Assessment of arterial pulsatility of cerebral perforating arteries using 7T high-resolution dual-VENC phase-contrast MRI.

PURPOSE: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T. METHODS: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated. RESULTS: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups. CONCLUSION: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD.

CSF-to-blood toxins clearance is modulated by breathing through cranio-spinal CSF oscillation.

Clearance of brain toxins occurs during sleep, although the mechanism remains unknown. Previous studies implied that the intracranial aqueductal cerebrospinal fluid (CSF) oscillations are involved, but no mechanism was suggested. The rationale for focusing on the aqueductal CSF oscillations is unclear. This study focuses on the cranio-spinal CSF oscillation and the factors that modulate this flow. We propose a mechanism where increased cranio-spinal CSF movements enhance CSF-to-blood metabolic waste clearance through the spinal CSF re-absorption sites. A recent study demonstrating that disturbed sleep impairs CSF-to-blood but not brain-to-CSF clearance, supports the fundamentals of our proposed mechanism. Eight healthy subjects underwent phase-contrast magnetic resonance imaging to quantify the effect of respiration on the cranio-spinal CSF oscillations. Maximal CSF volume displaced from the cranium to the spinal canal during each respiration and cardiac cycle were derived as measures of cranio-spinal CSF mixing level. Transition from normal to slow and abdominal breathing resulted in a 56% increase in the maximal displaced CSF volume. Maximal change in the arterial-venous blood volume, which is the driving force of the CSF oscillations, was increased by 41% during slow abdominal breathing. Cranio-spinal CSF oscillations are driven by the momentary difference between arterial inflow and venous outflow. Breathing modulates the CSF oscillation through changes in the venous outflow. The amount of toxins being transferred to the spinal canal during each respiratory cycle is significantly increased during slow and deeper abdominal breathing, which explains enhanced CSF-to-blood toxins clearance during slow-wave sleep and poor clearance during disrupted sleep.

Respiratory-resolved 5D Flow MRI: in-vivo validation and respiratory dependent flow changes in healthy volunteers and patients with congenital heart disease.

BACKGROUND: This study aimed to validate respiratory-resolved 5D flow MRI against real-time 2D phase contrast MRI, assess the impact of number of respiratory states, and measure the impact of respiration on hemodynamics in congenital heart disease (CHD) patients. METHODS: Respiratory-resolved 5D flow MRI derived net and peak flow measurements were compared to real-time 2D phase contrast MRI derived measurements in 10 healthy volunteers. Pulmonary to systemic flow ratios (Qp:Qs) were measured in 19 CHD patients and aortopulmonary collateral burden was measured in 5 Fontan patients. Additionally, the impact of number of respiratory states on measured respiratory-driven net flow changes was investigated in 10 healthy volunteers and 19 CHD patients (shunt physiology, n=11, single ventricle disease (SVD), n=8). RESULTS: There was good agreement between 5D flow MRI and real-time 2D phase contrast derived net and peak flow. Respiratory driven changes had good correlation (rho=0.64, p<0.001). In healthy volunteers, fewer than four respiratory states reduced measured respiratory driven flow changes in veins (5.2mL/cycle, p<0.001) and arteries (1.7mL/cycle, p=0.05). Respiration drove substantial venous net flow changes in SVD (64% change) and shunt patients (57% change). Respiration had significantly greater impact in SVD patients compared to shunt patients in the right and left pulmonary arteries (46% vs 15%, p=0.003 & 59% vs 20%, p=0.002). Qp:Qs varied by 37±24% over respiration in SVD patients and 12±20% in shunt patients. Aortopulmonary collateral burden varied by 118±84% over respiration in Fontan patients. The smallest collateral burden was measured during active inspiration in all patients and the greatest burden was during active expiration in 4 of 5 patients. Reduced respiratory resolution blunted measured flow changes in the caval veins of shunt and SVD patients (p<0.005). CONCLUSIONS: Respiratory-resolved 5D flow MRI measurements agree with real-time 2D phase contrast. Venous measurements are sensitive to number of respiratory states, whereas arterial measurements are more robust. Respiration has substantial impact on caval vein flow, Qp:Qs, and collateral burden in CHD patients.

Phase-contrast magnetic resonance imaging of intracranial and extracranial blood flow in carotid near-occlusion.

PURPOSE: Compare extracranial internal carotid artery flow rates and intracranial collateral use between conventional ≥ 50% carotid stenosis and carotid near-occlusion, and between symptomatic and asymptomatic carotid near-occlusion. METHODS: We included patients with ≥ 50% carotid stenosis. Degree of stenosis was diagnosed on CTA. Mean blood flow rates were assessed with four-dimensional phase-contrast MRI. RESULTS: We included 110 patients of which 83% were symptomatic, and 38% had near-occlusion. Near-occlusions had lower mean internal carotid artery flow (70 ml/min) than conventional ≥ 50% stenoses (203 ml/min, P < .001). Definite use of ≥ 1 collateral was found in 83% (35/42) of near-occlusions and 10% (7/68) of conventional stenoses (P < .001). However, there were no differences in total cerebral blood flow (514 ml/min vs. 519 ml/min, P = .78) or ipsilateral hemispheric blood flow (234 vs. 227 ml/min, P = .52), between near-occlusions and conventional ≥ 50% stenoses, based on phase-contrast MRI flow rates. There were no differences in total cerebral or hemispheric blood flow, or collateral use, between symptomatic and asymptomatic near-occlusions. CONCLUSION: Near-occlusions have lower internal carotid artery flow rates and more collateral use, but similar total cerebral blood flow and hemispheric blood flow, compared to conventional ≥ 50% carotid stenosis.

CSF and venous blood flow from childhood to adulthood studied by real-time phase-contrast MRI.

PURPOSE: In vivo measurements of CSF and venous flow using real-time phase-contrast (RT-PC) MRI facilitate new insights into the dynamics and physiology of both fluid systems. In clinical practice, however, use of RT-PC MRI is still limited. Because many forms of hydrocephalus manifest in infancy and childhood, it is a prerequisite to investigate normal flow parameters during this period to assess pathologies of CSF circulation. This study aims to establish reference values of CSF and venous flow in healthy subjects using RT-PC MRI and to determine their age dependency. METHODS: RT-PC MRI was performed in 44 healthy volunteers (20 females, age 5-40 years). CSF flow was quantified at the aqueduct (Aqd), cervical (C3) and lumbar (L3) spinal levels. Venous flow measurements comprised epidural veins, internal jugular veins and inferior vena cava. Parameters analyzed were peak velocity, net flow, pulsatility, and area of region of interest (ROI). STATISTICAL TESTS: linear regression, student's t-test and analysis of variance (ANOVA). RESULTS: In adults volunteers, no significant changes in flow parameters were observed. In contrast, pediatric subjects exhibited a significant age-dependent decrease of CSF net flow and pulsatility in Aqd, C3 and L3. Several venous flow parameters decreased significantly over age at C3 and changed more variably at L3. CONCLUSION: Flow parameters varies depending on anatomical location and age. We established changes of brain and spinal fluid dynamics over an age range from 5-40 years. The application of RT-PC MRI in clinical care may improve our understanding of CSF flow pathology in individual patients.

Assessment of neurofluid dynamics in relation to clinical improvement after tap-test: pilot study.

PURPOSE: Idiopathic Normal pressure hydrocephalus (iNPH) is an under-diagnosed in elderly patients but none of the diagnostic tests are currently sufficiently sensitive or specific. The objective of this study was to analyze the dynamics of neurofluids by PC-MRI in relation to clinical evolution as measured using the iNPH grading scale after tap-test. METHOD: We prospectively included patients with suspected iNPH. All these patients underwent PCMRI to assess craniospinal hemohydrodynamics with analysis of the stroke volume of the cephalospinal fluid (CSF) within the Sylvius' aqueduct, within the high cervical subarachnoid spaces and the arteriovenous stroke volume. By this means, we calculated a compliance index. Morphological analysis was carried out using the DESH score. The infusion test was measuring the resistance to CSF flow. We analysed all these parameters according to the clinical improvement of the patients. RESULTS: 23 patients were included. Compliance index assessed by PC-MRI was significantly higher in the group of patients with improvement > 10% (p = 0.015). CONCLUSIONS: Our study highlights the importance of investigating arteriovenous and CSF interactions in iNPH. This involves understanding the physiological and pathophysiological mechanisms related to the circulation of neurofluids. The analysis of the interactions of these neurofluids allows for a comprehensive understanding of the system.

A comparison of phase unwrapping methods in velocity-encoded MRI for aortic flows.

PURPOSE: The phase of a MRI signal is used to encode the velocity of blood flow. Phase unwrapping artifacts may appear when aiming to improve the velocity-to-noise ratio (VNR) of the measured velocity field. This study aims to compare various unwrapping algorithms on ground-truth synthetic data generated using computational fluid dynamics (CFD) simulations. METHODS: We compare four different phase unwrapping algorithms on two different synthetic datasets of four-dimensional flow MRI and 26 datasets of 2D PC-MRI acquisitions including the ascending and descending aorta. The synthetic datasets are constructed using CFD simulations of an aorta with a coarctation, with different levels of spatiotemporal resolutions and noise. The error of the unwrapped images was assessed by comparison against the ground truth velocity field in the synthetic data and dual-VENC reconstructions in the in vivo data. RESULTS: Using the unwrapping algorithms, we were able to remove aliased voxels in the data almost entirely, reducing the L2-error compared to the ground truth by 50%-80%. Results indicated that the best choice of algorithm depend on the spatiotemporal resolution and noise level of the dataset. Temporal unwrapping is most successful with a high temporal and low spatial resolution ( δ t = 30 $$ \delta t=30 $$ ms, h = 2 . 5 $$ h=2.5 $$ mm), reducing the L2-error by 70%-85%, while Laplacian unwrapping performs better with a lower temporal or better spatial resolution ( δ t = 60 $$ \delta t=60 $$ ms, h = 1 . 5 $$ h=1.5 $$ mm), especially for signal-to-noise ratio (SNR) 12 as opposed to SNR 15, with an error reduction of 55%-85% compared to the 50%-75% achieved by the Temporal method. The differences in performance between the methods are statistically significant. CONCLUSIONS: The temporal method and spatiotemporal Laplacian method provide the best results, with the spatiotemporal Laplacian being more robust. However, single- V enc $$ {V}_{\mathrm{enc}} $$ methods only situationally and not generally reach the performance of dual- V enc $$ {V}_{\mathrm{enc}} $$ unwrapping methods.

Motion-resolved real-time 4D flow MRI with low-rank and subspace modeling.

PURPOSE: To develop a new motion-resolved real-time four-dimensional (4D) flow MRI method, which enables the quantification and visualization of blood flow velocities with three-directional flow encodings and volumetric coverage without electrocardiogram (ECG) synchronization and respiration control. METHODS: An integrated imaging method is presented for real-time 4D flow MRI, which encompasses data acquisition, image reconstruction, and postprocessing. The proposed method features a specialized continuous ( k , t ) $$ \left(\mathbf{k},t\right) $$ -space acquisition scheme, which collects two sets of data (i.e., training data and imaging data) in an interleaved manner. By exploiting strong spatiotemporal correlation of 4D flow data, it reconstructs time-series images from highly-undersampled ( k , t ) $$ \left(\mathbf{k},t\right) $$ -space measurements with a low-rank and subspace model. Through data-binning-based postprocessing, it constructs a five-dimensional dataset (i.e., x-y-z-cardiac-respiratory), from which respiration-dependent flow information is further analyzed. The proposed method was evaluated in aortic flow imaging experiments with ten healthy subjects and two patients with atrial fibrillation. RESULTS: The proposed method achieves 2.4 mm isotropic spatial resolution and 34.4 ms temporal resolution for measuring the blood flow of the aorta. For the healthy subjects, it provides flow measurements in good agreement with those from the conventional 4D flow MRI technique. For the patients with atrial fibrillation, it is able to resolve beat-by-beat pathological flow variations, which cannot be obtained from the conventional technique. The postprocessing further provides respiration-dependent flow information. CONCLUSION: The proposed method enables high-resolution motion-resolved real-time 4D flow imaging without ECG gating and respiration control. It is able to resolve beat-by-beat blood flow variations as well as respiration-dependent flow information.

Spinal cord motion and CSF flow in the cervical spine of 70 healthy participants.

Pulsatile spinal cord and CSF velocities related to the cardiac cycle can be depicted by phase-contrast MRI. Among patients with spontaneous intracranial hypotension, we have recently described relevant differences compared with healthy controls in segment C2/C3. The method might be a promising tool to solve clinical and diagnostic ambiguities. Therefore, it is important to understand the physiological range and the effects of clinical and anatomical parameters in healthy volunteers. Within a prospective study, 3D T2 -weighted MRI for spinal canal anatomy and cardiac-gated phase-contrast MRI adapted to CSF flow and spinal cord motion for time-resolved velocity data and derivatives were performed in 70 participants (age 20-79 years) in segments C2/C3 and C5/C6. Correlations were analyzed by multiple linear regression models; p < 0.01 was required to assume a significant impact of clinical or anatomical data quantified by the regression coefficient B. Data showed that in C2/C3, the CSF and spinal cord craniocaudal velocity ranges were 4.5 ± 0.9 and 0.55 ± 0.15 cm/s; the total displacements were 1.1 ± 0.3 and 0.07 ± 0.02 cm, respectively. The craniocaudal range of the CSF flow rate was 8.6 ± 2.4 mL/s; the CSF stroke volume was 2.1 ± 0.7 mL. In C5/C5, physiological narrowing of the spinal canal caused higher CSF velocity ranges and lower stroke volume (C5/C6 B = +1.64 cm/s, p < 0.001; B = -0.4 mL, p = 0.002, respectively). Aging correlated to lower spinal cord motion (e.g., B = -0.01 cm per 10 years of aging, p < 0.001). Increased diastolic blood pressure was associated with lower spinal cord motion and CSF flow parameters (e.g., C2/C3 CSF stroke volume B = -0.3 mL per 10 mmHg, p < 0.001). Males showed higher CSF flow and spinal cord motion (e.g., CSF stroke volume B = +0.5 mL, p < 0.001; total displacement spinal cord B = +0.016 cm, p = 0.002). We therefore propose to stratify data for age and sex and to adjust for diastolic blood pressure and segmental narrowing in future clinical studies.

Highly Accelerated Compressed-Sensing 4D Flow for Intracardiac Flow Assessment.

BACKGROUND: Four-dimensional (4D) flow MRI allows for the quantification of complex flow patterns; however, its clinical use is limited by its inherently long acquisition time. Compressed sensing (CS) is an acceleration technique that provides substantial reduction in acquisition time. PURPOSE: To compare intracardiac flow measurements between conventional and CS-based highly accelerated 4D flow acquisitions. STUDY TYPE: Prospective. SUBJECTS: Fifty healthy volunteers (28.0 ± 7.1 years, 24 males). FIELD STRENGTH/SEQUENCE: Whole heart time-resolved 3D gradient echo with three-directional velocity encoding (4D flow) with conventional parallel imaging (factor 3) as well as CS (factor 7.7) acceleration at 3 T. ASSESSMENT: 4D flow MRI data were postprocessed by applying a valve tracking algorithm. Acquisition times, flow volumes (mL/cycle) and diastolic function parameters (ratio of early to late diastolic left ventricular peak velocities [E/A] and ratio of early mitral inflow velocity to mitral annular early diastolic velocity [E/e']) were quantified by two readers. STATISTICAL TESTS: Paired-samples t-test and Wilcoxon rank sum test to compare measurements. Pearson correlation coefficient (r), Bland-Altman-analysis (BA) and intraclass correlation coefficient (ICC) to evaluate agreement between techniques and readers. A P value < 0.05 was considered statistically significant. RESULTS: A significant improvement in acquisition time was observed using CS vs. conventional accelerated acquisition (6.7 ± 1.3 vs. 12.0 ± 1.3 min). Net forward flow measurements for all valves showed good correlation (r > 0.81) and agreement (ICCs > 0.89) between conventional and CS acceleration, with 3.3%-8.3% underestimation by the CS technique. Evaluation of diastolic function showed 3.2%-17.6% error: E/A 2.2 [1.9-2.4] (conventional) vs. 2.3 [2.0-2.6] (CS), BA bias 0.08 [-0.81-0.96], ICC 0.82; and E/e' 4.6 [3.9-5.4] (conventional) vs. 3.8 [3.4-4.3] (CS), BA bias -0.90 [-2.31-0.50], ICC 0.89. DATA CONCLUSION: Analysis of intracardiac flow patterns and evaluation of diastolic function using a highly accelerated 4D flow sequence prototype is feasible, but it shows underestimation of flow measurements by approximately 10%. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Validation of 4D flow cardiovascular magnetic resonance in TIPS stent grafts using a 3D-printed flow phantom.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is feasible for portal blood flow evaluation after placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with liver cirrhosis. However, clinical acceptance of 4D flow CMR in TIPS patients is limited due to the lack of validation studies. The purpose of this study was to validate 4D flow CMR-derived measurements in TIPS stent grafts using a three-dimensional (3D)-printed flow phantom. METHODS: A translucent flow phantom of the portal vasculature was 3D-printed. The phantom consisted of the superior mesenteric vein and the splenic vein draining into the portal vein, the TIPS-tract, and the hepatic vein. A TIPS stent graft (Gore® Viatorr®) was positioned within the TIPS-tract. Superior mesenteric vein and splenic vein served as inlets for blood-mimicking fluid. 4D flow CMR acquisitions were performed at 3T at preset flow rates of 0.8 to 2.8 l/min using velocity encoding of both 1.0 and 2.0 m/s. Flow rates and velocities were measured at predefined levels in the portal vasculature and within the stent graft. Accuracy of 4D flow CMR was assessed through linear regression with reference measurements obtained by flow sensors and two-dimensional (2D) phase contrast (PC) CMR. Intra- and interobserver agreement were assessed through Bland-Altman analyses. RESULTS: At a velocity encoding of 2.0 m/s, 4D flow CMR-derived flow rates and velocities showed an excellent correlation with preset flow rates and 2D PC CMR-derived flow velocities at all vascular levels and within the stent graft (all r ≥ 0.958, p ≤ 0.003). At a velocity encoding of 1.0 m/s, aliasing artifacts were present within the stent graft at flow rates ≥ 2.0 l/min. 4D flow CMR-derived measurements revealed high intra- and interobserver agreement. CONCLUSIONS: The in vitro accuracy and precision of 4D flow CMR is unaffected by the presence of TIPS stent grafts, suggesting that 4D flow CMR may be used to monitor TIPS patency in patients with liver cirrhosis.

Near-wall hemodynamic parameters quantification in in vitro intracranial aneurysms with 7 T PC-MRI.

OBJECTIVE: Wall shear stress (WSS) and its derived spatiotemporal parameters have proven to play a major role on intracranial aneurysms (IAs) growth and rupture. This study aims to demonstrate how ultra-high field (UHF) 7 T phase contrast magnetic resonance imaging (PC-MRI) coupled with advanced image acceleration techniques allows a highly resolved visualization of near-wall hemodynamic parameters patterns in in vitro IAs, paving the way for more robust risk assessment of their growth and rupture. MATERIALS AND METHODS: We performed pulsatile flow measurements inside three in vitro models of patient-specific IAs using 7 T PC-MRI. To this end, we built an MRI-compatible test bench, which faithfully reproduced a typical physiological intracranial flow rate in the models. RESULTS: The ultra-high field 7 T images revealed WSS patterns with high spatiotemporal resolution. Interestingly, the high oscillatory shear index values were found in the core of low WSS vortical structures and in flow stream intersecting regions. In contrast, maxima of WSS occurred around the impinging jet sites. CONCLUSIONS: We showed that the elevated signal-to-noise ratio arising from 7 T PC-MRI enabled to resolve high and low WSS patterns with a high degree of detail.

Relationship between diameter asymmetry and blood flow in the pre-communicating (A1) segment of the anterior cerebral arteries.

BACKGROUND: Asymmetry in diameter between pre-communicating (A1) segments of the anterior cerebral arteries is related to anterior communicating artery aneurysm formation. Diameter asymmetry definitions vary and have not been related to blood flow measurements using the same imaging modality. We aimed to evaluate the relationship between A1-diameter asymmetry and blood flow asymmetry and to define a hemodynamically significant cut-off value for A1-diameter asymmetry. We assessed sex differences between different groups of A1-asymmetry. MATERIALS AND METHODS: 3-Tesla time-of-flight MRA and 4D-phase-contrast MRI were performed in 122 healthy participants. Diameter and blood flow measurements were performed halfway in both A1-segments. Participants were subdivided based on A1-diameter asymmetry: ≤10% (symmetric); 11-20%; 21-30%; 31-40%; and >40% (increasing asymmetry) groups. We studied the relationship between A1-diameter asymmetry and corresponding flow asymmetry (scatterplot and correlation). A hemodynamic-based cutoff value for A1-asymmetry was determined by comparing dominant A1 blood flow in the asymmetry groups to the mean blood flow of the symmetric A1-group (linear mixed-effects model). Sex-related differences in A1-diameter, blood flow and asymmetry were assessed with t-tests. RESULTS: A1-diameter asymmetry was linearly related to blood flow asymmetry between dominant and non-dominant sides. A1-diameter asymmetry >30% yielded statistically significant increased blood flow in the dominant A1 compared to symmetric A1s. Men had statistically significant larger A1-diameters, higher blood flow and a similar degree of A1-diameter asymmetry compared to women. CONCLUSION: A1-diameter asymmetry is linearly related to blood flow asymmetry. A >30% A1-asymmetry can be used as hemodynamically significant cut-off value. There were no sex-related differences in A1-diameter asymmetry.

Measurement of CSF pulsation from EPI-based human fMRI.

It is recently discovered that the glymphatic system and meningeal lymphatic system are the primary routes for the clearance of brain waste products. The CSF flow is part of these systems, facilitating the clearance procedure. Nonetheless, the relationship between CSF flow and brain functional activity has been underexplored. To investigate CSF dynamics and functional brain activity simultaneously, recent studies have proposed a CSF inflow index measured on edge slices (CSFedge) of echo-planar imaging (EPI) based functional magnetic resonance imaging (fMRI), however, it lacks the quantitative aspect of the CSF pulsation. We proposed a new method for quantifying CSF pulsation (CSFpulse) based on an interslice CSF pulsation model in the 4th ventricle of EPI-based fMRI. The proposed CSFpulse successfully detected the higher CSF flow during the resting state than the typical task states (visual and motor) (p<.05), which is consistent with previous studies based on phase contrast (PC) MRI and CSF volume MRI, while it was not detected in CSFedge based indices or baseline CSF signals in various regions of interest (ROIs). Moreover, CSFpulse demonstrated dynamic functional changes in CSF pulsation: it decreased during the activation-on blocks while it increased during the activation-off blocks. CSFpulse significantly correlated with stroke volume measured using PC MRI, a standard method for CSF pulsation quantification, under the same functional state, while CSFedge based indices or CSF ROIs showed no correlation with the PC MRI stroke volume. Lastly, the correlation of CSFpulse with global BOLD was weaker than that of CSFedge, suggesting that CSFpulse may reflect distinct CSF physiological information that is less affected by global BOLD effects. Based on these results, the proposed CSFpulse provides CSF pulsatility information more accurately in a quantitative manner than CSFedge based indices from the recent CSF studies or the conventional ROI-based analysis. In addition to the high correlation with PC MRI, CSFpulse is much faster than PC MRI and provides information of functional brain activations simultaneously, advantageous over PC MRI or CSF volume MRI. Accordingly, the suggested CSFpulse can be used for investigating intra-subject functional changes in BOLD and CSF pulsation simultaneously and inter-subject CSF pulsation variations based on conventional EPI-based fMRI, which warrants further investigation.

4D flow MRI hemodynamic biomarkers for cerebrovascular diseases.

Alterations in cerebral blood flow are common in several neurological diseases among the elderly including stroke, cerebral small vessel disease, vascular dementia, and Alzheimer's disease. 4D flow magnetic resonance imaging (MRI) is a relatively new technique to investigate cerebrovascular disease, and makes it possible to obtain time-resolved blood flow measurements of the entire cerebral arterial venous vasculature and can be used to derive a repertoire of hemodynamic biomarkers indicative of cerebrovascular health. The information that can be obtained from one single 4D flow MRI scan allows both the investigation of aberrant flow patterns at a focal location in the vasculature as well as estimations of brain-wide disturbances in blood flow. Such focal and global hemodynamic biomarkers show the potential of being sensitive to impending cerebrovascular disease and disease progression and can also become useful during planning and follow-up of interventions aiming to restore a normal cerebral circulation. Here, we describe 4D flow MRI approaches for analyzing the cerebral vasculature. We then survey key hemodynamic biomarkers that can be reliably assessed using the technique. Finally, we highlight cerebrovascular diseases where one or multiple hemodynamic biomarkers are of central interest.

Echo planar imaging-induced errors in intracardiac 4D flow MRI quantification.

PURPOSE: To assess errors associated with EPI-accelerated intracardiac 4D flow MRI (4DEPI) with EPI factor 5, compared with non-EPI gradient echo (4DGRE). METHODS: Three 3T MRI experiments were performed comparing 4DEPI to 4DGRE: steady flow through straight tubes, pulsatile flow in a left-ventricle phantom, and intracardiac flow in 10 healthy volunteers. For each experiment, 4DEPI was repeated with readout and blip phase-encoding gradient in different orientations, parallel or perpendicular to the flow direction. In vitro flow rates were compared with timed volumetric collection. In the left-ventricle phantom and in vivo, voxel-based speed and spatio-temporal median speed were compared between sequences, as well as mitral and aortic transvalvular net forward volume. RESULTS: In steady-flow phantoms, the flow rate error was largest (12%) for high velocity (>2 m/s) with 4DEPI readout gradient parallel to the flow. Voxel-based speed and median speed in the left-ventricle phantom were ≤5.5% different between sequences. In vivo, mean net forward volume inconsistency was largest (6.4 ± 8.5%) for 4DEPI with nonblip phase-encoding gradient parallel to the main flow. The difference in median speed for 4DEPI versus 4DGRE was largest (9%) when the 4DEPI readout gradient was parallel to the flow. CONCLUSIONS: Velocity and flow rate are inaccurate for 4DEPI with EPI factor 5 when flow is parallel to the readout or blip phase-encoding gradient. However, mean differences in flow rate, voxel-based speed, and spatio-temporal median speed were acceptable (≤10%) when comparing 4DEPI to 4DGRE for intracardiac flow in healthy volunteers.

Whole-brain mapping of mouse CSF flow via HEAP-METRIC phase-contrast MRI.

PURPOSE: CSF plays important roles in clearing brain waste and homeostasis. However, mapping whole-brain CSF flow in the rodents is difficult, primarily due to its assumed very low velocity. Therefore, we aimed to develop a novel phase-contrast MRI method to map whole-brain CSF flow in the mouse brain. METHODS: A novel generalized Hadamard encoding-based multi-band scheme (dubbed HEAP-METRIC, Hadamard Encoding APproach of Multi-band Excitation for short TR Imaging aCcelerating) using complex Hadamard matrix was developed and incorporated into conventional phase contrast (PC)-MRI to significantly increase SNR. RESULTS: Slow flow phantom imaging validated HEAP-METRIC PC-MRI's ability to achieve fast and accurate mapping of slow flow velocities (~102  µm/s). With the SNR gain afforded by HEAP-METRIC scheme, high-resolution (0.08 × 0.08 mm in-plane resolution and 36 0.4 mm slices) PC-MRI was completed in 21 min for whole-brain CSF flow mapping in the mouse. Using this novel method, we provide the first report of whole-brain CSF flow in the awake mouse brain with an average flow velocity of ~200 µm/s. Furthermore, HEAP-METRIC PC-MRI revealed CSF flow was reduced by isoflurane anesthesia, accompanied by reduction of glymphatic function as measured by dynamic contrast-enhanced MRI. CONCLUSION: We developed and validated a generalized HEAP-METRIC PC-MRI for mapping low velocity flow. With this method, we have achieved the first whole-brain mapping of awake mouse CSF flow and have further revealed that anesthesia reduces CSF flow velocity.

Fundamentals of turbulent flow spectrum imaging.

PURPOSE: To introduce a mathematical framework and in-silico validation of turbulent flow spectrum imaging (TFSI) of stenotic flow using phase-contrast MRI, evaluate systematic errors in quantitative turbulence parameter estimation, and propose a novel method for probing the Lagrangian velocity spectra of turbulent flows. THEORY AND METHODS: The spectral response of velocity-encoding gradients is derived theoretically and linked to turbulence parameter estimation including the velocity autocorrelation function spectrum. Using a phase-contrast MRI simulation framework, the encoding properties of bipolar gradient waveforms with identical first gradient moments but different duration are investigated on turbulent flow data of defined characteristics as derived from computational fluid dynamics. Based on theoretical insights, an approach using velocity-compensated gradient waveforms is proposed to specifically probe desired ranges of the velocity autocorrelation function spectrum with increased accuracy. RESULTS: Practical velocity-encoding gradients exhibit limited encoding power of typical turbulent flow spectra, resulting in up to 50% systematic underestimation of intravoxel SD values. Depending on the turbulence level in fluids, the error due to a single encoding gradient spectral response can vary by 20%. When using tailored velocity-compensated gradients, improved quantification of the Lagrangian velocity spectrum on a voxel-by-voxel basis is achieved and used for quantitative correction of intravoxel SD values estimated with velocity-encoding gradients. CONCLUSION: To address systematic underestimation of turbulence parameters using bipolar velocity-encoding gradients in phase-contrast MRI of stenotic flows with short correlation times, tailored velocity-compensated gradients are proposed to improve quantitative mapping of turbulent blood flow characteristics.

Prospective motion correction and automatic segmentation of penetrating arteries in phase contrast MRI at 7 T.

PURPOSE: To develop a prospective motion correction (MC) method for phase contrast (PC) MRI of penetrating arteries (PAs) in centrum semiovale at 7 T and to evaluate its performance using automatic PA segmentation. METHODS: Head motion was monitored and corrected during the scan based on fat navigator images. Two convolutional neural networks (CNN) were developed to automatically segment PAs and exclude surface vessels. Real-life scans with MC and without MC (NoMC) were performed to evaluate the MC performance. Motion score was calculated from the ranges of translational and rotational motion parameters. MC versus NoMC pairs with similar motion scores during MC and NoMC scans were compared. Data corrupted by motion were reacquired to further improve PA visualization. RESULTS: PA counts (NPA ) and PC and magnitude contrasts (MgC) relative to neighboring tissue were significantly correlated with motion score and were higher in MC than NoMC images at motion scores above 0.5-0.8 mm. Data reacquisition further increased PC but had no significant effect on NPA and MgC. CNNs had higher sensitivity and Dice similarity coefficient for detecting PAs than a threshold-based method. CONCLUSIONS: Prospective MC can improve the count and contrast of segmented PAs in the presence of severe motion. CNN-based PA segmentation has improved performance in delineating PAs than the threshold-based method.

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI.

BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool. PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. STUDY TYPE: Systematic consensus process using a modified Delphi method. POPULATION: Not applicable. SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI. ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts. RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting. DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.