Fetal Cardiac MRI Using Doppler US Gating: Emerging Technology and Clinical Implications.

Fetal cardiac MRI using Doppler US gating is an emerging technique to support prenatal diagnosis of congenital heart disease and other cardiovascular abnormalities. Analogous to postnatal electrocardiographically gated cardiac MRI, this technique enables directly gated MRI of the fetal heart throughout the cardiac cycle, allowing for immediate data reconstruction and review of image quality. This review outlines the technical principles and challenges of cardiac MRI with Doppler US gating, such as loss of gating signal due to fetal movement. A practical workflow of patient preparation for the use of Doppler US-gated fetal cardiac MRI in clinical routine is provided. Currently applied MRI sequences (ie, cine or four-dimensional flow imaging), with special consideration of technical adaptations to the fetal heart, are summarized. The authors provide a literature review on the clinical benefits of Doppler US-gated fetal cardiac MRI for gaining additional diagnostic information on cardiovascular malformations and fetal hemodynamics. Finally, future perspectives of Doppler US-gated fetal cardiac MRI and further technical developments to reduce acquisition times and eliminate sources of artifacts are discussed. Keywords: MR Fetal, Ultrasound Doppler, Cardiac, Heart, Congenital, Obstetrics, Fetus Supplemental material is available for this article. © RSNA, 2024.

The Evolution and Developing Importance of Fetal Magnetic Resonance Imaging in the Diagnosis of Congenital Cardiac Anomalies: A Systematic Review.

Magnetic Resonance Imaging (MRI) is a reliable method, with a complementary role to Ultrasound (US) Echocardiography, that can be used to fully comprehend and precisely diagnose congenital cardiac malformations. Besides the anatomical study of the fetal cardiovascular system, it allows us to study the function of the fetal heart, remaining, at the same time, a safe adjunct to the classic fetal echocardiography. MRI also allows for the investigation of cardiac and placental diseases by providing information about hematocrit, oxygen saturation, and blood flow in fetal vessels. It is crucial for fetal medicine specialists and pediatric cardiologists to closely follow the advances of fetal cardiac MRI in order to provide the best possible care. In this review, we summarize the advance in techniques and their practical utility to date.

Fetal dynamic magnetic resonance imaging using Doppler ultrasound gating for the assessment of the aortic isthmus: A feasibility study.

INTRODUCTION: Cardiovascular magnetic resonance imaging (MRI) is established in cardiac evaluation in postnatal life, but its application to the fetus has been hampered by technical limitations. We aimed to investigate the feasibility of dynamic MRI of the fetal aortic isthmus using a magnetic resonance-compatible Doppler ultrasound device for cardiac gating. MATERIAL AND METHODS: This prospective study included 19 fetuses at a median gestational age of 32.3 weeks (range 26-38 weeks). Imaging of the fetal aortic isthmus was assessed by (a) dynamic steady-state free precession MRI using a magnetic resonance-compatible Doppler ultrasound device for cardiac gating and (b) echocardiography. Diameters of the aortic isthmus were compared by two blinded observers. Magnetic resonance image quality was assessed independently by two observers using a four-point scale (1 = low quality, 4 = high quality). Furthermore, we performed four-dimensional flow MRI of the fetal aorta in three of these fetuses. RESULTS: The Doppler ultrasound device for cardiac gating allowed successful dynamic MRI examinations of the aortic isthmus in 18/19 (95%) fetuses. Evaluation of the fetal aortic isthmus was possible by both MRI (15/18, 83%) and echocardiography (16/18, 89%) (P < .05). Diameters of the aortic isthmus were concordant for MRI (3.8 ± 0.9 mm) and echocardiography (4.0 ± 1.1 mm), with a variability of 10.8% (bias -2.3%, 95% limits of agreement -23.9% to 19.3%). Overall magnetic resonance image quality was good (score 4 in 67% and score 3 in 23%) with good inter-observer agreement (κ = 0.75; 95% CI 0.5-1). Fetal four-dimensional flow MRI allowed visualization of aortic flow dynamics. CONCLUSIONS: Doppler ultrasound-gating allows dynamic MRI of the fetal aorta with the potential to serve as a complementary imaging tool in cases where echocardiography is inconclusive.

Doppler ultrasound cardiac gating of intracranial flow at 7T.

BACKGROUND: Ultra-high field magnetic resonance imaging (MR) may be used to improve intracranial blood flow measurements. However, standard cardiac synchronization methods tend to fail at ultra-high field MR. Therefore, this study aims to investigate an alternative synchronization technique using Doppler ultrasound. METHODS: Healthy subjects (n = 9) were examined with 7T MR. Flow was measured in the M1-branch of the middle cerebral artery (MCA) and in the cerebral aqueduct (CA) using through-plane phase contrast (2D flow). Flow in the circle of Willis was measured with three-dimensional, three-directional phase contrast (4D flow). Scans were gated with Doppler ultrasound (DUS) and electrocardiogram (ECG), and pulse oximetry data (POX) was collected simultaneously. False negative and false positive trigger events were counted for ECG, DUS and POX, and quantitative flow measures were compared. RESULTS: There were fewer false positive triggers for DUS compared to ECG (5.3 ± 11 vs. 25 ± 31, p = 0.031), while no other measured parameters differed significantly. Net blood flow in M1 was similar between DUS and ECG for 2D flow (1.5 ± 0.39 vs. 1.6 ± 0.41, bias ± 1.96SD: - 0.021 ± 0.36) and 4D flow (1.8 ± 0.48 vs. 9 ± 0.59, bias ± 1.96SD: - 0.086 ± 0.57 ml). Net CSF flow per heart beat in the CA was also similar for DUS and ECG (3.6 ± 2.1 vs. 3.0 ± 5.8, bias ± 1.96SD: 0.61 ± 13.6 µl). CONCLUSION: Gating with DUS produced fewer false trigger events than using ECG, with similar quantitative flow values. DUS gating is a promising technique for cardiac synchronization at 7T.

Free-breathing fetal cardiac MRI with doppler ultrasound gating, compressed sensing, and motion compensation.

BACKGROUND: Fetal cardiovascular MRI complements ultrasound to assess fetal cardiovascular pathophysiology. PURPOSE: To develop a free-breathing method for retrospective fetal cine MRI using Doppler ultrasound (DUS) cardiac gating and tiny golden angle radial sampling (tyGRASP) for accelerated acquisition capable of detecting fetal movements for motion compensation. STUDY TYPE: Feasibility study. SUBJECTS: Nine volunteers (gestational week 34-40). Short-axis and four-chamber views were acquired during maternal free-breathing and breath-hold. FIELD STRENGTH/SEQUENCE: 1.5T cine balanced steady-state free precession. ASSESSMENT: A self-gated reconstruction method was improved for clinical application by using 1) retrospective DUS gating, and 2) motion detection and rejection/correction algorithms for compensating for fetal motion. The free-breathing reconstructions were qualitatively and quantitatively assessed, and DUS-gating was compared with self-gating in breath-hold reconstructions. A scoring of 1-4 for overall image quality, cardiac, and extracardiac diagnostic quality was used. STATISTICAL TESTS: Friedman's test was used to assess differences in qualitative scoring between observers. A Wilcoxon matched-pairs signed rank test was used to assess differences between breath-hold and free-breathing acquisitions and between observers' quantitative measurements. RESULTS: In all cases, 111 free-breathing and 145 breath-hold acquisitions, the automatically calculated DUS-based cardiac gating signal provided reconstructions of diagnostic quality (median score 4, range 1-4). Free-breathing did not affect the DUS-based cardiac gated retrospective radial reconstruction with respect to image or diagnostic quality (all P > 0.06). Motion detection with rejection/correction in k-space produced high-quality free-breathing DUS-based reconstructions [median 3, range (2-4)], whereas free-breathing self-gated methods failed in 80 out of 88 cases to produce a stable gating signal. DATA CONCLUSION: Free-breathing fetal cine cardiac MRI based on DUS gating and tyGRASP with motion compensation yields diagnostic images. This simplifies acquisition for the pregnant woman and thus could help increase fetal cardiac MRI acceptance in the clinic. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:260-272.

Quantification of blood flow in the fetus with cardiovascular magnetic resonance imaging using Doppler ultrasound gating: validation against metric optimized gating.

INTRODUCTION: Fetal cardiovascular magnetic resonance (CMR) imaging is used clinically and for research, but has been previously limited due to lack of direct gating methods. A CMR-compatible Doppler ultrasound (DUS) gating device has resolved this. However, the DUS-gating method is not validated against the current reference method for fetal phase-contrast blood flow measurements, metric optimized gating (MOG). Further, we investigated how different methods for vessel delineation affect flow volumes and observer variability in fetal flow acquisitions. AIMS: To 1) validate DUS gating versus MOG for quantifying fetal blood flow; 2) assess repeatability of DUS gating; 3) assess impact of region of interest (ROI) size on flow volume; and 4) compare time-resolved and static delineations for flow volume and observer variability. METHODS: Phase-contrast CMR was acquired in the fetal descending aorta (DAo) and umbilical vein by DUS gating and MOG in 22 women with singleton pregnancy in gestational week 360 (265-400) with repeated scans in six fetuses. Impact of ROI size on measured flow was assessed for ROI:s 50-150% of the vessel diameter. Four observers from two centers provided time-resolved and static delineations. Bland-Altman analysis was used to determine agreement between both observers and methods. RESULTS: DAo flow was 726 (348-1130) ml/min and umbilical vein flow 366 (150-782) ml/min by DUS gating. Bias±SD for DUS-gating versus MOG were - 45 ± 122 ml/min (-6 ± 15%) for DAo and 19 ± 136 ml/min (2 ± 24%) for umbilical vein flow. Repeated flow measurements in the same fetus showed similar volumes (median CoV = 11% (DAo) and 23% (umbilical vein)). Region of interest 50-150% of vessel diameter yielded flow 35-120%. Bias±SD for time-resolved versus static DUS-gated flow was 33 ± 39 ml/min (4 ± 6%) for DAo and 11 ± 84 ml/min (2 ± 15%) for umbilical vein flow. CONCLUSIONS: Quantification of blood flow in the fetal DAo and umbilical vein using DUS-gated phase-contrast CMR is feasible and agrees with the current reference method. Repeatability was generally high for CMR fetal blood flow assessment. An ROI similar to the vessel area or slightly larger is recommended. A static ROI is sufficient for fetal flow quantification using currently available CMR sequences.

Model checking for trigger loss detection during Doppler ultrasound-guided fetal cardiovascular MRI.

PURPOSE: Ultrasound (US) is the state of the art in prenatal diagnosis to depict fetal heart diseases. Cardiovascular magnetic resonance imaging (CMRI) has been proposed as a complementary diagnostic tool. Currently, only trigger-based methods allow the temporal and spatial resolutions necessary to depict the heart over time. Of these methods, only Doppler US (DUS)-based triggering is usable with higher field strengths. DUS is sensitive to motion. This may lead to signal and, ultimately, trigger loss. If too many triggers are lost, the image acquisition is stopped, resulting in a failed imaging sequence. Moreover, losing triggers may prolong image acquisition. Hence, if no actual trigger can be found, injected triggers are added to the signal based on the trigger history. METHOD: We use model checking, a technique originating from the computer science domain that formally checks if a model satisfies given requirements, to simultaneously model heart and respiratory motion and to decide whether respiration has a prominent effect on the signal. Using bounds on the physiological parameters and their variability, the method detects when changes in the signal are due to respiration. We use this to decide when to inject a trigger. RESULTS: In a real-world scenario, we can reduce the number of falsely injected triggers by 94% from more than 87% to less than 5%. On a subset of motion that would allow CMRI, the number can be further reduced to below 0.2%. In a study using simulations with a robot, we show that our method works for different types of motions, motion ranges, starting positions and heartbeat traces. CONCLUSION: While DUS is a promising approach for fetal CMRI, correct trigger injection is critical. Our model checking method can reduce the number of wrongly injected triggers substantially, providing a key prerequisite for fast and artifact free CMRI.

DCE MRI reveals early decreased and later increased placenta perfusion after a stress challenge during pregnancy in a mouse model.

OBJECTIVES: Stress during pregnancy is known to have negative effects on fetal outcome. The purpose of this exploratory study was to examine placental perfusion alterations after stress challenge during pregnancy in a mouse model. MATERIAL AND METHODS: Seven Tesla MRI was performed on pregnant mice at embrionic day (ED) 14.5 and 16.5. Twenty dams were exposed to an established acoustic stress challenge model while twenty non-exposed dams served as controls. Placental perfusion was analyzed in dynamic contrast-enhanced (DCE) MRI using the steepest slope model. The two functional placental compartments, the highly vascularized labyrinth and the endocrine junctional zone, were assessed separately. RESULTS: Statistical analysis revealed decreased perfusion levels in the stress group at ED 14.5 compared to controls in both placenta compartments. On ED 16.5, the perfusion level increased significantly in the stress group while placenta perfusion in controls remained similar or even slightly decreased leading to an overall increased perfusion in the stress group on ED 16.5 compared to controls. CONCLUSION: MR imaging allows noninvasive placenta perfusion assessment in this fetal stress mimicking animal model. In this exploratory study, we demonstrated that stress challenge during pregnancy leads to an initial reduction followed by an increase of placenta perfusion.

Dynamic fetal cardiovascular magnetic resonance imaging using Doppler ultrasound gating.

BACKGROUND: Fetal cardiovascular magnetic resonance (CMR) imaging may provide a valuable adjunct to fetal echocardiography in the evaluation of congenital cardiovascular pathologies. However, dynamic fetal CMR is difficult due to the lack of direct in-utero cardiac gating. The aim of this study was to investigate the effectiveness of a newly developed Doppler ultrasound (DUS) device in humans for fetal CMR gating. METHODS: Fifteen fetuses (gestational age 30-39 weeks) were examined using 1.5 T CMR scanners at three different imaging sites. A newly developed CMR-compatible DUS device was used to generate gating signals from fetal cardiac motion. Gated dynamic balanced steady-state free precession images were acquired in 4-chamber and short-axis cardiac views. Gating signals during data acquisition were analyzed with respect to trigger variability and sensitivity. Image quality was assessed by measuring endocardial blurring (EB) and by image evaluation using a 4-point scale. Left ventricular (LV) volumetry was performed using the single-plane ellipsoid model. RESULTS: Gating signals from the fetal heart were detected with a variability of 26 ± 22 ms and a sensitivity of trigger detection of 96 ± 4%. EB was 2.9 ± 0.6 pixels (4-chamber) and 2.5 ± 0.1 pixels (short axis). Image quality scores were 3.6 ± 0.6 (overall), 3.4 ± 0.7 (mitral valve), 3.4 ± 0.7 (foramen ovale), 3.6 ± 0.7 (atrial septum), 3.7 ± 0.5 (papillary muscles), 3.8 ± 0.4 (differentiation myocardium/lumen), 3.7 ± 0.5 (differentiation myocardium/lung), and 3.9 ± 0.4 (systolic myocardial thickening). Inter-observer agreement for the scores was moderate to very good (kappa 0.57-0.84) for all structures. LV volumetry revealed mean values of 2.8 ± 1.2 ml (end-diastolic volume), 0.9 ± 0.4 ml (end systolic volume), 1.9 ± 0.8 ml (stroke volume), and 69.1 ± 8.4% (ejection fraction). CONCLUSION: High-quality dynamic fetal CMR was successfully performed using a newly developed DUS device for direct fetal cardiac gating. This technique has the potential to improve the utility of fetal CMR in the evaluation of congenital pathologies.

Evaluation of a Portable Doppler Ultrasound Gating Device for Fetal Cardiac MR Imaging: Initial Results at 1.5T and 3T.

PURPOSE: Fetal cardiac MRI has the potential to play an important role in the assessment of fetal cardiac pathologies, but it is up to now not feasible due to a missing gating method. The purpose of this work was the evaluation of Doppler ultrasound (DUS) for external fetal cardiac gating with regard to compatibility, functionality, and reliability. Preliminary results were assessed performing fetal cardiac MRI. METHODS: An MRI conditional DUS device was developed to obtain a gating signal from the fetal heart. The MRI compatibility was evaluated at 1.5T and 3T using B1 field maps and gradient echo images. The quality and sensitivity of the DUS device to detect the fetal heart motion for cardiac gating were evaluated outside the MRI room in 15 fetuses. A dynamic fetal cardiac phantom was employed to evaluate distortions of the DUS device and gating signal due to electromagnetic interferences at 1.5T and 3T. In the first in vivo experience, dynamic fetal cardiac images were acquired in four-chamber view at 1.5T and 3T in two fetuses. RESULTS: The maximum change in the B1 field and signal intensity with and without the DUS device was <6.5% for 1.5T and 3T. The sensitivity of the DUS device to detect the fetal heartbeat was 99.1%. Validation of the DUS device using the fetal cardiac phantom revealed no electromagnetic interferences at 1.5T or 3T and a high correlation to the simulated heart frequencies. Fetal cardiac cine images were successfully applied and showed good image quality. CONCLUSION: An MR conditional DUS gating device was developed and evaluated revealing safety, compatibility, and reliability for different field strengths. In a preliminary experience, the DUS device was successfully applied for in vivo fetal cardiac imaging at 1.5T and 3T.

Doppler Ultrasound Triggering for Cardiovascular MRI at 3T in a Healthy Volunteer Study.

PURPOSE: Electrocardiogram (ECG) triggering for cardiac magnetic resonance (CMR) may be influenced by electromagnetic interferences with increasing magnetic field strength. The aim of this study was to evaluate the performance of Doppler ultrasound (DUS) as an alternative trigger technique for CMR in comparison to ECG and pulse oximetry (POX) at 3T and using different sequence types. METHODS: Balanced turbo field echo two-dimensional (2D) short axis cine CMR and 2D phase-contrast angiography of the ascending aorta was performed in 11 healthy volunteers at 3T using ECG, DUS, and POX for cardiac triggering. DUS and POX triggering were compared to the reference standard of ECG in terms of trigger quality (trigger detection and temporal variability), image quality [endocardial blurring (EB)], and functional measurements [left ventricular (LV) volumetry and aortic blood flow velocimetry]. RESULTS: Trigger signal detection and temporal variability did not differ significantly between ECG/DUS (I = 0.6) and ECG/POX (P = 0.4). Averaged EB was similar for ECG, DUS, and POX (pECG/DUS = 0.4, pECG/POX = 0.9). Diastolic EB was significantly decreased for DUS in comparison to ECG (P = 0.02) and POX (P = 0.04). The LV function assessment and aortic blood flow were not significantly different. CONCLUSION: This study demonstrated the feasibility of DUS for gating human CMR at 3T. The magnetohydrodynamic effect did not significantly disturb ECG triggering in this small healthy volunteer study. DUS showed a significant improvement in diastolic EB but could not be identified as a superior trigger method. The potential benefit of DUS has to be evaluated in a larger clinical patient population.

Quantitative Activity Measurements of Brown Adipose Tissue at 7 T Magnetic Resonance Imaging After Application of Triglyceride-Rich Lipoprotein 59Fe-Superparamagnetic Iron Oxide Nanoparticle: Intravenous Versus Intraperitoneal Approach.

OBJECTIVES: The aim of this study was to determine metabolic activity of brown adipose tissue (BAT) with in vivo magnetic resonance imaging (MRI) after intravenous (IV) and intraperitoneal (IP) injection of radioactively labeled superparamagnetic iron oxide nanoparticles (SPIOs) embedded into a lipoprotein layer. MATERIALS AND METHODS: Fe-labeled SPIOs were either polymer-coated or embedded into the lipid core of triglyceride-rich lipoproteins (TRL-Fe-SPIOs). First biodistribution and blood half time analysis in thermoneutral mice after IP injection of either TRL-Fe-SPIOs or polymer-coated Fe-SPIOs (n = 3) were performed. In the next step, cold-exposed (24 hours), BAT-activated mice (n = 10), and control thermoneutral mice (n = 10) were starved for 4 hours before IP (n = 10) or IV (n = 10) injection of TRL-Fe-SPIOs. In vivo MRI was performed before and 24 hours after the application of the particles at a 7 T small animal MRI scanner using a T2*-weighted multiecho gradient echo sequence. R2* and ΔR2* were estimated in the liver, BAT, and muscle. The biodistribution of polymer-coated Fe-SPIOs and TRL-Fe-SPIOs was analyzed ex vivo using a sensitive, large-volume Hamburg whole-body radioactive counter. The amount of Fe-SPIOs in the liver, BAT, and muscle was correlated with the MRI measurements using the Pearson correlation coefficient. Tissue uptake of Fe-SPIOs was confirmed by histological and transmission electron microscopy analyses. RESULTS: Triglyceride-rich lipoprotein Fe-SPIOs exhibited a higher blood concentration after IP injection (10.1% ± 0.91% after 24 hours) and a greater [INCREMENT]R2* in the liver (103 ± 5.0 s), while polymer-coated SPIOs did not increase substantially in the blood stream (0.19% ± 0.01% after 24 hours; P < 0.001) and the liver (57 ± 4.08 s; P < 0.001). In BAT activity studies, significantly higher uptake of TRL-Fe-SPIOs was detected in the BAT of cold-exposed mice, with [INCREMENT]R2* of 107 ± 5.5 s after IV application (control mice: [INCREMENT]R2* of 22 ± 5.8 s; P < 0.001) and 45 ± 5.5 s after IP application (control mice: [INCREMENT]R2* of 11 ± 2.9 s; P < 0.01). Fe radioactivity measurements and [INCREMENT]R2* values correlated strongly in BAT (r > 0.85; P < 0.001) and liver tissue (r > 0.85; P < 0.001). Histological and transmission electron microscopy analyses confirmed the uptake of TRL-Fe-SPIOs within the liver and BAT for both application approaches. CONCLUSIONS: Triglyceride-rich lipoprotein-embedded SPIOs were able to escape the abdominal cavity barrier, whereas polymer-coated SPIOs did not increase substantially in the blood stream. Brown adipose tissue activity can be determined via MRI using TRL-Fe-SPIOs. The quantification of [INCREMENT]R2* using TRL-Fe-SPIOs is feasible and may serve as a noninvasive tool for the quantitative estimation of BAT activity.

Doppler ultrasound compared with electrocardiogram and pulse oximetry cardiac triggering: A pilot study.

PURPOSE: Accurate triggering of the cardiac cycle is mandatory for optimal image acquisition and thus diagnostic quality in cardiac magnetic resonance imaging. The purpose of this work was to evaluate Doppler ultrasound as an alternative trigger method in cardiac MRI. METHODS: Steady-state free precession (SSFP) 2D cine CMR was performed in 11 healthy subjects at 1.5T. Doppler ultrasound (DUS), electrocardiogram (ECG) and pulse oximetry (POX) were used for cardiac triggering. DUS peak detection was verified in comparison to ECG. Quantitative analysis of image quality of each gating method was determined by calculating endocardial border sharpness (EBS) and left ventricular (LV) function parameters and compared with ECG. RESULTS: Mean difference between DUS and ECG in detected RR intervals was 0.04 ± 63 ms (r = 0.96). Trigger jitter was not different between ECG and DUS (P = 0.15) but significant different between ECG and POX (P = 0.01). EBS was similar between each method (3.1 ± 0.2 / 2.6 ± 0.2 / 2.9 ± 0.2 pixel). Mean differences in stroke volume were not significantly different with -1 ± 7 mL (ECG/DUS, P = 0.9) and 2 ± 10 mL (ECG/POX, P = 0.8). CONCLUSION: Cine cardiac MRI using DUS was successfully demonstrated. DUS triggering is an alternative method for cardiac MRI and may be applied in a clinical setting.

Gadospin F-enhanced magnetic resonance imaging for diagnosis and monitoring of atherosclerosis: validation with transmission electron microscopy and x-ray fluorescence imaging in the apolipoprotein e-deficient mouse.

The aim of this study was to investigate the feasibility of noninvasive monitoring of plaque burden in apolipoprotein E-deficient (ApoE-/-) mice by Gadospin F (GDF)-enhanced magnetic resonance imaging (MRI). Gadolinium uptake in plaques was controlled using transmission electron microscopy (TEM) and x-ray fluorescence (XRF) microscopy. To monitor the progression of atherosclerosis, ApoE-/- (n  =  5) and wild-type (n  =  2) mice were fed a Western diet and imaged at 5, 10, 15, and 20 weeks. Contrast-enhanced MRI was performed at 7 T Clinscan (Bruker, Ettlingen, Germany) before and 2 hours after intravenous injection of GDF (100 µmol/kg) to determine the blood clearance. Plaque size and contrast to noise ratio (CNR) were calculated for each time point using region of interest measurements to evaluate plaque progression. Following MRI, aortas were excised and GDF uptake was cross-validated by TEM and XRF microscopy. The best signal enhancement in aortic plaque was achieved 2 hours after application of GDF. No signal differences between pre- and postcontrast MRI were detectable in wild-type mice. We observed a gradual and considerable increase in plaque CNR and size for the different disease stages. TEM and XRF microscopy confirmed the localization of GDF within the plaque. GDF-enhanced MRI allows noninvasive and reliable estimation of plaque burden and monitoring of atherosclerotic progression in vivo.

Simultaneous assessment of vessel size index, relative blood volume, and vessel permeability in a mouse brain tumor model using a combined spin echo gradient echo echo-planar imaging sequence and viable tumor analysis.

PURPOSE: Combining multiple imaging biomarkers in one magnetic resonance imaging (MRI) session would be beneficial to gain more data pertaining to tumor vasculature under therapy. Therefore, simultaneous measurement of perfusion, permeability, and vessel size imaging (VSI) using a gradient echo spin echo (GE-SE) sequence with injection of a clinically approved gadolinium (Gd)-based contrast agent was assessed in an orthotopic glioma model. MATERIALS AND METHODS: A combined spin echo gradient echo echo-planar imaging sequence was implemented using a single contrast agent Gd diethylenetriaminepentaacetic acid (Gd-DTPA). This sequence was tested in a mouse brain tumor model (U87_MG), also under treatment with an antiangiogenic agent (bevacizumab). T2 maps and the apparent diffusion coefficient (ADC) were used to differentiate regions of cell death and viable tumor tissue. RESULTS: In viable tumor tissue regional blood volume was 5.7 ± 0.6% in controls and 5.2 ± 0.3% in treated mice. Vessel size was 18.1 ± 2.4 µm in controls and 12.8 ± 2.0 µm in treated mice, which correlated with results from immunohistochemistry. Permeability (K(trans) ) was close to zero in treated viable tumor tissue and 0.062 ± 0.024 min(-1) in controls. CONCLUSION: Our MRI method allows simultaneous assessment of several physiological and morphological parameters and extraction of MRI biomarkers for vasculature. These could be used for treatment monitoring of novel therapeutic agents such as antiangiogenic drugs.

Fetal blood flow velocimetry by phase-contrast MRI using a new triggering method and comparison with Doppler ultrasound in a sheep model: a pilot study.

OBJECT: We present the first study demonstrating the feasibility of antenatal blood flow velocimetry performing ECG triggered phase-contrast (PC)-MRI in the fetal aorta by using a newly developed Doppler ultrasound trigger. MATERIALS AND METHODS: Five pregnant sheep carrying singleton fetuses (gestational age 121 days) were anesthetized to undergo fetal 2D PC-MRI in the fetal descending aorta (1.5 T) using a newly developed MR-compatible Doppler ultrasound trigger for fetal cardiac triggering. Inter-operator variability was assessed for PC-MR measurements and reproducibility was tested by repeated scans in one fetus. Inter-modality comparison was performed by Doppler ultrasound velocimetry. RESULTS: Fetal cardiac triggering was possible in all examinations. PC-MR velocimetry revealed a mean inter-operator variability of 3 ± 5%. Average peak systolic flow velocities of 62.5 ± 4.4 cm/s were in good agreement with Doppler ultrasound measurements of 62.0 ± 9.2 cm/s (p (Lord's U test) ≫ 0.05). CONCLUSION: Fetal PC-MR velocimetry was successfully performed using the newly developed MR-compatible Doppler ultrasound trigger for intrauterine fetal cardiac triggering, demonstrating high inter-operator and inter-modality agreement. This new method has the high potential for alternative assessment of hemodynamic decompensation of the fetal circulation.