Cerebrospinal Fluid Flow and Brain Motion in Chiari I Malformation: Past, Present, and Future.

Cranio-spinal volume and pressure changes associated with the cardiac-cycle and respiration are altered in Chiari I malformation (CMI) due to obstruction of cerebrospinal fluid (CSF) flow at the foramen magnum. With the introduction of motion-sensitive MRI sequences, it was envisioned that these could provide noninvasive information about volume-pressure dynamics at the cranio-cervical junction in CMI hitherto available only through invasive pressure measurements. Since the early 1990s, multiple studies have assessed CSF flow and brain motion in CMI. However, differences in design and varied approaches in the presentation of results and conclusions makes it difficult to fully comprehend the role of MR imaging of CSF flow and brain motion in CMI. In this review, a cohesive summary of the current status of MRI assessment of CSF flow and brain motion in CMI is presented. Simplified versions of the results and conclusions of previous studies are presented by dividing the studies in distinct topics: 1) comparing CSF flow and brain motion between healthy subjects (HS) and CMI patients (before and after surgery), 2) comparing CSF flow and brain motion to CMI severity and symptoms, and 3) comparing CSF flow and brain motion in CMI with and without syringomyelia. Finally, we will discuss our vision of the future directions of MR imaging in CMI patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 5.

Assessment of Complex Flow Patterns in Patients With Carotid Webs, Patients With Carotid Atherosclerosis, and Healthy Subjects Using 4D Flow MRI.

BACKGROUND: Carotid webs (CaWs) are fibromuscular projections in the internal carotid artery (ICA) that cause mild luminal narrowing (<50%), but may be causative in up to one-third of seemingly cryptogenic strokes. Understanding hemodynamic alterations caused by CaWs is imperative to assessing stroke risk. Time-Average Wall Shear Stress (TAWSS) and Oscillatory Shear Index (OSI) are hemodynamic parameters linked to vascular dysfunction and thrombosis. PURPOSE: To test the hypothesis: "CaWs are associated with lower TAWSS and higher OSI than mild atherosclerosis or healthy carotid bifurcation." STUDY TYPE: Prospective study. POPULATION: A total of 35 subjects (N = 14 bifurcations with CaW, 11F, age: 49 ± 10, 10 mild atherosclerosis 6F, age: 72 ± 9, 11 healthy 9F, age: 42 ± 13). FIELD STRENGTH/SEQUENCE: 4D flow/STAR-MATCH/3D TOF/3T MRI, CTA. ASSESSMENT: 4D Flow velocity data were analyzed in two ways: 1) 3D ROI in the ICA bulbar segment (complex flow patterns are expected) was used to quantify the regions with low TAWSS and high OSI. 2) 2D planes were placed perpendicular to the centerline of the carotid bifurcation for detailed analysis of TAWSS and OSI. STATISTICAL TESTS: Independent-samples Kruskal-Wallis-H test with 0.05 used for statistical significance. RESULTS: The percent surface area where low TAWSS was present in the ICA bulb was 12.3 ± 8.0% (95% CI: 7.6-16.9) in CaW subjects, 1.6 ± 1.9% (95% CI: 0.2-2.9) in atherosclerosis, and 8.5 ± 7.7% (95% CI: 3.6-13.4) in healthy subjects, all differences were statistically significant (ƞ2 = 0.3 [95% CI: 0.05-0.5], P-value CaW vs. healthy = 0.2). OSI had similar values in the CCA between groups (ƞ2 = 0.07 [95% CI: 0.0-0.2], P-value = 0.5), but OSI was significantly higher downstream of the bifurcation in CaW subjects compared to atherosclerosis and normal subjects. OSI returned to similar values between groups 1.5 diameters distal to the bifurcation (ƞ2 = 0.03 [95% CI: 0.0-0.2], P-value = 0.7). CONCLUSION: Lower TAWSS and higher OSI are present in the ICA bulb in patients with CaW when compared to patients with atherosclerotic or healthy subjects. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Association between resistance to cerebrospinal fluid flow and cardiac-induced brain tissue motion for Chiari malformation type I.

PURPOSE: Chiari malformation type I (CMI) patients have been independently shown to have both increased resistance to cerebrospinal fluid (CSF) flow in the cervical spinal canal and greater cardiac-induced neural tissue motion compared to healthy controls. The goal of this paper is to determine if a relationship exists between CSF flow resistance and brain tissue motion in CMI subjects. METHODS: Computational fluid dynamics (CFD) techniques were employed to compute integrated longitudinal impedance (ILI) as a measure of unsteady resistance to CSF flow in the cervical spinal canal in thirty-two CMI subjects and eighteen healthy controls. Neural tissue motion during the cardiac cycle was assessed using displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) technique. RESULTS: The results demonstrate a positive correlation between resistance to CSF flow and the maximum displacement of the cerebellum for CMI subjects (r = 0.75, p = 6.77 × 10-10) but not for healthy controls. No correlation was found between CSF flow resistance and maximum displacement in the brainstem for CMI or healthy subjects. The magnitude of resistance to CSF flow and maximum cardiac-induced brain tissue motion were not statistically different for CMI subjects with and without the presence of five CMI symptoms: imbalance, vertigo, swallowing difficulties, nausea or vomiting, and hoarseness. CONCLUSION: This study establishes a relationship between CSF flow resistance in the cervical spinal canal and cardiac-induced brain tissue motion in the cerebellum for CMI subjects. Further research is necessary to understand the importance of resistance and brain tissue motion in the symptomatology of CMI.

The Relationship Between Imbalance Symptom and Cardiac Pulsation Induced Mechanical Strain in the Brainstem and Cerebellum for Chiari Malformation Type I.

Chiari malformation Type I (CMI) is known to have an altered biomechanical environment for the brainstem and cerebellum; however, it is unclear whether these altered biomechanics play a role in the development of CMI symptoms. We hypothesized that CMI subjects have a higher cardiac-induced strain in specific neurological tracts pertaining to balance, and postural control. We measured displacement over the cardiac cycle using displacement encoding with stimulated echoes magnetic resonance imaging in the cerebellum, brainstem, and spinal cord in 37 CMI subjects and 25 controls. Based on these measurements, we computed strain, translation, and rotation in tracts related to balance. The global strain on all tracts was small (<1%) for CMI subject and controls. Strain was found to be nearly doubled in three tracts for CMI subjects compared to controls (p < 0.03). The maximum translation and rotation were ∼150 µm and ∼1 deg, respectively and 1.5-2 times greater in CMI compared to controls in four tracts (p < 0.005). There was no significant difference between strain, translation, and rotation on the analyzed tracts in CMI subjects with imbalance compared to those without imbalance. A moderate correlation was found between cerebellar tonsillar position and strain on three tracts. The lack of statistically significant difference between strain in CMI subjects with and without imbalance could imply that the magnitude of the observed cardiac-induced strain was too small to cause substantial damage to the tissue (<1%). Activities such as coughing, or Valsalva may produce a greater strain.

In Vitro Validation of Regional Circumferential Strain Assessment in a Phantom Aortic Model Using Cine Displacement Encoding With Stimulated Echoes MRI.

BACKGROUND: A novel application of cine Displacement ENcoding with Stimulated Echoes Magnetic Resonance Imaging (DENSE MRI) has recently been described to assess regional heterogeneities in circumferential strain around the aortic wall in vivo; however, validation is first required for successful clinical translation. PURPOSE: To validate the quantification of regional circumferential strain around the wall of an aortic phantom using DENSE MRI. STUDY TYPE: In vitro phantom study. POPULATION: Three polyvinyl alcohol aortic phantoms with eight axially oriented nitinol wires embedded evenly around the walls. FIELD STRENGTH/SEQUENCE: 3 T; gradient-echo aortic DENSE MRI with spiral cine readout, gradient-echo phase-contrast MRI (PCMR) with Cartesian cine readout. ASSESSMENT: Phantoms were connected to a pulsatile flow loop and peak DENSE-derived regional circumferential Green strains at 16 equally spaced sectors around the wall were assessed according to previously published algorithms. "True" regional circumferential strains were calculated by manually tracking displacements of the nitinol wires by two independent observers. Normalized circumferential strains (NCS) were calculated by dividing regional strains by the mean strain. Finally, DENSE-derived regional strain was corrected by multiplying regional DENSE NCS by the mean strain calculated from the diameter change on the PCMR. STATISTICAL TESTS: One-sample t-test, Paired-sample t-test, and analysis of variance with Bonferroni correction, coefficient of variation (CoV), Bland-Altman analysis; P < 0.05 was considered statistically significant. RESULTS: Aortic DENSE MRI significantly overestimated circumferential strain compared to the wire-tracking method (mean difference and SD 0.030 ± 0.014, CoV 0.31). However, NCS demonstrated good agreement between DENSE and wire-tracking data (mean difference 0.000 ± 0.172, CoV 0.15). After correcting the DENSE-derived regional strain, the mean difference in regional circumferential strain between DENSE and wire-tracking was significantly reduced to 0.006 ± 0.008, and the CoV was reduced to 0.18. DATA CONCLUSION: For aortic phantoms with mild spatial heterogeneity in circumferential strain, the previously published aortic DENSE MRI technique successfully assessed the regional NCS distribution but overestimated the mean strain. This overestimation is correctable by computing a more accurate mean circumferential strain using a separate cine scan. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Reproducibility of global and segmental myocardial strain using cine DENSE at 3 T: a multicenter cardiovascular magnetic resonance study in healthy subjects and patients with heart disease.

BACKGROUND: While multiple cardiovascular magnetic resonance (CMR) methods provide excellent reproducibility of global circumferential and global longitudinal strain, achieving highly reproducible segmental strain is more challenging. Previous single-center studies have demonstrated excellent reproducibility of displacement encoding with stimulated echoes (DENSE) segmental circumferential strain. The present study evaluated the reproducibility of DENSE for measurement of whole-slice or global circumferential (Ecc), longitudinal (Ell) and radial (Err) strain, torsion, and segmental Ecc at multiple centers. METHODS: Six centers participated and a total of 81 subjects were studied, including 60 healthy subjects and 21 patients with various types of heart disease. CMR utilized 3 T scanners, and cine DENSE images were acquired in three short-axis planes and in the four-chamber long-axis view. During one imaging session, each subject underwent two separate DENSE scans to assess inter-scan reproducibility. Each subject was taken out of the scanner and repositioned between the scans. Intra-user, inter-user-same-site, inter-user-different-site, and inter-user-Human-Deep-Learning (DL) comparisons assessed the reproducibility of different users analyzing the same data. Inter-scan comparisons assessed the reproducibility of DENSE from scan to scan. The reproducibility of whole-slice or global Ecc, Ell and Err, torsion, and segmental Ecc were quantified using Bland-Altman analysis, the coefficient of variation (CV), and the intraclass correlation coefficient (ICC). CV was considered excellent for CV ≤ 10%, good for 10% < CV ≤ 20%, fair for 20% < CV ≤ 40%, and poor for CV > 40. ICC values were considered excellent for ICC > 0.74, good for ICC 0.6 < ICC ≤ 0.74, fair for ICC 0.4 < ICC ≤ 0.59, poor for ICC < 0.4. RESULTS: Based on CV and ICC, segmental Ecc provided excellent intra-user, inter-user-same-site, inter-user-different-site, inter-user-Human-DL reproducibility and good-excellent inter-scan reproducibility. Whole-slice Ecc and global Ell provided excellent intra-user, inter-user-same-site, inter-user-different-site, inter-user-Human-DL and inter-scan reproducibility. The reproducibility of torsion was good-excellent for all comparisons. For whole-slice Err, CV was in the fair-good range, and ICC was in the good-excellent range. CONCLUSIONS: Multicenter data show that 3 T CMR DENSE provides highly reproducible whole-slice and segmental Ecc, global Ell, and torsion measurements in healthy subjects and heart disease patients.

A New Method for Quantifying Abdominal Aortic Wall Shear Stress Using Phase Contrast Magnetic Resonance Imaging and the Womersley Solution.

Wall shear stress (WSS) is an important mediator of cardiovascular pathologies and there is a need for its reliable evaluation as a potential prognostic indicator. The purpose of this work was to develop a method that quantifies WSS from two-dimensional (2D) phase contrast magnetic resonance (PCMR) imaging derived flow waveforms, apply this method to PCMR data acquired in the abdominal aorta of healthy volunteers, and to compare PCMR-derived WSS values to values predicted from a computational fluid dynamics (CFD) simulation. The method uses PCMR-derived flow versus time waveforms constrained by the Womersley solution for pulsatile flow in a cylindrical tube. The method was evaluated for sensitivity to input parameters, intrastudy repeatability and was compared with results from a patient-specific CFD simulation. 2D-PCMR data were acquired in the aortas of healthy men (n = 12) and women (n = 15) and time-averaged WSS (TAWSS) was compared. Agreement was observed when comparing TAWSS between CFD and the PCMR flow-based method with a correlation coefficient of 0.88 (CFD: 15.0 ± 1.9 versus MRI: 13.5 ± 2.4 dyn/cm2) though comparison of WSS values between the PCMR-based method and CFD predictions indicate that the PCMR method underestimated instantaneous WSS by 3.7 ± 7.6 dyn/cm2. We found no significant difference in TAWSS magnitude between the sexes; 8.19 ± 2.25 versus 8.07 ± 1.71 dyn/cm2, p = 0.16 for men and women, respectively.

Cerebellar and Brainstem Displacement Measured with DENSE MRI in Chiari Malformation Following Posterior Fossa Decompression Surgery.

Background Posterior fossa decompression (PFD) surgery is a treatment for Chiari malformation type I (CMI). The goals of surgery are to reduce cerebellar tonsillar crowding and restore posterior cerebral spinal fluid flow, but regional tissue biomechanics may also change. MRI-based displacement encoding with stimulated echoes (DENSE) can be used to assess neural tissue displacement. Purpose To assess neural tissue displacement by using DENSE MRI in participants with CMI before and after PFD surgery and examine associations between tissue displacement and symptoms. Materials and Methods In a prospective, HIPAA-compliant study of patients with CMI, midsagittal DENSE MRI was performed before and after PFD surgery between January 2017 and June 2020. Peak tissue displacement over the cardiac cycle was quantified in the cerebellum and brainstem, averaged over each structure, and compared before and after surgery. Paired t tests and nonparametric Wilcoxon signed-rank tests were used to identify surgical changes in displacement, and Spearman correlations were determined between tissue displacement and presurgery symptoms. Results Twenty-three participants were included (mean age ± standard deviation, 37 years ± 10; 19 women). Spatially averaged (mean) peak tissue displacement demonstrated reductions of 46% (79/171 µm) within the cerebellum and 22% (46/210 µm) within the brainstem after surgery (P < .001). Maximum peak displacement, calculated within a circular 30-mm2 area, decreased by 64% (274/427 µm) in the cerebellum and 33% (100/300 µm) in the brainstem (P < .001). No significant associations were identified between tissue displacement and CMI symptoms (r < .74 and P > .012 for all; Bonferroni-corrected P = .0002). Conclusion Neural tissue displacement was reduced after posterior fossa decompression surgery, indicating that surgical intervention changes brain tissue biomechanics. For participants with Chiari malformation type I, no relationship was identified between presurgery tissue displacement and presurgical symptoms. © RSNA, 2021 Online supplemental material is available for this article.

Accuracy of cardiac-induced brain motion measurement using displacement-encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI): A phantom study.

PURPOSE: The goal of this study was to determine the accuracy of displacement-encoding with stimulated echoes (DENSE) MRI in a tissue motion phantom with displacements representative of those observed in human brain tissue. METHODS: The phantom was comprised of a plastic shaft rotated at a constant speed. The rotational motion was converted to a vertical displacement through a camshaft. The phantom generated repeatable cyclical displacement waveforms with a peak displacement ranging from 92 µm to 1.04 mm at 1-Hz frequency. The surface displacement of the tissue was obtained using a laser Doppler vibrometer (LDV) before and after the DENSE MRI scans to check for repeatability. The accuracy of DENSE MRI displacement was assessed by comparing the laser Doppler vibrometer and DENSE MRI waveforms. RESULTS: Laser Doppler vibrometer measurements of the tissue motion demonstrated excellent cycle-to-cycle repeatability with a maximum root mean square error of 9 µm between the ensemble-averaged displacement waveform and the individual waveforms over 180 cycles. The maximum difference between DENSE MRI and the laser Doppler vibrometer waveforms ranged from 15 to 50 µm. Additionally, the peak-to-peak difference between the 2 waveforms ranged from 1 to 18 µm. CONCLUSION: Using a tissue phantom undergoing cyclical motion, we demonstrated the percent accuracy of DENSE MRI to measure displacement similar to that observed for in vivo cardiac-induced brain tissue.

Fully-automated global and segmental strain analysis of DENSE cardiovascular magnetic resonance using deep learning for segmentation and phase unwrapping.

BACKGROUND: Cardiovascular magnetic resonance (CMR) cine displacement encoding with stimulated echoes (DENSE) measures heart motion by encoding myocardial displacement into the signal phase, facilitating high accuracy and reproducibility of global and segmental myocardial strain and providing benefits in clinical performance. While conventional methods for strain analysis of DENSE images are faster than those for myocardial tagging, they still require manual user assistance. The present study developed and evaluated deep learning methods for fully-automatic DENSE strain analysis. METHODS: Convolutional neural networks (CNNs) were developed and trained to (a) identify the left-ventricular (LV) epicardial and endocardial borders, (b) identify the anterior right-ventricular (RV)-LV insertion point, and (c) perform phase unwrapping. Subsequent conventional automatic steps were employed to compute strain. The networks were trained using 12,415 short-axis DENSE images from 45 healthy subjects and 19 heart disease patients and were tested using 10,510 images from 25 healthy subjects and 19 patients. Each individual CNN was evaluated, and the end-to-end fully-automatic deep learning pipeline was compared to conventional user-assisted DENSE analysis using linear correlation and Bland Altman analysis of circumferential strain. RESULTS: LV myocardial segmentation U-Nets achieved a DICE similarity coefficient of 0.87 ± 0.04, a Hausdorff distance of 2.7 ± 1.0 pixels, and a mean surface distance of 0.41 ± 0.29 pixels in comparison with manual LV myocardial segmentation by an expert. The anterior RV-LV insertion point was detected within 1.38 ± 0.9 pixels compared to manually annotated data. The phase-unwrapping U-Net had similar or lower mean squared error vs. ground-truth data compared to the conventional path-following method for images with typical signal-to-noise ratio (SNR) or low SNR (p < 0.05), respectively. Bland-Altman analyses showed biases of 0.00 ± 0.03 and limits of agreement of - 0.04 to 0.05 or better for deep learning-based fully-automatic global and segmental end-systolic circumferential strain vs. conventional user-assisted methods. CONCLUSIONS: Deep learning enables fully-automatic global and segmental circumferential strain analysis of DENSE CMR providing excellent agreement with conventional user-assisted methods. Deep learning-based automatic strain analysis may facilitate greater clinical use of DENSE for the quantification of global and segmental strain in patients with cardiac disease.

Endograft exclusion of the false lumen restores local hemodynamics in a model of type B aortic dissection.

OBJECTIVE: Endovascular intervention in uncomplicated type B dissection has not been shown conclusively to confer benefit on patients. The hemodynamic effect of primary entry tear coverage is not known. Endovascular stent grafts were deployed in a model of aortic dissection with multiple fenestrations to study these effects. It is hypothesized that endograft deployment will lead to restoration of parabolic true lumen flow as well as elimination of false lumen flow and transluminal jets and vortices locally while maintaining distal false lumen canalization. METHODS: Thoracic stent grafts were placed in silicone models of aortic dissection with a compliant and mobile intimal flap and installed in a flow loop. Pulsatile fluid flow was established with a custom positive displacement pump, and the models were imaged by four-dimensional flow magnetic resonance imaging. Full flow fields were acquired in the models, and velocities were extracted to calculate flow rates, reverse flow indices, and oscillatory shear index, the last two of which are measures of stagnant and disturbed flows. RESULTS: Complete obliteration of the false lumen was achieved in grafted aorta, with normal parabolic flow profiles in the true lumen (maximal velocity, 30.4 ± 8.4 cm/s). A blind false lumen pouch was created distal to this with low-velocity (5.8 ± 2.7 cm/s) and highly reversed (27.9% ± 13.9% reverse flow index) flows. In distal free false lumen segments, flows were comparable to ungrafted conditions with maximal velocities on the order of 7.0 ± 2.1 cm/s. Visualization studies revealed forward flow in these regions with left-handed vortices from true to false lumen. Shear calculations in free false lumen regions demonstrated reduced oscillatory shear index. CONCLUSIONS: Per the initial hypothesis, endovascular grafting improved true lumen hemodynamics in the grafted region. Just distally, a prothrombotic flow regimen was noted in the false lumen, yet free false lumen distal to this remained canalized. Clinically, this suggests a need for advancing endovascular intervention beyond sole entry tear coverage to prevent further false lumen canalization through uncovered fenestrations.

Transcatheter aortic valve deployment influences neo-sinus thrombosis risk: An in vitro flow study.

OBJECTIVES: We investigated the impact of (transcatheter heart valve) THV expansion at the level of the native annulus and implant depth on valve performance and neo-sinus flow stasis. BACKGROUND: Flow stasis in the neo-sinus is one of the identified risk factors of THV thrombosis. METHODS: A 29 mm CoreValve and 26 mm SAPIEN 3 were deployed under different expansions (CoreValve, SAPIEN 3) and implant depths (CoreValve) within a patient-derived aortic root in a pulse duplicator. Fluorescent dye was injected during diastole into the neo-sinus and imaged over 20 cardiac cycles. Washout times were computed as a measure of flow stasis for each deployment. RESULTS: The 10% CoreValve under-expansion improved neo-sinus washout over full expansion by 8% (p < .001), and higher CoreValve implant depth improved neo-sinus washout (p < .001). The 10% SAPIEN 3 under-expansion improved neo-sinus washout by 23% (p < .001). Under-expansion of both valve types caused higher pressure gradients and smaller effective orifice areas than full expansion. CONCLUSIONS: Neo-sinus flow stasis is influenced by THV expansion and implant depth (CoreValve). The 10% valve under-deployment (oversizing) may facilitate reduced flow stasis in the neo-sinus with minimal increase in pressure gradients. This strategy may be helpful for patient anatomies, which are in-between transcatheter valve sizes.

Demonstration of circumferential heterogeneity in displacement and strain in the abdominal aortic wall by spiral cine DENSE MRI.

BACKGROUND: Knowledge of tissue properties of the abdominal aorta can improve understanding of vascular disease and guide interventional approaches. Existing MRI methods to quantify aortic wall displacement and strain are unable to discern circumferential heterogeneity. PURPOSE: To assess regional variation in abdominal aortic wall displacement and strain as a function of circumferential position using spiral cine displacement encoding with stimulated echoes (DENSE). STUDY TYPE: Prospective. POPULATION: Cardiovascular disease-free men (n = 8) and women (n = 9) ages 30-42. SEQUENCES: Prospective electrocardiogram (ECG)-gated and navigator echo-gated spiral, cine 2D DENSE and retrospective ECG-gated phase contrast MR (PCMR) sequences at 3T. ASSESSMENT: In-plane displacement values of the aortic wall acquired with DENSE were used to determine radial and circumferential aortic wall motion. A quadrilateral-based 2D strain calculation method was implemented to determine strain from the displacement field. Peak displacement and its radial and circumferential contributions as well as peak circumferential strain were compared among eight circumferential wall segments. Distensibility was calculated using PCMR and compared with homogenized circumferential strain. STATISTICAL TESTS: To account for repeated measurements in volunteers, linear mixed models for mean sector values were created for displacement magnitude, circumferential displacement, radial displacement, and circumferential strain. Comparisons were made between sectors. Calculated distensibility and homogenized circumferential strain were compared using Bland-Altman analysis. Statistical significance was defined as P < 0.05. RESULTS: Displacement was highest in the anterior wall (1.5 ± 0.7 mm) and was primarily in the radial as compared with circumferential direction (1.04 ± 0.05 mm vs. 0.81 ± 0.42 mm). Circumferential strain was highest in the lateral walls (left 0.16 ± 0.05 and right 0.21 ± 0.12) with homogenized circumferential strain of 0.14 ± 0.05. DATA CONCLUSION: DENSE imaging in the abdominal aortic wall demonstrated that the anterior aortic wall exhibits the greatest displacement, while the lateral wall experiences the largest circumferential strain. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:731-743.

In Vivo Quantification of Regional Circumferential Green Strain in the Thoracic and Abdominal Aorta by Two-Dimensional Spiral Cine DENSE MRI.

Regional tissue mechanics play a fundamental role in the patient-specific function and remodeling of the cardiovascular system. Nevertheless, regional in vivo assessments of aortic kinematics remain lacking due to the challenge of imaging the thin aortic wall. Herein, we present a novel application of displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) to quantify the regional displacement and circumferential Green strain of the thoracic and abdominal aorta. Two-dimensional (2D) spiral cine DENSE and steady-state free procession (SSFP) cine images were acquired at 3T at either the infrarenal abdominal aorta (IAA), descending thoracic aorta (DTA), or distal aortic arch (DAA) in a pilot study of six healthy volunteers (22-59 y.o., 4 females). DENSE data were processed with multiple custom noise reduction techniques including time-smoothing, displacement vector smoothing, sectorized spatial smoothing, and reference point averaging to calculate circumferential Green strain across 16 equispaced sectors around the aorta. Each volunteer was scanned twice to evaluate interstudy repeatability. Circumferential Green strain was heterogeneously distributed in all volunteers and locations. The mean spatial heterogeneity index (standard deviation of all sector values divided by the mean strain) was 0.37 in the IAA, 0.28 in the DTA, and 0.59 in the DAA. Mean (homogenized) peak strain by DENSE for each cross section was consistent with the homogenized linearized strain estimated from SSFP cine. The mean difference in peak strain across all sectors following repeat imaging was -0.1±2.3%, with a mean absolute difference of 1.7%. Aortic cine DENSE MRI is a viable noninvasive technique for quantifying heterogeneous regional aortic wall strain and has significant potential to improve patient-specific clinical assessments of numerous aortopathies, as well as to provide the lacking spatiotemporal data required to refine patient-specific computational models of aortic growth and remodeling.

Combined Angiography and Late Gadolinium Enhancement Acquisition to Improve Assessment of Pulmonary Vein Isolation for Atrial Fibrillation.

PURPOSE: To develop a Shared K-space (SharK) magnetic resonance imaging (MRI) sequence that combines angiographic and late gadolinium enhancement (LGE) acquisitions to improve atrial wall segmentation and scar identification, and to develop a novel visualization method that quantifies scar encirclement of pulmonary veins postablation treatment for atrial fibrillation. MATERIALS AND METHODS: A SharK sequence was developed and used at 3T to image the left atrium in 11 patients postcryoballoon ablation. The effects of sharing k-space between the angiographic and LGE acquisitions on the accuracy of scar were assessed. The left atrial wall was segmented and points about each pulmonary vein (PV) ostia were projected onto a bullseye to quantitatively compare PV encirclement. The parameters used to quantify encirclement were varied to perform a sensitivity analysis. RESULTS: Compared to using a complete set of k-space, total atrial scar differences were significant only when sharing >75% k-space (P = 0.014), and 90% sensitivity and specificity for identifying scar was achieved when sharing 50% k-space. In patients, the right PVs showed more intersubject variance in encirclement compared to the left PVs. A 100° anteroinferior portion of the left PVs was always encircled, while the superior segments of both right PVs was ablated in only 6/11 patients. CONCLUSION: A SharK sequence was developed to combine angiographic and LGE imaging for atrial wall segmentation and scar identification. The PV bullseye quantifies and localizes encirclement about the PVs. The left PVs showed a higher amount of scar encirclement and less variability compared to the right PVs. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:477-486.

Magnetic Resonance Imaging-Guided Transplantation of Neural Stem Cells into the Porcine Spinal Cord.

BACKGROUND: Cell-based therapies are a promising treatment option for traumatic, tumorigenic and degenerative diseases of the spinal cord. Transplantation into the spinal cord is achieved with intravascular, intrathecal, or direct intraparenchymal injection. The current standard for direct injection is limited by surgical invasiveness, difficulty in reinjection, and the inability to directly target anatomical or pathological landmarks. The objective of this study was to present the proof of principle for minimally invasive, percutaneous transplantation of stem cells into the spinal cord parenchyma of live minipigs under MR guidance. METHODS: An MR-compatible spine injection platform was developed to work with the ClearPoint SmartFrame system (MRI Interventions Inc.). The system was attached to the spine of 2 live minipigs, a percutaneous injection cannula was advanced into the spinal cord under MR guidance, and cells were delivered to the cord. RESULTS: A graft of 2.5 × 106 human (n = 1) or porcine (n = 1) neural stem cells labeled with ferumoxytol nanoparticles was transplanted into the ventral horn of the spinal cord with MR guidance in 2 animals. Graft delivery was visualized with postprocedure MRI, and characteristic iron precipitates were identified in the spinal cord by Prussian blue histochemistry. Grafted stem cells were observed in the spinal cord of the pig injected with porcine neural stem cells. No postoperative morbidity was observed in either animal. CONCLUSION: This report supports the proof of principle for transplantation and visualization of pharmacological or biological agents into the spinal cord of a large animal under the guidance of MRI.

Nonuniform Moving Boundary Method for Computational Fluid Dynamics Simulation of Intrathecal Cerebrospinal Flow Distribution in a Cynomolgus Monkey.

A detailed quantification and understanding of cerebrospinal fluid (CSF) dynamics may improve detection and treatment of central nervous system (CNS) diseases and help optimize CSF system-based delivery of CNS therapeutics. This study presents a computational fluid dynamics (CFD) model that utilizes a nonuniform moving boundary approach to accurately reproduce the nonuniform distribution of CSF flow along the spinal subarachnoid space (SAS) of a single cynomolgus monkey. A magnetic resonance imaging (MRI) protocol was developed and applied to quantify subject-specific CSF space geometry and flow and define the CFD domain and boundary conditions. An algorithm was implemented to reproduce the axial distribution of unsteady CSF flow by nonuniform deformation of the dura surface. Results showed that maximum difference between the MRI measurements and CFD simulation of CSF flow rates was <3.6%. CSF flow along the entire spine was laminar with a peak Reynolds number of ∼150 and average Womersley number of ∼5.4. Maximum CSF flow rate was present at the C4-C5 vertebral level. Deformation of the dura ranged up to a maximum of 134 µm. Geometric analysis indicated that total spinal CSF space volume was ∼8.7 ml. Average hydraulic diameter, wetted perimeter, and SAS area were 2.9 mm, 37.3 mm and 27.24 mm2, respectively. CSF pulse wave velocity (PWV) along the spine was quantified to be 1.2 m/s.

Effect of Angiotensin II Type I Receptor Blockade with Valsartan on Carotid Artery Atherosclerosis: A Double Blind Randomized Clinical Trial Comparing Valsartan and Placebo (EFFERVESCENT).

BACKGROUND: Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis. METHODS: Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent vascular function. RESULTS: Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, -0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [-0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function. CONCLUSIONS: In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis warrants investigation.

SEX AND VASCULAR BIOMECHANICS: A HYPOTHESIS FOR THE MECHANISM UNDERLYING DIFFERENCES IN THE PREVALENCE OF ABDOMINAL AORTIC ANEURYSMS IN MEN AND WOMEN.

The prevalence of abdominal aortic aneurysms differs greatly between men and women across the spectrum of ages. The reason for this discrepancy is not clear and likely involves several factors including the impact of sex hormones. We hypothesize that the unique spatial localization of abdominal aortic aneurysms is dictated in part by local hemodynamic forces on the vascular wall. Specifically, we propose that oscillatory shear stress is a specific signal to the endothelium that initiates the events ultimately leading to abdominal aortic aneurysm formation. We are proposing that sex-dependent differences in oscillatory shear stress in the infra-renal aorta may explain the observed differences between men and women. Initial observations suggest that, indeed, men and women have different degrees of oscillatory blood flow in the infra-renal abdominal aorta. The challenge is to extend these observations to show a causal relationship between oscillatory flow and aneurysm formation.