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Background: 5D, free-running imaging resolves sets of 3D whole-heart images in both cardiac and respiratory dimensions. In an application such as coronary imaging when a single, static image is of interest, computationally expensive offline iterative reconstruction is still needed to compute the multiple 3D datasets., Purpose: Evaluate how the number of physiologic bins included in the reconstruction affects the computational cost and resulting image quality of a single, static volume reconstruction., Study Type: Retrospective., Subjects: 15 pediatric patients following Ferumoxytol infusion (4 mg/kg)., Field Strength/sequence: 1.5 T/Ungated 5D free-running GRE sequence., Assessment: The raw data of each subject were binned and reconstructed into a 5D (x-y-z-cardiac-respiratory) images. 1, 3, 5, 7, and 9 bins adjacent to both sides of the retrospectively determined cardiac resting phase and 1, 3 bins adjacent to the end-expiration phase are used for limited frame reconstructions. The static volume within each limited reconstruction was compared with the corresponding full 5D reconstruction using the structural similarity index measure (SSIM). A non-linear regression model was used to fit SSIM with the percentage of data used compared to full reconstruction (% data). A linear regression model was used to fit computation time with % raw data used. Coronary artery sharpness is measured on each limited reconstructed images to determine the minimal number of cardiac and respiratory bins needed to preserve image quality., Statistical Tests: The coefficient of determination (R 2 ) is computed for each regression model., Results: The % of data used in the reconstruction was linearly related to the computational time (R 2  = 0.99). The SSIM of the static image from the limited reconstructions is non-linearly related with the % of data used (R 2  = 0.80). Over the 15 patients, the model showed SSIM of 0.9 with 18% of data, and SSIM of 0.96 with 30% of data. The coronary artery sharpness of images reconstructed using no less than 5 cardiac and all respiratory phases is not significantly different from the full reconstructed images using all cardiac and respiratory bins., Data Conclusion: Reconstruction using only a limited number of acquired physiological states can linearly reduce the computational cost while preserving similarity to the full reconstruction image. It is suggested to use no less than 5 cardiac and all respiratory phases in the limited reconstruction to best preserve the original quality seen on the full reconstructed images., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Dr Leshnower is a speaker for Medtronic and a consultant for Endospan Inc. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

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 (ƞ 2  = 0.3 [95% CI: 0.05-0.5], P-value CaW vs. healthy = 0.2). OSI had similar values in the CCA between groups (ƞ 2  = 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 (ƞ 2  = 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., (© 2023 International Society for Magnetic Resonance in Medicine.)

Carotid artery webs (CaW) are non-atherosclerotic projections into the vascular lumen and have been linked to up to one-third of cryptogenic strokes in younger patients. Determining how CaW affects local hemodynamics is essential for understanding clot formation and stroke risk. Computational fluid dynamics simulations were used to investigate patient-specific hemodynamics in carotid artery bifurcations with CaW, bifurcations with atherosclerotic lesions having a similar degree of lumen narrowing, and with healthy carotid bifurcations. Simulations were conducted using segmented computed tomography angiography geometries with inlet boundary conditions extracted from 2D phase contrast MRI scans. The study included carotid bifurcations with CaW (n = 13), mild atherosclerosis (n = 7), and healthy bifurcation geometries (n = 6). Hemodynamic parameters associated with vascular dysfunction and clot formation, including shear rate, oscillatory shear index (OSI), low velocity, and flow stasis were calculated and compared between the subject groups. Patients with CaW had significantly larger regions containing low shear rate, high OSI, low velocity, and flow stasis in comparison to subjects with mild atherosclerosis or normal bifurcations. These abnormal hemodynamic metrics in patients with CaW are associated with clot formation and vascular dysfunction and suggest that hemodynamic assessment may be a tool to assess stroke risk in these patients., (© 2024. The Author(s).)

Objective: Currently, the long-term outcomes of uncomplicated type B aortic dissection (TBAD) patients managed with optimal medical therapy (OMT) remain poor. Aortic expansion is a major factor that determines patient long-term survival. The objective of this study was to investigate the association between anatomic shape features and (i) OMT outcome; (ii) aortic growth rate for TBAD patients initially treated with OMT., Methods: 108 CT images of TBAD in the acute and chronic phases were collected from 46 patients who were initially treated with OMT. Statistical shape models (SSM) of TBAD were constructed to extract shape features from the earliest initial CT scans of each patient by using principal component analysis (PCA) and partial least square (PLS) regression. Additionally, conventional shape features (e.g., aortic diameter) were quantified from the earliest CT scans as a baseline for comparison. We identified conventional and SSM features that were significant in separating OMT "success" and failure patients. Moreover, the aortic growth rate was predicted by SSM and conventional features using linear and nonlinear regression with cross-validations., Results: Size-related SSM and conventional features (mean aortic diameter: p=0.0484, centerline length: p=0.0112, PCA score c 1 : p=0.0192, and PLS scores t 1 : p=0.0004, t 2 : p=0.0274) were significantly different between OMT success and failure groups, but these features were incapable of predicting the aortic growth rate. SSM shape features showed superior results in growth rate prediction compared to conventional features. Using multiple linear regression, the conventional, PCA, and PLS shape features resulted in root mean square errors (RMSE) of 1.23, 0.85, and 0.84 mm/year, respectively, in leave-one-out cross-validations. Nonlinear support vector regression (SVR) led to improved RMSE of 0.99, 0.54, and 0.43 mm/year, for the conventional, PCA, and PLS features, respectively., Conclusion: Size-related shape features of the earliest scan were correlated with OMT failure but led to large errors in the prediction of the aortic growth rate. SSM features in combination with nonlinear regression could be a promising avenue to predict the aortic growth rate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recent advancements in diagnostic CT detector technology have made it possible to resolve anatomical features smaller than 20 LP/cm, referred to as ultra-high-resolution (UHR) CT. Subtle biological motions that did not affect standard-resolution (SR) CT may not be neglected in UHR. This study aimed to quantify the cardiac-induced motion of the pancreas and simulate its impact on the image quality of UHR-CT. We measured the displacement of the head of the pancreas in three healthy volunteers using Displacement Encoding with Stimulated Echoes (DENSE) MRI. The results were used to simulate SR- and UHR-CT acquisitions affected by pancreatic motion.We found pancreatic displacement in the 0.24-1.59 mm range during one cardiac cycle across the subjects. The greatest displacement was observed in the anterior-posterior direction. The time to peak displacement varied across subjects. Both SR and UHR images showed reduced image quality, as measured by radial modulation transfer function, due to cardiac-induced motion, but the motion artifacts caused more severe degradation in UHR acquisitions. Our investigation of cardiac-induced pancreatic displacement reveals its potential to degrade both standard and UHR-CT scans. To fully utilize the improvement in spatial resolution offered by UHR-CT, the effects of cardiac-induced motion in the abdomen need to be understood and corrected.Relevance statement Advancements in CT detector technology have enhanced CT scanner spatial resolution to approximately 100 µm. Consequently, previously ignored biological motions such as the cardiac-induced motion of the pancreas now demand attention to fully utilize this improved resolution., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., (© 2023 International Society for Magnetic Resonance in Medicine.)

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., (Copyright © 2023 by ASME.)

Introduction: Deep learning (DL)-based segmentation has gained popularity for routine cardiac magnetic resonance (CMR) image analysis and in particular, delineation of left ventricular (LV) borders for LV volume determination. Free-breathing, self-navigated, whole-heart CMR exams provide high-resolution, isotropic coverage of the heart for assessment of cardiac anatomy including LV volume. The combination of whole-heart free-breathing CMR and DL-based LV segmentation has the potential to streamline the acquisition and analysis of clinical CMR exams. The purpose of this study was to compare the performance of a DL-based automatic LV segmentation network trained primarily on computed tomography (CT) images in two whole-heart CMR reconstruction methods: (1) an in-line respiratory motion-corrected (Mcorr) reconstruction and (2) an off-line, compressed sensing-based, multi-volume respiratory motion-resolved (Mres) reconstruction. Given that Mres images were shown to have greater image quality in previous studies than Mcorr images, we hypothesized that the LV volumes segmented from Mres images are closer to the manual expert-traced left ventricular endocardial border than the Mcorr images., Method: This retrospective study used 15 patients who underwent clinically indicated 1.5 T CMR exams with a prototype ECG-gated 3D radial phyllotaxis balanced steady state free precession (bSSFP) sequence. For each reconstruction method, the absolute volume difference (AVD) of the automatically and manually segmented LV volumes was used as the primary quantity to investigate whether 3D DL-based LV segmentation generalized better on Mcorr or Mres 3D whole-heart images. Additionally, we assessed the 3D Dice similarity coefficient between the manual and automatic LV masks of each reconstructed 3D whole-heart image and the sharpness of the LV myocardium-blood pool interface. A two-tail paired Student's t -test (alpha = 0.05) was used to test the significance in this study., Results & Discussion: The AVD in the respiratory Mres reconstruction was lower than the AVD in the respiratory Mcorr reconstruction: 7.73 ± 6.54 ml vs. 20.0 ± 22.4 ml, respectively ( n  = 15, p -value = 0.03). The 3D Dice coefficient between the DL-segmented masks and the manually segmented masks was higher for Mres images than for Mcorr images: 0.90 ± 0.02 vs. 0.87 ± 0.03 respectively, with a p -value = 0.02. Sharpness on Mres images was higher than on Mcorr images: 0.15 ± 0.05 vs. 0.12 ± 0.04, respectively, with a p -value of 0.014 ( n  = 15)., Conclusion: We conclude that the DL-based 3D automatic LV segmentation network trained on CT images and fine-tuned on MR images generalized better on Mres images than on Mcorr images for quantifying LV volumes., Competing Interests: The author JNO declares that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision. Authors AJJ, TC, TP, DP, ZH, and PS are employed by Siemens. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yang, Shah, Jacob, Hair, Chitiboi, Passerini, Yerly, Di Sopra, Piccini, Hosseini, Sharma, Sahu, Stuber and Oshinski.)

Background: Three-dimensional, ECG-gated, time-resolved, three-directional, velocity-encoded phase-contrast MRI (4D flow MRI) has been applied extensively to measure blood velocity in great vessels but has been much less used in diseased carotid arteries. Carotid artery webs (CaW) are non-inflammatory intraluminal shelf-like projections into the internal carotid artery (ICA) bulb that are associated with complex flow and cryptogenic stroke., Purpose: Optimize 4D flow MRI for measuring the velocity field of complex flow in the carotid artery bifurcation model that contains a CaW., Methods: A 3D printed phantom model created from computed tomography angiography (CTA) of a subject with CaW was placed in a pulsatile flow loop within the MRI scanner. 4D Flow MRI images of the phantom were acquired with five different spatial resolutions (0.50-2.00  mm 3 ) and four different temporal resolutions (23-96 ms) and compared to a computational fluid dynamics (CFD) solution of the flow field as a reference. We examined four planes perpendicular to the vessel centerline, one in the common carotid artery (CCA) and three in the internal carotid artery (ICA) where complex flow was expected. At these four planes pixel-by-pixel velocity values, flow, and time average wall shear stress (TAWSS) were compared between 4D flow MRI and CFD., Hypothesis: An optimized 4D flow MRI protocol will provide a good correlation with CFD velocity and TAWSS values in areas of complex flow within a clinically feasible scan time (~ 10 min)., Results: Spatial resolution affected the velocity values, time average flow, and TAWSS measurements. Qualitatively, a spatial resolution of 0.50  mm 3 resulted in higher noise, while a lower spatial resolution of 1.50-2.00  mm 3 did not adequately resolve the velocity profile. Isotropic spatial resolutions of 0.50-1.00  mm 3 showed no significant difference in total flow compared to CFD. Pixel-by-pixel velocity correlation coefficients between 4D flow MRI and CFD were > 0.75 for 0.50-1.00  mm 3 but were < 0.5 for 1.50 and 2.00  mm 3 . Regional TAWSS values determined from 4D flow MRI were generally lower than CFD and decreased at lower spatial resolutions (larger pixel sizes). TAWSS differences between 4D flow and CFD were not statistically significant at spatial resolutions of 0.50-1.00  mm 3 but were different at 1.50 and 2.00 mm 3 . Differences in temporal resolution only affected the flow values when temporal resolution was > 48.4 ms; temporal resolution did not affect TAWSS values., Conclusion: A spatial resolution of 0.74-1.00  mm 3 and a temporal resolution of 23-48 ms (1-2 k-space segments) provides a 4D flow MRI protocol capable of imaging velocity and TAWSS in regions of complex flow within the carotid bifurcation at a clinically acceptable scan time., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: To develop a three-dimensional (two dimensions + time) convolutional neural network trained with displacement encoding with stimulated echoes (DENSE) data for displacement and strain analysis of cine MRI., Materials and Methods: In this retrospective multicenter study, a deep learning model (StrainNet) was developed to predict intramyocardial displacement from contour motion. Patients with various heart diseases and healthy controls underwent cardiac MRI examinations with DENSE between August 2008 and January 2022. Network training inputs were a time series of myocardial contours from DENSE magnitude images, and ground truth data were DENSE displacement measurements. Model performance was evaluated using pixelwise end-point error (EPE). For testing, StrainNet was applied to contour motion from cine MRI. Global and segmental circumferential strain (E cc ) derived from commercial feature tracking (FT), StrainNet, and DENSE (reference) were compared using intraclass correlation coefficients (ICCs), Pearson correlations, Bland-Altman analyses, paired t tests, and linear mixed-effects models., Results: The study included 161 patients (110 men; mean age, 61 years ± 14 [SD]), 99 healthy adults (44 men; mean age, 35 years ± 15), and 45 healthy children and adolescents (21 males; mean age, 12 years ± 3). StrainNet showed good agreement with DENSE for intramyocardial displacement, with an average EPE of 0.75 mm ± 0.35. The ICCs between StrainNet and DENSE and FT and DENSE were 0.87 and 0.72, respectively, for global E cc and 0.75 and 0.48, respectively, for segmental E cc . Bland-Altman analysis showed that StrainNet had better agreement than FT with DENSE for global and segmental E cc ., Conclusion: StrainNet outperformed FT for global and segmental E cc analysis of cine MRI. Keywords: Image Postprocessing, MR Imaging, Cardiac, Heart, Pediatrics, Technical Aspects, Technology Assessment, Strain, Deep Learning, DENSE Supplemental material is available for this article. © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: Y.W. Supported by the American Heart Association (2020AHAPRE0000203801); U.S. provisional patent applications serial numbers 63/149,900 ("System and Method for Improved Cardiac MRI Feature Tracking by Learning from Displacement-Encoded Imaging") and 63/408,760 ("Method and System for Strain Analysis that Includes CMR-trained StrainNet to Echocardiography"). C.S. U.S. provisional patent applications serial numbers 63/149,900 ("System and Method for Improved Cardiac MRI Feature Tracking by Learning from Displacement-Encoded Imaging") and 63/408,760 ("Method and System for Strain Analysis that Includes CMR-trained StrainNet to Echocardiography"). S.G. No relevant relationships. D.C.A. No relevant relationships. P.C. No relevant relationships. M.V. No relevant relationships. K.M. Co-applicant (2022) for National Health Service (NHS) Greater Glasgow and Clyde Endowment Funding (GN21CA412) for "Scar Characterisation with Cardiac MR to Predict Ventricular Arrhythmias" (£25 000); principal applicant (2021) for NHS Greater Glasgow and Clyde Endowment Funding (GN20CA408) for "Centre-specific Stress Perfusion Reference Ranges for the 3-T MRI Scanner" (£14 910); co-applicant (2021) for NHS Greater Glasgow and Clyde Endowment Funding (GN20ID164) for "CISCO-19 Visit 3" (£96 370); co-applicant (2021) for Chief Scientist Office–Long Term Effects of COVID (COV/LTE/20/10) for "Prevention and Early Treatment of COVID-19 Long Term Effects: A Randomised Clinical Trial of Resistance Exercise" (£288 660); principal applicant (2020) for Tenovus Scotland (S20-08) for "Investigating the Long-term Cardiac Sequelae of Trastuzumab Therapy" (£19 600); principal applicant (2022) for SoftMech Feasibility Funds for "Using Advanced CMR Techniques and Computational Modeling in Female Volunteers to Detect Pump Function Changes in Cancer Patients" (£10 000); principal applicant (2020) for Wellcome ISSF COVID Response Fund for "A Vascular Biology Nested Study within CISCO-19" (£10 000); co-applicant (2020) for Chief Scientist Office, Rapid Research COVID-19 for "Cardiovascular Imaging in SARS-CoV-2 (CISCO-19)" (COV/GLA/20/05) (£48, 618; MRI and CTCA scan costs in-kind); co-applicant (2020) for EPSRC Impact Acceleration Account (IAA) Cardiac Endotypes in COVID-19 for "Quantification and Mechanisms of Cardiac Injury" (£48 304) C.B. Employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Auxilius Pharma, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genenetech, GSK, HeartFlow, Menarini, Neovasc, Novartis, Siemens Healthcare, and Valo Health, with grants, contracts, consulting fees, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events paid to the institution, University of Glasgow; named on a pending patent for the use of zibotentan for microvascular angina, patent held by the University of Glasgow; participation on PROTECT-TAVR UK DSMB (unpaid); president of the British Society of Cardiovascular Magnetic Resonance (unpaid); past member of the Clinical Trials Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) (unpaid); in-kind support for clinical research studies involving Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Coroventis, GSK, HeartFlow, Novartis, and Siemens Healthcare, by contract with the University of Glasgow. C.M.H. Supported by the National Institutes of Health (NIH). L.J. No relevant relationships. B.K.F. Grant funding from the NIH (NIH DP5 OD-012132, NIH P20 GM-103527, NIH UL1 TR-000117) made to the institution where some of the cardiac MRI data was collected; full-time employment with Tempus Labs that began in late 2021 after the work was completed. J.J.C. No relevant relationships. J.C. No relevant relationships. A.D.S. The CMR Unit, Royal Brompton Hospital, receives research support from Siemens. P.F.F. Contribution to this work was funded by the British Heart Foundation (BHF), grant number RG/19/1/34160. J.N.O. No relevant relationships. D.B.E. NIH grant numbers NIH National Heart, Lung, and Blood Institute (NHLBI) R01 131975 and 131823; joint 6/8ths Stanford University/Veterans Affairs (SU/VA) appointment specified by a formal Memorandum of Understanding between SU and the VA, there is no possibility of dual compensation for the same work, no conflict of interest regarding such work, and the overall set of responsibilities meets the test of reasonableness; support for the following listed projects and proposals includes support managed through SU and through the investigator’s VA appointment, Palo Alto Veterans Institute for Research (PAVIR) and the VA Palo Alto Health Care System, primary place of performance for all is SU: "High Resolution Whole-Breast MRI at 3.0T Major," research to develop much higher resolution breast MRI, allowing better classification of small lesions to prevent unnecessary biopsy and detect cancer earlier, active support, project number R01 EB009055, source of support is IH/NIBIB, primary place of performance is SU, March 2020–November 2023, total award amount (including indirect costs) is $2 559 180; "Using Atrial Mechanics to Identify Fibrosis in Patients with Atrial Fibrillation," to use MRI of atrial mechanics to identify localized fibrosis and hypothesize that attenuated mechanics provide a robust measure of atrial fibrosis, active support, project number, source of support is NIH/NHLBI, June 2020–May 2024, total award amount (including indirect costs) is $2 787 583; "Biomechanical Optimization of Cardiac Valve Repair Operations," to validate our findings using large animal cardiac surgery models, and then hopefully translate these discoveries directly to the operating room in the human clinical arena, active support, project number R01 HL152155, source of support is NIH/NHLBI, primary place of performance is SU, May 2020–April 2024, total award amount (including indirect costs) is $2 762 997; "Advanced MR Applications Development–Tiger Team Years 13 & 14," comprises five projects in neuroimaging, high-field, pediatric, body, and musculoskeletal MRI, to advance clinical imaging capabilities, with the goals to develop and evaluate MR pulse sequences and hardware, active support, project number A117, source of support is GE Healthcare, June 2020–October 2022, total award amount (including indirect costs) is $1 936 583; "GE Healthcare–Stanford Artificial Intelligence in Medical Imaging Research," to develop methods of upstream medical imaging artificial intelligence to optimize the selection, scheduling, protocoling, and execution of exams, active support, project number A113, A114, A118, A120, source of support is GE Healthcare, July 2020–June 2024, total award amount (including indirect costs) is $3 342 138; "Abbreviated Non-Contrast-Enhanced MRI for Breast Cancer Screening," to provide accurate, low-cost, comfortable, MRI screening without intravenous contrast media, in a 10-minute exam, which will ultimately enable more effective and comfortable breast cancer screening for millions of women for whom x-ray mammography is insufficient, active support, project number R01 CA249893, source of support is NIH/NCI, primary place of performance is SU, February 2021–January 2026, total award amount (including indirect costs) is $3 127 573; "Enabling the Next Generation of High Performance Pediatric Whole-Body MR Imaging," to create and validate the next generation systems for pediatric MRI, active support, project number U01 EB029427, source of support is NIH/NIBIB, August 2020–July 2025, total award amount (including indirect costs) is $4 189 084; "Improved Diagnostic MRI Around Metallic Implants," active support, project number SPO#192723, source of support is the University of Southern California/NIH, February 2022–November 2026, total award amount (including indirect costs) is $967 045; "MR/PET Motion Correction from Coil Fingerprints," active support, project number, R01 EB029306, source of support is the NIH, September 2022–January 2024, total award amount (including indirect costs) is $1 261 824; "Developing ultra high field connectome hardware for order-of-magnitude increase in MRI sensitivity," pending support, project number SPO#280964, source of support is the NIH, primary place of performance is SU, July 1, 2023–June 30, 2028, total award amount (including indirect costs) is $4 403 210; "Fast and Accurate Cardiovascular 4D-Flow MRI for Pediatrics," pending support, project number SPO#232860, source of support is the NIH, April 1, 2023–March 31, 2028, total award amount (including indirect costs) is $3 861 471; projects managed and/or administered by PAVIR and VAPAHCS: "Using Atrial Mechanics to Identify Fibrosis in Patients with Atrial Fibrillation," to use MRI of atrial mechanics to identify localized fibrosis and hypothesize that attenuated mechanics provide a robust measure of atrial fibrosis, active support, project number R01 HL152256, source of support is NIH/NHLBI, June 2020–May 2024, total award amount (including indirect costs) is $271,187; "Implementing the Enhanced Liver Fibrosis (ELF) test to optimize prognostic screening and monitoring of hepatic fibrosis among patients at risk for non-alcoholic fatty liver disease (NAFLD)," to improve clinical care by using ELF to identify high-risk patients with hepatic fibrosis compared to standard-of-care and monitor patients for rapid disease progression or response to treatment, active support, project number C00239205, source of support is Siemens Medical Solutions USA, primary place of performance is VAPAHCS, September 2021–October 2024, total award amount (including indirect costs) is $718 147; "Abbreviated US and MRI versus FibroScan for diffuse liver disease," to improve clinical care by comparing the accuracy of vibration-controlled transient elastography (VCTE), US, and MRI for assessment of NAFLD/NASH and to introduce new US and MRI techniques to improve detection of NAFLD/NASH, active support, source of support is Siemens Medical Solutions USA, primary place of performance is VAPAHCS, September 2021–October 2024, total award amount (including indirect costs) is $551 656; author’s graduate students receive in-kind contributions. K.C.B. NHLBI grant, AHA grant, Medtronic grant, Siemens; consulting fees from Medtronic; payment or honoraria for speaker, ACC; US patent planned, issued, or pending; participation on a Data Safety Monitoring Board or Advisory Board for Left v. Left RCT funded by PCORI, 2022-present; vice-chair, HRS, research committee chair, SCMR, Clinical Trials Committee (starting in early February 2023, previously a member of the committee for several years), grant reviewer, NIH; research funding gift from Seraph Foundation. F.H.E. Research support from Siemens Healthineers Ivy Biomedical Innovation Fund; patents planned, issued, or pending, PCT/US2022/014903 Intramyocardial Tissue Displacement and Motion Measurement and Strain Analysis from MRI Cine Images Using DENSE Deep Learning; patent application number 63/408,760 entitled "Method and System for Strain Analysis that Includes CMR-trained StrainNet to Echocardiography.”, (© 2023 by the Radiological Society of North America, Inc.)

Purpose: To evaluate the agreement of 4D flow cMRI-derived bulk flow features and fluid (blood) velocities in the carotid bifurcation using prospective and retrospective gating techniques., Methods: Prospective and retrospective ECG-gated three-dimensional (3D) cine phase-contrast cardiac MRI with three-direction velocity encoding (i.e., 4D flow cMRI) data were acquired in ten carotid bifurcations from men (n = 3) and women (n = 2) that were cardiovascular disease-free. MRI sequence parameters were held constant across all scans except temporal resolution values differed. Velocity data were extracted from the fluid domain and evaluated across the entire volume or at defined anatomic planes (common, internal, external carotid arteries). Qualitative agreement between gating techniques was performed by visualizing flow streamlines and topographical images, and statistical comparisons between gating techniques were performed across the fluid volume and defined anatomic regions., Results: Agreement in the kinematic data (e.g., bulk flow features and velocity data) were observed in the prospectively and retrospectively gated acquisitions. Voxel differences in time-averaged, peak systolic, and diastolic-averaged velocity magnitudes between gating techniques across all volunteers were 2.7%, 1.2%, and 6.4%, respectively. No significant differences in velocity magnitudes or components ([Formula: see text], [Formula: see text], [Formula: see text]) were observed. Importantly, retrospective acquisitions captured increased retrograde flow in the internal carotid artery (i.e., carotid sinus) compared to prospective acquisitions (10.4 ± 6.3% vs. 4.6 ± 5.3%; [Formula: see text] < 0.05)., Conclusion: Prospective and retrospective ECG-gated 4D flow cMRI acquisitions provide comparable evaluations of fluid velocities, including velocity vector components, in the carotid bifurcation. However, the increased temporal coverage of retrospective acquisitions depicts increased retrograde flow patterns (i.e., disturbed flow) not captured by the prospective gating technique., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Four-dimensional flow magnetic resonance imaging (i.e., 4D flow MRI) has become a valuable tool for the in vivo assessment of blood flow within large vessels and cardiac chambers. As wall shear stress (WSS) has been correlated with the development and progression of cardiovascular disease, focus has been directed at developing techniques to quantify WSS directly from 4D flow MRI data. The goal of this study was to compare the accuracy of two such techniques - termed the velocity and flow-based methods - in the setting of simplified and complex flow scenarios. Synthetic MR data were created from exact solutions to the Navier-Stokes equations for the steady and pulsatile flow of an incompressible, Newtonian fluid through a rigid cylinder. In addition, synthetic MR data were created from the predicted velocity fields derived from a fluid-structure interaction (FSI) model of pulsatile flow through a thick-walled, multi-layered model of the carotid bifurcation. Compared to the analytical solutions for steady and pulsatile flow, the flow-based method demonstrated greater accuracy than the velocity-based method in calculating WSS across all changes in fluid velocity/flow rate, tube radius, and image signal-to-noise (p < 0.001). Furthermore, the velocity-based method was more sensitive to boundary segmentation than the flow-based method. When compared to results from the FSI model, the flow-based method demonstrated greater accuracy than the velocity-based method with average differences in time-averaged WSS of 0.31 ± 1.03 Pa and 0.45 ± 1.03 Pa, respectively (p <0.005). These results have implications on the utility, accuracy, and clinical translational of methods to determine WSS from 4D flow MRI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2022 by ASME.)

Background: Carotid webs (CaWs) are associated with ischemic strokes in younger patients without degrees of stenosis that are traditionally considered clinically significant., Objective: To compare the hemodynamic parameters in the internal carotid artery (ICA) bulbar segment in patients with CaW with those in patients with atherosclerotic lesions using time-density curve (TDC) analysis of digital subtraction angiography (DSA) images., Methods: We retrospectively assessed DSA images of 47 carotid arteries in 41 adult patients who underwent ICA catheter angiography for evaluation after ischemic stroke. Hemodynamic parameters, including full width at half maximum (FWHM) and area under the time-density curve (AUC) as proxies for increased flow stasis, were calculated using TDC analyses of a region of interest (ROI) in the ICA bulb immediately rostral to the web/atherosclerotic plaque, relative to a standardized ROI in the ipsilateral distal common carotid artery (eg, relative FWHM (rFWHM)). Hemodynamic parameters were compared using non-parametric Kruskal-Wallis tests. Logistic regression was used to predict CaW versus mild/moderate atherosclerosis for each hemodynamic parameter, adjusting for degree of stenosis., Results: Mean age of patients was 56.0±13 years, with 22 (53.7%) women. 17 CaWs, 22 atherosclerotic plaques (15 mild/moderate and 7 severe), and eight normal carotid arteries were assessed. Significant between-group differences were present in the relative total AUC (p<0.001), relative AUC at wash out (p=0.031), and relative FWHM (p=0.001). Logistic regression to predict CaW versus mild/moderate atherosclerosis showed that rAUC total had the highest predictive value (pAUC=0.96, 95% CI 0.90 to 1.00), followed by rFWHM (0.87, 95% CI 0.74 to 1.00), and rAUC WO (0.74, 95% CI (0.57 to 0.91)., Conclusion: CaW results in larger local hemodynamic disruption, characterized by flow stasis, than mild/moderate carotid atherosclerotic lesions, suggesting that CaWs may produce larger regions of thrombogenic flow stasis., Competing Interests: Competing interests: JNO receives research project funding from Siemens Medical Solutions., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A clinical study comparing the hemodynamic outcomes of transcatheter mitral valve replacement (TMVR) with vs. without Laceration of the Anterior Mitral leaflet to Prevent Outflow Obstruction (LAMPOON) has never been designed nor conducted., Aims: To quantify the hemodynamic impact of LAMPOON in TMVR using patient-specific computational ( in silico ) models., Materials: Eight subjects from the LAMPOON investigational device exemption trial were included who had acceptable computed tomography (CT) data for analysis. All subjects were anticipated to be at prohibitive risk of left ventricular outflow tract (LVOT) obstruction from TMVR, and underwent successful LAMPOON immediately followed by TMVR. Using post-procedure CT scans, two 3D anatomical models were created for each subject: (1) TMVR with LAMPOON (performed procedure), and (2) TMVR without LAMPOON (virtual control). A validated computational fluid dynamics (CFD) paradigm was then used to simulate the hemodynamic outcomes for each condition., Results: LAMPOON exposed on average 2 ± 0.6 transcatheter valve cells (70 ± 20 mm 2 total increase in outflow area) which provided an additional pathway for flow into the LVOT. As compared to TMVR without LAMPOON, TMVR with LAMPOON resulted in lower peak LVOT velocity, lower peak LVOT gradient, and higher peak LVOT effective orifice area by 0.4 ± 0.3 m/s (14 ± 7% improvement, p = 0.006), 7.6 ± 10.9 mmHg (31 ± 17% improvement, p = 0.01), and 0.2 ± 0.1 cm 2 (17 ± 9% improvement, p = 0.002), respectively., Conclusion: This was the first study to permit a quantitative, patient-specific comparison of LVOT hemodynamics following TMVR with and without LAMPOON. The LAMPOON procedure achieved a critical increment in outflow area which was effective for improving LVOT hemodynamics, particularly for subjects with a small neo-left ventricular outflow tract (neo-LVOT)., Competing Interests: KK has served as a consultant for Abbott Vascular. PB has served as a consultant for Edwards Lifesciences, Tendyne, Neovasc, and Circle Imaging. AG has served as a proctor for Edwards Lifesciences, Medtronic, and Abbott Vascular; and has served as a consultant for and is an equity holder in Transmural Systems. VB has served as a consultant for Edwards Lifesciences and Abbott Vascular; and has served as a consultant for and is an equity holder in Transmural Systems. JK and RL were co-inventors on patents, assigned to the NIH, on devices for leaflet laceration. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kohli, Wei, Sadri, Siefert, Blanke, Perdoncin, Greenbaum, Khan, Lederman, Babaliaros, Yoganathan and Oshinski.)

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., (© 2021 International Society for Magnetic Resonance in Medicine.)

Aims: To characterize the dynamic nature of the left ventricular outflow tract (LVOT) geometry and flow rate in patients following transcatheter mitral valve replacement (TMVR) with anterior leaflet laceration (LAMPOON) and derive insights to help guide future patient selection., Methods and Results: Time-resolved LVOT geometry and haemodynamics were analysed with post-procedure computed tomography and echocardiography in subjects (N = 19) from the LAMPOON investigational device exemption trial. A novel post hoc definition for LVOT obstruction was employed to account for systolic flow rate and quality of life improvement [obstruction was defined as LVOT gradient >30 mmHg or LVOT effective orifice area (EOA) ≤1.15 cm2]. The neo-LVOT and skirt neo-LVOT were observed to vary substantially in area throughout systole (64 ± 27% and 25 ± 14% change in area, respectively). The peak systolic flow rate occurred most commonly just prior to mid-systole, while minimum neo-LVOT (and skirt neo-LVOT) area occurred most commonly in early-diastole. Subjects with LVOT obstruction (n = 5) had smaller skirt neo-LVOT values across systole. Optimal thresholds for skirt neo-LVOT area were phase-specific (260, 210, 200, and 180 mm2 for early-systole, peak flow, mid-systole, and end-systole, respectively)., Conclusion: The LVOT geometry and flow rate exhibit dynamic characteristics following TMVR with LAMPOON. Subjects with LVOT obstruction had smaller skirt neo-LVOT areas across systole. The authors recommend the use of phase-specific threshold values for skirt neo-LVOT area to guide future patient selection for this procedure. LVOT EOA is a 'flow-independent' metric which has the potential to aid in characterizing LVOT obstruction severity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

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 (E cc ), longitudinal (E ll ) and radial (E rr ) strain, torsion, and segmental E cc 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 E cc , E ll and E rr , torsion, and segmental E cc 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 E cc 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 E cc and global E ll 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 E rr , 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 E cc , global E ll , and torsion measurements in healthy subjects and heart disease patients., (© 2022. The Author(s).)

Chiari malformation Type I (CMI) is characterized by herniation of the cerebellar tonsils through the foramen magnum. The pathophysiology of CMI is not well elucidated; however, the prevailing theory focuses on the underdevelopment of the posterior cranial fossa which results in tonsillar herniation. Symptoms are believed to be due to the herniation causing resistance to the natural flow of cerebrospinal fluid (CSF) and exerting a mass effect on nearby neural tissue. However, asymptomatic cases vastly outnumber symptomatic ones and it is not known why some people become symptomatic. Recently, it has been proposed that CMI symptoms are primarily due to instability of either the atlanto-axial (AA) or the atlanto-occipital (AO) joint and the cerebellar tonsils herniate to prevent mechanical pinching. However, only a small percentage of patients exhibit clinical instability and these theories do not account for asymptomatic herniations. We propose that the pathophysiology of adult CMI involves a combination of craniocervical abnormalities which leads to tonsillar herniation and reduced compliance of the cervical spinal canal. Specifically, abnormal AO and/or AA joint morphology leads to chronic cervical instability, often subclinical, in a large portion of CMI patients. This in turn causes overwork of the suboccipital muscles as they try to compensate for the instability. Over time, the repeated, involuntary activation of these muscles leads to mechanical overload of the myodural bridge complex, altering the mechanical properties of the dura it merges with. As a result, the dura becomes stiffer, reducing the overall compliance of the cervical region. This lower compliance, combined with CSF resistance at the same level, leads to intracranial pressure peaks during the cardiac cycle (pulse pressure) that are amplified during activities such as coughing, sneezing, and physical exertion. This increase in pulse pressure reduces the compliance of the cervical subarachnoid space which increases the CSF wave speed in the spinal canal, and further increases pulse pressure in a feedback loop. Finally, the abnormal pressure environment induces greater neural tissue motion and strain, causing microstructural damage to the cerebellum, brainstem, and cervical spinal cord, and leading to symptoms. This hypothesis explains how the combination of craniocervical bony abnormalities, anatomic CSF restriction, and reduced compliance leads to symptoms in adult CMI.

Currently, there is no large animal model of sustained limb ischemia suitable for testing novel angiogenic therapeutics for peripheral artery disease (PAD) such as drugs, genes, materials, or cells. We created a large animal model suitable for efficacy assessment of these therapies by testing 3 swine hind limb ischemia (HLI) variations and quantifying vascular perfusion, muscle histology, and limb function. Ligation of the ipsilateral external and bilateral internal iliac arteries produced sustained gait dysfunction compared to isolated external iliac or unilateral external and internal iliac artery ligations. Hyperemia-dependent muscle perfusion deficits, depressed limb blood pressure, arteriogenesis, muscle atrophy, and microscopic myopathy were quantifiable in ischemic limbs 6 weeks post-ligation. Porcine mesenchymal stromal cells (MSCs) engineered to express a reporter gene were visualized post-administration via positron emission tomography (PET) in vivo. These results establish a preclinical platform enabling better optimization of PAD therapies, including cellular therapeutics, increasing bench-to-bedside translational success. A preclinical platform for porcine studies of peripheral artery disease therapies including (1) a hind limb ischemia model and (2) non-invasive MSC viability and retention assessment via PET., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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-mm 2 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.

The heart is the first organ to develop in the human embryo through a series of complex chronological processes, many of which critically rely on the interplay between cells and the dynamic microenvironment. Tight spatiotemporal regulation of these interactions is key in heart development and diseases. Due to suboptimal experimental models, however, little is known about the role of microenvironmental cues in the heart development. This study investigates the use of 3D bioprinting and perfusion bioreactor technologies to create bioartificial constructs that can serve as high-fidelity models of the developing human heart. Bioprinted hydrogel-based, anatomically accurate models of the human embryonic heart tube (e-HT, day 22) and fetal left ventricle (f-LV, week 33) are perfused and analyzed both computationally and experimentally using ultrasound and magnetic resonance imaging. Results demonstrate comparable flow hemodynamic patterns within the 3D space. We demonstrate endothelial cell growth and function within the bioprinted e-HT and f-LV constructs, which varied significantly in varying cardiac geometries and flow. This study introduces the first generation of anatomically accurate, 3D functional models of developing human heart. This platform enables precise tuning of microenvironmental factors, such as flow and geometry, thus allowing the study of normal developmental processes and underlying diseases., (© 2020 Wiley-VCH GmbH.)

While the degree of cerebellar tonsillar descent is considered the primary radiologic marker of Chiari malformation type I (CMI), biomechanical forces acting on the brain tissue in CMI subjects are less studied and poorly understood. In this study, regional brain tissue displacement and principal strains in 43 CMI subjects and 25 controls were quantified using a magnetic resonance imaging (MRI) methodology known as displacement encoding with stimulated echoes (DENSE). Measurements from MRI were obtained for seven different brain regions-the brainstem, cerebellum, cingulate gyrus, corpus callosum, frontal lobe, occipital lobe, and parietal lobe. Mean displacements in the cerebellum and brainstem were found to be 106 and 64% higher, respectively, for CMI subjects than controls (p < .001). Mean compression and extension strains in the cerebellum were 52 and 50% higher, respectively, in CMI subjects (p < .001). Brainstem mean extension strain was 41% higher in CMI subjects (p < .001), but no significant difference in compression strain was observed. The other brain structures revealed no significant differences between CMI and controls. These findings demonstrate that brain tissue displacement and strain in the cerebellum and brainstem might represent two new biomarkers to distinguish between CMI subjects and controls.

In silico modeling has been proposed as a tool to simulate left ventricular (LV) outflow tract (LVOT) obstruction in patients undergoing transcatheter mitral valve replacement (TMVR). This study validated a simplified approach to simulate LV outflow hemodynamics in the setting of TMVR with anterior leaflet laceration, a clinical technique used to mitigate the risk of LVOT obstruction. Personalized, 3-dimensional computational fluid dynamics models were developed from computed tomography images of six patients who underwent TMVR with anterior leaflet laceration. LV outflow hemodynamics were simulated using the patient-specific anatomy and the peak systolic flow rate as boundary conditions. The peak outflow velocity, a clinically relevant hemodynamic metric, was extracted from each simulation (v sim-peak ) and compared with the clinical measurement from Doppler echocardiography (v clin-peak ) for validation. In silico models were successfully developed and implemented for all patients. The pre-processing time was 2 h per model and the simulation could be completed within 3 h. In three patients, the lacerated anterior leaflet exposed open cells of the transcatheter valve to flow. Good agreement was obtained between v sim-peak and v clin-peak (r = 0.97, p < 0.01) with average discrepancies of 5 ± 2% and 14 ± 1% for patients with exposed and unexposed cells of the transcatheter valve, respectively. The proposed in silico modeling paradigm therefore simulated LV outflow hemodynamics in a time-efficient manner and demonstrated good agreement with clinical measurements. Future studies should investigate the ability of this paradigm to support clinical applications.

Spaceflight is known to cause ophthalmic changes in a condition known as spaceflight-associated neuro-ocular syndrome (SANS). It is hypothesized that SANS is caused by cephalad fluid shifts and potentially mild elevation of intracranial pressure (ICP) in microgravity. Head-down tilt (HDT) studies are a ground-based spaceflight analogue to create cephalad fluid shifts. Here, we developed non-invasive magnetic resonance imaging (MRI)-based techniques to quantify ophthalmic structural changes under acute 15° HDT. We specifically quantified: (i) change in optic nerve sheath (ONS) and optic nerve (ON) cross-sectional area, (ii) change in ON deviation, an indicator of ON tortuosity, (iii) change in vitreous chamber depth, and (iv) an estimated ONS Young's modulus. Under acute HDT, ONS cross-sectional area increased by 4.04 mm 2 (95% CI 2.88-5.21 mm 2 , p < 0. 000), while ON cross-sectional area remained nearly unchanged (95% CI -0.12 to 0.43 mm 2 , p = 0.271). ON deviation increased under HDT by 0.20 mm (95% CI 0.08-0.33 mm, p = 0.002). Vitreous chamber depth decreased under HDT by -0.11 mm (95% CI -0.21 to -0.03 mm, p = 0.009). ONS Young's modulus was estimated to be 85.0 kPa. We observed a significant effect of sex and BMI on ONS parameters, of interest since they are known risk factors for idiopathic intracranial hypertension. The tools developed herein will be useful for future analyses of ON changes in various conditions.

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.

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., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: Astronauts undergoing long-duration spaceflight are exposed to numerous health risks, including Spaceflight-Associated Neuro-Ocular Syndrome (SANS), a spectrum of ophthalmic changes that can result in permanent loss of visual acuity. The etiology of SANS is not well understood but is thought to involve changes in cerebrovascular flow dynamics in response to microgravity. There is a paucity of knowledge in this area; in particular, cerebrospinal fluid (CSF) flow dynamics have not been well characterized under microgravity conditions. Our study was designed to determine the effect of simulated microgravity (head-down tilt [HDT]) on cerebrovascular flow dynamics. We hypothesized that microgravity conditions simulated by acute HDT would result in increases in CSF pulsatile flow., Methods: In a prospective cohort study, we measured flow in major cerebral arteries, veins, and CSF spaces in fifteen healthy volunteers using phase contrast magnetic resonance (PCMR) before and during 15° HDT., Results: We found a decrease in all CSF flow variables [systolic peak flow (p = 0.009), and peak-to-peak pulse amplitude (p = 0.001)]. Cerebral arterial average flow (p = 0.04), systolic peak flow (p = 0.04), and peak-to-peak pulse amplitude (p = 0.02) all also significantly decreased. We additionally found a decrease in average cerebral arterial flow (p = 0.040). Finally, a significant increase in cerebral venous cross-sectional area under HDT (p = 0.005) was also observed., Conclusions: These results collectively demonstrate that acute application of -15° HDT caused a reduction in CSF flow variables (systolic peak flow and peak-to-peak pulse amplitude) which, when coupled with a decrease in average cerebral arterial flow, systolic peak flow, and peak-to-peak pulse amplitude, is consistent with a decrease in cardiac-related pulsatile CSF flow. These results suggest that decreases in cerebral arterial inflow were the principal drivers of decreases in CSF pulsatile flow.

A detailed understanding of the CSF dynamics is needed for design and optimization of intrathecal drug delivery devices, drugs, and protocols. Preclinical research using large-animal models is important to help define drug pharmacokinetics-pharmacodynamics and safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there was a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with cervical implantation compared to lumbar implantation. CSF flow rate decreased up to 55% with the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation in Cynomolgus monkeys., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: This study was funded in part by Voyager Therapeutics. Authors BAM and GRS are employed by Alcyone Therapeutics. GRS was employed by Voyager Therapeutics during the course of this study. JRZ is a fulltime employee of Northern Biomedical. BAM has received grant support from Voyager Therapeutics, Genentech, Alcyone Lifesciences, Biogen, and Minnetronix; BAM is a member of the Neurapheresis Research Consortium. BAM is scientific advisory board member for Alcyone Lifesciences, Chiari and Syringomyelia Foundation, The International Society for Hydrocephalus and CSF Disorders, The International CSF Dynamics Society, and has served as a consultant to Voyager Therapeutics, Praxis Medicines, Roche, SwanBio Therapeutics, CereVasc, Minnetronix, Invicro, Genentech, Medtrad Biosystems, Behavior Imaging, Neurosyntek, and Cerebral Therapeutics. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The optic nerve sheath (ONS) is biomechanically important. It is acted on by tension due to ocular movements, and by fluid shifts and/or alterations in intracranial pressure (ICP) in human disease, specifically in pathologies leading to intracranial hypertension. It has also been hypothesized that the ONS is acted on by altered ICP in astronauts exposed chronically to microgravity. However, a non-invasive method to quantify ONS biomechanical properties is not presently available; knowledge of such properties is desirable to allow characterization of the biomechanical forces exerted on the optic nerve head and other ocular structures due to the ONS. Thus, the primary objective of this study was to characterize the biomechanical properties (stiffness) of the human ONS in vivo as a necessary step towards investigating the role of ICP in various conditions, including Spaceflight Associated Neuro-ocular Syndrome (SANS). We acquired non-invasive magnetic resonance imaging (MRI) scans of ostensibly healthy subjects (n = 18, age = 30.4 ± 11.6 [mean ± SD] years) during supine and 15-degree head-down-tilt (HDT) postures, and extracted ONS contours from these scans. We then used finite element modeling to quantify ONS expansion due to postural changes and an inverse approach to estimate ONS stiffness. Using this non-invasive procedure, we estimated an in vivo ONS stiffness of 39.2 ± 21.9 kPa (mean ± SD), although a small subset of individuals had very stiff ONS that precluded accurate estimates of their stiffness values. ONS stiffness was not correlated with age and was higher in males than females., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 Wiley Periodicals, Inc.)

Background: Prior studies have applied driver mutations targeting the RTK/RAS/PI3K and p53 pathways to induce the formation of high-grade gliomas in rodent models. In the present study, we report the production of a high-grade spinal cord glioma model in pigs using lentiviral gene transfer., Methods: Six Gottingen Minipigs received thoracolumbar (T14-L1) lateral white matter injections of a combination of lentiviral vectors, expressing platelet-derived growth factor beta (PDGF-B), constitutive HRAS, and shRNA-p53 respectively. All animals received injection of control vectors into the contralateral cord. Animals underwent baseline and endpoint magnetic resonance imaging (MRI) and were evaluated daily for clinical deficits. Hematoxylin and eosin (H&E) and immunohistochemical analysis was conducted. Data are presented using descriptive statistics including relative frequencies, mean, standard deviation, and range., Results: 100% of animals (n = 6/6) developed clinical motor deficits ipsilateral to the oncogenic lentiviral injections by a three-week endpoint. MRI scans at endpoint demonstrated contrast enhancing mass lesions at the site of oncogenic lentiviral injection and not at the site of control injections. Immunohistochemistry demonstrated positive staining for GFAP, Olig2, and a high Ki-67 proliferative index. Histopathologic features demonstrate consistent and reproducible growth of a high-grade glioma in all animals., Conclusions: Lentiviral gene transfer represents a feasible pathway to glioma modeling in higher order species. The present model is the first lentiviral vector induced pig model of high-grade spinal cord glioma and may potentially be used in preclinical therapeutic development programs.

Pulsatile, three-dimensional hemodynamic forces influence thrombosis, and may dictate progression of aortic dissection. Intimal flap fenestration and blood pressure are clinically relevant variables in this pathology, yet their effects on dissection hemodynamics are poorly understood. The goal of this study was to characterize these effects on flow in dissection models to better guide interventions to prevent aneurysm formation and false lumen flow. Silicone models of aortic dissection with mobile intimal flap were fabricated based on patient images and installed in a flow loop with pulsatile flow. Flow fields were acquired via 4-dimensional flow MRI, allowing for quantification and visualization of relevant fluid mechanics. Pulsatile vortices and jet-like structures were observed at fenestrations immediately past the proximal entry tear. False lumen flow reversal was significantly reduced with the addition of fenestrations, from 19.2 ± 3.3% in two-tear dissections to 4.67 ± 1.5% and 4.87 ± 1.7% with each subsequent fenestration. In contrast, increasing pressure did not cause appreciable differences in flow rates, flow reversal, and vortex formation. Increasing the number of intermediate tears decreased flow reversal as compared to two-tear dissection, which may prevent false lumen thrombosis, promoting persistent false lumen flow. Vortices were noted to result from transluminal fluid motion at distal tear sites, which may lead to degeneration of the opposing wall. Increasing pressure did not affect measured flow patterns, but may contribute to stress concentrations in the aortic wall. The functional and anatomic assessment of disease with 4D MRI may aid in stratifying patient risk in this population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 by ASME.)

Background: The aim of this study was to noninvasively measure regional contributions of vasculature in the human body using magnetohydrodynamic voltages (VMHD) obtained from electrocardiogram (ECG) recordings performed inside MRI's static magnetic field (B0). Integrating the regional VMHD over the Swave-Twave segment of the cardiac cycle (Vsegment) provides a non-invasive method for measuring regional blood volumes, which can be rapidly obtained during MRI without incurring additional cost., Methods: VMHD was extracted from 12-lead ECG traces acquired during gradual introduction into a 3T MRI. Regional contributions were computed utilizing weights based on B0's strength at specified distances from isocenter. Vsegment mapping was performed in six subjects and validated against MR angiograms (MRA)., Results: Fluctuations in Vsegment, which presented as positive trace deflections, were found to be associated with aortic-arch flow in the thoracic cavity, the main branches of the abdominal aorta, and the bifurcation of the common iliac artery. The largest fluctuation corresponded to the location where the aortic arch was approximately orthogonal to B0. The smallest fluctuations corresponded to areas of vasculature that were parallel to B0. Significant correlations (specifically, Spearman's ranked correlation coefficients of 0.96 and 0.97 for abdominal and thoracic cavities, respectively) were found between the MRA and Vsegment maps (p < 0.001)., Conclusions: A novel non-invasive method to extract regional blood volumes from ECGs was developed and shown to be a rapid means to quantify peripheral and abdominal blood volumes., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2018 International Society for Magnetic Resonance in Medicine.)

Recent advancements have been made toward understanding the diagnostic and therapeutic potential of cerebrospinal fluid (CSF) and related hydrodynamics. Increased understanding of CSF dynamics may lead to improved detection of central nervous system (CNS) diseases and optimized delivery of CSF based CNS therapeutics, with many proposed therapeutics hoping to successfully treat or cure debilitating neurological conditions. Before significant strides can be made toward the research and development of interventions designed for human use, additional research must be carried out with representative subjects such as non-human primates (NHP). This study presents a geometric and hydrodynamic characterization of CSF in eight cynomolgus monkeys (Macaca fascicularis) at baseline and two-week follow-up. Results showed that CSF flow along the entire spine was laminar with a Reynolds number ranging up to 80 and average Womersley number ranging from 4.1-7.7. Maximum CSF flow rate occurred ~25 mm caudal to the foramen magnum. Peak CSF flow rate ranged from 0.3-0.6 ml/s at the C3-C4 level. Geometric analysis indicated that average intrathecal CSF volume below the foramen magnum was 7.4 ml. The average surface area of the spinal cord and dura was 44.7 and 66.7 cm2 respectively. Subarachnoid space cross-sectional area and hydraulic diameter ranged from 7-75 mm2 and 2-3.7 mm, respectively. Stroke volume had the greatest value of 0.14 ml at an axial location corresponding to C3-C4., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: This study was funded in part by Voyager Therapeutics. Author GRS is employed by Axovant and was employed by Voyager Therapeutics during the course of this study. JRZ is a fulltime employee of Northern Biomedical. BAM has received grant support from Voyager Therapeutics, Alcyone Lifesciences, Biogen, and Minnetronix Medical; BAM is a member of the Neurapheresis Research Consortium. BAM is scientific advisory board member for Alcyone Lifesciences and the Chiari and Syringomyelia Foundation and served as a consultant to Voyager Therapeutics, SwanBio Therapeutics, Medtrad Biosystems, Neurosyntek, and Cerebral Therapeutics. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Animal models offer a flexible experimental environment for studying atherosclerosis. The mouse is the most commonly used animal, however, the underlying hemodynamics in larger animals such as the rabbit are far closer to that of humans. The aortic arch is a vessel with complex helical flow and highly heterogeneous shear stress patterns which may influence where atherosclerotic lesions form. A better understanding of intraspecies flow variation and the impact of geometry on flow may improve our understanding of where disease forms. In this work, we use magnetic resonance angiography (MRA) and 4D phase contrast magnetic resonance imaging (PC-MRI) to image and measure blood velocity in the rabbit aortic arch. Measured flow rates from the PC-MRI were used as boundary conditions in computational fluid dynamics (CFD) models of the arches. Helical flow, cross flow index (CFI), and time-averaged wall shear stress (TAWSS) were determined from the simulated flow field. Both traditional geometric metrics and shape modes derived from statistical shape analysis were analyzed with respect to flow helicity. High CFI and low TAWSS were found to colocalize in the ascending aorta and to a lesser extent on the inner curvature of the aortic arch. The Reynolds number was linearly associated with an increase in helical flow intensity (R = 0.85, p < 0.05). Both traditional and statistical shape analyses correlated with increased helical flow symmetry. However, a stronger correlation was obtained from the statistical shape analysis demonstrating its potential for discerning the role of shape in hemodynamic studies., (Copyright © 2019 by ASME.)

Background: Type 1 Chiari malformation (CM-I) has been historically defined by cerebellar tonsillar position (TP) greater than 3-5 mm below the foramen magnum (FM). Often, the radiographic findings are highly variable, which may influence the clinical course and patient outcome. In this study, we evaluate the inter-operator reliability (reproducibility) of MRI-based measurement of TP in CM-I patients and healthy controls., Methods: Thirty-three T2-weighted MRI sets were obtained for 23 CM-I patients (11 symptomatic and 12 asymptomatic) and 10 healthy controls. TP inferior to the FM was measured in the mid-sagittal plane by seven expert operators with reference to McRae's line. Overall agreement between the operators was quantified by intraclass correlation coefficient (ICC)., Results: The mean and standard deviation of cerebellar TP measurements for asymptomatic (CM-Ia) and symptomatic (CM-Is) patients in mid-sagittal plane was 6.38 ± 2.19 and 9.57 ± 2.63 mm, respectively. TP measurements for healthy controls was 0.48 ± 2.88 mm. The average range of TP measurements for all data sets analyzed was 7.7 mm. Overall operator agreement for TP measurements was relatively high with an ICC of 0.83., Conclusion: The results demonstrated a large average range (7.7 mm) of measurements among the seven expert operators and support that, if economically feasible, two radiologists should make independent measurements before radiologic diagnosis of CM-I and surgery is contemplated. In the future, an objective diagnostic parameter for CM-I that utilizes automated algorithms and results in smaller inter-operator variation may improve patient selection.

Purpose of Review: Transcatheter mitral valve replacement (TMVR) is an emerging alternative for patients with severe mitral valve regurgitation who are considered at high risk for conventional surgical options. The early clinical experience with TMVR has shown that pre-procedural planning with computed tomography (CT) is needed to mitigate the risk of potentially lethal procedural complications such as left ventricular outflow tract (LVOT) obstruction. The goal of this review is to provide an overview of key concepts relating to TMVR pre-procedural planning, with particular emphasis on imaging-based methods for predicting TMVR-related LVOT obstruction., Recent Findings: Risk of LVOT obstruction can be assessed with CT-based pre-procedural planning by using virtual device simulations to estimate the residual 'neo-LVOT' cross-sectional area which remains after device implantation. A neo-LVOT area of less than 2 cm 2 is currently thought to increase the risk of obstruction; however, additional studies are needed to further validate this cutoff value. Three-dimensional printing and personalized computational simulations are also emerging as valuable tools which may offer insights not readily confered by conventional two-dimensional image analysis. The simulated neo-LVOT should be routinely assessed on pre-procedural CT when evaluating anatomical suitability for TMVR.

Objective: Type 1 Chiari malformation (CM-I) is a craniospinal disorder historically defined by cerebellar tonsillar position greater than 3-5 mm below the foramen magnum (FM). This definition has come under question because quantitative measurements of cerebellar herniation do not always correspond with symptom severity. Researchers have proposed several additional radiographic diagnostic criteria based on dynamic motion of fluids and/or tissues. The present study objective was to determine if cardiac-related craniocaudal spinal cord tissue displacement is an accurate indicator of the presence of CM-I and if tissue displacement is altered with decompression., Methods: A cohort of 20 symptomatic patients underwent decompression surgery. Fifteen healthy volunteers were recruited for comparison with the CM-I group. Axial phase-contrast magnetic resonance imaging (PC-MRI) measurements were collected before and after surgery at the FM with cranial-caudal velocity encoding and 20 frames per cardiac cycle with retrospective reconstruction. Spinal cord motion (SCM) at the FM was quantified based on the peak-to-peak integral of average spinal cord velocity., Results: Tissue motion for the presurgical group was significantly greater than controls (P = 0.0009). Motion decreased after surgery (P = 0.058) with an effect size of -0.151 mm and a standard error of 0.066 mm. Postoperatively, no statistical difference from controls in bulk displacement at the FM was found (P = 0.200) after post hoc testing using the Tukey adjustment for multiple comparisons., Conclusions: These results support SCM measurement by PC-MRI as a possible noninvasive radiographic diagnostic for CM-I. Dynamic measurement of SCM provides unique diagnostic information about CM-I alongside static quantification of tonsillar position and other intracranial morphometrics., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The neurodegenerative disease amyotrophic lateral sclerosis (ALS) results in the death of motor neurons in voluntary muscles. There are no cures for ALS and few available treatments. In studies with small animal models, injection of cellular therapeutics into the anterior horn of the spinal cord has been shown to inhibit the progression of ALS. It was hypothesized that spinal injection could be made faster and less invasive with the aid of a robot. The robotic system presented-SpinoBot-uses MRI guidance to position a needle for percutaneous injection into the spinal cord. With four degrees of freedom (DOF) provided by two translation stages and two rotational axes, SpinoBot proved capable of advanced targeting with a mean error of 1.12 mm and standard deviation of 0.97 mm in bench tests, and a mean error of 2.2 mm and standard deviation of 0.85 mm in swine cadaver tests. SpinoBot has shown less than 3% signal-to-noise ratio reduction in 3T MR imaging quality, demonstrating its compliance to the MRI environment. With the aid of SpinoBot, the length of the percutaneous injection procedure is reduced to less than 60 min with 10 min for each additional insertion. Although SpinoBot is designed for ALS treatment, it could potentially be used for other procedures that require precise access to the spine.

Background and Purpose: Intracranial pressure is estimated invasively by using lumbar puncture with CSF opening pressure measurement. This study evaluated displacement encoding with stimulated echoes (DENSE), an MR imaging technique highly sensitive to brain motion, as a noninvasive means of assessing intracranial pressure status., Materials and Methods: Nine patients with suspected elevated intracranial pressure and 9 healthy control subjects were included in this prospective study. Controls underwent DENSE MR imaging through the midsagittal brain. Patients underwent DENSE MR imaging followed immediately by lumbar puncture with opening pressure measurement, CSF removal, closing pressure measurement, and immediate repeat DENSE MR imaging. Phase-reconstructed images were processed producing displacement maps, and pontine displacement was calculated. Patient data were analyzed to determine the effects of measured pressure on pontine displacement. Patient and control data were analyzed to assess the effects of clinical status (pre-lumbar puncture, post-lumbar puncture, or control) on pontine displacement., Results: Patients demonstrated imaging findings suggesting chronically elevated intracranial pressure, whereas healthy control volunteers demonstrated no imaging abnormalities. All patients had elevated opening pressure (median, 36.0 cm water), decreased by the removal of CSF to a median closing pressure of 17.0 cm water. Patients pre-lumbar puncture had significantly smaller pontine displacement than they did post-lumbar puncture after CSF pressure reduction ( P = .001) and compared with controls ( P = .01). Post-lumbar puncture patients had statistically similar pontine displacements to controls. Measured CSF pressure in patients pre- and post-lumbar puncture correlated significantly with pontine displacement ( r = 0.49; P = .04)., Conclusions: This study establishes a relationship between pontine displacement from DENSE MR imaging and measured pressure obtained contemporaneously by lumbar puncture, providing a method to noninvasively assess intracranial pressure status in idiopathic intracranial hypertension., (© 2018 by American Journal of Neuroradiology.)

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., (© 2017 International Society for Magnetic Resonance in Medicine.)