Computed tomographic findings in TBX4 mutation: a common cause of severe pulmonary artery hypertension in children.

BACKGROUND: Mutations in the T-Box 4 (TBX4) gene are a lesser-known cause of heritable pulmonary arterial hypertension (PAH). Patients with heritable PAH typically have worse outcomes when compared with patients with idiopathic PAH, yet little is known about the phenotypical presentation of this mutation. OBJECTIVE: This article reviews the pattern of chest CT findings in pediatric patients with PAH and TBX4 mutations and compares their radiographic presentation with those of age-matched patients with PAH but without TBX4 mutations. MATERIALS AND METHODS: A retrospective chart review of the pulmonary arterial hypertension database was performed. Pediatric patients with PAH-confirmed TBX4 mutations and an available high CT were included. Fifteen (9 females) patients met the inclusion criteria. Fourteen (8 females) age-matched controls with diagnosed PAH but without TBX4 mutations were also evaluated. The median age at diagnosis was 7.4 years (range: 0.1-16.4 years). Demographic information and clinical outcomes were collected. CTs of the chest were reviewed for multiple airway, parenchymal, and structural abnormalities (16 imaging findings in total). Chi-square tests were used to compare the prevalence of each imaging finding in the TBX4 cohort compared to the control group. RESULTS: Patients with TBX-4 mutations had increased presence of peripheral or subpleural irregularity (73% vs 0%, P < 0.01), cystic lucencies (67% vs 7%, P < 0.01), and linear or reticular opacity (53% vs 0%, P < 0.01) compared to the control group. Ground glass opacities, bronchiectasis, and centrilobular nodules were not significantly different between the two patient groups (P > 0.05). CONCLUSION: TBX4 mutations have distinct imaging phenotypes in pediatric patients with PAH. Compared to patients without this mutation, patients with TBX-4 genes typically present with peripheral or subpleural irregularity, cystic lucencies, and linear or reticular opacity.

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.

Reference Values for Fetal Cardiac Dimensions, Volumes, Ventricular Function and Left Ventricular Longitudinal Strain Using Doppler Ultrasound Gated Cardiac Magnetic Resonance Imaging in Healthy Third Trimester Fetuses.

BACKGROUND: Recent advances in hardware and software permit the use of cardiac MRI of late gestation fetuses, however there is a paucity of MRI-based reference values. PURPOSE: To provide initial data on fetal cardiac MRI-derived cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain in healthy developing fetuses >30 weeks gestational age. STUDY TYPE: Prospective. POPULATION: Twenty-five third trimester (34 ± 1 weeks, range of 32-37 weeks gestation) women with healthy developing fetuses. FIELD STRENGTH/SEQUENCE: Studies were performed at 1.5 T and 3 T. Cardiac synchronization was achieved with a Doppler ultrasound device. The protocol included T2 single shot turbo spin echo stacks for fetal weight and ultrasound probe positioning, and multiplanar multi-slice cine balanced steady state free precession gradient echo sequences. ASSESSMENT: Primary analyses were performed by a single observer. Weight indexed right ventricular (RV) and left ventricular (LV) volumes and function were calculated from short axis (SAX) stacks. Cardiac dimensions were calculated from the four-chamber and SAX stacks. Single plane LV longitudinal strain was calculated from the four-chamber stack. Interobserver variability was assessed in 10 participants. Cardiac MRI values were compared against available published normative fetal echocardiogram data using z-scores. STATISTICAL TESTS: Mean and SDs were calculated for baseline maternal/fetal demographics, cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain. Bland-Altman and intraclass correlation coefficient analysis was performed to test interobserver variability. RESULTS: The mean gestational age was 34 ± 1.4 weeks. The mean RV and LV end diastolic volumes were 3.1 ± 0.6 mL/kg and 2.4 ± 0.5 mL/kg respectively. The mean RV cardiac output was 198 ± 49 mL/min/kg while the mean LV cardiac output was 173 ± 43 mL/min/kg. DATA CONCLUSION: This paper reports initial reference values obtained by cardiac MRI in healthy developing third trimester fetuses. MRI generally resulted in slightly larger indexed values (by z-score) compared to reports in literature using fetal echocardiography. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Computed tomographic parenchymal lung findings in premature infants with pulmonary vein stenosis.

BACKGROUND: Developmental pulmonary vein pulmonary vein stenosis in the setting of prematurity is a rare and poorly understood condition. Diagnosis can be challenging in the setting of chronic lung disease of prematurity. High-resolution non-contrast chest computed tomography (CT) is the conventional method of evaluating neonates for potential structural changes contributing to severe lung dysfunction and pulmonary hypertension but may miss pulmonary venous stenosis due to the absence of contrast and potential overlap in findings between developmental pulmonary vein pulmonary vein stenosis and lung disease of prematurity. OBJECTIVE: To describe the parenchymal changes of pediatric patients with both prematurity and pulmonary vein stenosis, correlate them with venous disease and to describe the phenotypes associated with this disease. MATERIALS AND METHODS: A 5-year retrospective review of chest CT angiography (CTA) imaging in patients with catheterization-confirmed pulmonary vein stenosis was performed to identify pediatric patients (< 18 years) who had a history of prematurity (< 35 weeks gestation). Demographic and clinical data associated with each patient were collected, and the patients' CTAs were re-reviewed to evaluate pulmonary veins and parenchyma. Patients with post-operative pulmonary vein stenosis and those with congenital heart disease were excluded. Data was analyzed and correlated for descriptive purposes. RESULTS: A total of 17 patients met the inclusion criteria (12 female, 5 male). All had pulmonary hypertension. There was no correlation between mild, moderate, and severe grades of bronchopulmonary dysplasia and the degree of pulmonary vein stenosis. There was a median of 2 (range 1-4) diseased pulmonary veins per patient. In total, 41% of the diseased pulmonary veins were atretic. The right upper and left upper lobe pulmonary veins were the most frequently diseased (n = 13/17, 35%, n = 10/17, 27%, respectively). Focal ground glass opacification, interlobular septal thickening, and hilar soft tissue enlargement were always associated with the atresia of an ipsilateral vein. CONCLUSION: Recognition of the focal parenchymal changes that imply pulmonary vein stenosis, rather than chronic lung disease of prematurity changes, may improve the detection of a potentially treatable source of pulmonary hypertension, particularly where nonangiographic studies result in a limited direct venous assessment.

Impact of supervised exercise on skeletal muscle blood flow and vascular function measured with MRI in patients with peripheral artery disease.

Supervised exercise is a common therapeutic intervention for patients with peripheral artery disease (PAD), however, the mechanism underlying the improvement in claudication symptomatology is not completely understood. The hypothesis that exercise improves microvascular blood flow is herein tested via temporally resolved magnetic resonance imaging (MRI) measurement of blood flow and oxygenation dynamics during reactive hyperemia in the leg with the lower ankle-brachial index. One hundred and forty-eight subjects with PAD were prospectively assigned to standard medical care or 3 mo of supervised exercise therapy. Before and after the intervention period, subjects performed a graded treadmill walking test, and MRI data were collected with Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT), a method that simultaneously quantifies microvascular perfusion, as well as relative oxygenation changes in skeletal muscle and venous oxygen saturation in a large draining vein. The 3-mo exercise intervention was associated with an improvement in peak walking time (64% greater in those randomized to the exercise group at follow-up, P < 0.001). Significant differences were not observed in the MRI measures between the subjects randomized to exercise therapy versus standard medical care based on an intention-to-treat analysis. However, the peak postischemia perfusion averaged across the leg between baseline and follow-up visits increased by 10% (P = 0.021) in participants that were adherent to the exercise protocol (completed >80% of prescribed exercise visits). In this cohort of adherent exercisers, there was no difference in the time to peak perfusion or oxygenation metrics, suggesting that there was no improvement in microvascular function nor changes in tissue metabolism in response to the 3-mo exercise intervention.NEW & NOTEWORTHY Supervised exercise interventions can improve symptomatology in patients with peripheral artery disease, but the underlying mechanism remains unclear. Here, MRI was used to evaluate perfusion, relative tissue oxygenation, and venous oxygen saturation in response to cuff-induced ischemia. Reactive hyperemia responses were measured before and after 3 mo of randomized supervised exercise therapy or standard medical care. Those participants who were adherent to the exercise regimen had a significant improvement in peak perfusion.

Intravoxel Incoherent Motion Magnetic Resonance Imaging in Skeletal Muscle: Review and Future Directions.

Throughout the body, muscle structure and function can be interrogated using a variety of noninvasive magnetic resonance imaging (MRI) methods. Recently, intravoxel incoherent motion (IVIM) MRI has gained momentum as a method to evaluate components of blood flow and tissue diffusion simultaneously. Much of the prior research has focused on highly vascularized organs, including the brain, kidney, and liver. Unique aspects of skeletal muscle, including the relatively low perfusion at rest and large dynamic range of perfusion between resting and maximal hyperemic states, may influence the acquisition, postprocessing, and interpretation of IVIM data. Here, we introduce several of those unique features of skeletal muscle; review existing studies of IVIM in skeletal muscle at rest, in response to exercise, and in disease states; and consider possible confounds that should be addressed for muscle-specific evaluations. Most studies used segmented nonlinear least squares fitting with a b-value threshold of 200 sec/mm2 to obtain IVIM parameters of perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D). In healthy individuals, across all muscles, the average ± standard deviation of D was 1.46 ± 0.30 × 10-3  mm2 /sec, D* was 29.7 ± 38.1 × 10-3  mm2 /sec, and f was 11.1 ± 6.7%. Comparisons of reported IVIM parameters in muscles of the back, thigh, and leg of healthy individuals showed no significant difference between anatomic locations. Throughout the body, exercise elicited a positive change of all IVIM parameters. Future directions including advanced postprocessing models and potential sequence modifications are discussed. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Segmentation of the Aorta and Pulmonary Arteries Based on 4D Flow MRI in the Pediatric Setting Using Fully Automated Multi-Site, Multi-Vendor, and Multi-Label Dense U-Net.

BACKGROUND: Automated segmentation using convolutional neural networks (CNNs) have been developed using four-dimensional (4D) flow magnetic resonance imaging (MRI). To broaden usability for congenital heart disease (CHD), training with multi-institution data is necessary. However, the performance impact of heterogeneous multi-site and multi-vendor data on CNNs is unclear. PURPOSE: To investigate multi-site CNN segmentation of 4D flow MRI for pediatric blood flow measurement. STUDY TYPE: Retrospective. POPULATION: A total of 174 subjects across two sites (female: 46%; N = 38 healthy controls, N = 136 CHD patients). Participants from site 1 (N = 100), site 2 (N = 74), and both sites (N = 174) were divided into subgroups to conduct 10-fold cross validation (10% for testing, 90% for training). FIELD STRENGTH/SEQUENCE: 3 T/1.5 T; retrospectively gated gradient recalled echo-based 4D flow MRI. ASSESSMENT: Accuracy of the 3D CNN segmentations trained on data from single site (single-site CNNs) and data across both sites (multi-site CNN) were evaluated by geometrical similarity (Dice score, human segmentation as ground truth) and net flow quantification at the ascending aorta (Qs), main pulmonary artery (Qp), and their balance (Qp/Qs), between human observers, single-site and multi-site CNNs. STATISTICAL TESTS: Kruskal-Wallis test, Wilcoxon rank-sum test, and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: No difference existed between single-site and multi-site CNNs for geometrical similarity in the aorta by Dice score (site 1: 0.916 vs. 0.915, P = 0.55; site 2: 0.906 vs. 0.904, P = 0.69) and for the pulmonary arteries (site 1: 0.894 vs. 0.895, P = 0.64; site 2: 0.870 vs. 0.869, P = 0.96). Qs site-1 medians were 51.0-51.3 mL/cycle (P = 0.81) and site-2 medians were 66.7-69.4 mL/cycle (P = 0.84). Qp site-1 medians were 46.8-48.0 mL/cycle (P = 0.97) and site-2 medians were 76.0-77.4 mL/cycle (P = 0.98). Qp/Qs site-1 medians were 0.87-0.88 (P = 0.97) and site-2 medians were 1.01-1.03 (P = 0.43). Bland-Altman analysis for flow quantification found equivalent performance. DATA CONCLUSION: Multi-site CNN-based segmentation and blood flow measurement are feasible for pediatric 4D flow MRI and maintain performance of single-site CNNs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Free-breathing magnetic resonance imaging with radial k-space sampling for neonates and infants to reduce anesthesia.

BACKGROUND: Conventional chest and abdominal MRI require breath-holds to reduce motion artifacts. Neonates and infants require general anesthesia with intubation to enable breath-held acquisitions. OBJECTIVE: We aimed to validate a free-breathing approach to reduce general anesthesia using a motion-insensitive radial acquisition with respiratory gating. MATERIALS AND METHODS: We retrospectively enrolled children <3 years old who were referred for MRI of the chest or abdomen. They were divided into two groups according to MRI protocol: (1) breath-held scans under general anesthesia with T2-weighted single-shot fast spin-echo (SSFSE) and contrast-enhanced T1-weighted modified Dixon, and (2) free-breathing scans using radial sequences (T2-W MultiVane XD and contrast-enhanced T1-W three-dimensional [3-D] Vane XD). Two readers graded image quality and motion artifacts. RESULTS: We included 23 studies in the free-breathing cohort and 22 in the breath-hold cohort. The overall imaging scores for the free-breathing radial T2-W sequence were similar to the scores for the breath-held T2-W SSFSE sequence (chest, 3.6 vs. 3.2, P=0.07; abdomen, 3.9 vs. 3.7, P=0.66). The free-breathing 3-D radial T1-W sequence also had image quality scores that were similar to the breath-held T1-W sequence (chest, 4.0 vs. 3.0, P=0.06; abdomen, 3.7 vs. 3.9, P=0.15). Increased motion was seen in the abdomen on the radial T2-W sequence (P<0.001), but increased motion was not different in the chest (P=0.73) or in contrast-enhanced T1-W sequences (chest, P=0.39; abdomen, P=0.15). The mean total sequence time was longer in free-breathing compared to breath-held exams (P<0.01); however, this did not translate to longer overall exam times (P=0.94). CONCLUSION: Motion-insensitive radial sequences used for infants and neonates were of similar image quality to breath-held sequences and had decreased sedation and intubation.

Varying diffusion time to discriminate between simulated skeletal muscle injury models using stimulated echo diffusion tensor imaging.

PURPOSE: Evaluate the relationship between muscle microstructure, diffusion time (Δ), and the diffusion tensor (DT) to identify the optimal Δ where changes in muscle fiber size may be detected. METHODS: The DT was simulated in models with histology informed geometry over a range of Δ with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Δ between healthy and injured skeletal muscle models was calculated, to identify the optimal Δ at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth. RESULTS: Across all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models. CONCLUSION: These findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Δ should be ~170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should be sampled in order to maximize diffusion contrast, particularly when the disease process is unknown.

Intravoxel incoherent motion imaging predicts exercise-based rehabilitation response in individuals with low back pain.

Exercises to strengthen and stabilize the trunk musculature are a common conservative treatment strategy for low back pain (LBP), despite the possible presence of impairments in muscle activation in this population. Intravoxel incoherent motion (IVIM) MRI permits evaluation of activation-induced blood flow through diffusion-weighted images that are sensitized to microvascular blood flow. In the current study we aimed to evaluate IVIM signal changes after exercise in patients with LBP compared with pain-free healthy controls and determine if these changes were related to reductions in disability with a 12-week rehabilitation program. We hypothesize that the magnitude of changes in IVIM parameters in the lumbar extensor muscles will be smaller in patients with LBP compared with those without LBP, and that these magnitudes will be correlated with responsiveness to a 12-week, resistance-based exercise program. IVIM MR data for molecular diffusion (D), blood flow pseudodiffusion (D*) and perfusion fraction (f) were collected before and immediately after an ~ 3-min session of high-intensity lumbar extension resistance exercise in 16 healthy participants and 17 participants with LBP. Improvements in LBP-related disability after the 12-week, machine-based, high-intensity exercise rehabilitation program were measured in the LBP group. We observed a significant increase in all IVIM parameters (f, D*, D) in response to exercise (p < 0.0001) and an interaction of group-by-time for D (p = 0.016). Thresholds were identified using receiver operating characteristic (ROC) curves for diffusion and pseudodiffusion coefficients, which predicted a reduction in LBP-related disability in response to the 12-week, exercise-based rehabilitation program. Exercise was associated with an increase in (f), capillary blood flow-based pseudodiffusion (D*) and diffusion coefficient (D), regardless of the presence of LBP. Additionally, subgroup analysis identified patients who were not responsive to the acute exercise session, for whom, based on ROC analysis, there was no clinically significant change in disability following the 12-week program.

The effect of high-intensity resistance exercise on lumbar musculature in patients with low back pain: a preliminary study.

BACKGROUND: Muscle atrophy and fatty infiltration of the lumbar extensors is associated with LBP. Exercise-based rehabilitation targets strengthening these muscles, but few studies show consistent changes in muscle quality with standard-of-care rehabilitation. The goal of this study was to assess the effect of high-intensity resistance exercise on lumbar extensor muscle size (cross sectional area) and quality (fat fraction) in individuals with low back pain (LBP). METHODS: Fourteen patients with LBP were recruited from a local rehabilitation clinic. Patients underwent MRI scanning before and after a standardized 10-week high-intensity machine-based, resistance exercise program. Patient pain, disability, anxiety/depression, satisfaction, strength, and range of motion was compared pre- and post-rehabilitation using analysis of covariance (covariates: age, gender). Exercise-induced changes in MRI, and patient functional outcome measures were correlated using Pearson's correlation test. RESULTS: No significant differences were found in muscle size or fatty infiltration of the lumbar extensors over the course of rehabilitation (p > 0.31). However, patients reported reduced pain (p = 0.002) and were stronger (p = 0.03) at the conclusion of the program. Improvements in muscle size and quality for both multifidus and erector spinae correlated with improvements in disability, anxiety/depression, and strength. CONCLUSION: While average muscle size and fatty infiltration levels did not change with high-intensity exercise, the results suggest that a subgroup of patients who demonstrate improvements in muscle health demonstrate the largest functional improvements. Future research is needed to identify which patients are most likely to respond to this type of treatment.

Interleaved quantitative BOLD: Combining extravascular R2' - and intravascular R2-measurements for estimation of deoxygenated blood volume and hemoglobin oxygen saturation.

Quantitative BOLD (qBOLD), a non-invasive MRI method for assessment of hemodynamic and metabolic properties of the brain in the baseline state, provides spatial maps of deoxygenated blood volume fraction (DBV) and hemoglobin oxygen saturation (HbO2) by means of an analytical model for the temporal evolution of free-induction-decay signals in the extravascular compartment. However, mutual coupling between DBV and HbO2 in the signal model results in considerable estimation uncertainty precluding achievement of a unique set of solutions. To address this problem, we developed an interleaved qBOLD method (iqBOLD) that combines extravascular R2' and intravascular R2 mapping techniques so as to obtain prior knowledge for the two unknown parameters. To achieve these goals, asymmetric spin echo and velocity-selective spin-labeling (VSSL) modules were interleaved in a single pulse sequence. Prior to VSSL, arterial blood and CSF signals were suppressed to produce reliable estimates for cerebral venous blood volume fraction (CBVv) as well as venous blood R2 (to yield HbO2). Parameter maps derived from the VSSL module were employed to initialize DBV and HbO2 in the qBOLD processing. Numerical simulations and in vivo experiments at 3 T were performed to evaluate the performance of iqBOLD in comparison to the parent qBOLD method. Data obtained in eight healthy subjects yielded plausible values averaging 60.1 ±â€¯3.3% for HbO2 and 3.1 ±â€¯0.5 and 2.0 ±â€¯0.4% for DBV in gray and white matter, respectively. Furthermore, the results show that prior estimates of CBVv and HbO2 from the VSSL component enhance the solution stability in the qBOLD processing, and thus suggest the feasibility of iqBOLD as a promising alternative to the conventional technique for quantifying neurometabolic parameters.

Simultaneous measurement of macro- and microvascular blood flow and oxygen saturation for quantification of muscle oxygen consumption.

PURPOSE: To investigate the relationship between blood flow and oxygen consumption in skeletal muscle, a technique called "Velocity and Perfusion, Intravascular Venous Oxygen saturation and T2*" (vPIVOT) is presented. vPIVOT allows the quantification of feeding artery blood flow velocity, perfusion, draining vein oxygen saturation, and muscle T2*, all at 4-s temporal resolution. Together, the measurement of blood flow and oxygen extraction can yield muscle oxygen consumption ( V˙O2) via the Fick principle. METHODS: In five subjects, vPIVOT-derived results were compared with those obtained from stand-alone sequences during separate ischemia-reperfusion paradigms to investigate the presence of measurement bias. Subsequently, in 10 subjects, vPIVOT was applied to assess muscle hemodynamics and V˙O2 following a bout of dynamic plantar flexion contractions. RESULTS: From the ischemia-reperfusion paradigm, no significant differences were observed between data from vPIVOT and comparison sequences. After exercise, the macrovascular flow response reached a maximum 8 ± 3 s after relaxation; however, perfusion in the gastrocnemius muscle continued to rise for 101 ± 53 s. Peak V˙O2 calculated based on mass-normalized arterial blood flow or perfusion was 15.2 ± 6.7 mL O2 /min/100 g or 6.0 ± 1.9 mL O2 /min/100 g, respectively. CONCLUSIONS: vPIVOT is a new method to measure blood flow and oxygen saturation, and therefore to quantify muscle oxygen consumption. Magn Reson Med 79:846-855, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

High-speed whole-brain oximetry by golden-angle radial MRI.

PURPOSE: To determine whole-brain cerebral metabolic rate of oxygen (CMRO2 ), an improved imaging approach, based on radial encoding, termed radial OxFlow (rOxFlow), was developed to simultaneously quantify draining vein venous oxygen saturation (SvO2 ) and total cerebral blood flow (tCBF). METHODS: To evaluate the efficiency and precision of the rOxFlow sequence, 10 subjects were studied during a paradigm of repeated breath-holds with both rOxFlow and Cartesian OxFlow (cOxFlow) sequences. CMRO2 was calculated at baseline from OxFlow-measured data assuming an arterial O2 saturation of 97%, and the SvO2 and tCBF breath-hold responses were quantified. RESULTS: Average neurometabolic-vascular parameters across the 10 subjects for cOxFlow and rOxFlow were, respectively: SvO2 (%) baseline: 64.6 ± 8.0 versus 64.2 ± 6.6; SvO2 peak: 70.5 ± 8.5 versus 72.6 ± 5.4; tCBF (mL/min/100 g) baseline: 39.2 ± 3.8 versus 40.6 ± 8.0; tCBF peak: 53.2 ± 5.1 versus 56.1 ± 11.7; CMRO2 (µmol O2 /min/100 g) baseline: 111.5 ± 26.8 versus 120.1 ± 19.6. The above measures were not significantly different between sequences (P > 0.05). CONCLUSION: There was good agreement between the two methods in terms of the physiological responses measured. Comparing the two, rOxFlow provided higher temporal resolution and greater flexibility for reconstruction while maintaining high SNR. Magn Reson Med 79:217-223, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Susceptibility-based time-resolved whole-organ and regional tissue oximetry.

The magnetism of hemoglobin - being paramagnetic in its deoxy and diamagnetic in its oxy state - offers unique opportunities to probe oxygen metabolism in blood and tissues. The magnetic susceptibility χ of blood scales linearly with blood oxygen saturation, which can be obtained by measuring the magnetic field ΔB of the intravascular MR signal relative to tissue. In contrast to χ, the induced field ΔB is non-local. Therefore, to obtain the intravascular susceptibility Δχ relative to adjoining tissue from the measured ΔB demands solution of an inverse problem. Fortunately, for ellipsoidal structures, to which a straight, cylindrically shaped blood vessel segment conforms, the solution is trivial. The article reviews the principle of MR susceptometry-based blood oximetry. It then discusses applications for quantification of whole-brain oxygen extraction - typically on the basis of a measurement in the superior sagittal sinus - and, in conjunction with total cerebral blood flow, the cerebral metabolic rate of oxygen (CMRO2 ). By simultaneously measuring flow and venous oxygen saturation (SvO2 ) a temporal resolution of a few seconds can be achieved, allowing the study of the response to non-steady-state challenges such as volitional apnea. Extensions to regional measurements in smaller cerebral veins are also possible, as well as voxelwise quantification of venous blood saturation in cerebral veins accomplished by quantitative susceptibility mapping (QSM) techniques. Applications of susceptometry-based oximetry to studies of metabolic and degenerative disorders of the brain are reviewed. Lastly, the technique is shown to be applicable to other organ systems such as the extremities using SvO2 as a dynamic tracer to monitor the kinetics of the microvascular response to induced ischemia. Copyright © 2016 John Wiley & Sons, Ltd.

Perfusion has no effect on the in vivo CEST effect from Cr (CrCEST) in skeletal muscle.

Creatine, a key component of muscle energy metabolism, exhibits a chemical exchange saturation transfer (CEST) effect between its amine group and bulk water, which has been exploited to spatially and temporally map creatine changes in skeletal muscle before and after exercise. In addition, exercise leads to an increase in muscle perfusion. In this work, we determined the effects of perfused blood on the CEST effects from creatine in skeletal muscle. Experiments were performed on healthy human subjects (n = 5) on a whole-body Siemens 7T magnetic resonance imaging (MRI) scanner with a 28-channel radiofrequency (RF) coil. Reactive hyperemia, induced by inflation and subsequent deflation of a pressure cuff secured around the thigh, was used to increase tissue perfusion whilst maintaining the levels of creatine kinase metabolites. CEST, arterial spin labeling (ASL) and 31 P MRS data were acquired at baseline and for 6 min after cuff deflation. Reactive hyperemia resulted in substantial increases in perfusion in human skeletal muscle of the lower leg as measured by the ASL mean percentage difference. However, no significant changes in CrCEST asymmetry (CrCESTasym ) or 31 P MRS-derived PCr levels of skeletal muscle were observed following cuff deflation. This work demonstrates that perfusion changes do not have a major confounding effect on CrCEST measurements.

Calibrated bold fMRI with an optimized ASL-BOLD dual-acquisition sequence.

Calibrated fMRI techniques estimate task-induced changes in the cerebral metabolic rate of oxygen (CMRO2) based on simultaneous measurements of cerebral blood flow (CBF) and blood-oxygen-level-dependent (BOLD) signal changes evoked by stimulation. To determine the calibration factor M (corresponding to the maximum possible BOLD signal increase), BOLD signal and CBF are measured in response to a gas breathing challenge (usually CO2 or O2). Here we describe an ASL dual-acquisition sequence that combines a background-suppressed 3D-GRASE readout with 2D multi-slice EPI. The concatenation of these two imaging sequences allowed separate optimization of the acquisition for CBF and BOLD data. The dual-acquisition sequence was validated by comparison to an ASL sequence with a dual-echo EPI readout, using a visual fMRI paradigm. Results showed a 3-fold increase in temporal signal-to-noise ratio (tSNR) of the ASL time-series data while BOLD tSNR was similar to that obtained with the dual-echo sequence. The longer TR of the proposed dual-acquisition sequence, however, resulted in slightly lower T-scores (by 30%) in the BOLD activation maps. Further, the potential of the dual-acquisition sequence for M-mapping on the basis of a hypercapnia gas breathing challenge and for quantification of CMRO2 changes in response to a motor activation task was assessed. In five subjects, an average gray matter M-value of 8.71±1.03 and fractional changes of CMRO2 of 12.5±5% were found. The new sequence remedies the deficiencies of prior combined BOLD-ASL acquisition strategies by substantially enhancing perfusion tSNR, which is essential for accurate BOLD calibration.

Measurement of skeletal muscle perfusion dynamics with pseudo-continuous arterial spin labeling (pCASL): Assessment of relative labeling efficiency at rest and during hyperemia, and comparison to pulsed arterial spin labeling (PASL).

PURPOSE: To compare calf skeletal muscle perfusion measured with pulsed arterial spin labeling (PASL) and pseudo-continuous arterial spin labeling (pCASL) methods, and to assess the variability of pCASL labeling efficiency in the popliteal artery throughout an ischemia-reperfusion paradigm. MATERIALS AND METHODS: At 3T, relative pCASL labeling efficiency was experimentally assessed in five subjects by measuring the signal intensity of blood in the popliteal artery just distal to the labeling plane immediately following pCASL labeling or control preparation pulses, or without any preparation pulses throughout separate ischemia-reperfusion paradigms. The relative label and control efficiencies were determined during baseline, hyperemia, and recovery. In a separate cohort of 10 subjects, pCASL and PASL sequences were used to measure reactive hyperemia perfusion dynamics. RESULTS: Calculated pCASL labeling and control efficiencies did not differ significantly between baseline and hyperemia or between hyperemia and recovery periods. Relative to the average baseline, pCASL label efficiency was 2 ± 9% lower during hyperemia. Perfusion dynamics measured with pCASL and PASL did not differ significantly (P > 0.05). Average leg muscle peak perfusion was 47 ± 20 mL/min/100g or 50 ± 12 mL/min/100g, and time to peak perfusion was 25 ± 3 seconds and 25 ± 7 seconds from pCASL and PASL data, respectively. Differences of further metrics parameterizing the perfusion time course were not significant between pCASL and PASL measurements (P > 0.05). CONCLUSION: No change in pCASL labeling efficiency was detected despite the almost 10-fold increase in average blood flow velocity in the popliteal artery. pCASL and PASL provide precise and consistent measurement of skeletal muscle reactive hyperemia perfusion dynamics. J. MAGN. RESON. IMAGING 2016;44:929-939.

Rapid T2- and susceptometry-based CMRO2 quantification with interleaved TRUST (iTRUST).

Susceptometry-based oximetry (SBO) and T2-relaxation-under-spin-tagging (TRUST) are two promising methods for quantifying the cerebral metabolic rate of oxygen (CMRO2), a critical parameter of brain function. We present a combined method, interleaved TRUST (iTRUST), which achieves rapid, simultaneous quantification of both susceptometry- and T2-based CMRO2 via insertion of a flow-encoded, dual-echo gradient-recalled echo (OxFlow) module within the T1 recovery portion of the TRUST sequence. In addition to allowing direct comparison between SBO- and TRUST-derived venous oxygen saturation (Yv) values, iTRUST substantially improves TRUST temporal resolution for CMRO2 quantification and obviates the need for a separate blood flow measurement following TRUST acquisition. iTRUST was compared directly to TRUST and OxFlow alone in three resting subjects at baseline, exhibiting close agreement with the separate techniques and comparable precision. These baseline data as well as simulation results support the use of two instead of the traditional four T2 preparation times for T2 fitting, allowing simultaneous quantification of susceptometry- and T2-based Yv (and CMRO2) with three- and six-second temporal resolution, respectively. In 10 young healthy subjects, iTRUST was applied during a 5% CO2 gas mixture-breathing paradigm. T2-based Yv values were lower at baseline relative to susceptometry (62.3 ± 3.1 vs. 66.7 ± 5.1 %HbO2, P<0.05), but increased more in response to hypercapnia. As a result, T2-based CMRO2 decreased from 140.4 ± 9.7 to 120.0 ± 9.5 µMol/100g/min, a significant -14.6 ± 3.6% response (P < 0.0001), whereas susceptometry-based CMRO2 changed insignificantly from 123.4 ± 18.7 to 127.9 ± 25.7, a 3.3 ± 9.7% response (P = 0.31). These differing results are in accord with previous studies applying the parent OxFlow or TRUST sequences individually, thus supporting the reliability of iTRUST but also strongly suggesting that a systematic bias exists between the susceptometry- and T2-based Yv quantification techniques.

Effects of age and smoking on endothelial function assessed by quantitative cardiovascular magnetic resonance in the peripheral and central vasculature.

BACKGROUND: Both age and smoking promote endothelial dysfunction and impair vascular reactivity. Here, we tested this hypothesis by quantifying new cardiovascular magnetic resonance (CMR)-based biomarkers in smokers and nonsmokers. METHODS: Study population: young non-smokers (YNS: N = 45, mean age = 30.2 ± 0.7 years), young smokers (YS: N = 39 mean age 32.1 ± 0.7 years), older non-smokers (ONS: N = 45, mean age = 57.8 ± 0.6 years), and older smokers (OS: N = 40, mean age = 56.3 ± 0.6 years), all without overt cardiovascular disease. Vascular reactivity was evaluated following cuff-induced hyperemia via time-resolved blood flow velocity and oxygenation (SvO2) in the femoral artery and vein, respectively. SvO2 dynamics yielded washout time (time to minimum SvO2), resaturation rate (upslope) and maximum change from baseline (overshoot). Arterial parameters included pulse ratio (PR), hyperemic index (HI) and duration of hyperemia (TFF). Pulse-wave velocity (PWV) was assessed in aortic arch, thoracoabdominal aorta and iliofemoral arteries. Ultrasound-based carotid intimal-medial thickness (IMT) and brachial flow-mediated dilation were measured for comparison. RESULTS: Age and smoking status were independent for all parameters. Smokers had reduced upslope (-28.4%, P < 0.001), increased washout time (+15.3%, P < 0.01), and reduced HI (-19.5%, P < 0.01). Among non-smokers, older subjects had lower upslope (-22.7%, P < 0.01) and overshoot (-29.4%, P < 0.01), elevated baseline pulse ratio (+14.9%, P < 0.01), central and peripheral PWV (all P < 0.05). Relative to YNS, YS had lower upslope (-23.6%, P < 0.01) and longer washout time (13.5%, P < 0.05). Relative to ONS, OS had lower upslope (-33.0%, P < 0.01). IMT was greater in ONS than in YNS (+45.6%, P < 0.001), and also in YS compared to YNS (+14.7%, P < 0.05). CONCLUSIONS: Results suggest CMR biomarkers of endothelial function to be sensitive to age and smoking independent of each other.