Phase-contrast Magnetic Resonance Imaging Measurements Research Articles

Quantitative noninvasive measurement of cerebrospinal fluid flow in shunted hydrocephalus.

Standard MRI protocols lack a quantitative sequence that can be used to evaluate shunt-treated patients with a history of hydrocephalus. The objective of this study was to investigate the use of phase-contrast MRI (PC-MRI), a quantitative MR sequence, to measure CSF flow through the shunt and demonstrate PC-MRI as a useful adjunct in the clinical monitoring of shunt-treated patients. The rapid (96 seconds) PC-MRI sequence was calibrated using a flow phantom with known flow rates ranging from 0 to 24 mL/hr. Following phantom calibration, 21 patients were scanned with the PC-MRI sequence. Multiple, successive proximal and distal measurements were gathered in 5 patients to test for measurement error in different portions of the shunt system and to determine intrapatient CSF flow variability. The study also includes the first in vivo validations of PC-MRI for CSF shunt flow by comparing phase-contrast-measured flow rate with CSF accumulation in a collection burette obtained in patients with externalized distal shunts. The PC-MRI sequence successfully measured CSF flow rates ranging from 6 to 54 mL/hr in 21 consecutive pediatric patients. Comparison of PC-MRI flow measurement and CSF volume collected in a bedside burette showed good agreement in a patient with an externalized distal shunt. Notably, the distal portion of the shunt demonstrated lower measurement error when compared with PC-MRI measurements acquired in the proximal catheter. The PC-MRI sequence provided accurate and reliable clinical measurements of CSF flow in shunt-treated patients. This work provides the necessary framework to include PC-MRI as an immediate addition to the clinical setting in the noninvasive evaluation of shunt function and in future clinical investigations of CSF physiology.

Verification Study of in Silico Computed Intracardiac Blood Flow With 4D Flow MRI.

Major challenges for clinical applications of in silico medicine are limitations in time and computational resources. Computational approaches should therefore be tailored to specific applications with relatively low complexity and must be verified and validated against clinical gold standards. This study performed computational fluid dynamics simulations of left ventricular hemodynamics of different complexity based on shape reconstruction from steady state gradient echo magnetic resonance imaging (MRI) data. Computed flow results of a rigid wall model (RWM) and a prescribed motion fluid-structure interaction (PM-FSI) model were compared against phase-contrast MRI measurements for three healthy subjects. Extracted boundary conditions from the steady state MRI sequences as well as computed metrics, such as flow rate, valve velocities, and kinetic energy show good agreement with in vivo flow measurements. Regional flow analysis reveals larger differences. Basic flow structures are well captured with RWM and PM-FSI. For the computation of further biomarkers like washout or flow efficiency, usage of PM-FSI is required. Regarding boundary-near flow, more accurate anatomical models are inevitable. These results delineate areas of application of both methods and lay a foundation for larger validation studies and sensitivity analysis for healthy and diseased cases, being an essential step upon clinical translations.

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

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

Estimation of glomerular filtration rate in a pediatric population using non-contrast kidney phase contrast magnetic resonance imaging.

Glomerular filtration rate (GFR) is a key measure of kidney function but often inaccurately ascertained by serum creatinine and cystatin C in pediatrics. In this pilot trial, we evaluated the relationship between GFR calculated by using phase-contrast MRI (PC-MRI) biomarkers and GFR by 125I-iothalamate clearance in youth undergoing bone marrow transplantation (BMT). A total of twenty-one pediatric BMT candidates (8-21years of age) were recruited for a research kidney PC-MRI. After completion of 125I-iothalamate clearance, same-day PC-MRI measurements were completed of the kidney circulation without a gadolinium-based contrast agent. MRI included a non-contrast balanced-SSFP-triggered angiography to position ECG-gated breath-held 2D PC-MRI flow measurements (1.2 × 1.2 × 6 mm3). A multivariate model of MRI biomarkers estimating GFR (GFR-MRI) was selected using the elastic net approach. The GFR-MRI variables selected by elastic net included average heart rate during imaging (bpm), peak aorta flow below the kidney artery take-offs (ml/s), average kidney artery blood flow, average peak kidney vein blood flow, and average kidney vein blood flow (ml/s). The GFR-MRI model demonstrated strong agreement with GFR by 125I-iothalamate (R2 = 0.65), which was stronger than what was observed with eGFR by the full age spectrum and Chronic Kidney Disease in Children under 25 (CKiD U25) approaches. In this pilot study, noninvasive GFR-MRI showed strong agreement with gold standard GFR in youth scheduled for BMT. Further work is needed to evaluate whether non-contrast GFR-MRI holds promise to become a superior alternative to eGFR and GFR by clearance techniques. A higher resolution version of the Graphical abstract is available as Supplementary information.

Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy.

The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup. Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses. The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p&lt;.001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07±0.19cm/second; C4: -0.12±0.30cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23cm/second at C2; maximum -0.58cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3cm/second) showed comparable results. This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression).

Patient-specific computational fluid dynamic simulation of cerebrospinal fluid flow in the intracranial space

BackgroundAbnormal cerebrospinal fluid (CSF) flow is associated with a variety of poorly understood neurological disorders such as Alzheimer’s Disease and hydrocephalus. The lack of comprehensive understanding of the fluid and solid mechanics of CSF flow remains a critical barrier in the development of diagnostic assessment and potential treatment options for these diseases. We have developed a whole brain, patient-specific computational fluid dynamics (CFD) simulation of CSF flow in the cranial cavity as a step towards comprehensive understanding of CSF dynamics and how they relate to neurodegenerative diseases. MethodsA patient-specific 3D geometry of the CSF filled spaces was segmented from structural MRI. Patient-specific boundary conditions were measured using phase contrast MRI. A rigid wall three-dimensional CFD simulation was conducted using only patient-specific waveforms as boundary conditions. Deformation of brain tissue is accounted for using volumetric flowrate boundary conditions calculated via the conservation of mass. Phase contrast MRI measurement of maximum velocity at the cerebral aqueduct was used to validate the simulation with excellent agreement. ResultsThe CSF dynamics across the cardiac cycle are presented, illustrating the relationship between arterial flow and CSF flow. Flow in and out of the ventricles was shown to have a slight phase delay (∼20 % of the cardiac cycle) from flow in the subarachnoid space. Intracranial pressure dynamics are presented, with pressure in the Lateral Ventricles demonstrating less significant transient effects than pressure in the subarachnoid space. ConclusionsThis work presents a quantitatively validated whole-brain simulation of CSF flow for a single healthy subject. The computational methodology improves over the state of the art by eliminating non-physiological boundary conditions and unnecessary assumptions about the mechanical properties of brain tissue, providing an essential step towards clinically useful tools for assessing the development of neurodegenerative disorders.

A one-dimensional model for the pulsating flow of cerebrospinal fluid in the spinal canal.

The monitoring of intracranial pressure (ICP) fluctuations, which is needed in the context of a number of neurological diseases, requires the insertion of pressure sensors, an invasive procedure with considerable risk factors. Intracranial pressure fluctuations drive the wave-like pulsatile motion of cerebrospinal fluid (CSF) along the compliant spinal canal. Systematically derived simplified models relating the ICP fluctuations with the resulting CSF flow rate can be useful in enabling indirect evaluations of the former from non-invasive magnetic resonance imaging (MRI) measurements of the latter. As a preliminary step in enabling these predictive efforts, a model is developed here for the pulsating viscous motion of CSF in the spinal canal, assumed to be a linearly elastic compliant tube of slowly varying section, with a Darcy pressure-loss term included to model the fluid resistance introduced by the trabeculae, which are thin collagen-reinforced columns that form a web-like structure stretching across the spinal canal. Use of Fourier-series expansions enables predictions of CSF flow rate for realistic anharmonic ICP fluctuations. The flow rate predicted using a representative ICP waveform together with a realistic canal anatomy is seen to compare favourably with in vivo phase-contrast MRI measurements at multiple sections along the spinal canal. The results indicate that the proposed model, involving a limited number of parameters, can serve as a basis for future quantitative analyses targeting predictions of ICP temporal fluctuations based on MRI measurements of spinal-canal anatomy and CSF flow rate.

Noninvasive Quantification of Cerebral Blood Flow Using Hybrid PET/MR Imaging to Extract the [15 O]H2 O Image-Derived Input Function Free of Partial Volume Errors.

Quantification of cerebral blood flow (CBF) with [15 O]H2 O-positron emission tomography (PET) requires arterial sampling to measure the input function. This invasive procedure can be avoided by extracting an image-derived input function (IDIF); however, IDIFs are sensitive to partial volume errors due to the limited spatial resolution of PET. To present an alternative hybrid PET/MR imaging of CBF (PMRFlowIDIF ) that uses phase-contrast (PC) MRI measurements of whole-brain (WB) CBF to calibrate an IDIF extracted from a WB [15 O]H2 O time-activity curve. Technical development and validation. Twelve juvenile Duroc pigs (83% female). Thirteen healthy individuals (38% female). 3 T; gradient-echo PC-MRI. PMRFlowIDIF was validated against PET-only in a porcine model that included arterial sampling. CBF maps were generated by applying PMRFlowIDIF and two previous PMRFlow methods (PC-PET and double integration method [DIM]) to [15 O]H2 O-PET data acquired from healthy individuals. PMRFlow and PET CBF measurements were compared with regression and correlation analyses. Paired t-tests were performed to evaluate differences. Potential biases were assessed using one-sample t-tests. Reliability was assessed by intraclass correlation coefficients. Statistical significance: =0.05. In the animal study, strong agreement was observed between PMRFlowIDIF (average voxel-wise CBF, 58.0 ± 16.9mL/100 g/min) and PET (63.0 ± 18.9mL/100 g/min). In the human study, PMRFlowDIM (y=1.11x - 5.16, R2 =0.99 ± 0.01) and PMRFlowPC-PET (y=0.87x + 3.82, R2 =0.97 ± 0.02) performed similarly to PMRFlowIDIF, and CBF was within the expected range (eg, 49.7 ± 7.2mL/100 g/min for gray matter). Accuracy of PMRFlowIDIF was confirmed in the animal study with the primary source of error attributed to differences in WB CBF measured by PC MRI and PET. In the human study, differences in CBF from PMRFlowIDIF , PMRFlowDIM , and PMRFlowPC-PET were due to the latter two not accounting for blood-borne activity. 2 TECHNICAL EFFICACY STAGE: 1.

Gastric Emptying Is Not Delayed and Does Not Correlate With Attenuated Postprandial Blood Flow Increase in Medicated Patients With Early Parkinson's Disease.

BackgroundWe have recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in 23 medicated patients with Parkinson's disease (PD) compared to 23 age- and sex-matched healthy controls.ObjectiveTo investigate in a sub-sample of the original cohort whether the observed blood flow response in SMA after oral food intake is related to a delay in gastric emptying.MethodsWe studied 15 patients with PD in an “ON-medication” state with a mean disease duration of 3.9 ± 2.2 years and 15 healthy age- and sex-matched individuals. Participants underwent dynamic gastric scintigraphy 0, 30, 60, 120, 180 and 240 minutes after the intake of a standardized radiolabeled test meal. Gastric emptying was compared between groups. 14 of the 15 PD patients and 12 of the 15 healthy control subjects had previously undergone serial postprandial PC-MRI measurements. In these individuals, we tested for a relationship between gastric emptying and postprandial blood flow response in the SMA.ResultsThe dynamics of gastric emptying did not differ between groups (p = 0.68). There was substantial inter-subject variability of gastric emptying in PD patients and healthy participants. Only a single PD patient had delayed gastric emptying. In those participants who had undergone PC-MRI, postprandial increase in SMA blood flow was attenuated in PD compared to healthy controls as reported previously (p = 0.006). Gastric emptying did not correlate with the timing and amplitude of postprandial blood flow increase in SMA.ConclusionOur preliminary results, obtained in a small group of early-stage PD patients who continued their usual dopamine replacement therapy, suggest that variations in gastric emptying after solid meal intake is within the normal range in the majority of cases. There is also no evidence for a tight relationship between the attenuated postprandial blood flow response in the SMA and normal variations in gastric emptying.

Dynamic MR imaging of cerebral perfusion during bicycling exercise

Habitual physical activity is beneficial for cerebrovascular health and cognitive function. Physical exercise therefore constitutes a clinically relevant cerebrovascular stimulus. This study demonstrates the feasibility of quantitative cerebral blood flow (CBF) measurements during supine bicycling exercise with pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) at 3 Tesla.Twelve healthy volunteers performed a steady-state exercise-recovery protocol on an MR-compatible bicycle ergometer, while dynamic pCASL data were acquired at rest, during moderate (60% of the age-predicted supine maximal heart rate (HRmax)) and vigorous (80% of supine HRmax) exercise, and subsequent recovery. These CBF measurements were compared with 2D phase-contrast MRI measurements of blood flow through the carotid arteries. Procedures were repeated on a separate day for an assessment of measurement repeatability.Whole-brain (WB) CBF was 41.2 ± 6.9 mL/100 g/min at rest (heart rate 63 [57-71] beats/min), remained similar at moderate exercise (102 [97-107] beats/min), decreased by 10% to 37.1 ± 5.7 mL/100 g/min (p = 0.001) during vigorous exercise (139 [136-142] beats/min) and decreased further to 34.2 ± 6.0 mL/100 g/min (p < 0.001) during recovery. Hippocampus CBF decreased by 12% (p = 0.001) during moderate exercise, decreased further during vigorous exercise (-21%; p < 0.001) and was even lower during recovery (-31%; p < 0.001). In contrast, motor cortex CBF increased by 12% (p = 0.027) during moderate exercise, returned to resting-state values during vigorous exercise, and decreased by 17% (p = 0.006) during recovery. The inter-session repeatability coefficients for WB CBF were approximately 20% for all stages of the exercise-recovery protocol. Phase-contrast blood flow measurements through the common carotid arteries overestimated the WB CBF because of flow directed to the face and scalp. This bias increased with exercise.We have demonstrated the feasibility of dynamic pCASL-MRI of the human brain for a quantitative evaluation of cerebral perfusion during bicycling exercise. Our spatially resolved measurements revealed a differential response of CBF in the motor cortex as well as the hippocampus compared with the brain as a whole. Caution is warranted when using flow through the common carotid arteries as a surrogate measure for cerebral perfusion.

Abstract P344: Validation of Computational Fluid Dynamics Against PC-MRI Measurements of Blood Flow in Healthy Intracranial Arteries: On the Threshold to Clinical Utility for Stroke Prediction

Aim: Computational Fluid Dynamics (CFD) modeling of blood flow is a promising technique to obtain hemodynamic biomarkers and predict recurrent strokes. Few studies, however, have validated CFD against other methods for measuring hemodynamics, e.g. phase contrast MRI (PC-MRI). To resolve the uncertainties about the accuracy of CFD, this study validates the results of an automated software that combines deep learning and CFD for simulating blood flow given an MR angiogram against PC-MRI. Methods: Intracranial arteries in 10 healthy volunteers (60% male, mean age 38 ± 16 years) were automatically segmented from TOF MRA obtained at 3T using deep learning. Subject-specific CFD modelling was undertaken. PC-MRI flow rate for each subject was used at the inlet boundary condition, but not at the outlets. Outlet boundary condition was set to lumped parameter Windkessel model, with the resistance programmatically determined using allometric scaling laws based on the dimension and branching of vasculature. For comparison, two commonly used outlet conditions (exponent 2 &amp; 3 in Murray’s Law) were also considered. CFD results for flow rate and wall shear stress were compared against PC-MRI using Pearson’s correlation coefficient. Results: The flow rate across major intracranial arteries from CFD was in excellent agreement with the PC-MRI (MCA: r = 0.83, ACA: r = 0.81 &amp; PCA: r = 0.82). In addition, there was good correlation for both wall shear stress (WSS) and WSS Ratio (WSSR, i.e. the ratio of WSS between a branch and its parent vessel) (MCA (WSS/WSSR): r = 0.6/0.77, ACA (WSS/WSSR): r = 0.86/0.93 &amp; PCA (WSS/WSSR): r = 0.72/0.85). The inter-subject variability of the flow rate (i.e. standard deviation) obtained from CFD matched closely the variation range observed from PC-MRI and the literature. The two alternative outlet models behaved similarly but suffered from vessel truncation and high errors in some cases. Conclusion: CFD modelling of blood flow in intracranial arteries from static images has good agreement with PC-MRI measurements when allometric scaling laws are applied for setting Windkessel outflow conditions. This lays the foundation for using CFD to predict recurrent strokes as the technique uses standard MRA images already commonly acquired for stroke evaluation.

Fetal Flow Quantification in Great Vessels Using Motion-Corrected Radial Phase Contrast MRI: Comparison With Cartesian.

Phase contrast MRI in the great vessels is a potential clinical tool for managing fetal pathologies. One challenge is the uncontrollable fetal motion, potentially corrupting flow quantifications. To demonstrate improvements in fetal blood flow quantification in great vessels using retrospectively motion-corrected golden-angle radial phase contrast MRI relative to Cartesian phase contrast MRI. Method comparison. Computer simulation. Seventeen pregnant volunteers. 1.5T and 3T. Cartesian and golden-angle radial phase contrast MRI. Through computer simulations, radial (with and without retrospective motion correction) and Cartesian phase contrast MRI were compared using flow deviations. in vivo Cartesian and radial phase contrast MRI measurements and reconstruction qualities were compared in pregnancies. Cartesian data were reconstructed into gated reconstructions (CINEs) after cardiac gating with metric optimized gating (MOG). For radial data, real-time reconstructions were performed for motion correction and MOG followed by CINE reconstructions. Wilcoxon signed-rank test. Linear regression. Bland-Altman plots. Student's t-test. Simulations showed significant improvements (P < 0.05) in flow accuracy and reconstruction quality with motion correction ([mean/peak] flow errors with ±5 mm motion corruption: Cartesian [35 ± 1/115 ± 7] mL/s, motion uncorrected radial [25 ± 1/75 ± 2] mL/s and motion-corrected radial [1.0 ± 0.5/-5 ± 1] mL/s). in vivo Cartesian reconstructions without motion correction had lower quality than the motion-corrected radial reconstructions (P < 0.05). Across all fetal mean flow measurements, the bias [limits of agreement] between the two measurements were -0.2 [-76, 75] mL/min/kg, while the linear regression coefficients were (Mradial = 0.81 × MCartesian + 29.8 [mL/min/kg], r2 = 0.67). The corresponding measures for the peak fetal flows were -23 [-214, 167] mL/min/kg and (Pradial = 0.95 × PCartesian -1.2 [mL/min/kg], r2 = 0.80). Cartesian reconstructions of low quality showed significantly higher estimated mean and peak (P < 0.05) flows than the corresponding radial reconstructions. Simulations showed that radial phase contrast MRI with motion compensation improved flow accuracy. For fetal measurements, motion-corrected radial reconstructions showed better image quality than, and different flow values from, Cartesian reconstructions. Level of Evidence 1. Technical Efficacy Stage 1. J. MAGN. RESON. IMAGING 2021;53:540-551.

Abstract WMP64: From Static Imaging to Hemodynamic Modelling: Validation of Intracranial Blood Flow Simulations Against Population-Based PC-MRI Studies

Purpose: Modelling blood flow in cerebral arteries presents an opportunity to go beyond current luminal stenosis. These models could improve stroke prognostication by adding hemodynamic biomarkers such as translesional shear stress and pressure gradient. Such models, however, are rarely validated against real clinical data. We evaluated the accuracy of a computational fluid dynamics (CFD) model which uses allometric scaling laws against population-based Phase Contrast MRI (PC-MRI) measurements of blood flow in the brain. Methods: 3D models of the anterior circulation of 23 healthy subjects were reconstructed based on their MRA Time of Flight (TOF) images and CFD was used for modelling the blood flow. Lumped parameter Windkessel models were used as boundary conditions and allometric scaling laws were used to divide the flow and tune these boundary conditions, i.e. the resistance at each boundary was automatically adjusted based on the dimensions and branching of upstream vasculature. The results were compared against 4 PC-MRI studies from literature, covering a combined number of 417 healthy subjects. Results: The flow rate across 3 major intracranial arteries (ICA, MCA, and ACA) was obtained from the CFD simulations and was in good agreement with population-based PC-MRI studies. The agreement was 82.6% for the ICA, 85.9% for the MCA, and 80.4% for the ACA when comparing the average flow rate. The inter-patient variability of the flow rate (i.e. standard deviation) obtained from CFD simulations matched closely with the variation range measured in the literature. Allometric scaling enabled the model to accurately divide the flow at bifurcations (MCA/ICA flow ratio was 58.6% for the model vs 56.3% in the literature). We observed an average of 8 mmHg in pressure drop along the anterior circulation of healthy subjects (from ICA to MCA-M1 and ACA-A1), which agrees with the physiological range reported in the literature. Conclusion: This study shows the potential of accurately modelling blood flow based only on static images and demonstrates the validity of using allometric scaling in intracranial CFD simulations. The current modelling approach can potentially assist in stroke prognostication by obtaining hemodynamic risk factors from standard MRA TOF or CTA.

Phase contrast MRI measurements of net cerebrospinal fluid flow through the cerebral aqueduct are confounded by respiration.

BackgroundNet cerebrospinal fluid (CSF) flow through the cerebral aqueduct may serve as a marker of CSF production in the lateral ventricles, and changes that occur with aging and in disease.PurposeTo investigate the confounding influence of the respiratory cycle on net CSF flow and stroke volume measurements.Study TypeCross‐sectional study.SubjectsTwelve young, healthy subjects (seven male, age range 19–39 years, average age 28.3 years).Field Strength/SequencePhase contrast MRI (PC‐MRI) measurements were performed at 7T, with and without respiratory gating on expiration and on inspiration. All measurements were repeated.AssessmentNet CSF flow and stroke volume in the aqueduct, over the cardiac cycle, was determined.Statistical TestsRepeatability was determined using the intraclass correlation coefficient (ICC) and linear regression analysis between the repeated measurements. Repeated measures analysis of variance (ANOVA) was performed to compare the measurements during inspiration/expiration/no gating. Linear regression analysis was performed between the net CSF flow difference (inspiration minus expiration) and stroke volume.ResultsNet CSF flow (average ± standard deviation) was 0.64 ± 0.32 mL/min (caudal) during expiration, 0.12 ± 0.49 mL/min (cranial) during inspiration, and 0.31 ± 0.18 mL/min (caudal) without respiratory gating. Respiratory gating did not affect stroke volume measurements (41 ± 18, 42 ± 19, 42 ± 19 μL/cycle for expiration, no respiratory gating and inspiration, respectively). Repeatability was best during inspiration (ICC = 0.88/0.56/–0.31 for gating on inspiration/expiration/no gating). A positive association was found between average stroke volume and net flow difference between inspiration and expiration (R = 0.678/0.605, P = 0.015/0.037 for the first/second repeated measurement).Data ConclusionMeasured net CSF flow is confounded by respiration effects. Therefore, net CSF flow measurements with PC‐MRI cannot in isolation be directly linked to CSF production. Level of Evidence: 1 Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;49:433–444.

Influence of principal component analysis acceleration factor on velocity measurement in 2D and 4D PC-MRI.

The objective of the study was to determine how to optimize 2D and 4D phase-contrast magnetic resonance imaging (PC-MRI) acquisitions to acquire flow velocities in millimetric vessels. In particular, we search for the best compromise between acquisition time and accuracy and assess the influence of the principal component analysis (PCA). 2D and 4D PC-MRI measurements are conducted within two in vitro vessel phantoms: a Y-bifurcation phantom, the branches of which range from 2 to 5mm in diameter, and a physiological subject-specific phantom of the carotid bifurcation. The same sequences are applied in vivo in carotid vasculature. For a vessel oriented in the axial direction, both 2D and axial 4D PC-MRI provided accuracy measurements regardless of the k-t PCA factor, while the acquisition time is reduced by a factor 6 for k-t PCA maximum value. The in vivo measurements show that the proposed sequences are adequate to acquire 2D and 4D velocity fields in millimetric vessels and with clinically realistic time durations. The study shows the feasibility of conducting fast, high-resolution PC-MRI flow measurements in millimetric vessels and that it is worth maximizing the k-t PCA factor to reduce the acquisition time in the case of 2D and 4D axial acquisitions.

Patient-Specific Left Ventricular Flow Simulations From Transthoracic Echocardiography: Robustness Evaluation and Validation Against Ultrasound Doppler and Magnetic Resonance Imaging.

The combination of medical imaging with computational fluid dynamics (CFD) has enabled the study of 3-D blood flow on a patient-specific level. However, with models based on gated high-resolution data, the study of transient flows, and any model implementation into routine cardiac care, is challenging. This paper presents a novel pathway for patient-specific CFD modelling of the left ventricle (LV), using 4-D transthoracic echocardiography (TTE) as input modality. To evaluate the clinical usability, two sub-studies were performed. First, a robustness evaluation was performed, where repeated models with alternating input variables were generated for six subjects and changes in simulated output quantified. Second, a validation study was carried out, where the pathway accuracy was evaluated against pulsed-wave Doppler (100 subjects), and 2-D through-plane phase-contrast magnetic resonance imaging measurements over seven intraventricular planes (6 subjects). The robustness evaluation indicated a model deviation of <12%, with highest regional and temporal deviations at apical segments and at peak systole, respectively. The validation study showed an error of <11% (velocities <10 cm/s) for all subjects, with no significant regional or temporal differences observed. With the patient-specific pathway shown to provide robust output with high accuracy, and with the pathway dependent only on 4-D TTE, the method has a high potential to be used within future clinical studies on 3-D intraventricular flow patterns. To this, future model developments in the form of e.g., anatomically accurate LV valves may further enhance the clinical value of the simulations.

Echo Particle Image Velocimetry for Estimation of Carotid Artery Wall Shear Stress: Repeatability, Reproducibility and Comparison with Phase-Contrast Magnetic Resonance Imaging

Measurement of hemodynamic wall shear stress (WSS) is important in investigating the role of WSS in the initiation and progression of atherosclerosis. Echo particle image velocimetry (echo PIV) is a novel ultrasound-based technique for measuring WSS in vivo that has previously been validated in vitro using the standard optical PIV technique. We evaluated the repeatability and reproducibility of echo PIV for measuring WSS in the human common carotid artery. We measured WSS in 28 healthy participants (18 males and 10 females, mean age: 56 ± 12 y). Echo PIV was highly repeatable, with an intra-observer variability of 1.0 ± 0.1 dyn/cm2 for peak systolic (maximum), 0.9 dyn/cm2 for mean and 0.5 dyn/cm2 for end-diastolic (minimum) WSS measurements. Likewise, echo PIV was reproducible, with a low inter-observer variability (max: 2.0 ± 0.2 dyn/cm2, mean: 1.3 ± 0.1 dyn/cm2, end-diastolic: 0.7 dyn/cm2) and more variable inter-scan (test–retest) variability (max: 7.1 ± 2.3 dyn/cm2, mean: 2.9 ± 0.4 dyn/cm2, min: 1.5 ± 0.1 dyn/cm2). We compared echo PIV with the reference method, phase-contrast magnetic resonance imaging (PC-MRI); echo PIV-based WSS measurements agreed qualitatively with PC-MRI measurements (r = 0.89, p < 0.05). Significant differences were observed in some WSS measurements (echo PIV vs. PC-MRI): WSS at peak systole: 21 ± 7.0 dyn/cm2 vs. 15 ± 5.0 dyn/cm2; time-averaged WSS: 8.9 ± 3.0 dyn/cm2 vs. 7.1 ± 3.0 dyn/cm2 (p < 0.05); WSS at end diastole: 3.8 ± 2.8 dyn/cm2 vs. 3.9 ± 2 dyn/cm2 (p > 0.05). For the first time, we report that echo PIV can measure WSS with good repeatability and reproducibility in adult humans with a broad age range. Echo PIV is feasible in humans and offers an easy-to-use, ultrasound-based, quantitative technique for measuring WSS in vivo in humans with good repeatability and reproducibility.

Caval Subtraction 2D Phase-Contrast MRI to Measure Total Liver and Hepatic Arterial Blood Flow: Proof-of-Principle, Correlation With Portal Hypertension Severity and Validation in Patients With Chronic Liver Disease.

Caval subtraction phase-contrast magnetic resonance imaging (PCMRI) noninvasive measurements of total liver blood flow (TLBF) and hepatic arterial (HA) flow have been validated in animal models and translated into normal volunteers, but not patients. This study aims to demonstrate its use in patients with liver cirrhosis, evaluate measurement consistency, correlate measurements with portal hypertension severity, and invasively validate TLBF measurements. Local research ethics committee approval was obtained. Twelve patients (mean, 50.8 ± 3.1 years; 10 men) with histologically confirmed cirrhosis were recruited prospectively, undergoing 2-dimensional PCMRI of the portal vein (PV) and the infrahepatic and suprahepatic inferior vena cava. Total liver blood flow and HA flow were estimated by subtracting infrahepatic from suprahepatic inferior vena cava flow and PV flow from estimated TLBF, respectively. Invasive hepatic venous pressure gradient (HVPG) and indocyanine green (ICG) clearance TLBF were measured within 7 days of PCMRI. Bland-Altman (BA) analysis of agreement, coefficients of variation, and Pearson correlation coefficients were calculated for comparisons with direct inflow PCMRI, HVPG, and ICG clearance. The mean difference between caval subtraction TLBF and direct inflow PCMRI was 6.3 ± 4.2 mL/min/100 g (BA 95% limits of agreement, ±28.7 mL/min/100 g). Significant positive correlations were observed between HVPG and caval subtraction HA fraction (r = 0.780, P = 0.014), but not for HA flow (r = 0.625, P = 0.053), PV flow (r = 0.244, P = 0.469), or caval subtraction TLBF (r = 0.473, P = 0.141). Caval subtraction and ICG TLBF agreement was modest (mean difference, -32.6 ± 16.6 mL/min/100 g; BA 95% limits of agreement, ±79.7 mL/min/100 g), but coefficients of variation were not different (65.7% vs 48.1%, P = 0.28). In this proof-of-principle study, caval subtraction PCMRI measurements are consistent with direct inflow PCMRI, correlate with portal hypertension severity, and demonstrate modest agreement with invasive TLBF measurements. Larger studies investigating the clinical role of TLBF and HA flow measurement in patients with liver disease are justified.

The Effect of Spatial and Temporal Resolution of Cine Phase Contrast MRI on Wall Shear Stress and Oscillatory Shear Index Assessment.

IntroductionWall shear stress (WSS) and oscillatory shear index (OSI) are associated with atherosclerotic disease. Both parameters are derived from blood velocities, which can be measured with phase-contrast MRI (PC-MRI). Limitations in spatiotemporal resolution of PC-MRI are known to affect these measurements. Our aim was to investigate the effect of spatiotemporal resolution using a carotid artery phantom.MethodsA carotid artery phantom was connected to a flow set-up supplying pulsatile flow. MRI measurement planes were placed at the common carotid artery (CCA) and internal carotid artery (ICA). Two-dimensional PC-MRI measurements were performed with thirty different spatiotemporal resolution settings. The MRI flow measurement was validated with ultrasound probe measurements. Mean flow, peak flow, flow waveform, WSS and OSI were compared for these spatiotemporal resolutions using regression analysis. The slopes of the regression lines were reported in %/mm and %/100ms. The distribution of low and high WSS and OSI was compared between different spatiotemporal resolutions.ResultsThe mean PC-MRI CCA flow (2.5±0.2mL/s) agreed with the ultrasound probe measurements (2.7±0.02mL/s). Mean flow (mL/s) depended only on spatial resolution (CCA:-13%/mm, ICA:-49%/mm). Peak flow (mL/s) depended on both spatial (CCA:-13%/mm, ICA:-17%/mm) and temporal resolution (CCA:-19%/100ms, ICA:-24%/100ms). Mean WSS (Pa) was in inverse relationship only with spatial resolution (CCA:-19%/mm, ICA:-33%/mm). OSI was dependent on spatial resolution for CCA (-26%/mm) and temporal resolution for ICA (-16%/100ms). The regions of low and high WSS and OSI matched for most of the spatiotemporal resolutions (CCA:30/30, ICA:28/30 cases for WSS; CCA:23/30, ICA:29/30 cases for OSI).ConclusionWe show that both mean flow and mean WSS are independent of temporal resolution. Peak flow and OSI are dependent on both spatial and temporal resolution. However, the magnitude of mean and peak flow, WSS and OSI, and the spatial distribution of OSI and WSS did not exhibit a strong dependency on spatiotemporal resolution.

Normal age-related changes in left ventricular function: Role of afterload and subendocardial dysfunction

BackgroundIn normal ageing, both vascular and ventricular properties change, and how these affect left ventricular function is not clear. Methods96 subjects (ages 20–79) without cardiovascular disease underwent cardiac magnetic resonance (MR) imaging for measurement of global function, diastolic function (E/A ratio), MR tagging for measurement of torsion to shortening ratio (TSR, ratio of epicardial torsion to endocardial circumferential shortening, with increase in TSR suggesting subendocardial dysfunction relative to the subepicardium), and phase contrast MR imaging measurement of central aortic pulse wave velocity (PWV). The Vicorder device was used to measure carotid to femoral PWV. ResultsUnivariate correlations established that the 4 principal age-related changes in the left ventricular function were: 1) diastolic function: E/A ratio (r: −0.61, p<0.00001); 2) global systolic function: cardiac output (r: −0.49, p<0.00001), 3) structure: end-diastolic volume index (r: −0.39, p<0.0001), and 4) systolic strains: TSR (r: 0.49, p<0.0001). Multiple linear regression analysis showed that age was the dominant factor in predicting changes in cardiac output and E/A ratio (both p<0.01). Increased TSR was significantly related to reduced cardiac output and end-diastolic volume index (p<0.05 and p<0.01 respectively). Measures of vascular stiffness were not significantly related to any of these variables, but increased effective arterial elastance (afterload) was significantly related to reduced E/A ratio (p<0.05). ConclusionsIn this group of normal ageing subjects, afterload but not vascular stiffness is significantly related to diastolic dysfunction. Increased TSR, suggesting relative subendocardial dysfunction, has a significant role in reductions of cardiac output and end-diastolic volume index.