Combined T2 -preparation and multidimensional outer volume suppression for coronary artery imaging with 3D cones trajectories.

PURPOSE: To develop a modular magnetization preparation sequence for combined T2 -preparation and multidimensional outer volume suppression (OVS) for coronary artery imaging. METHODS: A combined T2 -prepared 1D OVS sequence with fat saturation was defined to contain a 90°-60 180°60 composite nonselective tip-down pulse, two 180°Y hard pulses for refocusing, and a -90° spectral-spatial sinc tip-up pulse. For 2D OVS, 2 modules were concatenated, selective in X and then Y. Bloch simulations predicted robustness of the sequence to B0 and B1 inhomogeneities. The proposed sequence was compared with a T2 -prepared 2D OVS sequence proposed by Luo et al, which uses a spatially selective 2D spiral tip-up. The 2 sequences were compared in phantom studies and in vivo coronary artery imaging studies with a 3D cones trajectory. RESULTS: Phantom results demonstrated superior OVS for the proposed sequence compared with the Luo sequence. In studies on 15 healthy volunteers, the proposed sequence had superior image edge profile acutance values compared with the Luo sequence for the right (P < .05) and left (P < .05) coronary arteries, suggesting superior vessel sharpness. The proposed sequence also had superior signal-to-noise ratio (P < .05) and passband-to-stopband ratio (P < .05). Reader scores and reader preference indicated superior coronary image quality of the proposed sequence for both the right (P < .05) and left (P < .05) coronary arteries. CONCLUSION: The proposed sequence with concatenated 1D spatially selective tip-ups and integrated fat saturation has superior image quality and suppression compared with the Luo sequence with 2D spatially selective tip-up.

Whole-heart coronary MR angiography using a 3D cones phyllotaxis trajectory.

PURPOSE: To develop a 3D cones steady-state free precession sequence with improved robustness to respiratory motion while mitigating eddy current artifacts for free-breathing whole-heart coronary magnetic resonance angiography. METHOD: The proposed sequence collects cone interleaves using a phyllotaxis pattern, which allows for more distributed k-space sampling for each heartbeat compared to a typical sequential collection pattern. A Fibonacci number of segments is chosen to minimize eddy current effects with the trade-off of an increased number of acquisition heartbeats. For verification, phyllotaxis-cones is compared to sequential-cones through simulations, phantom studies, and in vivo coronary scans with 8 subjects using 2D image-based navigators for retrospective motion correction. RESULTS: Simulated point spread functions and moving phantom results show less coherent motion artifacts for phyllotaxis-cones compared to sequential-cones. Assessment of the right and left coronary arteries using reader scores and the image edge profile acutance vessel sharpness metric indicate superior image quality and sharpness for phyllotaxis-cones. CONCLUSION: Phyllotaxis 3D cones results in improved qualitative image scores and coronary vessel sharpness for free-breathing whole-heart coronary magnetic resonance angiography compared to standard sequential ordering when using a steady-state free precession sequence.

3D image-based navigators for coronary MR angiography.

PURPOSE: To develop a method for acquiring whole-heart 3D image-based navigators (iNAVs) with isotropic resolution for tracking and correction of localized motion in coronary magnetic resonance angiography (CMRA). METHODS: To monitor motion in all regions of the heart during a free-breathing scan, a variable-density cones trajectory was designed to collect a 3D iNAV every heartbeat in 176 ms with 4.4 mm isotropic spatial resolution. The undersampled 3D iNAV data were reconstructed with efficient self-consistent parallel imaging reconstruction (ESPIRiT). 3D translational and nonrigid motion-correction methods using 3D iNAVs were compared to previous translational and nonrigid methods using 2D iNAVs. RESULTS: Five subjects were scanned with a 3D cones CMRA sequence, accompanied by both 2D and 3D iNAVs. The quality of the right and left anterior descending coronary arteries was assessed on 2D and 3D iNAV-based motion-corrected images using a vessel sharpness metric and qualitative reader scoring. This assessment showed that nonrigid motion correction based on 3D iNAVs produced results that were noninferior to correction based on 2D iNAVs. CONCLUSION: The ability to acquire isotropic-resolution 3D iNAVs every heartbeat during a CMRA scan was demonstrated. Such iNAVs enabled direct measurement of localized motion for nonrigid motion correction in free-breathing whole-heart CMRA. Magn Reson Med 77:1874-1883, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Nonrigid Motion Correction With 3D Image-Based Navigators for Coronary MR Angiography.

PURPOSE: To develop a retrospective nonrigid motion-correction method based on 3D image-based navigators (iNAVs) for free-breathing whole-heart coronary magnetic resonance angiography (MRA). METHODS: The proposed method detects global rigid-body motion and localized nonrigid motion from 3D iNAVs and compensates them with an autofocusing algorithm. To model the global motion, 3D rotation and translation are estimated from the 3D iNAVs. Two sets of localized nonrigid motions are obtained from deformation fields between 3D iNAVs and reconstructed binned images, respectively. A bank of motion-corrected images is generated and the final image is assembled pixel-by-pixel by selecting the best focused pixel from this bank. In vivo studies with six healthy volunteers were conducted to compare the performance of the proposed method with 3D translational motion correction and no correction. RESULTS: In vivo studies showed that compared to no correction, 3D translational motion correction and the proposed method increased the vessel sharpness by 13% ± 13% and 19% ± 16%, respectively. Out of 90 vessel segments, 75 segments showed improvement with the proposed method compared to 3D translational correction. CONCLUSION: We have developed a nonrigid motion-correction method based on 3D iNAVs and an autofocusing algorithm that improves the vessel sharpness of free-breathing whole-heart coronary MRA. Magn Reson Med 77:1884-1893, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

High-resolution variable-density 3D cones coronary MRA.

PURPOSE: To improve the spatial/temporal resolution of whole-heart coronary MR angiography by developing a variable-density (VD) 3D cones acquisition suitable for image reconstruction with parallel imaging and compressed sensing techniques. METHODS: A VD 3D cones trajectory design incorporates both radial and spiral trajectory undersampling techniques to achieve higher resolution. This design is used to generate a VD 3D cones trajectory with 0.8 mm/66 ms isotropic spatial/temporal resolution, using a similar number of readouts as our previous fully sampled cones trajectory (1.2 mm/100 ms). Scans of volunteers and patients are performed to evaluate the performance of the VD trajectory, using non-Cartesian L1 -ESPIRiT for high-resolution image reconstruction. RESULTS: With gridding reconstruction, the high-resolution scans experience an expected drop in signal-to-noise and contrast-to-noise ratios, but with L1 -ESPIRiT, the apparent noise is substantially reduced. Compared with 1.2 mm images, in each volunteer, the L1 -ESPIRiT 0.8 mm images exhibit higher vessel sharpness values in the right and left anterior descending arteries. CONCLUSION: Coronary MR angiography with isotropic submillimeter spatial resolution and high temporal resolution can be performed with VD 3D cones to improve the depiction of coronary arteries.

Non-contrast-enhanced peripheral angiography using a sliding interleaved cylinder acquisition.

PURPOSE: To develop a new sequence for non-contrast-enhanced peripheral angiography using a sliding interleaved cylinder (SLINCYL) acquisition. METHODS: A venous saturation pulse was incorporated into a three-dimensional magnetization-prepared balanced steady-state free precession sequence for non-contrast-enhanced peripheral angiography to improve artery-vein contrast. The SLINCYL acquisition, which consists of a series of overlapped thin slabs for volumetric coverage similar to the original sliding interleaved ky (SLINKY) acquisition, was used to evenly distribute the venous-suppression effects over the field of view. In addition, the thin-slab-scan nature of SLINCYL and the centric-ordered sampling geometry of its readout trajectory were exploited to implement efficient fluid-suppression and parallel imaging schemes. The sequence was tested in healthy subjects and a patient. RESULTS: Compared to a multiple overlapped thin slab acquisition, both SLINKY and SLINCYL suppressed the venetian blind artifacts and provided similar artery-vein contrast. However, SLINCYL achieved this with shorter scan times and less noticeable artifacts from k-space amplitude modulation than SLINKY. The fluid-suppression and parallel imaging schemes were also validated. A patient study using the SLINCYL-based sequence well identified stenoses at the superficial femoral arteries, which were also confirmed with digital subtraction angiography. CONCLUSION: Non-contrast-enhanced angiography using SLINCYL can provide angiograms with improved artery-vein contrast in the lower extremities.

Self-gated fat-suppressed cardiac cine MRI.

PURPOSE: To develop a self-gated alternating repetition time balanced steady-state free precession (ATR-SSFP) pulse sequence for fat-suppressed cardiac cine imaging. METHODS: Cardiac gating is computed retrospectively using acquired magnetic resonance self-gating data, enabling cine imaging without the need for electrocardiogram (ECG) gating. Modification of the slice-select rephasing gradients of an ATR-SSFP sequence enables the acquisition of a one-dimensional self-gating readout during the unused short repetition time (TR). Self-gating readouts are acquired during every TR of segmented, breath-held cardiac scans. A template-matching algorithm is designed to compute cardiac trigger points from the self-gating signals, and these trigger points are used for retrospective cine reconstruction. The proposed approach is compared with ECG-gated ATR-SSFP and balanced steady-state free precession in 10 volunteers and five patients. RESULTS: The difference of ECG and self-gating trigger times has a variability of 13 ± 11 ms (mean ± SD). Qualitative reviewer scoring and ranking indicate no statistically significant differences (P > 0.05) between self-gated and ECG-gated ATR-SSFP images. Quantitative blood-myocardial border sharpness is not significantly different among self-gated ATR-SSFP ( 0.61±0.15 mm -1), ECG-gated ATR-SSFP ( 0.61±0.15 mm -1), or conventional ECG-gated balanced steady-state free precession cine MRI ( 0.59±0.15 mm -1). CONCLUSION: The proposed self-gated ATR-SSFP sequence enables fat-suppressed cardiac cine imaging at 1.5 T without the need for ECG gating and without decreasing the imaging efficiency of ATR-SSFP.

Combined outer volume suppression and T2 preparation sequence for coronary angiography.

PURPOSE: To develop a magnetization preparation sequence for simultaneous outer volume suppression (OVS) and T2 weighting in whole-heart coronary magnetic resonance angiography. METHODS: A combined OVS and T2 preparation sequence (OVS-T2 Prep) was designed with a nonselective adiabatic 90° tipdown pulse, two adiabatic 180° refocusing pulses, and a 2D spiral -90° tipup pulse. The OVS-T2 Prep preserves the magnetization inside an elliptic cylinder with T2 weighting, while saturating the magnetization outside the cylinder. Its performance was tested on phantoms and on 13 normal subjects with coronary magnetic resonance angiography using 3D cones trajectories. RESULTS: Phantom studies showed expected T2 -dependent signal amplitude in the spatial passband and suppressed signal in the spatial stopband. In vivo studies with full-field-of-view cones yielded a passband-to-stopband signal ratio of 3.18 ± 0.77 and blood-myocardium contrast-to-noise ratio enhancement by a factor of 1.43 ± 0.20 (P < 0.001). In vivo studies with reduced-field-of-view cones showed that OVS-T2 Prep well suppressed the aliasing artifacts, as supported by significantly reduced signal in the regions with no tissues compared to the images acquired without preparation (P < 0.0001). CONCLUSION: OVS-T2 Prep is a compact sequence that can accelerate coronary magnetic resonance angiography by suppressing signals from tissues surrounding the heart while simultaneously enhancing the blood-myocardium contrast.

Nonrigid autofocus motion correction for coronary MR angiography with a 3D cones trajectory.

PURPOSE: To implement a nonrigid autofocus motion correction technique to improve respiratory motion correction of free-breathing whole-heart coronary magnetic resonance angiography acquisitions using an image-navigated 3D cones sequence. METHODS: 2D image navigators acquired every heartbeat are used to measure superior-inferior, anterior-posterior, and right-left translation of the heart during a free-breathing coronary magnetic resonance angiography scan using a 3D cones readout trajectory. Various tidal respiratory motion patterns are modeled by independently scaling the three measured displacement trajectories. These scaled motion trajectories are used for 3D translational compensation of the acquired data, and a bank of motion-compensated images is reconstructed. From this bank, a gradient entropy focusing metric is used to generate a nonrigid motion-corrected image on a pixel-by-pixel basis. The performance of the autofocus motion correction technique is compared with rigid-body translational correction and no correction in phantom, volunteer, and patient studies. RESULTS: Nonrigid autofocus motion correction yields improved image quality compared to rigid-body-corrected images and uncorrected images. Quantitative vessel sharpness measurements indicate superiority of the proposed technique in 14 out of 15 coronary segments from three patient and two volunteer studies. CONCLUSION: The proposed technique corrects nonrigid motion artifacts in free-breathing 3D cones acquisitions, improving image quality compared to rigid-body motion correction.

Rapid single-breath-hold 3D late gadolinium enhancement cardiac MRI using a stack-of-spirals acquisition.

PURPOSE: To develop a rapid single-breath-hold 3D late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) method, and demonstrate its feasibility in cardiac patients. MATERIALS AND METHODS: An inversion recovery dual-density 3D stack-of-spirals imaging sequence was developed. The spiral acquisition was 2-fold accelerated by self-consistent parallel imaging reconstruction (SPIRiT), which resulted in a total scan time of 12 heartbeats. Field map-based linear off-resonance correction was incorporated to the SPIRiT reconstruction. The 3D spiral LGE scans were performed in 15 patients who were referred for clinically ordered cardiac MR examinations that included the standard 2D multislice LGE imaging. Image sharpness and overall quality were qualitatively assessed based on 5-point scales. RESULTS: Scar-induced hyper-LGE was identified in 4 out of the 15 patients by both 3D spiral and 2D multislice LGE tests. On average over all datasets (n = 15), the image sharpness scores were 3.9 (3D spiral) and 4.0 (2D multislice), and the image quality scores were 4.1 (3D spiral) and 4.0 (2D multislice) with no significant difference in both metrics (paired t-test; P > 0.1). The average scar contrast enhancement ratios were 0.72 and 0.75 in 3D and 2D images, respectively (n = 4). The average difference of fractional scar volumes measured in 3D and 2D images was 4.3% (n = 3). CONCLUSION: Stack-of-spiral acquisition combined with non-Cartesian SPIRiT parallel imaging enables rapid 3D LGE MRI in a 12 heartbeat-long breath-hold.J.

Off-resonance-robust velocity-selective magnetization preparation for non-contrast-enhanced peripheral MR angiography.

PURPOSE: To develop a new velocity-selective (VS) excitation pulse sequence which is robust to field inhomogeneity, and demonstrate its application to non-contrast-enhanced peripheral MR angiography (MRA). METHODS: The off-resonance-robust VS saturation pulse is designed by incorporating 180° refocusing pulses into the k-space-based reference design and tailoring sequence parameters in a velocity region of interest. The VS saturation pulse is used as magnetization preparation for non-contrast-enhanced peripheral MRA to suppress background tissues but not arterial blood based on their velocities. Non-contrast-enhanced peripheral MRA using the proposed VS preparation was tested in healthy volunteers and a patient with arterial stenosis. RESULTS: Calf angiograms obtained using the new VS preparation show more uniform background suppression than the reference VS preparation, as demonstrated by larger mean values and smaller standard deviations of artery-to-vein and artery-to-muscle contrast-to-noise ratios (71.0 ± 11.4 and 75.3 ± 12.1 versus 61.7 ± 22.7 and 58.5 ± 27.8). Two-station peripheral MRA using the new VS preparation identifies stenosis of the femoral and popliteal arteries in the patient, as validated by digital subtraction angiography. CONCLUSION: Non-contrast-enhanced MRA using the new VS magnetization preparation can reliably provide high angiographic contrast in the lower extremities with significantly improved immunity to field inhomogeneity.

Non-contrast-enhanced renal and abdominal MR angiography using velocity-selective inversion preparation.

Non-contrast-enhanced MR angiography is a promising alternative to the established contrast-enhanced approach as it reduces patient discomfort and examination costs and avoids the risk of nephrogenic systemic fibrosis. Inflow-sensitive slab-selective inversion recovery imaging has been used with great promise, particularly for abdominal applications, but has limited craniocaudal coverage due to inflow time constraints. In this work, a new non-contrast-enhanced MR angiography method using velocity-selective inversion preparation is developed and applied to renal and abdominal angiography. Based on the excitation k-space formalism and Shinnar-Le-Roux transform, a velocity-selective excitation pulse is designed that inverts stationary tissues and venous blood while preserving inferiorly flowing arterial blood. As the magnetization of the arterial blood in the abdominal aorta and iliac arteries is well preserved during the magnetization preparation, artery visualization over a large abdominal field of view is achievable with an inversion delay time that is chosen for optimal background suppression. Healthy volunteer tests demonstrate that the proposed method significantly increases the extent of visible arteries compared with the slab-selective approach, covering renal arteries through iliac arteries over a craniocaudal field of view of 340 mm.

Free-breathing multiphase whole-heart coronary MR angiography using image-based navigators and three-dimensional cones imaging.

Noninvasive visualization of the coronary arteries in vivo is one of the most important goals in cardiovascular imaging. Compared to other paradigms for coronary MR angiography, a free-breathing three-dimensional whole-heart iso-resolution approach simplifies prescription effort, requires less patient cooperation, reduces overall exam time, and supports retrospective reformats at arbitrary planes. However, this approach requires a long continuous acquisition and must account for respiratory and cardiac motion throughout the scan. In this work, a new free-breathing coronary MR angiography technique that reduces scan time and improves robustness to motion is developed. Data acquisition is accomplished using a three-dimensional cones non-Cartesian trajectory, which can reduce the number of readouts 3-fold or more compared to conventional three-dimensional Cartesian encoding and provides greater robustness to motion/flow effects. To further enhance robustness to motion, two-dimensional navigator images are acquired to directly track respiration-induced displacement of the heart and enable retrospective compensation of all acquired data (none discarded) for image reconstruction. In addition, multiple cardiac phases are imaged to support retrospective selection of the best phase(s) for visualizing each coronary segment. Experimental results demonstrate that whole-heart coronary angiograms can be obtained rapidly and robustly with this proposed technique.

Three-dimensional first-pass myocardial perfusion MRI using a stack-of-spirals acquisition.

Three-dimensional cardiac magnetic resonance perfusion imaging is promising for the precise sizing of defects and for providing high perfusion contrast, but remains an experimental approach primarily due to the need for large-dimensional encoding, which, for traditional 3DFT imaging, requires either impractical acceleration factors or sacrifices in spatial resolution. We demonstrated the feasibility of rapid three-dimensional cardiac magnetic resonance perfusion imaging using a stack-of-spirals acquisition accelerated by non-Cartesian k-t SENSE, which enables entire myocardial coverage with an in-plane resolution of 2.4 mm. The optimal undersampling pattern was used to achieve the largest separation between true and aliased signals, which is a prerequisite for k-t SENSE reconstruction. Flip angle and saturation recovery time were chosen to ensure negligible magnetization variation during the transient data acquisition. We compared the proposed three-dimensional perfusion method with the standard 2DFT approach by consecutively acquiring both data during each R-R interval in cardiac patients. The mean and standard deviation of the correlation coefficients between time intensity curves of three-dimensional versus 2DFT were 0.94 and 0.06 across seven subjects. The linear correlation between the two sets of upslope values was significant (r = 0.78, P < 0.05).

High-resolution, respiratory-resolved coronary MRA using a Phyllotaxis-reordered variable-density 3D cones trajectory.

PURPOSE: To develop a respiratory-resolved motion-compensation method for free-breathing, high-resolution coronary magnetic resonance angiography (CMRA) using a 3D cones trajectory. METHODS: To achieve respiratory-resolved 0.98 mm resolution images in a clinically relevant scan time, we undersample the imaging data with a variable-density 3D cones trajectory. For retrospective motion compensation, translational estimates from 3D image-based navigators (3D iNAVs) are used to bin the imaging data into four phases from end-expiration to end-inspiration. To ensure pseudo-random undersampling within each respiratory phase, we devise a phyllotaxis readout ordering scheme mindful of eddy current artifacts in steady state free precession imaging. Following binning, residual 3D translational motion within each phase is computed using the 3D iNAVs and corrected for in the imaging data. The noise-like aliasing characteristic of the combined phyllotaxis and cones sampling pattern is leveraged in a compressed sensing reconstruction with spatial and temporal regularization to reduce aliasing in each of the respiratory phases. RESULTS: In initial studies of six subjects, respiratory motion compensation using the proposed method yields improved image quality compared to non-respiratory-resolved approaches with no motion correction and with 3D translational correction. Qualitative assessment by two cardiologists and quantitative evaluation with the image edge profile acutance metric indicate the superior sharpness of coronary segments reconstructed with the proposed method (P < 0.01). CONCLUSION: We have demonstrated a new method for free-breathing, high-resolution CMRA based on a variable-density 3D cones trajectory with modified phyllotaxis ordering and respiratory-resolved motion compensation with 3D iNAVs.

Reducing artifacts in one-dimensional Fourier velocity encoding for fast and pulsatile flow.

When evaluating the severity of valvular stenosis, the peak velocity of the blood flow is routinely used to estimate the transvalvular pressure gradient. One-dimensional Fourier velocity encoding effectively detects the peak velocity with an ungated time series of spatially resolved velocity spectra in real time. However, measurement accuracy can be degraded by the pulsatile and turbulent nature of stenotic flow and the existence of spatially varying off-resonance. In this work, we investigate the feasibility of improving the peak velocity detection capability of one-dimensional Fourier velocity encoding for stenotic flow using a novel echo-shifted interleaved readout combined with a variable-density circular k-space trajectory. The shorter echo and readout times of the echo-shifted interleaved acquisitions are designed to reduce sensitivity to off-resonance. Preliminary results from limited phantom and in vivo results also indicate that some artifacts from pulsatile flow appear to be suppressed when using this trajectory compared to conventional single-shot readouts, suggesting that peak velocity detection may be improved. The efficiency of the new trajectory improves the temporal and spatial resolutions. To realize the proposed readout, a novel multipoint-traversing algorithm is introduced for flexible and automated gradient-waveform design.

Magnetization-prepared IDEAL bSSFP: a flow-independent technique for noncontrast-enhanced peripheral angiography.

PURPOSE: To propose a new noncontrast-enhanced flow-independent angiography sequence based on balanced steady-state free precession (bSSFP) that produces reliable vessel contrast despite the reduced blood flow in the extremities. MATERIALS AND METHODS: The proposed technique addresses a variety of factors that can compromise the exam success including insufficient background suppression, field inhomogeneity, and large volumetric coverage requirements. A bSSFP sequence yields reduced signal from venous blood when long repetition times are used. Complex-sum bSSFP acquisitions decrease the sensitivity to field inhomogeneity but retain phase information, so that data can be processed with the Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-Squares Estimation (IDEAL) method for robust fat suppression. Meanwhile, frequent magnetization preparation coupled with parallel imaging reduces the muscle and long-T(1) fluid signals without compromising scan efficiency. RESULTS: In vivo flow-independent peripheral angiograms with reliable background suppression and high spatial resolution are produced. Comparisons with phase-sensitive bSSFP angiograms (that yield out-of-phase fat and water signals, and exploit this phase difference to suppress fat) demonstrate enhanced vessel depiction with the proposed technique due to reduced partial-volume effects and improved venous suppression. CONCLUSION: Magnetization-prepared complex-sum bSSFP with IDEAL fat/water separation can create reliable flow-independent angiographic contrast in the lower extremities.

In vivo high-resolution magnetic resonance skin imaging at 1.5 T and 3 T.

As a noninvasive modality, MR is attractive for in vivo skin imaging. Its unique soft tissue contrast makes it an ideal imaging modality to study the skin water content and to resolve the different skin layers. In this work, the challenges of in vivo high-resolution skin imaging are addressed. Three 3D Cartesian sequences are customized to achieve high-resolution imaging and their respective performance is evaluated. The balanced steady-state free precession (bSSFP) and gradient echo (GRE) sequences are fast but can be sensitive to off-resonance artifacts. The fast large-angle spin echo (FLASE) sequence provides a sharp depiction of the hypodermis structures but results in more specific absorption rate (SAR). The effect of increasing the field strength is assessed. As compared to 1.5 T, signal-to-noise ratio at 3 T slightly increases in the hypodermis and almost doubles in the dermis. The need for fat/water separation is acknowledged and a solution using an interleaved three-point Dixon method and an iterative reconstruction is shown to be effective. The effects of motion are analyzed and two techniques to prevent motion and correct for it are evaluated. Images with 117 x 117 x 500 microm(3) resolution are obtained in imaging times under 6 min.

Noninvasive assessment of coronary vasodilation using magnetic resonance angiography.

OBJECTIVES: The purpose of this study was to investigate the use of coronary magnetic resonance angiography (MRA) for assessing human epicardial coronary artery vasodilation. BACKGROUND: Coronary vasodilation plays a vital role in the human coronary circulation. Previous studies of epicardial coronary vasodilation have used invasive coronary angiography. Coronary MRA may provide an alternative noninvasive method to directly assess changes in coronary size. METHODS: Thirty-two subjects were studied: 12 patients (age 55 +/- 18 years) and 20 healthy subjects (age 34 +/- 4 years). High-resolution multi-slice spiral coronary MRA (in-plane resolution of 0.52 to 0.75 mm) was performed before and after sublingual nitroglycerin (NTG). Quantitative analysis of coronary vasodilation was performed on cross-sectional images of the right coronary artery (RCA). A time-course analysis of coronary vasodilation was performed in a subset of eight subjects for 30 min after NTG. Signal-to-noise ratio was also measured on the in-plane RCA images. RESULTS: Coronary MRA demonstrated a 23% increase in cross-sectional area after NTG (16.9 +/- 7.8 mm2 to 20.8 +/- 8.9 mm2, p <0.0001), with significant vasodilation between 3 and 15 min after NTG on time-course analysis. The MRA measurements had low interobserver variability (< or =5%) and good correlation with X-ray angiography (r=0.98). The magnitude of vasodilation correlated with baseline cross-sectional area (r=0.52, p=0.03) and age (r=0.40, p=0.019). Post-NTG images also demonstrated a 31% improvement in coronary signal-to-noise ratio (p = 0.002). CONCLUSIONS: Nitroglycerin-enhanced coronary MRA can noninvasively measure coronary artery vasodilation and is a promising noninvasive technique to study coronary vasomotor function.

Developmental endothelial locus-1 (Del-1), a novel angiogenic protein: its role in ischemia.

BACKGROUND: Developmentally regulated endothelial locus-1 (Del-1) is an extracellular matrix protein that is expressed by endothelial cells during embryological vascular development. We speculated that Del-1 may be reexpressed in ischemia and may be involved in endogenous angiogenesis. METHODS AND RESULTS: Del-1 protein was detected by immunohistochemistry in murine ischemic hindlimb after femoral artery excision. To determine whether exogenous Del-1 would augment angiogenesis in vivo, Del-1 or vehicle was administered for 3 weeks by intramuscular injection of murine ischemic hindlimbs. Angiogenesis was quantified by gadolinium-MRI perfusion and capillary densitometry. We used a disc angiogenesis system (DAS) to characterize the angiogenic response to vehicle (PBS), Del-1, Del-1 mutant (altered RGD domain), Del-1 minor (truncated discoidin-I-like domain), or basic fibroblast growth factor. After 14 days, the discs were extracted and sectioned to quantify vascular growth by morphometry. Endogenous Del-1 protein expression was increased in ischemic hindlimbs. Administration of Del-1 increased hindlimb vascular flow index and capillary density. In the DAS, Del-1 doubled fibrovascular growth, as did basic fibroblast growth factor. However, angiogenesis was not enhanced by the Del-1 mutant or Del-1 minor proteins. CONCLUSIONS: Del-1 is expressed in ischemic tissue. Del-1 stimulates angiogenesis, an effect that is dependent on the RGD motif and a second signaling sequence in the discoidin-I-like domain. Exogenous intramuscular administration of Del-1 significantly enhances angiogenesis in the murine ischemic hindlimb. Del-1 may prove to be a novel therapeutic agent for patients with ischemia.