Impact of Vasodilation on Oxygen-Enhanced Functional Lung MRI at 0.55 T.

BACKGROUND: Oxygen-enhanced magnetic resonance imaging (OE-MRI) can be used to assess regional lung function without ionizing radiation. Inhaled oxygen acts as a T1-shortening contrast agent to increase signal in T1-weighted (T1w) images. However, increase in proton density from pulmonary hyperoxic vasodilation may also contribute to the measured signal enhancement. Our aim was to quantify the relative contributions of the T1-shortening and vasodilatory effects of oxygen to signal enhancement in OE-MRI in both swine and healthy volunteers. METHODS: We imaged 14 anesthetized female swine (47 ± 8 kg) using a prototype 0.55 T high-performance MRI system while experimentally manipulating oxygenation and blood volume independently through oxygen titration, partial occlusion of the vena cava for volume reduction, and infusion of colloid fluid (6% hydroxyethyl starch) for volume increase. Ten healthy volunteers were imaged before, during, and after hyperoxia. Two proton density-weighted (PDw) and 2 T1w ultrashort echo time images were acquired per experimental state. The median PDw and T1w percent signal enhancement (PSE), compared with baseline room air, was calculated after image registration and correction for lung volume changes. Differences in median PSE were compared using Wilcoxon signed rank test. RESULTS: The PSE in PDw images after 100% oxygen was similar in swine (1.66% ± 1.41%, P = 0.01) and in healthy volunteers (1.99% ± 1.79%, P = 0.02), indicating that oxygen-induced pulmonary vasodilation causes ~2% lung proton density increase. The PSE in T1w images after 100% oxygen was also similar (swine, 9.20% ± 1.68%, P < 0.001; healthy volunteers, 10.10% ± 3.05%, P < 0.001). The PSE in T1w enhancement was oxygen dose-dependent in anesthetized swine, and we measured a dose-dependent PDw image signal increase from infused fluids. CONCLUSIONS: The contribution of oxygen-induced vasodilation to T1w OE-MRI signal was measurable using PDw imaging and was found to be ~2% in both anesthetized swine and in healthy volunteers. This finding may have implications for patients with regional or global hypoxia or vascular dysfunction undergoing OE-MRI and suggest that PDw imaging may be useful to account for oxygen-induced vasodilation in OE-MRI.

Dynamic pressure-volume loop analysis by simultaneous real-time cardiovascular magnetic resonance and left heart catheterization.

BACKGROUND: Left ventricular (LV) contractility and compliance are derived from pressure-volume (PV) loops during dynamic preload reduction, but reliable simultaneous measurements of pressure and volume are challenging with current technologies. We have developed a method to quantify contractility and compliance from PV loops during a dynamic preload reduction using simultaneous measurements of volume from real-time cardiovascular magnetic resonance (CMR) and invasive LV pressures with CMR-specific signal conditioning. METHODS: Dynamic PV loops were derived in 16 swine (n = 7 naïve, n = 6 with aortic banding to increase afterload, n = 3 with ischemic cardiomyopathy) while occluding the inferior vena cava (IVC). Occlusion was performed simultaneously with the acquisition of dynamic LV volume from long-axis real-time CMR at 0.55 T, and recordings of invasive LV and aortic pressures, electrocardiogram, and CMR gradient waveforms. PV loops were derived by synchronizing pressure and volume measurements. Linear regression of end-systolic- and end-diastolic- pressure-volume relationships enabled calculation of contractility. PV loops measurements in the CMR environment were compared to conductance PV loop catheter measurements in 5 animals. Long-axis 2D LV volumes were validated with short-axis-stack images. RESULTS: Simultaneous PV acquisition during IVC-occlusion was feasible. The cardiomyopathy model measured lower contractility (0.2 ± 0.1 mmHg/ml vs 0.6 ± 0.2 mmHg/ml) and increased compliance (12.0 ± 2.1 ml/mmHg vs 4.9 ± 1.1 ml/mmHg) compared to naïve animals. The pressure gradient across the aortic band was not clinically significant (10 ± 6 mmHg). Correspondingly, no differences were found between the naïve and banded pigs. Long-axis and short-axis LV volumes agreed well (difference 8.2 ± 14.5 ml at end-diastole, -2.8 ± 6.5 ml at end-systole). Agreement in contractility and compliance derived from conductance PV loop catheters and in the CMR environment was modest (intraclass correlation coefficient 0.56 and 0.44, respectively). CONCLUSIONS: Dynamic PV loops during a real-time CMR-guided preload reduction can be used to derive quantitative metrics of contractility and compliance, and provided more reliable volumetric measurements than conductance PV loop catheters.

Native contrast visualization and tissue characterization of myocardial radiofrequency ablation and acetic acid chemoablation lesions at 0.55 T.

PURPOSE: Low-field (0.55 T) high-performance cardiovascular magnetic resonance (CMR) is an attractive platform for CMR-guided intervention as device heating is reduced around 7.5-fold compared to 1.5 T. This work determines the feasibility of visualizing cardiac radiofrequency (RF) ablation lesions at low field CMR and explores a novel alternative method for targeted tissue destruction: acetic acid chemoablation. METHODS: N = 10 swine underwent X-ray fluoroscopy-guided RF ablation (6-7 lesions) and acetic acid chemoablation (2-3 lesions) of the left ventricle. Animals were imaged at 0.55 T with native contrast 3D-navigator gated T1-weighted T1w) CMR for lesion visualization, gated single-shot imaging to determine potential for real-time visualization of lesion formation, and T1 mapping to measure change in T1 in response to ablation. Seven animals were euthanized on ablation day and hearts imaged ex vivo. The remaining animals were imaged again in vivo at 21 days post ablation to observe lesion evolution. RESULTS: Chemoablation lesions could be visualized and displayed much higher contrast than necrotic RF ablation lesions with T1w imaging. On the day of ablation, in vivo myocardial T1 dropped by 19 ± 7% in RF ablation lesion cores, and by 40 ± 7% in chemoablation lesion cores (p < 4e-5). In high resolution ex vivo imaging, with reduced partial volume effects, lesion core T1 dropped by 18 ± 3% and 42 ± 6% for RF and chemoablation, respectively. Mean, median, and peak lesion signal-to-noise ratio (SNR) were all at least 75% higher with chemoablation. Lesion core to myocardium contrast-to-noise (CNR) was 3.8 × higher for chemoablation. Correlation between in vivo and ex vivo CMR and histology indicated that the periphery of RF ablation lesions do not exhibit changes in T1 while the entire extent of chemoablation exhibits T1 changes. Correlation of T1w enhancing lesion volumes indicated in vivo estimates of lesion volume are accurate for chemoablation but underestimate extent of necrosis for RF ablation. CONCLUSION: The visualization of coagulation necrosis from cardiac ablation is feasible using low-field high-performance CMR. Chemoablation produced a more pronounced change in lesion T1 than RF ablation, increasing SNR and CNR and thereby making it easier to visualize in both 3D navigator-gated and real-time CMR and more suitable for low-field imaging.

Radiation-free CMR diagnostic heart catheterization in children.

BACKGROUND: Children with heart disease may require repeated X-Ray cardiac catheterization procedures, are more radiosensitive, and more likely to survive to experience oncologic risks of medical radiation. Cardiovascular magnetic resonance (CMR) is radiation-free and offers information about structure, function, and perfusion but not hemodynamics. We intend to perform complete radiation-free diagnostic right heart catheterization entirely using CMR fluoroscopy guidance in an unselected cohort of pediatric patients; we report the feasibility and safety. METHODS: We performed 50 CMR fluoroscopy guided comprehensive transfemoral right heart catheterizations in 39 pediatric (12.7 ± 4.7 years) subjects referred for clinically indicated cardiac catheterization. CMR guided catheterizations were assessed by completion (success/failure), procedure time, and safety events (catheterization, anesthesia). Pre and post CMR body temperature was recorded. Concurrent invasive hemodynamic and diagnostic CMR data were collected. RESULTS: During a twenty-two month period (3/2015 - 12/2016), enrolled subjects had the following clinical indications: post-heart transplant 33%, shunt 28%, pulmonary hypertension 18%, cardiomyopathy 15%, valvular heart disease 3%, and other 3%. Radiation-free CMR guided right heart catheterization attempts were all successful using passive catheters. In two subjects with septal defects, right and left heart catheterization were performed. There were no complications. One subject had six such procedures. Most subjects (51%) had undergone multiple (5.5 ± 5) previous X-Ray cardiac catheterizations. Retained thoracic surgical or transcatheter implants (36%) did not preclude successful CMR fluoroscopy heart catheterization. During the procedure, two subjects were receiving vasopressor infusions at baseline because of poor cardiac function, and in ten procedures, multiple hemodynamic conditions were tested. CONCLUSIONS: Comprehensive CMR fluoroscopy guided right heart catheterization was feasible and safe in this small cohort of pediatric subjects. This includes subjects with previous metallic implants, those requiring continuous vasopressor medication infusions, and those requiring pharmacologic provocation. Children requiring multiple, serial X-Ray cardiac catheterizations may benefit most from radiation sparing. This is a step toward wholly CMR guided diagnostic (right and left heart) cardiac catheterization and future CMR guided cardiac intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02739087 registered February 17, 2016.

Acute Cardiac MRI Assessment of Radiofrequency Ablation Lesions for Pediatric Ventricular Arrhythmia: Feasibility and Clinical Correlation.

BACKGROUND: Arrhythmia ablation with current techniques is not universally successful. Inadequate ablation lesion formation may be responsible for some arrhythmia recurrences. Periprocedural visualization of ablation lesions may identify inadequate lesions and gaps to guide further ablation and reduce risk of arrhythmia recurrence. METHODS: This feasibility study assessed acute postprocedure ablation lesions by MRI, and correlated these findings with clinical outcomes. Ten pediatric patients who underwent ventricular tachycardia ablation were transferred immediately postablation to a 1.5T MRI scanner and late gadolinium enhancement (LGE) imaging was performed to characterize ablation lesions. Immediate and mid-term arrhythmia recurrences were assessed. RESULTS: Patient characteristics include median age 14 years (1-18 years), median weight 52 kg (11-81 kg), normal cardiac anatomy (n = 6), d-transposition of great arteries post arterial switch repair (n = 2), anomalous coronary artery origin post repair (n = 1), and cardiac rhabdomyoma (n = 1). All patients underwent radiofrequency catheter ablation of ventricular arrhythmia with acute procedural success. LGE was identified at the reported ablation site in 9/10 patients, all arrhythmia-free at median 7 months follow-up. LGE was not visible in 1 patient who had recurrence of frequent premature ventricular contractions within 2 hours, confirmed on Holter at 1 and 21 months post procedure. CONCLUSIONS: Ventricular ablation lesion visibility by MRI in the acute post procedure setting is feasible. Lesions identifiable with MRI may correlate with clinical outcomes. Acute MRI identification of gaps or inadequate lesions may provide the unique temporal opportunity for additional ablation therapy to decrease arrhythmia recurrence.

Free-breathing motion-corrected late-gadolinium-enhancement imaging improves image quality in children.

BACKGROUND: The value of late-gadolinium-enhancement (LGE) imaging in the diagnosis and management of pediatric and congenital heart disease is clear; however current acquisition techniques are susceptible to error and artifacts when performed in children because of children's higher heart rates, higher prevalence of sinus arrhythmia, and inability to breath-hold. Commonly used techniques in pediatric LGE imaging include breath-held segmented FLASH (segFLASH) and steady-state free precession-based (segSSFP) imaging. More recently, single-shot SSFP techniques with respiratory motion-corrected averaging have emerged. OBJECTIVE: This study tested and compared single-shot free-breathing LGE techniques with standard segmented breath-held techniques in children undergoing LGE imaging. MATERIALS AND METHODS: Thirty-two consecutive children underwent clinically indicated late-enhancement imaging using intravenous gadobutrol 0.15 mmol/kg. Breath-held segSSFP, breath-held segFLASH, and free-breathing single-shot SSFP LGE sequences were performed in consecutive series in each child. Two blinded reviewers evaluated the quality of the images and rated them on a scale of 1-5 (1 = poor, 5 = superior) based on blood pool-myocardial definition, presence of cardiac motion, presence of respiratory motion artifacts, and image acquisition artifact. We used analysis of variance (ANOVA) to compare groups. RESULTS: Patients ranged in age from 9 months to 18 years, with a mean +/- standard deviation (SD) of 13.3 +/- 4.8 years. R-R interval at the time of acquisition ranged 366-1,265 milliseconds (ms) (47-164 beats per minute [bpm]), mean +/- SD of 843+/-231 ms (72+/-21 bpm). Mean +/- SD quality ratings for long-axis imaging for segFLASH, segSSFP and single-shot SSFP were 3.1+/-0.9, 3.4+/-0.9 and 4.0+/-0.9, respectively (P < 0.01 by ANOVA). Mean +/- SD quality ratings for short-axis imaging for segFLASH, segSSFP and single-shot SSFP were 3.4+/-1, 3.8+/-0.9 and 4.3+/-0.7, respectively (P < 0.01 by ANOVA). CONCLUSION: Single-shot late-enhancement imaging with motion-corrected averaging is feasible in children, robust at high heart rates and with variable R-R intervals, and can be performed without breath-holding with higher image quality ratings than standard breath-held techniques. Use of free-breathing single-shot motion-corrected technique does not compromise LGE image quality in children who can hold their breath, and it can significantly improve image quality in children who cannot hold their breath or who have significant arrhythmia.

Quantitative MR characterization of disease activity in the knee in children with juvenile idiopathic arthritis: a longitudinal pilot study.

BACKGROUND: The development of a quantifiable and noninvasive method of monitoring disease activity and response to therapy is vital for arthritis management. OBJECTIVE: The purpose of this study was to investigate the utility of quantitative dynamic contrast-enhanced MRI (DCE-MRI) based on pharmacokinetic (PK) modeling to evaluate disease activity in the knee and correlate the results with the clinical assessment in children with juvenile idiopathic arthritis (JIA). MATERIALS AND METHODS: A group of 17 children with JIA underwent longitudinal clinical and laboratory assessment and DCE-MRI of the knee at enrollment, 3 months, and 12 months. A PK model was employed using MRI signal enhancement data to give three parameters, K(trans') (min(-1)), k(ep) (min(-1)), and V(p) (') and to calculate synovial volume. RESULTS: The PK parameters, synovial volumes, and clinical and laboratory assessments in most children were significantly decreased (P < 0.05) at 12 months when compared to the enrollment values. There was excellent correlation between the PK and synovial volume and the clinical and laboratory assessments. Differences in MR and clinical parameter values in individual subjects illustrate persistent synovitis when in clinical remission. CONCLUSION: A decrease in PK parameter values obtained from DCE-MRI in children with JIA likely reflects diminution of disease activity. This technique may be used as an objective follow-up measure of therapeutic efficacy in patients with JIA. MR imaging can detect persistent synovitis in patients considered to be in clinical remission.

Visceral abdominal fat is correlated with whole-body fat and physical activity among 8-y-old children at risk of obesity.

BACKGROUND: Abdominal fat is more related to health risk than is whole-body fat. Determining the factors related to children's visceral fat could result in interventions to improve child health. OBJECTIVE: Given the effects of physical activity on adults' visceral fat, it was hypothesized that, after accounting for whole-body fat, physical activity would be inversely related to children's visceral (VAT), but not to subcutaneous (SAT), abdominal adipose tissue. DESIGN: In this cross-sectional observational study conducted in forty-two 8-y-old children (21 boys, 21 girls) at risk of obesity [>75th body mass index (BMI) percentile, with at least one overweight parent], familial factors (eg, maternal BMI), historic weight-related factors (eg, birth weight), and the children's current physical activity (self-reported and measured with accelerometry) and diet were examined as potential correlates of the children's whole-body composition (measured with BMI and dual-energy X-ray absorptiometry) and abdominal fat distribution (measured by magnetic resonance imaging). RESULTS: Accelerometer-measured physical activity was related to whole-body fat (r = -0.32, P < 0.10), SAT (r = -0.29, P < 0.10), and VAT (r = -0.43, P < 0.05). In regression models, whole-body fat was positively associated with and the only significant correlate of SAT. Whole-body fat was positively related and accelerometer-measured physical activity was negatively and independently related to the children's VAT. CONCLUSIONS: Both SAT and VAT in 8-y-old children at risk of obesity are most closely associated with whole-body fat. However, after control for whole-body fat, greater physical activity is only associated with lower VAT, not SAT, in these children.

MRI of fat distribution in a mouse model of lysosomal acid lipase deficiency.

OBJECTIVE: We assessed the use of MRI in the evaluation of abdominal fat distribution in a lysosomal acid lipase (LAL)-deficient mouse model. MATERIALS AND METHODS: LAL-deficient mice are born with a normal fat distribution but over time deplete the fat stores in the subcutaneous and retroperitoneal tissues and accumulate fat in the liver, spleen, and bowel. Four MRI studies of LAL-deficient mice and control mice were obtained with 3-T T1-weighted spin-echo images and volume segmentation processing to create parameters for the study of fat distribution: intraabdominal adipose tissue-subcutaneous adipose tissue (IAT/SAT) ratio, liver volume, reproductive fat, and retroperitoneal fat. MRI adiposity parameters in LAL-deficient mice were compared with those in control mice. Adiposity volumes calculated on MRI were compared with those calculated at autopsy. RESULTS: Statistically significant differences were found between LAL-deficient and control mice for IAT/SAT ratio (p=0.0336), liver volume (p=0.0336), and reproductive fat (p=0.0336), and a statistically significant trend was found for retroperitoneal fat (p=0.0514). No statistically significant difference was found between adiposity volumes calculated on MRI and adiposity volumes found at autopsy (all p >0.2). CONCLUSION: Use of an in vivo model showed MRI techniques to be accurate in predicting visceral adiposity. LAL-deficient mice provided a unique model showing a pattern of adipose distribution that is markedly different from that in control mice, and MRI may provide a means of evaluating therapeutic interventions sequentially.

Quantification of dynamic contrast-enhanced MR imaging of the knee in children with juvenile rheumatoid arthritis based on pharmacokinetic modeling.

Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k(ep) (min(-1)), the rate constant; k(el) (min(-1)), the elimination rate constant; and E(R) (min(-1)), the initial enhancement rate, which is proportional to the transfer constant K(trans) (min(-1)). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, E(R), in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 min(-1) over the distal femoral physis and 1 to 10 min(-1) in the synovium. The E(R) of the synovium was correlated with the E(R) of the distal femoral physis (P<.05). In addition, the E(R) of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where T(1)-weighted contrast is used (breast cancer, brain tumors).

Using a phantom to compare MR techniques for determining the ratio of intraabdominal to subcutaneous adipose tissue.

OBJECTIVE: Patients who have a greater distribution of intraabdominal adipose tissue as compared with subcutaneous adipose tissue and an increased ratio of intraabdominal adipose tissue to subcutaneous adipose tissue are at greater risk for developing cardiovascular disease and type 2 diabetes mellitus. In previous MR investigations, researchers have used conventional T1-weighted spin-echo images to determine the ratio of intraabdominal adipose tissue to subcutaneous adipose tissue. However, no investigation, to our knowledge, has been performed to determine the accuracy of using different MR sequences to estimate adipose distribution. The purpose of our investigation was to compare MR imaging and segmentation techniques in calculating the ratio of intraabdominal to subcutaneous adipose tissue using an adiposity phantom. MATERIALS AND METHODS: A phantom was created to simulate the distribution of subcutaneous and intraabdominal fat (with known volumes). Axial MR images were obtained twice through the phantom using a 5-mm slice thickness and zero gap for the following T1-weighted sequences: spin-echo, fast Dixon, and three-dimensional (3D) spoiled gradient-echo. An in-house computer software program was then used to segment the volumes of fat and calculate the volume of intraabdominal adipose tissue and subcutaneous adipose tissue and the ratio of intraabdominal to subcutaneous adipose tissue. Each imaging data set was segmented three times, so six sets of data were yielded for each imaging technique. The percentage predicted of the true volume was calculated for each MR imaging technique for each fat variable. The mean percentages for each variable were then compared using one-factor analysis of variance to determine whether differences exist among the three MR techniques. RESULTS: The three MR imaging techniques had statistically significant different means for the predicted true volume of two variables: volume of subcutaneous adipose tissue (p < 0.001) and volume of intraabdominal adipose tissue (p = 0.0426). Estimates based on fast Dixon images were closest to the true volumes for all the variables. All MR imaging techniques performed similarly in estimating the ratio of intraabdominal adipose tissue to subcutaneous adipose tissue (p = 0.9117). The acquisition time for the 3D spoiled gradient-echo images was 10-22 times faster than for the other sequences. CONCLUSION: Conventional T1-weighted spin-echo MR imaging, the current sequence used in practice for measuring visceral adiposity, may not be the optimal MR sequence for this purpose. We found that the T1-weighted fast Dixon sequence was the most accurate at estimating all fat volumes. The T1-weighted 3D spoiled gradient-echo sequence generated similar ratios of intraabdominal to subcutaneous adipose tissue in a fraction of the acquisition time.