled Isotropic PRojection).

BACKGROUND: Vein of Galen malformations (VoGMs) induce cerebrovascular dysfunction through arterial steal and venous hypertension resulting, if untreated, in severe neurologic morbidity and mortality. Noninvasive techniques for quantitative, serial evaluation of cerebrovascular hemodynamics in VoGMs are lacking. This proof of concept study using quantitative blood flow measurements from 4-dimensional flow magnetic resonance imaging may be useful as a noninvasive biomarker to guide timing of intervention and assess disease progression and treatment outcomes. CASE DESCRIPTION: Between July 2016 and July 2018, 4 patients harboring VoGMs underwent Phase Contrast Vastly undersampled Isotropic PRojection (PCVIPR) imaging at the University of Wisconsin Hospitals and Clinics. We applied PCVIPR imaging to assess its potential for obtaining anatomic and physiologic flow data before and after surgical embolization of VoGMs. Hemodynamic pressure parameters obtained from PCVIPR imaging were compared with stump pressures recorded in vivo. We found a decrease in mean arterial pressure from 97 mm Hg pretreatment to 65 mm Hg post treatment. These findings corroborate the decrement in venous pressure gradients documented on PCVIPR imaging. For all patients, pressure gradient changes on PCVIPR imaging correlated with in vivo arterial pressures and aided in clinical decision related to cerebrovascular evaluation, treatment planning, and clinical course. CONCLUSIONS: Four-dimensional flow magnetic resonance imaging/PCVIPR imaging has a potential role in determining endovascular embolization and therapeutic outcomes on the basis of objective and reproducible hemodynamic characteristics of the vascular lesion. It represents a novel, noninvasive approach that may guide the extent and timing of therapeutic intervention and treatment of cerebrovascular diseases in pediatric patients.

Measurement of microvascular cerebral blood volume changes over the cardiac cycle with ferumoxytol-enhanced T2* MRI.

PURPOSE: This feasibility study investigates the non-invasive measurement of microvascular cerebral blood volume (BV) changes over the cardiac cycle using cardiac-gated, ferumoxytol-enhanced T2∗ MRI. METHODS: Institutional review board approval was obtained and all subjects provided written informed consent. Cardiac gated MR scans were prospectively acquired on a 3.0T scanner in 22 healthy subjects using T2∗ -weighted sequences with 2D-EPI and 3D spiral trajectories. Images were collected before and after the intravenous administration of 2 doses of ferumoxytol (1 mg FE/kg and 4 mg FE/kg). Cardiac cycle-induced R2∗ (1/ T2∗ ) changes (Δ R2∗ ) and BV changes (ΔBV) throughout the cardiac cycle in gray matter (GM) and white matter (WM) were quantified and differences assessed using ANOVA followed by post hoc analysis. RESULTS: Δ R2∗ was found to increase in a dose-dependent fashion. A significantly larger increase was observed in GM compared to WM in both 2D and 3D acquisitions (P < 0.050). In addition, Δ R2∗ increased significantly (P < 0.001) post versus pre-contrast injection in GM in both T2∗ MRI acquisitions. Mean GM Δ R2∗ derived from 2D-EPI images was 0.14 ± 0.06 s-1 pre-contrast and 0.33 ± 0.13 s-1 after 5 mg FE/kg. In WM, Δ R2∗ was 0.19 ± 0.06 s-1 pre-contrast, and 0.23 ± 0.06 s-1 after 5 mg FE/kg. The fractional changes in BV throughout the cardiac cycle were 0.031 ± 0.019% in GM and 0.011 ± 0.008% in WM (P < 0.001) after 5 mg FE/kg. CONCLUSION: Cardiac-gated, ferumoxytol-enhanced T2∗ MRI enables characterization of microvascular BV changes throughout the cardiac cycle in GM and WM tissue of healthy subjects.

Robust Motion Correction Strategy for Structural MRI in Unsedated Children Demonstrated with Three-dimensional Radial MPnRAGE.

Purpose To develop and evaluate a retrospective method to minimize motion artifacts in structural MRI. Materials and Methods The motion-correction strategy was developed for three-dimensional radial data collection and demonstrated with MPnRAGE, a technique that acquires high-resolution volumetric magnetization-prepared rapid gradient-echo, or MPRAGE, images with multiple tissue contrasts. Forty-four pediatric participants (32 with autism spectrum disorder [mean age ± standard deviation, 13 years ± 3] and 12 age-matched control participants [mean age, 12 years ± 3]) were imaged without sedation. Images with and images without retrospective motion correction were scored by using a Likert scale (0-4 for unusable to excellent) by two experienced neuroradiologists. The Tenengrad metric (a reference-free measure of image sharpness) and statistical analyses were performed to determine the effects of performing retrospective motion correction. Results MPnRAGE T1-weighted images with retrospective motion correction were all judged to have good or excellent quality. In some cases, retrospective motion correction improved the image quality from unusable (Likert score of 0) to good (Likert score of 3). Overall, motion correction improved mean Likert scores from 3.0 to 3.8 and reduced standard deviations from 1.1 to 0.4. Image quality was significantly improved with motion correction (Mann-Whitney U test; P < .001). Intraclass correlation coefficients for absolute agreement of Tenengrad scores with reviewers 1 and 2 were 0.92 and 0.88 (P < .0005 for both), respectively. In no cases did the retrospective motion correction induce severe image degradation. Conclusion Retrospective motion correction of MPnRAGE data were shown to be highly effective for consistently improving image quality of T1-weighted MRI in unsedated pediatric participants, while also enabling multiple tissue contrasts to be reconstructed for structural analysis. © RSNA, 2018 Online supplemental material is available for this article.

Circumferential Thick Enhancement at Vessel Wall MRI Has High Specificity for Intracranial Aneurysm Instability.

Purpose To identify wall enhancement patterns on vessel wall MRI that discriminate between stable and unstable unruptured intracranial aneurysm (UIA). Materials and Methods Patients were included from November 2012 through January 2016. Vessel wall MR images were acquired at 3 T in patients with stable (incidental and nonchanging over 6 months) or unstable (symptomatic or changing over 6 months) UIA. Each aneurysm was evaluated by using a four-grade classification of enhancement: 0, none; 1, focal; 2, thin circumferential; and 3, thick (>1 mm) circumferential. Inter- and intrareader agreement for the presence and the grade of enhancement were assessed by using κ statistics and 95% confidence interval (CI). The sensitivity, specificity, and negative and positive predictive values of each enhancement grade for differentiating stable from unstable aneurysms was compared. Results The study included 263 patients with 333 aneurysms. Inter- and intrareader agreement was excellent for both the presence of enhancement (κ values, 0.82 [95% CI: 0.67, 0.99] and 0.87 [95% CI: 0.7, 1.0], respectively) and enhancement grade (κ = 0.92 [95% CI: 0.87, 0.95]). In unruptured aneurysms (n = 307), grade 3 enhancement exhibited the highest specificity (84.4%; 233 of 276; 95% CI: 80.1%, 88.7%; P = .02) and negative predictive value (94.3%; 233 of 247) for differentiating between stable and unstable lesions. There was a significant association between grade 3 enhancement and aneurysm instability (P < .0001). Conclusion In patients with intracranial aneurysm, a thick (>1 mm) circumferential pattern of wall enhancement demonstrated the highest specificity for differentiating between stable and unstable aneurysms. © RSNA, 2018.

Non contrast, Pseudo-Continuous Arterial Spin Labeling and Accelerated 3-Dimensional Radial Acquisition Intracranial 3-Dimensional Magnetic Resonance Angiography for the Detection and Classification of Intracranial Arteriovenous Shunts.

OBJECTIVES: The aim of this study was to assess the sensitivity and specificity of pseudo-continuous arterial spin labeling (PCASL) magnetic resonance angiography (MRA) with 3-dimensional (3D) radial acquisition for the detection of intracranial arteriovenous (AV) shunts. MATERIALS AND METHODS: A total of 32 patients who underwent PCASL-MRA, clinical magnetic resonance imaging (MRI)/MRA exam, and digital subtraction angiography (DSA) were included in this retrospective analysis. Twelve patients presented with AV shunts. Among these were 8 patients with AV malformations (AVM) and 4 patients with AV fistulas (AVF). The clinical MRI/MRA included 3D time-of-flight MRA in all cases and time-resolved, contrast-enhanced MRA in 9 cases (6 cases with AV shunting). Research MRI and clinical MRI were independently evaluated by 2 neuroradiologists blinded to patient history. A third radiologist evaluated DSA imaging. A diagnostic confidence score was used for the presence of abnormalities associated with AV shunting (1-5). The AVMs were characterized using the Spetzler-Martin scale, whereas AVFs were characterized using the Borden classification. κ Statistics were applied to assess intermodality agreement. RESULTS: Compared with clinical MRA, noncontrast PCASL-MRA with 3D radial acquisition yielded excellent sensitivity and specificity for the detection of intracranial AV shunts (reader 1: 100%/100%, clinical MRA: 91.7%, 94.4%; reader 2: 91.7%/100%, clinical MRA: 91.7%/100%). Diagnostic confidence was 4.8/4.66 with PCASL-MRA and 4.25/4.66 with clinical MRA. For AVM characterization with PCASL-MRA, intermodality agreement with DSA showed κ values of 0.43 and 0.6 for readers 1 and 2, respectively. For AVF characterization, intermodality agreement showed κ values of 0.56 for both readers. CONCLUSION: Noncontrast PCASL-MRA with 3D radial acquisition is a potential tool for the detection and characterization of intracranial AV shunts with a sensitivity and specificity equivalent or higher than routine clinical MRA.

Comparison of ferumoxytol-based cerebral blood volume estimates using quantitative R1 and R2* relaxometry.

PURPOSE: Cerebral perfusion is commonly assessed clinically with dynamic susceptibility contrast MRI using a bolus injection of gadolinium-based contrast agents, resulting in semi-quantitative values of cerebral blood volume (CBV). Steady-state imaging with ferumoxytol allows estimation of CBV with the potential for higher precision and accuracy. Prior CBV studies have focused on the signal disrupting T2* effects, but ferumoxytol also has high signal-enhancing T1 relaxivity. The purpose of this study was to investigate and compare CBV estimation using T1 and T2*, with the goal of understanding the contrast mechanisms and quantitative differences. METHODS: Changes in R1 (1/T1 ) and R2* (1/ T2*) were measured after the administration of ferumoxytol using high-resolution quantitative approaches. Images were acquired at 3.0T and R1 was estimated from an ultrashort echo time variable flip angle approach, while R2* was estimated from a multiple gradient echo sequence. Twenty healthy volunteers were imaged at two doses. CBV was derived and compared from relaxometry in gray and white matter using different approaches. RESULTS: R1 measurements showed a linear dependence of blood R1 with respect to dose in large vessels, in contrast to the nonlinear dose-dependence of blood R2* estimates. In the brain parenchyma, R2* showed linear dose-dependency whereas R1 showed nonlinearity. CBV calculations based on R2* changes in tissue and ferumoxytol blood concentration estimates based on R1 relaxivity showed the lowest variability in our cohort. CONCLUSIONS: CBV measurements were successfully derived using a combined approach of R1 and R2* relaxometry. Magn Reson Med 79:3072-3081, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Intracranial Arterial 4D Flow in Individuals with Mild Cognitive Impairment is Associated with Cognitive Performance and Amyloid Positivity.

It is becoming increasingly recognized that cerebrovascular disease is a contributing factor in the pathogenesis of Alzheimer's disease (AD). A unique 4D-Flow magnetic resonance imaging (MRI) technique, phase contrast vastly undersampled isotropic projection imaging (PC VIPR), enables examination of angiographic and quantitative metrics of blood flow in the arteries of the Circle of Willis within a single MRI acquisition. Thirty-eight participants with mild cognitive impairment (MCI) underwent a comprehensive neuroimaging protocol (including 4D-Flow imaging) and a standard neuropsychological battery. A subset of participants (n = 22) also underwent lumbar puncture and had cerebrospinal fluid (CSF) assayed for AD biomarkers. Cut-offs for biomarker positivity in CSF resulting from a receiver operating characteristic curve analysis of AD cases and controls from the larger Wisconsin Alzheimer's Disease Research Center cohort were used to classify MCI participants as biomarker positive or negative on amyloid-ß (Aß42), total-tau and total-tau/Aß42 ratio. Internal carotid artery (ICA) and middle cerebral artery (MCA) mean flow were associated with executive functioning performance, with lower mean flow corresponding to worse performance. MCI participants who were biomarker positive for Aß42 had lower ICA mean flow than did those who were Aß42 negative. In sum, mean ICA and MCA arterial flow was associated with cognitive performance in participants with MCI and lower flow in the ICA was associated with amyloid positivity. This provides further evidence for vascular health as a contributing factor in the etiopathogenesis of AD, and could represent a point to intervene in the disease process.

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.

Macrovascular and microvascular cerebral blood flow in adults at risk for Alzheimer's disease.

INTRODUCTION: Capillary hypoperfusion is reported in asymptomatic adults at-risk for Alzheimer's disease (AD), but the extent that can be explained by reduced flow in intracranial arteries is unknown. METHODS: One hundred fifty-five asymptomatic adults enriched for AD risk (mean age 61 years) completed arterial spin labeling (pcASL) and 4D-flow MRI sequences. Voxel-wise regression models investigated the relationship between mean flow in bilateral cerebral arteries and capillary perfusion, and tested potential moderators of this relationship. RESULTS: Mean arterial blood flow through middle cerebral arteries (MCAs) and internal carotid arteries was positively associated with perfusion in large cortical clusters (P < .05, false discovery rate corrected). Trends were observed for the interactions MCA flow × age and MCA flow × cardiovascular risk on cerebral perfusion (P < .001, uncorrected). DISCUSSION: These findings provide evidence that capillary perfusion measured via pseudocontinuous arterial spin labeling is strongly dependent on inflow from larger cerebral arteries. Further studies are warranted to investigate possible alterations between macrovascular and microvascular flow in advanced age and elevated cardiovascular risk in asymptomatic adults at risk for AD.

Changes in intracranial venous blood flow and pulsatility in Alzheimer's disease: A 4D flow MRI study.

Cerebral blood flow, arterial pulsation, and vasomotion may be important indicators of cerebrovascular health in aging and diseases of aging such as Alzheimer's disease. Noninvasive markers that assess these characteristics may be helpful in the study of co-occurrence of these diseases and potential additive and interacting effects. In this study, 4D flow MRI was used to measure intra-cranial flow features with cardiac-gated phase contrast MRI in cranial arteries and veins. Mean blood flow and pulsatility index as well as the transit time of the peak flow from the middle cerebral artery to the superior sagittal sinus were measured in a total of 104 subjects comprising of four groups: (a) subjects with Alzheimer's disease, (b) age-matched controls, (c) subjects with mild cognitive impairment, and (d) a group of late middle-aged with parental history of sporadic Alzheimer's disease. The Alzheimer's disease group exhibited: a significant decrease in mean blood flow in the superior sagittal sinus, transverse sinus, middle cerebral artery, and internal carotid arteries; a significant decrease of the peak and end diastolic blood flow in the middle cerebral artery and superior sagittal sinus; a faster transmission of peak flow from the middle cerebral artery to the superior sagittal sinus and increased pulsatility index along the carotid siphon.

Time-of-Arrival Parametric Maps and Virtual Bolus Images Derived From Contrast-Enhanced Time-Resolved Radial Magnetic Resonance Angiography Improve the Display of Brain Arteriovenous Malformation Vascular Anatomy.

OBJECTIVES: Time-of-arrival (TOA) maps can be derived from high-resolution 4-dimensional (4D) contrast-enhanced magnetic resonance angiography (MRA) data sets to provide a quantitative description of contrast material arrival time in each voxel. This information can further be processed to create a compressed time evolution curve that virtually shortens the contrast bolus (virtual bolus [VB]). The purpose of this project was to determine whether TOA-enhanced 4D MRA and/or VB imaging improve the display of contrast kinetics in patients with vascular disease. METHODS: High-resolution whole-brain contrast-enhanced 4D MRA examinations with 1.2-second temporal reconstruction were acquired by using radial acquisition and highly constrained projection reconstruction (radial 4D contrast-enhanced HYPRFlow, abbreviated as HFMRA in this article) in 10 patients (8 patients with arteriovenous malformations [AVM], 1 patient with an arteriovenous fistula, and 1 patient with a high-grade intracranial stenosis). The TOA for each voxel was defined as the time point when the signal intensity reached 20% of its maximum. In the first method, TOA maps were generated, color-encoded, and then multiplied with the time-resolved contrast-enhanced MRA images at each time frame to form new 4D MRA images (TOA-enhanced HFMRA), which contains the contrast arrival times with defined color encoding. In the second method, each time frame was weighted by a Gaussian distribution in the time domain to form a virtual 4D bolus map. This 4D bolus map was then color-coded and multiplied with the HFMRA images to form a digital subtraction angiography (DSA)-like VB, where at each time frame, only vessels with certain TOA values within the defined bolus length appear. HFMRA, TOA maps, and VB images were scored qualitatively with regard to delineation of arteries, veins, and nidus, as well as artifacts. Furthermore, diagnostic confidence and arteriovenous overlap were evaluated and compared between techniques. A comparison with DSA was performed where DSA served as the reference standard in terms of number of arterial feeders, draining veins, and Spetzler-Martin score of AVMs. In addition, TOA maps were evaluated quantitatively. RESULTS: Overall, diagnostic confidence score of TOA was significantly higher compared with that of HFMRA (P = 0.03). Virtual bolus showed significantly higher scores for overall diagnostic confidence (P = 0.02) and reduced arteriovenous overlap (0.01) compared with HFMRA. Furthermore, VB-reduced arteriovenous overlap scores were significantly higher compared with TOA (P = 0.04). Agreement regarding AVM draining veins was lower between DSA and HFMRA (κ = 0.3) compared with TOA and VB (κ = 0.56). Agreement regarding Spetzler-Martin score was lower between DSA and HFMRA (κ = 0.56) compared with TOA and VB (κ = 0.74). CONCLUSIONS: TOA-enhanced HFMRA provides serial images and time of arrival maps in one inclusive display. In this study, TOA mapping combined with Virtual Bolus imaging improved diagnostic confidence in AVM patients and facilitated arteriovenous separation. The VB method further reduced overlap of arterial and venous structures.

Accelerated Time-Resolved Contrast-Enhanced Magnetic Resonance Angiography of Dural Arteriovenous Fistulas Using Highly Constrained Reconstruction of Sparse Cerebrovascular Data Sets.

OBJECTIVE: Time-resolved contrast-enhanced magnetic resonance angiography (MRA) is commonly used to noninvasively characterize vascular malformations. However, the spatial and temporal resolution of current methods often compromises the clinical value of the examinations. Constrained reconstruction is a temporal spatial correlation strategy that exploits the relative sparsity of vessels in space to dramatically reduce the amount of data required to generate fast high-resolution time-resolved contrast-enhanced MRA studies. In this report, we use a novel temporal spatial acceleration method termed HYPRFlow to diagnose and classify dural arteriovenous fistulas (DAVFs). Our hypothesis is that HYPRFlow images are of adequate diagnostic image quality to delineate the arterial and venous components of DAVFs and allow correct classification using the Cognard system. SUBJECTS AND METHODS: Eight patients with known DAVFs underwent HYPRFlow imaging with isotropic resolution of 0.68 mm and temporal resolution of 0.75 second and 3-dimensional time-of-flight (3DTOF) MRA. The 3DTOF images and HYPRFlow images were evaluated by 2 readers and scored for arterial anatomic image quality. Digital subtraction angiography (DSA) was available for comparison in 7 subjects, and for these patients, each DAVF was classified according to the Cognard system using HYPRFlow and DSA examinations. Digital subtraction angiography was considered the reference examination or criterion standard. RESULTS: HYPRFlow imaging classification was concordant with DSA in all but 1 case. There was no difference in the arterial image quality scores between HYPRFlow and 3DTOF MRA (95% confidence interval). Arterial-to-venous separation was rated excellent (n = 3), good (n = 4), or poor (n = 1), and arteriovenous shunting was easily appreciated. Undersampling artifacts were reduced by using a low pass filter and did not interfere with the diagnostic quality of the examinations. CONCLUSIONS: HYPRFlow is a novel acquisition and reconstruction technique that exploits the relative sparsity of intracranial vessels in space to increase temporal and spatial resolution and provides accurate delineation of DAVF vasculature.

4D flow MRI for intracranial hemodynamics assessment in Alzheimer's disease.

Cerebral blood flow, arterial pulsation, and vasomotion play important roles in the transport of waste metabolites out of the brain. Impaired vasomotion results in reduced driving force for the perivascular/glymphatic clearance of beta-amyloid. Noninvasive cerebrovascular characteristic features that potentially assess these transport mechanisms are mean blood flow (MBF) and pulsatility index (PI). In this study, 4D flow MRI was used to measure intra-cranial flow features, particularly MBF, PI, resistive index (RI) and cross-sectional area in patients with Alzheimer's disease (AD), mild cognitive impairment and in age matched and younger cognitively healthy controls. Three-hundred fourteen subjects participated in this study. Volumetric, time-resolved phase contrast (PC) MRI data were used to quantify hemodynamic parameters from 11 vessel segments. Anatomical variants of the Circle of Willis were also cataloged. The AD population reported a statistically significant decrease in MBF and cross-sectional area, and also an increase in PI and RI compared to age matched cognitively healthy control subjects. The 4D flow MRI technique used in this study provides quantitative measurements of intracranial vessel geometry and the velocity of flow. Cerebrovascular characteristics features of vascular health such as pulsatility index can be extracted from the 4D flow MRI data.