Improved abdominal T1 weighted imaging at 0.55T.

PURPOSE: Breath-held fat-suppressed volumetric T1-weighted MRI is an important and widely-used technique for evaluating the abdomen. Both fat-saturation and Dixon-based fat-suppression methods are used at conventional field strengths; however, both have challenges at lower field strengths (<1.5T) due to insufficient fat suppression and/or inadequate resolution. Specifically, at lower field strengths, fat saturation often fails due to the short T1 of lipid; and Cartesian Dixon imaging provides poor spatial resolution due to the need for a long ∆TE, due to the smaller ∆f between water and lipid. The purpose of this work is to demonstrate a new approach capable of simultaneously achieving excellent fat suppression and high spatial resolution on a 0.55T whole-body system. METHODS: We applied 3D stack-of-spirals Dixon imaging at 0.55T, with compensation of concomitant field phase during reconstruction. The spiral readouts make efficient use of the requisite ∆TE. We compared this with 3D Cartesian Dixon imaging. Experiments were performed in 2 healthy and 10 elevated liver fat volunteers. RESULTS: Stack-of-spirals Dixon imaging at 0.55T makes excellent use of the required ∆TE, provided high SNR efficiency and finer spatial resolution (1.7 × 1.7 × 5 mm3) compared Cartesian Dixon (3.5 × 3.5 × 5 mm3), within a 17-s breath-hold. We observed successful fat suppression, and improved definition of structures such as the liver, kidneys, and bowel. CONCLUSION: We demonstrate that high-resolution single breath-hold volumetric abdominal T1-weighted imaging is feasible at 0.55T using spiral sampling and concomitant field correction. This is an attractive alternative to existing Cartesian-based methods, as it simultaneously provides high-resolution and excellent fat-suppression.

Diffusion tensor brain imaging at 0.55T: A feasibility study.

PURPOSE: To investigate the feasibility of diffusion tensor brain imaging at 0.55T with comparisons against 3T. METHODS: Diffusion tensor imaging data with 2 mm isotropic resolution was acquired on a cohort of five healthy subjects using both 0.55T and 3T scanners. The signal-to-noise ratio (SNR) of the 0.55T data was improved using a previous SNR-enhancing joint reconstruction method that jointly reconstructs the entire set of diffusion weighted images from k-space using shared-edge constraints. Quantitative diffusion tensor parameters were estimated and compared across field strengths. We also performed a test-retest assessment of repeatability at each field strength. RESULTS: After applying SNR-enhancing joint reconstruction, the diffusion tensor parameters obtained from 0.55T data were strongly correlated ( R 2 ≥ 0 . 70 $$ {R}^2\ge 0.70 $$ ) with those obtained from 3T data. Test-retest analysis showed that SNR-enhancing reconstruction improved the repeatability of the 0.55T diffusion tensor parameters. CONCLUSION: High-resolution in vivo diffusion MRI of the human brain is feasible at 0.55T when appropriate noise-mitigation strategies are applied.

Lung parenchyma transverse relaxation rates at 0.55 T.

PURPOSE: To determine R2 and R 2 ' $$ {R}_2^{\prime } $$ transverse relaxation rates in healthy lung parenchyma at 0.55 T. This is important in that it informs the design and optimization of new imaging methods for 0.55T lung MRI. METHODS: Experiments were performed in 3 healthy adult volunteers on a prototype whole-body 0.55T MRI, using a custom free-breathing electrocardiogram-triggered, single-slice echo-shifted multi-echo spin echo (ES-MCSE) pulse sequence with respiratory navigation. Transverse relaxation rates R2 and R 2 ' $$ {R}_2^{\prime } $$ and off-resonance ∆f were jointly estimated using nonlinear least-squares estimation. These measurements were compared against R2 estimates from T2 -prepared balanced SSFP (T2 -Prep bSSFP) and R 2 * $$ {R}_2^{\ast } $$ estimates from multi-echo gradient echo, which are used widely but prone to error due to different subvoxel weighting. RESULTS: The mean R2 and R 2 ' $$ {R}_2^{\prime } $$ values of lung parenchyma obtained from ES-MCSE were 17.3 ± 0.7 Hz and 127.5 ± 16.4 Hz (T2  = 61.6 ± 1.7 ms; T 2 ' $$ {\mathrm{T}}_2^{\prime } $$  = 9.5 ms ± 1.6 ms), respectively. The off-resonance estimates ranged from -60 to 30 Hz. The R2 from T2 -Prep bSSFP was 15.7 ± 1.7 Hz (T2  = 68.6 ± 8.6 ms) and R 2 * $$ {R}_2^{\ast } $$ from multi-echo gradient echo was 131.2 ± 30.4 Hz ( T 2 * $$ {\mathrm{T}}_2^{\ast } $$  = 8.0 ± 2.5 ms). Paired t-test indicated that there is a significant difference between the proposed and reference methods (p < 0.05). The mean R2 estimate from T2 -Prep bSSFP was slightly smaller than that from ES-MCSE, whereas the mean R 2 ' $$ {R}_2^{\prime } $$ and R 2 * $$ {R}_2^{\ast } $$ estimates from ES-MCSE and multi-echo gradient echo were similar to each other across all subjects. CONCLUSIONS: Joint estimation of transverse relaxation rates and off-resonance is feasible at 0.55 T with a free-breathing electrocardiogram-gated and navigator-gated ES-MCSE sequence. At 0.55 T, the mean R2 of 17.3 Hz is similar to the reported mean R2 of 16.7 Hz at 1.5 T, but the mean R 2 ' $$ {R}_2^{\prime } $$ of 127.5 Hz is about 5-10 times smaller than that reported at 1.5 T.

Contrast-optimal simultaneous multi-slice bSSFP cine cardiac imaging at 0.55 T.

PURPOSE: To determine if contemporary 0.55 T MRI supports the use of contrast-optimal flip angles (FA) for simultaneous multi-slice (SMS) balanced SSFP (bSSFP) cardiac function assessment, which is impractical at conventional field strengths because of excessive SAR and/or banding artifacts. METHODS: Blipped-CAIPI bSSFP was combined with spiral sampling for ventricular function assessment at 0.55 T. Cine movies with single band and SMS factors of 2 and 3 (SMS 2 and 3), and FA ranging from 60° to 160°, were acquired in seven healthy volunteers. Left ventricular blood and myocardial signal intensity (SI) normalized by background noise and blood-myocardium contrast were measured and compared across acquisition settings. RESULTS: Myocardial SI was slightly higher in single band than in SMS and decreased with an increasing FA. Blood SI increased as the FA increased for single band, and increment was small for FA ≥120°. Blood SI for SMS 2 and 3 increased with an increasing FA up to ∼100°. Blood-myocardium contrast increased with an increasing FA for single band, peaked at FA = 160° (systole: 28.43, diastole: 29.15), attributed mainly to reduced myocardial SI when FA ≥120°. For SMS 2, contrast peaked at 120° (systole: 21.43, diastole: 19.85). For SMS 3, contrast peaked at 120° in systole (16.62) and 100° in diastole (19.04). CONCLUSIONS: Contemporary 0.55 T MR scanners equipped with high-performance gradient systems allow the use of contrast-optimal FA for SMS accelerated bSSFP cine examinations without compromising image quality. The contrast-optimal FA was found to be 140° to 160° for single band and 100° to 120° for SMS 2 and 3.

Body composition profiling at 0.55T: Feasibility and precision.

PURPOSE: Body composition MRI captures the distribution of fat and lean tissues throughout the body, and provides valuable biomarkers of obesity, metabolic disease, and muscle disorders, as well as risk assessment. Highly reproducible protocols have been developed for 1.5T and 3T MRI. The purpose of this work was to demonstrate the feasibility and test-retest repeatability of MRI body composition profiling on a 0.55T whole-body system. METHODS: Healthy adult volunteers were scanned on a whole-body 0.55T MRI system using the integrated body RF coil. Experiments were performed to refine parameter settings such as TEs, resolution, flip angle, bandwidth, acceleration, and oversampling factors. The final protocol was evaluated using a test-retest study with subject removal and replacement in 10 adult volunteers (5 M/5F, age 25-60, body mass index 20-30). RESULTS: Compared to 1.5T and 3T, the optimal flip angle at 0.55T was higher (15°), due to the shorter T1 times, and the optimal echo spacing was larger, due to smaller chemical shift between water and fat. Overall image quality was comparable to conventional field strengths, with no significant issues with fat/water swapping or inadequate SNR. Repeatability coefficient of visceral fat, subcutaneous fat, total thigh muscle volume, muscle fat infiltration, and liver fat were 11.8 cL (2.2%), 46.9 cL (1.9%), 14.6 cL (0.5%), 0.1 pp (2%), and 0.2 pp (5%), respectively (coefficient of variation in parenthesis). CONCLUSIONS: We demonstrate that 0.55T body composition MRI is feasible and present optimized scan parameters. The resulting images provide satisfactory quality for automated post-processing and produce repeatable results.

Evaluation of a novel 8-channel RX coil for speech production MRI at 0.55 T.

OBJECTIVE: Speech production MRI benefits from lower magnetic fields due to reduced off-resonance effects at air-tissue interfaces and from the use of dedicated receiver coils due to higher SNR and parallel imaging capability. Here we present a custom designed upper airway coil for 1H imaging at 0.55 Tesla and evaluate its performance in comparison with a vendor-provided prototype 16-channel head/neck coil. MATERIALS AND METHODS: Four adult volunteers were scanned with both custom speech and prototype head-neck coils. We evaluated SNR gains of each of the coils over eleven upper airway volumes-of-interest measured relative to the integrated body coil. We evaluated parallel imaging performance of both coils by computing g-factors for SENSE reconstruction of uniform and variable density Cartesian sampling schemes with R = 2, 3, and 4. RESULTS: The dedicated coil shows approximately 3.5-fold SNR efficiency compared to the head-neck coil. For R = 2 and 3, both uniform and variable density samplings have g-factor values below 1.1 in the upper airway region. For R = 4, g-factor values are higher for both trajectories. DISCUSSION: The dedicated coil configuration allows for a significant SNR gain over the head-neck coil in the articulators. This, along with favorable g values, makes the coil useful in speech production MRI.

Low-field 0.55 T MRI evaluation of the fetus.

Fetal magnetic resonance imaging (MRI) is an important adjunct modality for the evaluation of fetal abnormalities. Recently, low-field MRI systems at 0.55 Tesla have become available which can produce images on par with 1.5 Tesla systems but with lower power deposition, acoustic noise, and artifact. In this article, we describe a technical innovation using low-field MRI to perform diagnostic quality fetal MRI.

Nitroxide-enhanced MRI of cardiovascular oxidative stress.

BACKGROUND: In vivo imaging of oxidative stress can facilitate the understanding and treatment of cardiovascular diseases. We evaluated nitroxide-enhanced MRI with 3-carbamoyl-proxyl (3CP) for the detection of myocardial oxidative stress. METHODS: Three mouse models of cardiac oxidative stress were imaged, namely angiotensin II (Ang II) infusion, myocardial infarction (MI), and high-fat high-sucrose (HFHS) diet-induced obesity (DIO). For the Ang II model, mice underwent MRI at baseline and after 7 days of Ang II (n = 8) or saline infusion (n = 8). For the MI model, mice underwent MRI at baseline (n = 10) and at 1 (n = 8), 4 (n = 9), and 21 (n = 8) days after MI. For the HFHS-DIO model, mice underwent MRI at baseline (n = 20) and 18 weeks (n = 13) after diet initiation. The 3CP reduction rate, Kred , computed using a tracer kinetic model, was used as a metric of oxidative stress. Dihydroethidium (DHE) staining of tissue sections was performed on Day 1 after MI. RESULTS: For the Ang II model, Kred was higher after 7 days of Ang II versus other groups (p < 0.05). For the MI model, Kred , in the infarct region was significantly elevated on Days 1 and 4 after MI (p < 0.05), whereas Kred in the noninfarcted region did not change after MI. DHE confirmed elevated oxidative stress in the infarct zone on Day 1 after MI. After 18 weeks of HFHS diet, Kred was higher in mice after diet versus baseline (p < 0.05). CONCLUSIONS: Nitroxide-enhanced MRI noninvasively quantifies tissue oxidative stress as one component of a multiparametric preclinical MRI examination. These methods may facilitate investigations of oxidative stress in cardiovascular disease and related therapies.

MRI assessment of coronary microvascular endothelial nitric oxide synthase function using myocardial T1 mapping.

PURPOSE: Endothelial nitric oxide synthase (eNOS) plays a central role in regulating vascular tone, blood flow, and microvascular permeability. Endothelial dysfunction, including eNOS dysfunction, is an early biomarker of vascular disease. This study aimed to show that myocardial T1 mapping during nitric oxide synthase (NOS) inhibition could assess coronary microvascular eNOS function. METHODS: Wild-type mice, eNOS-/- mice, and wild-type mice fed a high-fat diet underwent T1 mapping at baseline and for 20 min after injection of NG -nitro-L-arginine methyl ester (LNAME), a NOS inhibitor. First-pass perfusion MRI was performed in wild-type mice at baseline and 5 min after LNAME injection. RESULTS: T1 mapping detected an increase in myocardial T1 5 min after an injection of 4 mg/kg LNAME compared with baseline in control mice (T1 = 1515 ± 30 ms with LNAME versus T1 = 1402 ± 30 ms at baseline, P < 0.05). No change in myocardial T1 after LNAME injection was observed in eNOS-/- mice. The change in T1 after LNAME injection was less in high-fat-diet mice (ΔT1 = 31 ± 14 ms at 12 weeks of diet and ΔT1 = 16 ± 17 ms at 18 weeks of diet) compared with mice fed a standard diet (ΔT1 = 113 ± 15 ms), with P < 0.05. First-pass MRI measured similar perfusion at baseline and 5 min after LNAME injection. CONCLUSIONS: NOS inhibition causes an increase in myocardial T1 in healthy mice, and this effect is mediated through eNOS. T1 mapping during NOS inhibition detects coronary microvascular eNOS dysfunction in high-fat-diet mice. T1 mapping during NOS inhibition may be useful in preclinical studies aiming to investigate mechanisms underlying and therapies for coronary microvascular eNOS dysfunction. Magn Reson Med 79:2246-2253, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Imaging left-ventricular mechanical activation in heart failure patients using cine DENSE MRI: Validation and implications for cardiac resynchronization therapy.

PURPOSE: To image late mechanical activation and identify effective left-ventricular (LV) pacing sites for cardiac resynchronization therapy (CRT). There is variability in defining mechanical activation time, with some studies using the time to peak strain (TPS) and some using the time to the onset of circumferential shortening (TOS). We developed improved methods for imaging mechanical activation and evaluated them in heart failure (HF) patients undergoing CRT. MATERIALS AND METHODS: We applied active contours to cine displacement encoding with stimulated echoes (DENSE) strain images to detect TOS. Six healthy volunteers underwent magnetic resonance imaging (MRI) at 1.5T, and 50 patients underwent pre-CRT MRI (strain, scar, volumes) and echocardiography, assessment of the electrical activation time (Q-LV) at the LV pacing site, and echocardiography assessment of LV reverse remodeling 6 months after CRT. TPS at the LV pacing site was also measured by DENSE. RESULTS: The latest TOS was greater in HF patients vs. healthy subjects (112 ± 28 msec vs. 61 ± 7 msec, P < 0.01). The correlation between TOS and Q-LV was strong (r > 0.75; P < 0.001) and better than between TPS and Q-LV (r < 0.62; P ≥ 0.006). Twenty-three of 50 patients had the latest activating segment in a region other than the mid-ventricular lateral wall, the most common site for the CRT LV lead. Using a multivariable model, TOS/QRS was significantly associated with LV reverse remodeling even after adjustment for overall dyssynchrony and scar (P < 0.05), whereas TPS was not (P = 0.49). CONCLUSION: Late activation by cine DENSE TOS analysis is associated with improved LV reverse remodeling with CRT and deserves further study as a tool to achieve optimal LV lead placement in CRT. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:887-896.

Real-time MRI of the moving wrist at 0.55 tesla.

OBJECTIVES: Magnetic resonance imaging (MRI) using 1.5T or 3.0T systems is routinely employed for assessing wrist pathology; however, due to off-resonance artifacts and high power deposition, these high-field systems have drawbacks for real-time (RT) imaging of the moving wrist. Recently, high-performance 0.55T MRI systems have become available. In this proof-of-concept study, we tested the hypothesis that RT-MRI during continuous, active, and uninterrupted wrist motion is feasible with a high-performance 0.55T system at temporal resolutions below 100 ms and that the resulting images provide visualization of tissues commonly interrogated for assessing dynamic wrist instability. METHODS: Participants were scanned during uninterrupted wrist radial-ulnar deviation and clenched fist maneuvers. Resulting images (nominal temporal resolution of 12.7-164.6 ms per image) were assessed for image quality. Feasibility of static MRI to supplement RT-MRI acquisition was also tested. RESULTS: The RT images with temporal resolutions < 100 ms demonstrated low distortion and image artifacts, and higher reader assessment scores. Static MRI scans showed the ability to assess anatomical structures of interest in the wrist. CONCLUSION: RT-MRI of the wrist at a high temporal resolution, coupled with static MRI, is feasible with a high-performance 0.55T system, and may enable improved assessment of wrist dynamic dysfunction and instability. ADVANCES IN KNOWLEDGE: Real-time MRI of the moving wrist is feasible with high-performance 0.55T and may improve the evaluation of dynamic dysfunction of the wrist.

MRI analysis to map interstitial flow in the brain tumor microenvironment.

Glioblastoma (GBM), a highly aggressive form of brain tumor, is a disease marked by extensive invasion into the surrounding brain. Interstitial fluid flow (IFF), or the movement of fluid within the spaces between cells, has been linked to increased invasion of GBM cells. Better characterization of IFF could elucidate underlying mechanisms driving this invasion in vivo. Here, we develop a technique to noninvasively measure interstitial flow velocities in the glioma microenvironment of mice using dynamic contrast-enhanced magnetic resonance imaging (MRI), a common clinical technique. Using our in vitro model as a phantom "tumor" system and in silico models of velocity vector fields, we show we can measure average velocities and accurately reconstruct velocity directions. With our combined MR and analysis method, we show that velocity magnitudes are similar across four human GBM cell line xenograft models and the direction of fluid flow is heterogeneous within and around the tumors, and not always in the outward direction. These values were not linked to the tumor size. Finally, we compare our flow velocity magnitudes and the direction of flow to a classical marker of vessel leakage and bulk fluid drainage, Evans blue. With these data, we validate its use as a marker of high and low IFF rates and IFF in the outward direction from the tumor border in implanted glioma models. These methods show, for the first time, the nature of interstitial fluid flow in models of glioma using a technique that is translatable to clinical and preclinical models currently using contrast-enhanced MRI.

A fully implantable pacemaker for the mouse: from battery to wireless power.

Animal models have become a popular platform for the investigation of the molecular and systemic mechanisms of pathological cardiovascular physiology. Chronic pacing studies with implantable pacemakers in large animals have led to useful models of heart failure and atrial fibrillation. Unfortunately, molecular and genetic studies in these large animal models are often prohibitively expensive or not available. Conversely, the mouse is an excellent species for studying molecular mechanisms of cardiovascular disease through genetic engineering. However, the large size of available pacemakers does not lend itself to chronic pacing in mice. Here, we present the design for a novel, fully implantable wireless-powered pacemaker for mice capable of long-term (>30 days) pacing. This design is compared to a traditional battery-powered pacemaker to demonstrate critical advantages achieved through wireless inductive power transfer and control. Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Mice (n = 24) were implanted with endocardial, battery-powered devices (n = 14) and epicardial, wireless-powered devices (n = 10). Wireless-powered devices were associated with reduced implant mortality and more reliable device function compared to battery-powered devices. Eight of 14 (57.1%) mice implanted with battery-powered pacemakers died following device implantation compared to 1 of 10 (10%) mice implanted with wireless-powered pacemakers. Moreover, device function was achieved for 30 days with the wireless-powered device compared to 6 days with the battery-powered device. The wireless-powered pacemaker system presented herein will allow electrophysiology studies in numerous genetically engineered mouse models as well as rapid pacing-induced heart failure and atrial arrhythmia in mice.