Publications by authors named "Oliver Wieben"

112 Publications

Automatic measurement plane placement for 4D Flow MRI of the great vessels using deep learning.

Int J Comput Assist Radiol Surg 2021 Aug 17. Epub 2021 Aug 17.

Departments of Medical Physics and Radiology, University of Wisconsin-Madison, Madison, WI, USA.

Purpose: Despite the great potential and flexibility of 4D flow MRI for hemodynamic analysis, a major limitation is the need for time-consuming and user-dependent post-processing. We propose a fast four-step algorithm for rapid, robust, and repeatable flow measurements in the great vessels based on automatic placement of measurement planes and vessel segmentation.

Methods: Our algorithm works by (1) subsampling the 3D image into 3D patches, (2) predicting the probability of each patch containing individual vessels and location/orientation of the vessel within the patch via a convolutional neural network, (3) selecting the predicted planes with highest probabilities for each vessel, and (4) shifting the plane centers to the maximum velocity within each plane. The method was trained on 283 scans and evaluated on 40 unseen scans by comparing algorithm-derived processing times, plane locations, and flow measurements to those of two manual observers (graduate students) using t-tests, Pearson correlation, and Bland-Altman analysis.

Results: The average processing time for the algorithm (18 s) was shorter than observer 1 (362 s; P < 0.001) and observer 2 (317 s; P < 0.001). The distance between planes placed by the algorithm and those placed by manual observers was slightly greater (O1 vs. algorithm: 9.0 mm, O2 vs. algorithm: 10.3 mm) than the distance between planes placed by the two manual observers (8.3 mm). The correlation between flow values for planes placed by the algorithm and those placed by manual observers was slightly lower (O1 vs. algorithm: R = 0.68, O2 vs. algorithm: R = 0.72) than the flow correlation between the two manual observers (R = 0.81).

Conclusion: Our method is a feasible and accurate approach for fast, reproducible, and automated flow measurement and visualization in 4D flow MRI of the great vessels, with similar variability compared to a manual annotator as the variability between two manual observers. This approach could be applied in other anatomical regions.
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http://dx.doi.org/10.1007/s11548-021-02475-1DOI Listing
August 2021

Decreased ventricular size and mass mediate the reduced exercise capacity in adolescents and adults born premature.

Early Hum Dev 2021 Sep 24;160:105426. Epub 2021 Jul 24.

Department of Pediatrics, Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, United States of America.

Background: Premature birth is associated with lower levels of cardiorespiratory fitness (CRF) but the underlying mechanisms responsible remain unclear. This study assessed whether differences in cardiac morphology or function mediate differences in CRF among adolescents and young adults born preterm.

Methods: Adolescents and young adults born moderately to extremely premature (gestational age ≤ 32 weeks or birth weight < 1500 g) and age-matched term born participants underwent resting cardiac MRI and maximal exercise testing. Mediation analysis assessed whether individual cardiovascular variables accounted for a significant proportion of the difference in maximal aerobic capacity between groups.

Results: Individuals born preterm had lower VO2max than those born term (41.7 ± 8.6 v 47.5 ± 8.7, p < 0.01). Several variables differed between term and preterm born subjects, including systolic and diastolic blood pressure, mean pulmonary artery pressure, indexed left ventricular end-diastolic volume (LVEDVi), right ventricular end-diastolic volume (RVEDVi), LV mass (LVMi), LV stroke volume index (LVSVi), and LV strain (p < 0.05 for all). Of these variables, LVEDVi, RVEDVi, LVSVi, LVMi, and LV longitudinal strain were significantly related to VO2max (p < 0.05 for all). Significant portions of the difference in VO2max between term and preterm born subjects were mediated by LVEDVi (74.3%, p = 0.010), RVEDVi (50.6%, p = 0.016), and LVMi (43.0%, p = 0.036).

Conclusions: Lower levels of CRF in adolescents and young adults born preterm are mediated by differences in LVEDVi, RVEDVi, and LVMi. This may represent greater risk for long-term cardiac morbidity and mortality in preterm born individuals.
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http://dx.doi.org/10.1016/j.earlhumdev.2021.105426DOI Listing
September 2021

Altered Right Ventricular Filling at Four-dimensional Flow MRI in Young Adults Born Prematurely.

Radiol Cardiothorac Imaging 2021 Jun 3;3(3):e200618. Epub 2021 Jun 3.

Departments of Medical Physics, Radiology, Pediatrics, and Medicine, University of Wisconsin-Madison, Madison, Wis (P.A.C., M.W.E., O.W.); Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8558 (G.P.B., K.N.G.); Department of Radiology, University of Michigan, Ann Arbor, Mich (J.A.M.); and Department of Radiology, Mayo Clinic, Rochester, Minn (C.J.F.).

Purpose: To use four-dimensional (4D) flow MRI to measure intraventricular flow in young adults who were born prematurely to investigate mechanisms that may account for increased heart failure risk in this population.

Materials And Methods: In this secondary analysis of a prospective study, a total of 56 young adults participated in an observational cardiac 4D flow MRI study from 2016 to 2020. There were 35 participants who had been born moderately to extremely prematurely (birth weight <1500 g or gestational age ≤32 weeks; 23 women; mean age, 26 years ± 4) and 21 term-born participants (11 women; mean age, 25 years ± 3). Participants underwent cardiac MRI, including cine cardiac structure and function assessment, as well as 4D flow MRI. In each ventricle, normalized kinetic energy (KE/end diastolic volume) and flow through the atrioventricular valve were computed and compared between term-born and preterm participants at systolic and diastolic (early diastolic filling rate [E wave] and late diastolic filling [atrial contraction] rate [A wave]) time points by using Wilcoxon rank-sum tests.

Results: Preterm-born participants had lower right ventricular (RV) E wave/A wave (E/A) KE ratios (2.4 ± 1.7 vs 3.5 ± 1.4; <.01) and lower E/A peak filling rate ratios (computed from RV volume-time curves; 2.3 ± 1.3 vs 3.5 ± 2.5; = .03). Additionally, viscous energy dissipation was increased during systole (5.7 µW/mL ± 3.0 vs 4.2 µW/mL ± 1.6; = .03), increased during late diastole (3.9 µW/mL ± 4.0 vs 2.2 µW/mL ± 1.6; = .03), and summed over the cardiac cycle (2.4 µJ/mL ± 1.0 vs 1.9 µJ/mL ± 0.6; = .02) in preterm relative to term participants.

Conclusion: These results suggest that RV diastolic filling is altered in young adults who were born moderately to severely prematurely. Adults, Cardiac, Comparative Studies, MR-Imaging, Right Ventricle © RSNA, 2021.
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http://dx.doi.org/10.1148/ryct.2021200618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259661PMC
June 2021

Coronary Endothelial Wall Shear Stress: Another Piece of the Puzzle?

Radiology 2021 Sep 29;300(3):557-558. Epub 2021 Jun 29.

From the Department of Radiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, Madison, WI 53792 (J.E.K.); Departments of Medical Physics and Radiology, Wisconsin Institutes for Medical Research, Madison, Wis (O.W.).

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http://dx.doi.org/10.1148/radiol.2021211116DOI Listing
September 2021

Aortic flow dynamics and stiffness in Loeys-Dietz syndrome patients: a comparison with healthy volunteers and Marfan syndrome patients.

Eur Heart J Cardiovasc Imaging 2021 Jun 9. Epub 2021 Jun 9.

Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.

Aims: To assess aortic flow and stiffness in patients with Loeys-Dietz syndrome (LDS) by 4D flow and cine cardiovascular magnetic resonance (CMR) and compare the results with those of healthy volunteers (HV) and Marfan syndrome (MFS) patients.

Methods And Results: Twenty-one LDS and 44 MFS patients with no previous aortic dissection or surgery and 35 HV underwent non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), and aortic diameters were obtained at 20 planes from the ascending (AAo) to the proximal descending aorta (DAo). IRF and SFRR were also quantified for aortic regions (proximal and distal AAo, arch and proximal DAo). Peak-systolic wall shear stress (WSS) maps were also estimated. Aortic stiffness was quantified using pulse wave velocity (PWV) and proximal AAo longitudinal strain. Compared to HV, LDS patients had lower rotational flow at the distal AAo (P = 0.002), arch (P = 0.002), and proximal DAo (P < 0.001) even after adjustment for age, stroke volume, and local diameter. LDS patients had higher SFRR in the proximal DAo compared to both HV (P = 0.024) and MFS patients (P = 0.015), even after adjustment for age and local diameter. Axial and circumferential WSS in LDS patients were lower than in HV. AAo circumferential WSS was lower in LDS compared to MFS patients. AAo and DAo PWV and proximal AAo longitudinal strain revealed stiffer aortas in LDS patients compared to HV (P = 0.007, 0.005, and 0.029, respectively) but no differences vs. MFS patients.

Conclusion: Greater aortic stiffness as well as impaired IRF and WSS were present in LDS patients compared to HV. Conversely, similar aortic stiffness and overlapping aortic flow features were found in Loeys-Dietz and Marfan patients.
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http://dx.doi.org/10.1093/ehjci/jeab069DOI Listing
June 2021

Leaflet fusion length is associated with aortic dilation and flow alterations in non-dysfunctional bicuspid aortic valve.

Eur Radiol 2021 May 12. Epub 2021 May 12.

Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.

Objective: Bicuspid aortic valve (BAV), the most common congenital valve defect, is associated with increased risk of aortic dilation and related complications; however, current risk assessment is not effective. Most of BAV have three leaflets with a fusion between two of them of variable length. This study aimed to ascertain whether the extent of leaflet fusion (often called raphe) is related to aortic dilation and flow abnormalities in BAV with no significant valvular dysfunction.

Methods: One hundred and twenty BAV patients with no significant valvular dysfunction or history of surgical repair or aortic valve replacement were consecutively and prospectively enrolled (September 2014-October 2018). Cardiac magnetic resonance protocol included a 4D flow sequence for haemodynamic assessment. Moreover, a stack of double-oblique cine images of the aortic valve were used to quantify fusion length (in systole) and leaflet length (diastole). Inter- and intra-observer reproducibility was tested in 30 randomly selected patients.

Results: Aortic valve leaflet fusion was measurable in 112 of 120 (93%) cases with good reproducibility (ICC = 0.826). Fusion length varied greatly (range: 2.3-15.4 mm; mean: 7.8 ± 3.2 mm). After correction for demographic and clinical conditions, fusion length was independently associated with diameter and z-score at the sinus of Valsalva (p = 0.002 and p = 0.002, respectively) and ascending aorta (p = 0.028 and p = 0.046). Fusion length was positively related to flow asymmetry, vortices and circumferential wall shear stress, thereby possibly providing a pathophysiological link with aortic dilation.

Conclusions: Aortic valve fusion length is related to aortic dilation and flow abnormalities in BAV patients.

Key Points: • The length of the fusion between leaflets in non-dysfunctional bicuspid aortic valves varies substantially and can be reliably measured by cine CMR. • Aortic valve leaflet fusion length is independently related to aortic sinus and ascending aorta diameter. • Increased flow asymmetry, circumferential wall shear stress and presence of vortices are positively related to aortic valve leaflet fusion length.
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http://dx.doi.org/10.1007/s00330-021-08016-3DOI Listing
May 2021

Sildenafil administration improves right ventricular function on 4D flow MRI in young adults born premature.

Am J Physiol Heart Circ Physiol 2021 06 16;320(6):H2295-H2304. Epub 2021 Apr 16.

Department of Medicine, University of Texas Southwestern, Dallas, Texas.

Extreme preterm birth conveys an elevated risk of heart failure by young adulthood. Smaller biventricular chamber size, diastolic dysfunction, and pulmonary hypertension may contribute to reduced ventricular-vascular coupling. However, how hemodynamic manipulations may affect right ventricular (RV) function and coupling remains unknown. As a pilot study, 4D flow MRI was used to assess the effect of afterload reduction and heart rate reduction on cardiac hemodynamics and function. Young adults born premature were administered sildenafil (a pulmonary vasodilator) and metoprolol (a β blocker) on separate days, and MRI with 4D flow completed before and after each drug administration. Endpoints include cardiac index (CI), direct flow fractions, and ventricular kinetic energy including / wave kinetic energy ratio. Sildenafil resulted in a median CI increase of 0.24 L/min/m ( = 0.02), mediated through both an increase in heart rate (HR) and stroke volume. Although RV ejection fraction improved only modestly, there was a significant increase (4% of end diastolic volume) in RV direct flow fraction ( = 0.04), consistent with hemodynamic improvement. Metoprolol administration resulted in a 5-beats/min median decrease in HR ( = 0.01), a 0.37 L/min/m median decrease in CI ( = 0.04), and a reduction in time-averaged kinetic energy (KE) in both ventricles ( < 0.01), despite increased RV diastolic / KE ratio ( = 0.04). Despite reduced right atrial workload, metoprolol significantly depressed overall cardiac systolic function. Sildenafil, however, increased CI and improved RV function, as quantified by the direct flow fraction. The preterm heart appears dependent on HR but sensitive to RV afterload manipulations. We assessed the effect of right ventricular afterload reduction with sildenafil and heart rate reduction with metoprolol on cardiac hemodynamics and function in young adults born premature using 4D flow MRI. Metoprolol depressed cardiac function, whereas sildenafil improved cardiac function including right ventricular direct flow fraction by 4D flow, consistent with hemodynamic improvement. This suggests that the preterm heart is dependent on heart rate and sensitive to right ventricular afterload changes.
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http://dx.doi.org/10.1152/ajpheart.00824.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289359PMC
June 2021

Dynamic FDG PET Imaging to Probe for Cardiac Metabolic Remodeling in Adults Born Premature.

J Clin Med 2021 Mar 22;10(6). Epub 2021 Mar 22.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Individuals born very premature have an increased cardiometabolic and heart failure risk. While the structural differences of the preterm heart are now well-described, metabolic insights into the physiologic mechanisms underpinning this risk are needed. Here, we used dynamic fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET-MRI) in young adults born term and preterm during normoxic (N = 28 preterm; 18 term) and hypoxic exposure (12% O; N = 26 preterm; 17 term) to measure the myocardial metabolic rate of glucose (MMRglc) in young adults born term (N = 18) and preterm (N = 32), hypothesizing that young adults born preterm would have higher rates of MMRglc under normoxic conditions and a reduced ability to augment glucose metabolism under hypoxic conditions. MMRglc was calculated from the myocardial and blood pool time-activity curves by fitting the measured activities to the 3-compartment model of FDG kinetics. MMRglc was similar at rest between term and preterm subjects, and decreased during hypoxia exposure in both groups ( = 0.02 for MMRglc hypoxia effect). There were no differences observed between groups in the metabolic response to hypoxia, either globally (serum glucose and lactate measures) or within the myocardium. Thus, we did not find evidence of altered myocardial metabolism in the otherwise healthy preterm-born adult. However, whether subtle changes in myocardial metabolism may preceed or predict heart failure in this population remains to be determined.
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http://dx.doi.org/10.3390/jcm10061301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004130PMC
March 2021

Exaggerated Cardiac Contractile Response to Hypoxia in Adults Born Preterm.

J Clin Med 2021 Mar 10;10(6). Epub 2021 Mar 10.

Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53792, USA.

Individuals born prematurely have smaller hearts, cardiac limitations to exercise, and increased overall cardiometabolic risk. The cardiac effects of acute hypoxia exposure as another physiologic stressor remain under explored. The purpose of this study was to determine the effects of hypoxia on ventricular function in adults born preterm. Adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g, = 32) and born at term ( = 18) underwent cardiac magnetic resonance imaging under normoxic (21% O) and hypoxic (12% O) conditions to assess cardiovascular function. In normoxia, cardiac function parameters were similar between groups. During hypoxia, the right ventricular (RV) contractile response was significantly greater in participants born premature, demonstrated by greater increases in RV ejection fraction (EF) ( = 0.002), ventricular-vascular coupling (VVC) ( = 0.004), and strain ( < 0.0001) measures compared to term-born participants, respectively. Left ventricular contractile reserve was similar to term-born participants. Adults born preterm exhibit an exaggerated contractile response to acute hypoxia, particularly in the RV. This suggests that adults born preterm may have contractile reserve, despite the lack of volume reserve identified in previous exercise studies. However, this exaggerated and hyper-adapted response may also increase their risk for late RV failure.
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http://dx.doi.org/10.3390/jcm10061166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999333PMC
March 2021

Pseudo-Enhancement in Intracranial Aneurysms on Black-Blood MRI: Effects of Flow Rate, Spatial Resolution, and Additional Flow Suppression.

J Magn Reson Imaging 2021 09 10;54(3):888-901. Epub 2021 Mar 10.

Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein, Kiel, Germany.

Background: Vessel-wall enhancement (VWE) on black-blood MRI (BB MRI) has been proposed as an imaging marker for a higher risk of rupture and associated with wall inflammation. Whether VWE is causally linked to inflammation or rather induced by flow phenomena has been a subject of debate.

Purpose: To study the effects of slow flow, spatial resolution, and motion-sensitized driven equilibrium (MSDE) preparation on signal intensities in BB MRI of patient-specific aneurysm flow models.

Study Type: Prospective.

Subjects/flow Aneurysm Model/virtual Vessels: Aneurysm flow models based on 3D rotational angiography datasets of three patients with intracranial aneurysms were 3D printed and perfused at two different flow rates, with and without Gd-containing contrast agent.

Field Strength/sequence: Variable refocusing flip angle 3D fast-spin echo sequence at 3 T with and without MSDE with three voxel sizes ((0.5 mm) , (0.7 mm) , and (0.9 mm) ); time-resolved with phase-contrast velocity-encoding 3D spoiled gradient echo sequence (4D flow MRI).

Assessment: Three independent observers performed a qualitative visual assessment of flow patterns and signal enhancement. Quantitative analysis included voxel-wise evaluation of signal intensities and magnitude velocity distributions in the aneurysm.

Statistical Tests: Kruskal-Wallis test, potential regressions.

Results: A hyperintense signal in the lumen and adjacent to the aneurysm walls on BB MRI was colocalized with slow flow. Signal intensities increased by a factor of 2.56 ± 0.68 (P < 0.01) after administering Gd contrast. After Gd contrast administration, the signal was suppressed most in conjunction with high flows and with MSDE (2.41 ± 2.07 for slow flow without MSDE, and 0.87 ± 0.99 for high flow with MSDE). A clear result was not achieved by modifying the spatial resolution .

Data Conclusions: Slow-flow phenomena contribute substantially to aneurysm enhancement and vary with MRI parameters. This should be considered in the clinical setting when assessing VWE in patients with an unruptured aneurysm.

Evidence Level: 2 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403769PMC
September 2021

Non-invasive assessment of mesenteric hemodynamics in patients with suspected chronic mesenteric ischemia using 4D flow MRI.

Abdom Radiol (NY) 2021 Feb 6. Epub 2021 Feb 6.

Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA.

Purpose: Chronic mesenteric ischemia (CMI) is a rare disease with a particularly difficult diagnosis. In this study, 4D flow MRI is used to quantitatively evaluate mesenteric hemodynamics before and after a meal in patients suspected of having CMI and healthy individuals.

Methods: Nineteen patients suspected of CMI and twenty control subjects were analyzed. Subjects were scanned using a radially undersampled 4D flow MR sequence (PC-VIPR). Flow rates were assessed in the supraceliac (SCAo) and infrarenal aorta, celiac artery, superior mesenteric artery (SMA), left and right renal arteries, superior mesenteric vein (SMV), splenic vein, and portal vein (PV) in a fasting state (preprandial) and 20 min after a 700-kcal meal (postprandial). Patients were subcategorized into positive diagnosis (CMI+, N = 6) and negative diagnosis (CMI-, N = 13) groups based on imaging and clinical findings. Preprandial, postprandial, and percent change in flow rates were compared between subgroups using a Welch t test.

Results: In controls and CMI- patients, SCAo, SMA, SMV, and PV flow increased significantly after meal ingestion. No significant flow increases were observed in CMI+ patients. Percent changes in SMA, SMV, and PV flow were significantly greater in controls compared to CMI+ patients. Additionally, percent changes in flow in the SMV and PV were significantly greater in CMI- patients compared to CMI+ patients.

Conclusions: 4D flow MRI with large volumetric coverage demonstrated significant differences in the redistribution of blood flow in SMA, SMV, and PV in CMI+ patients after a meal challenge. This approach may assist in the challenging diagnosis of CMI.
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http://dx.doi.org/10.1007/s00261-020-02900-0DOI Listing
February 2021

A phantom study comparing radial trajectories for accelerated cardiac 4D flow MRI against a particle imaging velocimetry reference.

Magn Reson Med 2021 07 5;86(1):363-371. Epub 2021 Feb 5.

Departments of Medical Physics and Radiology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Purpose: Radial sampling is one method to accelerate 4D flow MRI acquisition, making feasible dual-velocity encoding (Venc) assessment of slow flow in the left ventricle (LV). Here, two radial trajectories are compared in vitro for this application: 3D radial (phase-contrast vastly undersampled isotropic projection, PC-VIPR) versus stack of stars (phase-contrast stack of stars, PC-SOS), with benchtop particle imaging velocimetry (PIV) serving as a reference standard.

Methods: The study contained three steps: (1) Construction of an MRI- and PIV-compatible LV model from a healthy adult's CT images. (2) In vitro PIV using a pulsatile flow pump. (3) In vitro dual-Venc 4D flow MRI using PC-VIPR and PC-SOS (two repeat experiments). Each MR image set was retrospectively undersampled to five effective scan durations and compared with the PIV reference. The root-mean-square velocity vector difference (RMSE) between MRI and PIV images was compared, along with kinetic energy (KE) and wall shear stress (WSS).

Results: RMSE increased as scan time decreased for both MR acquisitions. RMSE was 3% lower in PC-SOS images than PC-VIPR images in 30-min scans (3.8 vs. 3.9 cm/s) but 98% higher in 2.5-min scans (9.5 vs. 4.8 cm/s). PIV intrasession repeatability showed a RMSE of 4.4 cm/s, reflecting beat-to-beat flow variation, while MRI had intersession RMSEs of 3.8/3.5 cm/s for VIPR/SOS, respectively. Speed, KE, and WSS were overestimated voxel-wise in 30-min MRI scans relative to PIV by 0.4/0.3 cm/s, 0.2/0.1 μJ/mL, and 36/43 mPa, respectively, for VIPR/SOS.

Conclusions: PIV is feasible for application-specific 4D flow MRI protocol optimization. PC-VIPR is better-suited to dual-Venc LV imaging with short scan times.
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http://dx.doi.org/10.1002/mrm.28698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109233PMC
July 2021

Daikenchuto increases blood flow in the superior mesenteric artery in humans: A comparison study between four-dimensional phase-contrast vastly undersampled isotropic projection reconstruction magnetic resonance imaging and Doppler ultrasound.

PLoS One 2021 27;16(1):e0245878. Epub 2021 Jan 27.

Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.

Respiratory-gated four-dimensional phase-contrast vastly undersampled isotropic projection reconstruction (4D PC-VIPR) is magnetic resonance (MR) imaging technique that enables analysis of vascular morphology and hemodynamics in a single examination using cardiac phase resolved 3D phase-contrast magnetic resonance imaging. The present study aimed to assess the usefulness of 4D PC-VIPR for the superior mesenteric artery (SMA) flowmetry before and after flow increase was induced by the herbal medicine Daikenchuto (TJ-100) by comparing it with Doppler ultrasound (DUS) as a current standard. Twenty healthy volunteers were enrolled in this prospective single-arm study. The peak cross-sectionally averaged velocity was measured by 4D PC-VIPR, peak velocity was measured by DUS, and flow volume (FV) of SMA and aorta were measured by 4D PC-VIPR and DUS 25 min before and after the peroral administration of TJ-100. The peak cross-sectionally averaged velocity, peak velocity, and FV of SMA measured by 4D PC-VIPR and DUS significantly increased after administration of TJ-100 (4D PC-VIPR: the peak cross-sectionally averaged velocity; p = 0.004, FV; p = 0.035, DUS: the peak velocity; p = 0.003, FV; p = 0.010). Furthermore, 4D PC-VIPR can analyze multiple blood vessels simultaneously. The ratio of the SMA FV to the aorta, before and after oral administration on the 4D PC-VIPR test also increased (p = 0.015). The rate of change assessed by 4D PC-VIPR and DUS were significantly correlated (the peak cross-sectionally averaged velocity and peak velocity: r = 0.650; p = 0.005, FV: r = 0.659; p = 0.004). Retrospective 4D PC-VIPR was a useful modality for morphological and hemodynamic analysis of SMA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245878PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840032PMC
June 2021

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

Brain Plast 2020 Oct 1;5(2):175-184. Epub 2020 Oct 1.

Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Background: There is increasing evidence that vascular disease risk factors contribute to evolution of the dementia syndrome of Alzheimer's disease (AD). One important measure of cerebrovascular health is pulsatility index (PI) which is thought to represent distal vascular resistance, and has previously been reported to be elevated in AD clinical syndrome. Physical inactivity has emerged as an independent risk factor for cardiovascular disease.

Objective: This study aims to examine the relationship between a measure of habitual physical activity, cardiorespiratory fitness (CRF), and PI in the large cerebral vessels.

Methods: Ninety-two cognitively-healthy adults (age = 65.34±5.95, 72% female) enrolled in the Wisconsin Registry for Alzheimer's Prevention participated in this study. Participants underwent 4D flow brain MRI to measure PI in the internal carotid artery (ICA), basilar artery, middle cerebral artery (MCA), and superior sagittal sinus. Participants also completed a self-report physical activity questionnaire. CRF was calculated using a previously-validated equation that incorporates sex, age, body-mass index, resting heart rate, and self-reported physical activity. A series of linear regression models adjusted for age, sex, APOE4 status, and 10-year atherosclerotic cardiovascular disease risk were used to analyze the relationship between CRF and PI.

Results: Inverse associations were found between CRF and mean PI in the inferior ICA (p = .001), superior ICA (p = .035), and basilar artery (p = .040). No other cerebral vessels revealed significant associations between CRF and PI (p≥.228).

Conclusions: Higher CRF was associated with lower PI in several large cerebral vessels. Since increased pulsatility has been associated with poor brain health and reported in persons with AD, this suggests that aerobic fitness might provide protection against cerebrovascular changes related to the progression of AD clinical syndrome.
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http://dx.doi.org/10.3233/BPL-190096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685671PMC
October 2020

Feasibility of Cardiovascular Four-dimensional Flow MRI during Exercise in Healthy Participants.

Radiol Cardiothorac Imaging 2020 Jun 18;2(3):e190033. Epub 2020 Jun 18.

Departments of Medical Physics (J.A.M., P.A.C., O.W.), Pediatrics (A.G.B., G.P.B., K.N.G., M.W.E.), Medicine (K.N.G.), Biomedical Engineering (M.W.E., O.W.), and Radiology (C.J.F., O.W.), University of Wisconsin, 1111 Highland Ave, Room 1005, Madison, WI 53705.

Purpose: To explore the feasibility of using four-dimensional (4D) flow MRI to quantify blood flow and kinetic energy (KE) in the heart during strenuous exercise.

Materials And Methods: For this prospective study, cardiac 4D flow MRI was performed in 11 healthy young adult participants (eight men, three women; mean age, 26 years ± 1 [standard deviation]) at rest and during exercise with an MRI-compatible exercise stepper between March 2016 and July 2017. Flow was measured in the ascending aorta (AAo) and main pulmonary artery (MPA). KE was quantified in the left and right ventricle. Significant changes in flow and KE during exercise were identified by using tests. Repeatability was assessed with inter- and intraobserver comparisons and an analysis of internal flow consistency.

Results: Nine participants successfully completed both rest and exercise imaging. Internal flow consistency analysis in systemic and pulmonary circulation showed average relative differences of 10% at rest and 16% during exercise. For flow measurements in the AAo and MPA, relative differences between observers never exceeded 6% in any vessel and showed excellent correlation, even during exercise. Relative differences were increased for KE, typically on the order of 30%, with poor interobserver correlation between measurements.

Conclusion: Four-dimensional flow MRI can quantify increases in flow in the AAo and MPA during strenuous exercise and is highly repeatable. KE had reduced repeatability because of suboptimal segmentation methods and requires further development before clinical implementation. © RSNA, 2020See also the commentary by Markl and Lee in this issue.
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http://dx.doi.org/10.1148/ryct.2020190033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373355PMC
June 2020

Association Between Preterm Birth and Arrested Cardiac Growth in Adolescents and Young Adults.

JAMA Cardiol 2020 Aug;5(8):910-919

Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison.

Importance: Premature birth is associated with substantially higher lifetime risk for cardiovascular disease, including arrhythmia, ischemic disease, and heart failure, although the underlying mechanisms are poorly understood.

Objective: To characterize cardiac structure and function in adolescents and young adults born preterm using cardiac magnetic resonance imaging (MRI).

Design, Setting, And Participants: This cross-sectional cohort study at an academic medical center included adolescents and young adults born moderately to extremely premature (20 in the adolescent cohort born from 2003 to 2004 and 38 in the young adult cohort born in the 1980s and 1990s) and 52 age-matched participants who were born at term and underwent cardiac MRI. The dates of analysis were February 2016 to October 2019.

Exposures: Premature birth (gestational age ≤32 weeks) or birth weight less than 1500 g.

Main Outcomes And Measures: Main study outcomes included MRI measures of biventricular volume, mass, and strain.

Results: Of 40 adolescents (24 [60%] girls), the mean (SD) age of participants in the term and preterm groups was 13.3 (0.7) years and 13.0 (0.7) years, respectively. Of 70 adults (43 [61%] women), the mean (SD) age of participants in the term and preterm groups was 25.4 (2.9) years and 26.5 (3.5) years, respectively. Participants from both age cohorts who were born prematurely had statistically significantly smaller biventricular cardiac chamber size compared with participants in the term group: the mean (SD) left ventricular end-diastolic volume index was 72 (7) vs 80 (9) and 80 (10) vs 92 (15) mL/m2 for adolescents and adults in the preterm group compared with age-matched participants in the term group, respectively (P < .001), and the mean (SD) left ventricular end-systolic volume index was 30 (4) vs 34 (6) and 32 (7) vs 38 (8) mL/m2, respectively (P < .001). Stroke volume index was also reduced in adolescent vs adult participants in the preterm group vs age-matched participants in the term group, with a mean (SD) of 42 (7) vs 46 (7) and 48 (7) vs 54 (9) mL/m2, respectively (P < .001), although biventricular ejection fractions were preserved. Biventricular mass was statistically significantly lower in adolescents and adults born preterm: the mean (SD) left ventricular mass index was 39.6 (5.9) vs 44.4 (7.5) and 40.7 (7.3) vs 49.8 (14.0), respectively (P < .001). Cardiac strain analyses demonstrated a hypercontractile heart, primarily in the right ventricle, in adults born prematurely.

Conclusions And Relevance: In this cross-sectional study, adolescents and young adults born prematurely had statistically significantly smaller biventricular cardiac chamber size and decreased cardiac mass. Although function was preserved in both age groups, these morphologic differences may be associated with elevated lifetime cardiovascular disease risk after premature birth.
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http://dx.doi.org/10.1001/jamacardio.2020.1511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240643PMC
August 2020

Optimal Plane Selection for Measuring Post-prandial Blood Flow Increase within the Superior Mesenteric Artery: Analysis Using 4D Flow and Computational Fluid Dynamics.

Magn Reson Med Sci 2020 Dec 31;19(4):366-374. Epub 2020 Jan 31.

GE Healthcare, Global Applied Science Laboratory.

Purpose: 2D cine phase contrast (PC)-MRI is a standard velocimetry for the superior mesenteric artery (SMA); however, the optimal localization of the measurement plane has never been fully discussed previously. The purpose of this Institutional Review Board approved prospective and single arm study is to test whether flow velocimetry of the SMA with combined use of 2D cine PC-MRI and meal challenge is dependent on the localizations of the measurement planes and to seek optimal section for velocimetry.

Methods: Seven healthy volunteers underwent cardiac phase resolved ECG gated 2D cine PC-MRI pre- and 30 min post-meal challenge at three measurement planes: proximal, curved mid section and distal straight section of the SMA at 3T. 4D Flow using 3D cine PC-MRI with vastly undersampled isotropic projection imaging (PC VIPR) was also performed right after 2D cine PC-MRI to delineate the flow dynamics within the SMA using streamline analysis. Two radiologists measured flow velocities, and rated the appearances of the abnormal flow in the SMA on streamlines derived from the 4D Flow and the computational fluid dynamics (CFD).

Results: 2D cine PC-MRI measured increased temporally averaged flow velocity (mm/s) after the meal challenge only in the proximal (129.3 vs. 97.8, P = 0.0313) and distal section (166.9 vs. 96.2, P = 0.0313), not in the curved mid section (113.1 vs. 85.5, P = 0.0625). The average velocities were highest and their standard errors (8.5-26.5) were smallest at the distal straight section both before and after the meal challenge as compared with other sections. The streamline analysis depicted more frequent appearances of vertical or helical flow in the curved mid section both on 4D Flow and CFD (κ: 0.27-0.68).

Conclusion: SMA velocimetry with 2D cine PC-MRI was dependent on the localization of the measurement planes. Distal straight section, not in the curved mid section is recommended for MR velocimetry.
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http://dx.doi.org/10.2463/mrms.mp.2019-0089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809144PMC
December 2020

Right Pulmonary Vein Atresia in a Mildly Symptomatic Boy: Comprehensive Analysis of Flow Dynamics Using Non-contrast-enhanced 4D Flow MR Imaging.

Magn Reson Med Sci 2020 Dec 17;19(4):287-289. Epub 2020 Jan 17.

Department of Radiology, University of Yamanashi.

We present multimodal imaging in the rare case of isolated unilateral pulmonary vein atresia in a 6 year-old boy, including analysis of hemodynamics by magnetic resonance acquisition technique of time-resolved three-dimensional phase contrast imaging (4D flow magnetic resonance imaging). This novel imaging method enables the quantification and especially comprehensive visualization of blood flow patterns, even in complex congenital anomalies which abducted detailed assessment so far, and therefore constitutes a promising alternative to conventional vascular imaging techniques.
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http://dx.doi.org/10.2463/mrms.ici.2019-0109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809145PMC
December 2020

Reduced regional flow in the left ventricle after anterior acute myocardial infarction: a case control study using 4D flow MRI.

BMC Med Imaging 2019 12 30;19(1):101. Epub 2019 Dec 30.

Departments of Medical Physics and Radiology, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI, 53705, USA.

Background: Acute myocardial infarction (AMI) alters left ventricular (LV) hemodynamics, resulting in decreased global LV ejection fraction and global LV kinetic energy. We hypothesize that anterior AMI effects localized alterations in LV flow and developed a regional approach to analyze these local changes with 4D flow MRI.

Methods: 4D flow cardiac magnetic resonance (CMR) data was compared between 12 anterior AMI patients (11 males; 66 ± 12yo; prospectively acquired in 2016-2017) and 19 healthy volunteers (10 males; 40 ± 16yo; retrospective from 2010 to 2011 study). The LV cavity was contoured on short axis cine steady-state free procession CMR and partitioned into three regions: base, mid-ventricle, and apex. 4D flow data was registered to the short axis segmentation. Peak systolic and diastolic through-plane flows were compared region-by-region between groups using linear models of flow with age, sex, and heart rate as covariates.

Results: Peak systolic flow was reduced in anterior AMI subjects compared to controls in the LV mid-ventricle (fitted reduction = 3.9 L/min; P = 0.01) and apex (fitted reduction = 1.4 L/min; P = 0.02). Peak diastolic flow was also lower in anterior AMI subjects compared to controls in the apex (fitted reduction = 2.4 L/min; P = 0.01).

Conclusions: A regional method to analyze 4D LV flow data was applied in anterior AMI patients and controls. Anterior AMI patients had reduced regional flow relative to controls.
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http://dx.doi.org/10.1186/s12880-019-0404-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937788PMC
December 2019

Differential contribution of cyclooxygenase to basal cerebral blood flow and hypoxic cerebral vasodilation.

Am J Physiol Regul Integr Comp Physiol 2020 02 23;318(2):R468-R479. Epub 2019 Dec 23.

Department of Kinesiology, University of Wisconsin, Madison, Wisconsin.

Cyclooxygenase (COX) is proposed to regulate cerebral blood flow (CBF); however, accurate regional contributions of COX are relatively unknown at baseline and particularly during hypoxia. We hypothesized that COX contributes to both basal and hypoxic cerebral vasodilation, but COX-mediated vasodilation is greater in the posterior versus anterior cerebral circulation. CBF was measured in 9 healthy adults (28 ± 4 yr) during normoxia and isocapnic hypoxia (fraction of inspired oxygen = 0.11), with COX inhibition (oral indomethacin, 100mg) or placebo. Four-dimensional flow magnetic resonance imaging measured cross-sectional area (CSA) and blood velocity to quantify CBF in 11 cerebral arteries. Cerebrovascular conductance (CVC) was calculated (CVC = CBF × 100/mean arterial blood pressure) and hypoxic reactivity was expressed as absolute and relative change in CVC [ΔCVC/Δ pulse oximetry oxygen saturation ()]. At normoxic baseline, indomethacin reduced CVC by 44 ± 5% ( < 0.001) and artery CSA ( < 0.001), which was similar across arteries. Hypoxia ( 80%-83%) increased CVC ( < 0.01), reflected as a similar relative increase in reactivity (% ΔCVC/-Δ) across arteries ( < 0.05), in part because of increases in CSA ( < 0.05). Indomethacin did not alter ΔCVC or ΔCVC/Δ to hypoxia. These findings indicate that ) COX contributes, in a largely uniform fashion, to cerebrovascular tone during normoxia and ) COX is not obligatory for hypoxic vasodilation in any regions supplied by large extracranial or intracranial arteries.
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http://dx.doi.org/10.1152/ajpregu.00132.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199240PMC
February 2020

Low and Oscillatory Wall Shear Stress Is Not Related to Aortic Dilation in Patients With Bicuspid Aortic Valve: A Time-Resolved 3-Dimensional Phase-Contrast Magnetic Resonance Imaging Study.

Arterioscler Thromb Vasc Biol 2020 01 5;40(1):e10-e20. Epub 2019 Dec 5.

From the Department of Cardiology, CIBERCV, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d´Hebron, Barcelona, Spain (L.D.-S., A.G., G.T.-.T., A.R.-M., F.V., L.G.-.G., L.G., T.G.-A., I.F., A.E., J.F.R.P.).

Objective: To assess the relationship between regional wall shear stress (WSS) and oscillatory shear index (OSI) and aortic dilation in patients with bicuspid aortic valve (BAV). Approach and Results: Forty-six consecutive patients with BAV (63% with right-left-coronary-cusp fusion, aortic diameter ≤ 45 mm and no severe valvular disease) and 44 healthy volunteers were studied by time-resolved 3-dimensional phase-contrast magnetic resonance imaging. WSS and OSI were quantified at different levels of the ascending aorta and the aortic arch, and regional WSS and OSI maps were obtained. Seventy percent of BAV had ascending aorta dilation. Compared with healthy volunteers, patients with BAV had increased WSS and decreased OSI in most of the ascending aorta and the aortic arch. In both BAV and healthy volunteers, regions of high WSS matched regions of low OSI and vice versa. No regions of both low WSS and high OSI were identified in BAV compared with healthy volunteers. Patients with BAV with dilated compared with nondilated aorta presented low and oscillatory WSS in the aortic arch, but not in the ascending aorta where dilation is more prevalent. Furthermore, no regions of concomitant low WSS and high OSI were identified when BAV were compared according to leaflet fusion pattern, despite the well-known differences in regional dilation prevalence.

Conclusions: Regions with low WSS and high OSI do not match those with the highest prevalence of dilation in patients with BAV, thus providing no evidence to support the low and oscillatory shear stress theory in the pathogenesis of proximal aorta dilation in the presence of BAV.
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http://dx.doi.org/10.1161/ATVBAHA.119.313636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771642PMC
January 2020

Age-Related Reductions in Cerebrovascular Reactivity Using 4D Flow MRI.

Front Aging Neurosci 2019 17;11:281. Epub 2019 Oct 17.

Bruno Balke Biodynamics Laboratory, Department of Kinesiology, University of Wisconsin-Madison, Madison, WI, United States.

Cerebrovascular reactivity (CVR), is important for determining future risk of cerebrovascular disease. It is unclear if primary aging is associated with reductions in CVR because previous studies often include participants with vascular risk factors. Additionally, the inconsistency in the literature may be due to the inherent difficulty in quantifying intracranial cerebral blood flow and CVR. To address these limitations, we determined the effect of age on CVR in the large intracranial vessels in adults with low vascular risk using state-of-the-art MRI techniques. We also determined if the effect of age on CVR was sex-specific. Young ( = 20; 25 ± 3 years) and older ( = 19; 61 ± 5 years) healthy, physically active adults participated in the study. CVR was measured in response to hypercapnia using 4D flow MRI, which allows for simultaneous angiographic and quantitative blood flow measurements in the intracranial arteries. Older adults had lower global CVR and CVR in multiple intracranial arteries [right and left internal carotid arteries (ICA), right and left middle cerebral arteries (MCA), and basilar artery (BA)] compared with young adults ( < 0.05 for all). In addition, the MCA dilated significantly in response to hypercapnia in young ( < 0.05), but not older adults. Young men demonstrated higher global CVR and CVR in multiple intracranial arteries (ICAs, MCAs, and BA) compared with young women and older men ( < 0.05 for both); however, CVR did not differ between young women and older women. Our results demonstrate that, using 4D flow MRI, primary aging is associated with lower CVR in adults with low vascular risk. In addition, the effect of age on CVR may be driven by men. The 4D flow MRI technique may provide a promising new alternative to measure cerebrovascular physiology without the limitations of commonly used techniques. Future studies could utilize this MRI technique to examine interventions to maintain CVR with advancing age. This study was registered under clinicaltrials.gov # NCT02840851.
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http://dx.doi.org/10.3389/fnagi.2019.00281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811507PMC
October 2019

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

J Alzheimers Dis 2019 ;72(3):919-929

Division of Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Background: Alzheimer's disease (AD) has a higher prevalence among African Americans. Targeting cardiovascular and metabolic risk factors may be potential mechanisms to modify AD risk and address racial/ethnic disparities in AD dementia.

Objective: This study investigated relationships among cardiovascular and metabolic risk factors, APOE genotype, AD biomarkers, and intracranial arterial blood flow in Whites and African Americans enriched for AD risk.

Methods: 399 cognitively unimpaired adults from the Wisconsin Alzheimer's Disease Research Center completed physical and neuroimaging examinations. A 4D Flow MRI sequence (phase-contrast vastly under sampled isotropic projection imaging) measured intracranial arterial flow in the Circle of Willis. Linear mixed-effects regression models estimated relationships between risk factors and intracranial arterial flow and tested interactions with racial group, APOE genotype, and AD biomarkers, with separate models per risk factor.

Results: Higher fasting glucose was associated with lower intracranial arterial flow; no additional relationships between flow and risk factors were observed. Main effects of racial group were observed, without an interaction, indicating lower flow in African Americans compared to Whites. In race-stratified analyses, higher glucose and triglycerides were associated with lower flow for African Americans, but not for Whites. No main effects or interactions among risk factors, APOE, or AD biomarkers, and flow were observed.

Conclusion: Elevated fasting glucose and triglycerides were associated with lower intracranial arterial flow; these relationships were more prominent in African Americans. Targeting metabolic risk factors may impact intracranial arterial health. Additional research is needed to determine if this will impact disparities in dementia prevalence.
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http://dx.doi.org/10.3233/JAD-190645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081660PMC
November 2020

Quantitative ferumoxytol-enhanced MRI in pregnancy: A feasibility study in the nonhuman primate.

Magn Reson Imaging 2020 01 23;65:100-108. Epub 2019 Oct 23.

Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA; Department of Radiology, University of Wisconsin, Madison, WI, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA; Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI, USA. Electronic address:

Objectives: To assess the feasibility of ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model.

Materials And Methods: In this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student's t-test.

Results: In fetuses, a slope of 0.3 s/day (P = 0.008), 0.00 ppm/day (P = 0.699) and - 0.2 s/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after ferumoxytol administration (P < 0.001) and decreased to baseline within two days. The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points. In maternal livers, R2* increased immediately after ferumoxytol administration, further increased at one-day, and then decreased but remained elevated (P < 0.001). The mean change from baseline showed no significant difference between the SC group and the IT group at all scan time points.

Conclusions: This work demonstrates the feasibility of quantitative ferumoxytol-enhanced MRI to measure dynamics of ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal ferumoxytol exposure.
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http://dx.doi.org/10.1016/j.mri.2019.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956847PMC
January 2020

Impact of ferumoxytol magnetic resonance imaging on the rhesus macaque maternal-fetal interface†.

Biol Reprod 2020 02;102(2):434-444

Wisconsin National Primate Research Center (WNPRC), Madison, Wisconsin, USA.

Ferumoxytol is a superparamagnetic iron oxide nanoparticle used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent. Additionally, ferumoxytol-uptake by macrophages facilitates detection of inflammatory sites by MRI through ferumoxytol-induced image contrast changes. Therefore, ferumoxytol-enhanced MRI holds great potential for assessing vascular function and inflammatory response, critical to determine placental health in pregnancy. This study sought to assess the fetoplacental unit and selected maternal tissues, pregnancy outcomes, and fetal well-being after ferumoxytol administration. In initial developmental studies, seven pregnant rhesus macaques were imaged with or without ferumoxytol administration. Pregnancies went to term with vaginal delivery and infants showed normal growth rates compared to control animals born the same year that did not undergo MRI. To determine the impact of ferumoxytol on the maternal-fetal interface (MFI), fetal well-being, and pregnancy outcome, four pregnant rhesus macaques at ~100 gestational day underwent MRI before and after ferumoxytol administration. Collection of the fetoplacental unit and selected maternal tissues was performed 2-3 days following ferumoxytol administration. A control group that did not receive ferumoxytol or MRI was used for comparison. Iron levels in fetal and MFI tissues did not differ between groups, and there was no significant difference in tissue histopathology with or without exposure to ferumoxytol, and no effect on placental hormone secretion. Together, these results suggest that the use of ferumoxytol and MRI in pregnant rhesus macaques does not negatively impact the MFI and can be a valuable experimental tool in research with this important animal model.
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http://dx.doi.org/10.1093/biolre/ioz181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016288PMC
February 2020

Reproducibility and Changes in Vena Caval Blood Flow by Using 4D Flow MRI in Pulmonary Emphysema and Chronic Obstructive Pulmonary Disease (COPD): The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Substudy.

Radiology 2019 09 23;292(3):585-594. Epub 2019 Jul 23.

From the Department of Radiology, Feinberg School of Medicine, Northwestern University, 737 N Michigan Ave, Suite 1600, Chicago, IL 60611 (O.R., M.M., H.B., C.B., K.S., J.C.); Departments of Radiology (O.R., S.D., M.R.P., Y.S.), Medicine (P.B., Y.S., R.G.B.), and Epidemiology (R.G.B.), Columbia University Medical Center, New York, NY; Department of Radiology, NewYork-Presbyterian Hospital, New York, NY (O.R.); Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, Ill (M.M.); Departments of Medical Physics (O.W.) and Radiology (D.A.B.), University of Wisconsin School of Medicine and Public Health, Madison, Wis; Division of Cardiology, Johns Hopkins University, Baltimore, Md (J.L., E.M., B.A.V.); Department of Radiology, Biomedical Engineering and Medicine, University of Iowa, Iowa City, Iowa (E.A.H.); and Departments of Radiology (A.S.G.) and Medicine (K.W.), University of California Los Angeles, Los Angeles, Calif.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with hemodynamic changes in the pulmonary vasculature. However, cardiac effects are not fully understood and vary by phenotype of chronic lower respiratory disease.PurposeTo use four-dimensional (4D) flow MRI for comprehensive assessment of the right-sided cardiovascular system, assess its interrater and intraobserver reproducibility, and examine associations with venous return to the right heart in individuals with chronic COPD and emphysema.Materials and MethodsThe Multi-Ethnic Study of Atherosclerosis COPD substudy prospectively recruited participants who smoked and who had COPD and nested control participants from population-based samples. Electrocardiography and respiratory gated 4D flow 1.5-T MRI was performed at three sites with full volumetric coverage of the thoracic vessels in 2014-2017 with postbronchodilator spirometry and inspiratory chest CT to quantify percent emphysema. Net flow, peak velocity, retrograde flow, and retrograde fraction were measured on 14 analysis planes. Interrater reproducibility was assessed by two independent observers, and the principle of conservation of mass was employed to evaluate the internal consistency of flow measures. Partial correlation coefficients were adjusted for age, sex, race/ethnicity, height, weight, and smoking status.ResultsAmong 70 participants (29 participants with COPD [mean age, 73.5 years ± 8.1 {standard deviation}; 20 men] and 41 control participants [mean age, 71.0 years ± 6.1; 22 men]), the interrater reproducibility of the 4D flow MRI measures was good to excellent (intraclass correlation coefficient range, 0.73-0.98), as was the internal consistency. There were no statistically significant differences in venous flow parameters according to COPD severity ( > .05). Greater percent emphysema at CT was associated with greater regurgitant flow in the superior and inferior caval veins and tricuspid valve (adjusted = 0.28-0.55; all < .01), particularly in the superior vena cava.ConclusionFour-dimensional flow MRI had good-to-excellent observer variability and flow consistency. Percent emphysema at CT was associated with statistically significant differences in retrograde flow, greatest in the superior vena cava.© RSNA, 2019See also the editorial by Choe in this issue.
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http://dx.doi.org/10.1148/radiol.2019182143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736177PMC
September 2019

Evaluation of a motion-robust 2D chemical shift-encoded technique for R2* and field map quantification in ferumoxytol-enhanced MRI of the placenta in pregnant rhesus macaques.

J Magn Reson Imaging 2020 02 5;51(2):580-592. Epub 2019 Jul 5.

Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, USA.

Background: 3D chemical shift-encoded (CSE)-MRI techniques enable assessment of ferumoxytol concentration but are unreliable in the presence of motion.

Purpose: To evaluate a motion-robust 2D-sequential CSE-MRI for R2* and B0 mapping in ferumoxytol-enhanced MRI of the placenta.

Study Type: Prospective.

Animal Model: Pregnant rhesus macaques.

Field Strength/sequence: 3.0T/CSE-MRI.

Assessment: 2D-sequential CSE-MRI was compared with 3D respiratory-gated CSE-MRI in placental imaging of 11 anesthetized animals at multiple timepoints before and after ferumoxytol administration, and in ferumoxytol phantoms (0 μg/mL-440 μg/mL). Motion artifacts of CSE-MRI in 10 pregnant women without ferumoxytol administration were assessed retrospectively by three blinded readers (4-point Likert scale). The repeatability of CSE-MRI in seven pregnant women was also prospectively studied.

Statistical Tests: Placental R2* and boundary B0 field measurements (ΔB0) were compared between 2D-sequential and 3D respiratory-gated CSE-MRI using linear regression and Bland-Altman analysis.

Results: In phantoms, a slope of 0.94 (r = 0.99, concordance correlation coefficient ρ = 0.99), and bias of -4.8 s (limit of agreement [LOA], -41.4 s , +31.8 s ) in R2*, and a slope of 1.07 (r = 1.00, ρ = 0.99) and bias of 11.4 Hz (LOA -12.0 Hz, +34.8 Hz) in ΔB0 were obtained in 2D CSE-MRI compared with 3D CSE-MRI for reference R2* ≤390 s . In animals, a slope of 0.92 (r = 0.97, ρ = 0.98) and bias of -2.2 s (LOA -55.6 s , +51.3 s ) in R2*, and a slope of 1.05 (r = 0.95, ρ = 0.97) and bias of 0.4 Hz (LOA -9.0 Hz, +9.7 Hz) in ΔB0 were obtained. In humans, motion-impaired R2* maps in 3D CSE-MRI (Reader 1: 1.8 ± 0.6, Reader 2: 1.3 ± 0.7, Reader 3: 1.9 ± 0.6), while 2D CSE-MRI was motion-free (Reader 1: 2.9 ± 0.3, Reader 2: 3.0 ± 0, Reader 3: 3.0 ± 0). A mean difference of 0.66 s and coefficient of repeatability of 9.48 s for placental R2* were observed in the repeated 2D CSE-MRI.

Data Conclusion: 2D-sequential CSE-MRI provides accurate R2* and B0 measurements in ferumoxytol-enhanced placental MRI of animals in the presence of respiratory motion, and motion-robustness in human placental imaging.

Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:580-592.
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http://dx.doi.org/10.1002/jmri.26849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839098PMC
February 2020

Partial Aortic Valve Leaflet Fusion Is Related to Deleterious Alteration of Proximal Aorta Hemodynamics.

Circulation 2019 06 3;139(23):2707-2709. Epub 2019 Jun 3.

Hospital Universitari Vall d´Hebron, Department of Cardiology, CIBER-CV. Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Spain (A.G., J.R.-P., L.G.-G., G.T.-T., A.S.A., A.E.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.039693DOI Listing
June 2019

Increased rotational flow in the proximal aortic arch is associated with its dilation in bicuspid aortic valve disease.

Eur Heart J Cardiovasc Imaging 2019 Dec;20(12):1407-1417

Department of Cardiology, CIBER-CV, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Passeig de la Vall d'Hebron 119-129, 08035 Barcelona, Spain.

Aims: Aortic dilation in bicuspid aortic valve (BAV) might extend to the proximal arch. Arch flow dynamics and their relationship with this segment dilation are still unexplored. Using 4D-flow cardiovascular magnetic resonance, we analysed flow dynamics in the arch for each BAV morphotype and their association with this segment dilation.

Methods And Results: One hundred and eleven BAV patients (aortic diameters ≤55 mm, non-severe valvular disease), 21 age-matched tricuspid aortic valve (TAV) patients with dilated arch and 24 healthy volunteers (HV) underwent 4D-flow. BAV were classified per fusion morphotype: 75% right-left (RL-BAV), and per arch dilation: 57% dilated, mainly affecting the right-noncoronary (RN) BAV (86% dilated vs. 47% in RL-BAV). Peak velocity, jet angle, normalized displacement, in-plane rotational flow (IRF), wall shear stress, and systolic flow reversal ratio (SFRR) were calculated along the thoracic aorta. ANCOVA and multivariate linear regression analyses were used to identify correlates of arch dilation. BAV had higher rotational flow and eccentricity than TAV in the proximal arch. Dilated compared with non-dilated BAV had higher IRF being more pronounced in the RN-morphotype. RN-BAV, IRF, and SFRR were independently associated with arch dilation. Aortic stenosis and male sex were independently associated with arch dilation in RL-BAV. Flow parameters associated with dilation converged to the values found in HV in the distal arch.

Conclusion: Increased rotational flow could explain dilation of the proximal arch in RN-BAV and in RL-BAV patients of male sex and with valvular stenosis. These patients may benefit from a closer follow-up with cardiac magnetic resonance or computed tomography.
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http://dx.doi.org/10.1093/ehjci/jez046DOI Listing
December 2019

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

Magn Reson Med 2019 06 12;81(6):3588-3598. Epub 2019 Feb 12.

Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Purpose: This feasibility study investigates the non-invasive measurement of microvascular cerebral blood volume (BV) changes over the cardiac cycle using cardiac-gated, ferumoxytol-enhanced MRI.

Methods: Institutional review board approval was obtained and all subjects provided written informed consent. Cardiac gated MR scans were prospectively acquired on a 3.0T scanner in 22 healthy subjects using -weighted sequences with 2D-EPI and 3D spiral trajectories. Images were collected before and after the intravenous administration of 2 doses of ferumoxytol (1 mg FE/kg and 4 mg FE/kg). Cardiac cycle-induced (1/ ) changes (Δ ) and BV changes (ΔBV) throughout the cardiac cycle in gray matter (GM) and white matter (WM) were quantified and differences assessed using ANOVA followed by post hoc analysis.

Results: Δ was found to increase in a dose-dependent fashion. A significantly larger increase was observed in GM compared to WM in both 2D and 3D acquisitions (P < 0.050). In addition, Δ increased significantly (P < 0.001) post versus pre-contrast injection in GM in both MRI acquisitions. Mean GM Δ derived from 2D-EPI images was 0.14 ± 0.06 s pre-contrast and 0.33 ± 0.13 s after 5 mg FE/kg. In WM, Δ was 0.19 ± 0.06 s pre-contrast, and 0.23 ± 0.06 s after 5 mg FE/kg. The fractional changes in BV throughout the cardiac cycle were 0.031 ± 0.019% in GM and 0.011 ± 0.008% in WM (P < 0.001) after 5 mg FE/kg.

Conclusion: Cardiac-gated, ferumoxytol-enhanced MRI enables characterization of microvascular BV changes throughout the cardiac cycle in GM and WM tissue of healthy subjects.
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http://dx.doi.org/10.1002/mrm.27670DOI Listing
June 2019
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