High-resolution anatomical imaging of the fetal brain with a reduced field of view using outer volume suppression.

PURPOSE: To achieve high-resolution fetal brain anatomical imaging without introducing image artifacts by reducing the FOV, and to demonstrate improved image quality compared to conventional full-FOV fetal brain imaging. METHODS: Reduced FOV was achieved by applying outer volume suppression (OVS) pulses immediately prior to standard single-shot fast spin echo (SSFSE) imaging. In the OVS preparation, a saturation RF pulse followed by a gradient spoiler was repeated three times with optimized flip-angle weightings and a variable spoiler scheme to enhance signal suppression. Simulations and phantom and in-vivo experiments were performed to evaluate OVS performance. In-vivo high-resolution SSFSE images acquired using the proposed approach were compared with conventional and high-resolution SSFSE images with a full FOV, using image quality scores assessed by neuroradiologists and calculated image metrics. RESULTS: Excellent signal suppression in the saturation bands was confirmed in phantom and in-vivo experiments. High-resolution SSFSE images with a reduced FOV acquired using OVS demonstrated the improved depiction of brain structures without significant motion and blurring artifacts. The proposed method showed the highest image quality scores in the criteria of sharpness, contrast, and artifact and was selected as the best method based on overall image quality. The calculated image sharpness and tissue contrast ratio were also the highest with the proposed method. CONCLUSION: High-resolution fetal brain anatomical images acquired using a reduced FOV with OVS demonstrated improved image quality both qualitatively and quantitatively, suggesting the potential for enhanced diagnostic accuracy in detecting fetal brain abnormalities in utero.

Update on state-of-the-art for arterial spin labeling (ASL) human perfusion imaging outside of the brain.

This review article provides an overview of developments for arterial spin labeling (ASL) perfusion imaging in the body (i.e., outside of the brain). It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. In this review, we focus on specific challenges and developments tailored for ASL in a variety of body locations. After presenting common challenges, organ-specific reviews of challenges and developments are presented, including kidneys, lungs, heart (myocardium), placenta, eye (retina), liver, pancreas, and muscle, which are regions that have seen the most developments outside of the brain. Summaries and recommendations of acquisition parameters (when appropriate) are provided for each organ. We then explore the possibilities for wider adoption of body ASL based on large standardization efforts, as well as the potential opportunities based on recent advances in high/low-field systems and machine-learning. This review seeks to provide an overview of the current state-of-the-art of ASL for applications in the body, highlighting ongoing challenges and solutions that aim to enable more widespread use of the technique in clinical practice.

QSM Throughout the Body.

Magnetic materials in tissue, such as iron, calcium, or collagen, can be studied using quantitative susceptibility mapping (QSM). To date, QSM has been overwhelmingly applied in the brain, but is increasingly utilized outside the brain. QSM relies on the effect of tissue magnetic susceptibility sources on the MR signal phase obtained with gradient echo sequence. However, in the body, the chemical shift of fat present within the region of interest contributes to the MR signal phase as well. Therefore, correcting for the chemical shift effect by means of water-fat separation is essential for body QSM. By employing techniques to compensate for cardiac and respiratory motion artifacts, body QSM has been applied to study liver iron and fibrosis, heart chamber blood and placenta oxygenation, myocardial hemorrhage, atherosclerotic plaque, cartilage, bone, prostate, breast calcification, and kidney stone.

Spatially and velocity-selective magnetization preparation for noncontrast-enhanced peripheral MR angiography.

The purpose of the current study was to develop spatially and velocity-selective (SVS) magnetization preparation pulses for noncontrast-enhanced peripheral MR angiography (MRA) to provide comparisons with velocity-selective (VS) MRA with comparison to velocity-selective (VS). VS preparation pulses were designed by concatenating multiple excitation steps, each of which was a combination of a hard RF pulse, VS unipolar gradient pulses, and refocusing RF pulses. SVS preparation pulses were designed by replacing the hard RF pulse with a sinc-shaped RF pulse combined with a symmetric tripolar gradient pulse (which does not perturb the velocity encoding by the VS unipolar gradient pulses). Numerical simulations were performed to verify the intended hybrid excitation selectivity of SVS pulses taking account of tissue relaxation, magnetic field errors, and eddy currents. In vivo experiments were performed in healthy subjects to verify the hybrid excitation selectivity, as well as to demonstrate the visualization of the entire peripheral arteries using six-station protocols. As demonstrated by numerical simulations, SVS preparation yielded a notch-shaped longitudinal magnetization (Mz )-velocity response within the spatial stopband (the same as VS preparation) and preserved the Mz of spins outside the stopband, regardless of its velocity. We confirmed these observations also through in vivo tests with good agreement in normalized arterial and muscle signal intensities. In six-station peripheral MRA experiments, the proposed SVS-MRA yielded significantly higher arterial signal-to-noise ratio (SNR) (51.6 ± 14.3 vs. 38.9 ± 10.9; p < 0.001) and contrast-to-noise ratio (CNR) (41.2 ± 13.0 vs. 31.3 ± 10.5; p < 0.001) compared with VS-MRA. The proposed SVS-MRA improves arterial SNR and CNR compared with VS-MRA by mitigating undesired presaturation of arterial blood upstream the imaging field of view.

Rapid anatomical imaging of the neonatal brain using T2 -prepared 3D balanced steady-state free precession.

PURPOSE: To develop a new approach to 3D gradient echo-based anatomical imaging of the neonatal brain with a substantially shorter scan time than standard 3D fast spin echo (FSE) methods, while maintaining a high SNR. METHODS: T2 -prepration was employed immediately prior to image acquisition of 3D balanced steady-state free precession (bSSFP) with a single trajectory of center-out k-space view ordering, which requires no magnetization recovery time between imaging segments during the scan. This approach was compared with 3D FSE, 2D single-shot FSE, and product 3D bSSFP imaging in numerical simulations, plus phantom and in vivo experiments. RESULTS: T2 -prepared 3D bSSFP generated image contrast of gray matter, white matter, and CSF very similar to that of reference T2 -weighted imaging methods, without major image artifacts. Scan time of T2 -prepared 3D bSSFP was remarkably shorter compared to 3D FSE, whereas SNR was comparable to that of 3D FSE and higher than that of 2D single-shot FSE. Specific absorption rate of T2 -prepared 3D bSSFP remained within the safety limit. Determining an optimal imaging flip angle of T2 -prepared 3D bSSFP was critical to minimizing blurring of images. CONCLUSION: T2 -prepared 3D bSSFP offers an alternative method for anatomical imaging of the neonatal brain with dramatically reduced scan time compared to standard 3D FSE and higher SNR than 2D single-shot FSE.

Velocity-selective excitation: Principles and applications.

Velocity-selective (VS) excitation is a relatively new type of excitation that can be useful for generating image contrast based on spin's motion. This review aims to explain the principles of VS excitation and their utilization for clinical applications. We first review the generalized excitation k-space formalism, which reveals a Fourier relationship between sequence parameters and excitation profiles for spins with arbitrary spatial location, off-resonance, and velocity. Based on the k-space framework, we analyze practical VS excitation pulse sequences that yield sinusoidal or sinc-shaped velocity profiles. Then we demonstrate how these two types of VS excitation can be used as magnetization preparation for clinical applications, including saturation- or inversion-based arterial spin labeling and black- or bright-blood angiography. We also discuss practical considerations and issues for each application, including the determination of design parameters and the effects of MR system errors, such as magnetic field offsets and eddy currents.

Velocity-selective arterial spin labeling perfusion MRI: A review of the state of the art and recommendations for clinical implementation.

This review article provides an overview of the current status of velocity-selective arterial spin labeling (VSASL) perfusion MRI and is part of a wider effort arising from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. Since publication of the 2015 consensus paper on arterial spin labeling (ASL) for cerebral perfusion imaging, important advancements have been made in the field. The ASL community has, therefore, decided to provide an extended perspective on various aspects of technical development and application. Because VSASL has the potential to become a principal ASL method because of its unique advantages over traditional approaches, an in-depth discussion was warranted. VSASL labels blood based on its velocity and creates a magnetic bolus immediately proximal to the microvasculature within the imaging volume. VSASL is, therefore, insensitive to transit delay effects, in contrast to spatially selective pulsed and (pseudo-) continuous ASL approaches. Recent technical developments have improved the robustness and the labeling efficiency of VSASL, making it a potentially more favorable ASL approach in a wide range of applications where transit delay effects are of concern. In this review article, we (1) describe the concepts and theoretical basis of VSASL; (2) describe different variants of VSASL and their implementation; (3) provide recommended parameters and practices for clinical adoption; (4) describe challenges in developing and implementing VSASL; and (5) describe its current applications. As VSASL continues to undergo rapid development, the focus of this review is to summarize the fundamental concepts of VSASL, describe existing VSASL techniques and applications, and provide recommendations to help the clinical community adopt VSASL.

Hyperpolarized 13C MR Spectroscopy Depicts in Vivo Effect of Exercise on Pyruvate Metabolism in Human Skeletal Muscle.

Background Pyruvate dehydrogenase (PDH) and lactate dehydrogenase are essential for adenosine triphosphate production in skeletal muscle. At the onset of exercise, oxidation of glucose and glycogen is quickly enabled by dephosphorylation of PDH. However, direct measurement of PDH flux in exercising human muscle is daunting, and the net effect of covalent modification and other control mechanisms on PDH flux has not been assessed. Purpose To demonstrate the feasibility of assessing PDH activation and changes in pyruvate metabolism in human skeletal muscle after the onset of exercise using carbon 13 (13C) MRI with hyperpolarized (HP) [1-13C]-pyruvate. Materials and Methods For this prospective study, sedentary adults in good general health (mean age, 42 years ± 18 [standard deviation]; six men) were recruited from August 2019 to September 2020. Subgroups of the participants were injected with HP [1-13C]-pyruvate at resting, during plantar flexion exercise, or 5 minutes after exercise during recovery. In parallel, hydrogen 1 arterial spin labeling MRI was performed to estimate muscle tissue perfusion. An unpaired t test was used for comparing 13C data among the states. Results At rest, HP [1-13C]-lactate and [1-13C]-alanine were detected in calf muscle, but [13C]-bicarbonate was negligible. During moderate flexion-extension exercise, total HP 13C signals (tC) increased 2.8-fold because of increased muscle perfusion (P = .005), and HP [1-13C]-lactate-to-tC ratio increased 1.7-fold (P = .04). HP [13C]-bicarbonate-to-tC ratio increased 8.4-fold (P = .002) and returned to the resting level 5 minutes after exercise, whereas the lactate-to-tC ratio continued to increase to 2.3-fold as compared with resting (P = .008). Conclusion Lactate and bicarbonate production from hyperpolarized (HP) [1-carbon 13 {13C}]-pyruvate in skeletal muscle rapidly reflected the onset and the termination of exercise. These results demonstrate the feasibility of imaging skeletal muscle metabolism using HP [1-13C]-pyruvate MRI and the sensitivity of in vivo pyruvate metabolism to exercise states. © RSNA, 2021 Online supplemental material is available for this article.

Longitudinal Trajectories of Regional Cerebral Blood Flow in Very Preterm Infants during Third Trimester Ex Utero Development Assessed with MRI.

Background The third trimester of gestation is a crucial phase of rapid brain development, but little has been reported on the trajectories of cerebral blood flow (CBF) in preterm infants in this period. Purpose To quantify regional CBF in very preterm infants longitudinally across the ex utero third trimester and to determine its relationship with clinical factors associated with brain injury and premature birth. Materials and Methods In this prospective study, very preterm infants were enrolled for three longitudinal MRI scans, and 22 healthy full-term infants were enrolled for one term MRI scan between November 2016 and February 2019. Global and regional CBF in the cortical gray matter, white matter, deep gray matter, and cerebellum were measured using arterial spin labeling with postlabeling delay of 2025 msec at 1.5 T and 3.0 T. Brain injury and clinical risk factors in preterm infants were investigated to determine associations with CBF. Generalized estimating equations were used to account for correlations between repeated measures in the same individual. Results A total of 75 preterm infants (mean postmenstrual age [PMA]: 29.5 weeks ± 2.3 [standard deviation], 34.9 weeks ± 0.8, and 39.3 weeks ± 2.0 for each scan; 43 male infants) and 22 full-term infants (mean PMA, 42.1 weeks ± 2.0; 13 male infants) were evaluated. In preterm infants, global CBF was 11.9 mL/100 g/min ± 0.2 (standard error). All regional CBF increased significantly with advancing PMA (P ≤ .02); the cerebellum demonstrated the most rapid CBF increase and the highest mean CBF. Lower CBF was associated with intraventricular hemorrhage in all regions (P ≤ .05) and with medically managed patent ductus arteriosus in the white matter and deep gray matter (P = .03). Mean CBF of preterm infants at term-equivalent age was significantly higher compared with full-term infants (P ≤ .02). Conclusion Regional cerebral blood flow increased significantly in preterm infants developing in an extrauterine environment across the third trimester and was associated with intraventricular hemorrhage and patent ductus arteriosus. © RSNA, 2021 Online supplemental material is available for this article.

Feasibility of QSM in the human placenta.

PURPOSE: Quantitative susceptibility mapping (QSM) is an emerging tool for the precise characterization of human tissue, including regional oxygenation. A critical function of the human placenta is oxygen transfer to the developing fetus, which remains difficult to study in utero. The purpose of this study is to investigate the feasibility of performing QSM in the human placenta in utero. METHODS: In healthy pregnant women, 3D gradient echo data of the placenta were acquired with prospective respiratory gating at 1.5 Tesla and 3 Tesla. A brief period (6-7 min) of maternal hyperoxia was induced to increase placental oxygenation in a subset of women scanned at 3 Tesla, and data were acquired before and during oxygen administration. Susceptibility and T2∗ / R2∗ maps were reconstructed from gradient echo data, and mean and SD of these measures within the whole placenta were calculated. RESULTS: A total of 54 women were studied at a mean gestational age of 30.7 ± 4.2 (range: 24 5/7-38 4/7) weeks. Susceptibility and T2∗ maps demonstrated lobular contrast reflecting regional oxygenation difference at both field strengths. SD of susceptibilities, mean R2∗ , and SD of R2∗ of the placenta showed a linear relationship with gestational age (P < .01 for all). These measures were also responsive to maternal hyperoxia, and there was an increasing response with advancing gestational age (P < .01 for all). CONCLUSION: This study demonstrates the feasibility of performing placental QSM in pregnant women and supports the potential for placental QSM to provide noninvasive in vivo assessment of placental oxygenation.

Comparing accuracy and reproducibility of sequential and Hadamard-encoded multidelay pseudocontinuous arterial spin labeling for measuring cerebral blood flow and arterial transit time in healthy subjects: A simulation and in vivo study.

PURPOSE: To compare performance of sequential and Hadamard-encoded pseudocontinuous arterial spin labeling (PCASL). MATERIALS AND METHODS: Monte Carlo simulations and in vivo experiments were performed in 10 healthy subjects. Field strength and sequence: 5-delay sequential (5-del. Seq.), 7-delay Hadamard-encoded (7-del. Had.), and a single-delay (1-del.) PCASL, without and with vascular crushing at 3.0T. The errors and variations of cerebral blood flow (CBF) and arterial transit time (ATT) from simulations and the CBF and ATT estimates and variations in gray matter (GM) with different ATT ranges were compared. Pairwise t-tests with Bonferroni correction were used. RESULTS: The simulations and in vivo experiments showed that 1-del. PCASL underestimated GM CBF due to insufficient postlabeling delay (PLD) (37.2 ± 8.1 vs. 47.3 ± 8.5 and 47.3 ± 9.0 ml/100g/min, P ≤ 6.5 × 10-6 ), while 5-del. Seq. and 7-del. Had. yielded comparable GM CBF (P ≥ 0.49). 5-del. Seq. was more reproducible for CBF (P = 4.7 × 10-4 ), while 7-del. Had. was more reproducible for ATT (P = 0.033). 5-del. Seq. was more prone to intravascular artifacts and yielded lower GM ATTs compared to 7-del. Had. without crushing (1.13 ± 0.18 vs. 1.23 ± 0.13 seconds, P = 2.3 × 10-3 ), but they gave comparable ATTs with crushing (P = 0.12). ATTs measured with crushing were longer than those without crushing (P ≤ 6.7 × 10-4 ), but CBF was not affected (P ≥ 0.16). CONCLUSION: The theoretical signal-to-noise ratio (SNR) gain through Hadamard encoding was confirmed experimentally. For 1-del., a PLD of 1.8 seconds is recommended for healthy subjects. With current parameters, 5-del. Seq. was more reproducible for CBF, and 7-del. Had. for ATT. Vascular crushing may help reduce variations in multidelay experiments without compromising tissue CBF or ATT measurements. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1119-1132.

Non-Invasive Placental Perfusion Imaging in Pregnancies Complicated by Fetal Heart Disease Using Velocity-Selective Arterial Spin Labeled MRI.

The placenta is a vital organ for fetal growth and development during pregnancy. Congenital heart disease (CHD) is a leading cause of morbidity and mortality in newborns. Despite the parallel development of the placenta and fetal heart early in pregnancy, very few studies suggested an association between placental dysfunction and fetal CHD. In this study, we report placental perfusion of healthy pregnancies and pregnancies complicated by fetal CHD measured using advanced fetal MRI techniques. We studied forty-eight pregnant women (31 healthy volunteers and 17 with fetal CHD) that underwent fetal MRI during their second or third trimester of pregnancy. Placental perfusion imaging was performed using velocity-selective arterial spin labeling (VSASL) and 3D image acquisition with whole-placenta coverage. In pregnancies with fetal CHD, global placental perfusion significantly decreased and regional variation of placental perfusion significantly increased with advancing gestational age; however, no such correlation was found in healthy pregnancies. Also, global placental perfusion was significantly higher in fetal CHD versus controls, in the lateral side-lying patient position versus supine, and in the posterior placental position versus anterior placental position. This study reports for the first time non-invasive whole-placenta perfusion imaging in utero. These data suggest that placental VSASL may serve as a potential biomarker of placental dysfunction in fetuses diagnosed with CHD.

Composite iron oxide-Prussian blue nanoparticles for magnetically guided T1-weighted magnetic resonance imaging and photothermal therapy of tumors.

Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe3O4@GdPB) as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe3O4 nanoparticles and gadolinium-containing Prussian blue nanoparticles. The Fe3O4@GdPB nanoparticles function both as effective MRI contrast agents and PTT agents as determined by characterizing studies performed in vitro and retain their properties in the presence of cells. Importantly, the Fe3O4@GdPB nanoparticles function as effective MRI contrast agents in vivo by increasing signal:noise ratios in T1-weighted scans of tumors and as effective PTT agents in vivo by decreasing tumor growth rates and increasing survival in an animal model of neuroblastoma. These findings demonstrate the potential of the Fe3O4@GdPB nanoparticles to function as effective theranostic agents.

Semi-automatic segmentation of the placenta into fetal and maternal compartments using intravoxel incoherent motion MRI.

Intravoxel incoherent motion (IVIM) magnetic resonance imaging is an emerging non-invasive technique that has been recently applied to quantify in vivo global placental perfusion. We propose a robust semi-automated method for segmenting the placenta into fetal and maternal compartments from IVIM data, using a multi-label image segmentation algorithm called 'GrowCut'. Placental IVIM data were acquired on a 1.5T scanner from 16 healthy pregnant women between 21-37 gestational weeks. The voxel-wise perfusion fraction was then estimated after non-rigid image registration. The seed regions of the fetal and maternal compartments were determined using structural T2-weighted reference images, and improved progressively through an iterative process of the GrowCut algorithm to accurately encompass fetal and maternal compartments. We demonstrated that the placental perfusion fraction decreased in both fetal (-0.010/week) and maternal compartments (-0.013/week) while their relative difference (ffetal-fmaternal) gradually increased with advancing gestational age (+0.003/week, p=0.065). Our preliminary results show that the proposed method was effective in distinguishing placental compartments using IVIM.

Imaging of cerebrovascular reserve and oxygenation in Moyamoya disease.

This study aimed to determine whether measurements of cerebrovascular reserve and oxygenation, assessed with spin relaxation rate R2', yield similar information about pathology in pre-operative Moyamoya disease patients, and to assess whether R2' is a better measure of oxygenation than other proposed markers, such as R2* and R2. Twenty-five pre-operative Moyamoya disease patients were scanned at 3.0T with acetazolamide challenge. Cerebral blood flow mapping with multi-delay arterial spin labeling, and R2*, R2, and R2' mapping with Gradient-Echo Sampling of Free Induction Decay and Echo were performed. No baseline cerebral blood flow difference was found between angiographically abnormal and normal regions (49 ± 12 vs. 48 ± 11 mL/100 g/min, p = 0.44). However, baseline R2' differed between these regions (3.2 ± 0.7 vs. 2.9 ± 0.6 s-1, p < 0.001), indicating reduced oxygenation in abnormal regions. Cerebrovascular reserve was lower in angiographically abnormal regions (21 ± 38 vs. 41 ± 26%, p = 0.001). All regions showed trend toward significantly improved oxygenation post-acetazolamide. Regions with poorer cerebrovascular reserve had lower baseline oxygenation (Kendall's τ = -0.24, p = 0.003). A number of angiographically abnormal regions demonstrated preserved cerebrovascular reserve, likely due to the presence of collaterals. Finally, of the concurrently measured relaxation rates, R2' was superior for oxygenation assessment.

Cerebral blood flow, transit time, and apparent diffusion coefficient in moyamoya disease before and after acetazolamide.

INTRODUCTION: The goal of this study was to assess the changes in arterial spin labeling (ASL) cerebral blood flow (CBF) and arterial transit time (ATT), and in apparent diffusion coefficient (ADC), before and after an acetazolamide challenge in moyamoya patients, as function of arterial stenosis severity. METHODS: Pre-operative patients diagnosed with moyamoya disease who could undergo MRI at 3.0T were recruited for this study. A multi-delay pseudo-continuous ASL and a diffusion-weighted sequence were acquired before and 15 min after acetazolamide injection. The severity of anterior, middle, and posterior cerebral artery pathology was graded on time-of-flight MR angiographic images. CBF, ATT, and ADC were measured on standardized regions of interest as function of the vessel stenosis severity. RESULTS: Thirty patients were included. Fifty-four percent of all vessels were normal, 28% mildly/moderately stenosed, and 18% severely stenosed/occluded. Post-acetazolamide, a significantly larger CBF (ml/100 g/min) increase was observed in territories of normal (+19.6 ± 14.9) compared to mildly/moderately stenosed (+14.2 ± 27.2, p = 0.007), and severely stenosed/occluded arteries (+9.9 ± 24.2, p < 0.0001). ATT was longer in territories of vessel anomalies compared with normal regions at baseline. ATT decreases were observed in all territories post-acetazolamide. ADC did not decrease after acetazolamide in any regions, and no correlation was found between ADC changes and baseline ATT, change in ATT, or CVR. CONCLUSION: The hemodynamic response in moyamoya disease, as measured with ASL CBF, is impaired mostly in territories with severe arterial stenosis/occlusion, while ATT was prolonged in all non-normal regions. No significant changes in ADC were observed after acetazolamide.

Robust preprocessing for stimulus-based functional MRI of the moving fetus.

Fetal motion manifests as signal degradation and image artifact in the acquired time series of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We present a robust preprocessing pipeline to specifically address fetal and placental motion-induced artifacts in stimulus-based fMRI with slowly cycled block design in the living fetus. In the proposed pipeline, motion correction is optimized to the experimental paradigm, and it is performed separately in each phase as well as in each region of interest (ROI), recognizing that each phase and organ experiences different types of motion. To obtain the averaged BOLD signals for each ROI, both misaligned volumes and noisy voxels are automatically detected and excluded, and the missing data are then imputed by statistical estimation based on local polynomial smoothing. Our experimental results demonstrate that the proposed pipeline was effective in mitigating the motion-induced artifacts in stimulus-based fMRI data of the fetal brain and placenta.