Publications by authors named "Jacob A Macdonald"

6 Publications

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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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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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June 2021

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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June 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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December 2019

MRI assessment of aortic flow in patients with pulmonary arterial hypertension in response to exercise.

BMC Med Imaging 2018 12 22;18(1):55. Epub 2018 Dec 22.

Department of Medical Physics, University of Wisconsin, 1111 Highland Avenue, Room 1005, Madison, WI, 53705, USA.

Background: While primarily a right heart disease, pulmonary arterial hypertension (PAH) can impact left heart function and aortic flow through a shifted interventricular septum from right ventricular pressure overload and reduced left ventricular preload, among other mechanisms. In this study, we used phase contrast (PC) MRI and a modest exercise challenge to examine the effects of PAH on systemic circulation. While exercise challenges are typically performed with ultrasound in the clinic, MRI exercise studies allow for more reproducible image alignment, more accurate flow quantification, and improved tissue contrast.

Methods: Six PAH patients and fifteen healthy controls (8 older age-matched, 7 younger) exercised in the magnet bore with an MRI-compatible exercise device that allowed for scanning immediately following cessation of exercise. PC scans were performed in the ascending aorta during a breath hold immediately after modest exercise to non-invasively measure stroke volume (SV), cardiac output (CO), aortic peak systolic flow (PSF), and aortic wall stiffness via relative area change (RAC).

Results: Images following exercise showed mild blurring, but were high enough quality to allow for segmentation of the aorta. While SV was approximately 30% lower in PAH patients (SV = 67 ± 16 mL; SV = 90 ± 42 mL) than age-matched controls (SV = 93 ± 16 mL; SV = 133 ± 40 mL) at both rest and following exercise, CO was similar for both groups following exercise (CO = 10.8 ± 5.7 L/min; CO = 11.8 ± 5.0 L/min). This was achieved through a compensatory increase in heart rate in the PAH subjects (74% increase as compared to 29% in age-matched controls). The PAH subjects also demonstrated reduced aortic peak systolic flow relative to the healthy controls (PSF, = 309 ± 52 mL/s; PSF, = 416 ± 114 mL/s; PSF, = 388 ± 113 mL/s; PSF, = 462 ± 176 mL/s). PAH patients and older controls demonstrated stiffer aortic walls when compared to younger controls (RAC = 0.15 ± 0.05; RAC = 0.17 ± 0.05; RAC = 0.28 ± 0.08).

Conclusions: PC MRI following a modest exercise challenge was capable of detecting differences in left heart dynamics likely induced from PAH. These results demonstrated that PAH can have a significant influence on systemic flow, even when the patient has no prior left heart disease. Image quantification following exercise could likely be improved in future studies through the implementation of free-breathing or real-time MRI acquisitions.

Trial Registration: Retrospectively registered on 02/26/2018 (TRN: NCT03523910 ).
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December 2018

Uteroplacental and Fetal 4D Flow MRI in the Pregnant Rhesus Macaque.

J Magn Reson Imaging 2019 02 13;49(2):534-545. Epub 2018 Aug 13.

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

Background: Pregnancy complications are often associated with poor uteroplacental vascular adaptation and standard diagnostics are unable to reliably quantify flow in all uteroplacental vessels and have poor sensitivity early in gestation.

Purpose: To investigate the feasibility of using 4D flow MRI to assess total uteroplacental blood flow in pregnant rhesus macaques as a precursor to human studies.

Study Type: Retrospective feasibility study.

Animal Model: Fifteen healthy, pregnant rhesus macaques ranging from the 1 trimester to 3 trimester of gestation.

Field Strength/sequence: Abdominal 4D flow MRI was performed on a 3.0T scanner with a radially undersampled phase contrast (PC) sequence. Reference ferumoxytol-enhanced angiograms were acquired with a 3D ultrashort echo time sequence with a center-out radial trajectory.

Assessment: Repeatability of flow measurements was assessed with scans performed same-day and on consecutive days in the uterine arteries and ovarian veins. In-flow was compared against out-flow in the uterus, umbilical cord, and fetal heart with a conservation of mass analysis. Conspicuity of uteroplacental vessels was qualitatively compared between PC angiograms derived from 4D flow data and ferumoxytol-enhanced angiograms.

Statistical Tests: Bland-Altman analysis was used to quantify same-day and consecutive-day repeatability.

Results: Same-day flow measurements showed an average difference between scans of 13% in both the uterine arteries and ovarian veins, while consecutive-day measurements showed average differences of 22% and 24%, respectively. Comparisons of in-flow and out-flow showed average differences of 15% in the uterus, 8% in fetal heart, and 15% in the umbilical cord. PC angiograms showed similar depiction of main uteroplacental vessels as high-resolution, ferumoxytol-enhanced angiograms.

Data Conclusion: 4D flow MRI could be used in the rhesus macaque for repeatable flow measurements in the uteroplacental and fetal vasculature, setting the stage for future human studies.

Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:534-545.
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February 2019