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1.  Contrast-Enhanced Whole-Heart Coronary MRA at 3T Using Interleaved EPI 
Investigative radiology  2010;45(8):458-464.
The goal of this work was to reduce the scan time of contrast-enhanced whole-heart coronary magnetic resonance angiography (MRA) by using a gradient echo interleaved echo planar imaging (GRE-EPI) sequence at 3T field strength.
Materials and Methods
A GRE-EPI sequence was optimized to acquire contrast-enhanced whole-heart coronary MRA at 3T. First order phase correction was used for alignment of the odd and even echoes in the GRE-EPI echo train. Single and dual reference scan techniques for estimation of the linear phase correction parameters were evaluated using both phantom and volunteer studies. The GRE-EPI readout was combined with parallel imaging for a further reduction in scan time. To avoid image distortions, calibration signals for coil sensitivity estimation were acquired in a separate low resolution GRE scan prior to the whole-heart GRE-EPI scan. 8 healthy volunteers were scanned with the optimized contrast-enhanced GRE-EPI sequence. GRE-EPI images were acquired during slow infusion (0.3 ml/sec) of 0.1 mmol/kg body weight of Gd-BOPTA. For comparison purposes, the same 8 volunteers were scanned again in a separate scan session using a traditional GRE sequence with double the dose (0.2 mmol/kg body weight) of the same contrast agent with the same injection rate. The contrast-enhanced GRE-EPI and contrast-enhanced GRE techniques were compared in terms of relative SNR and CNR, image quality scores and visualized vessel lengths.
Both, phantom and volunteer studies demonstrated that the dual reference scan phase correction technique was a key step for obtaining satisfactory image quality using GRE-EPI at 3T. Whole-heart coronary MRA with a spatial resolution of 1.0 × 1.0 × 2.0 mm3 was acquired with the GRE-EPI sequence in an average scan time of 2.5 ± 0.6 minutes, compared with 8.6 ± 2.7 minutes for the GRE technique. The GRE-EPI technique had lower relative CNR compared with the GRE sequence. The image quality and coronary artery visualization with the GRE-EPI technique were adequate and there was no statistically significant difference in the image quality scores, relative SNR and visualized coronary artery lengths between the GRE-EPI and GRE techniques.
Contrast-enhanced whole-heart coronary MRA using the GRE-EPI technique resulted in excellent delineation of all the major coronary arteries and compared with current GRE techniques demonstrated a factor of two reduction in contrast agent dose and a factor of three reduction in scan time.
PMCID: PMC2902693  PMID: 20479653
2.  3D Whole-Heart Coronary MR Angiography at 1.5T in Healthy Volunteers: Comparison between Unenhanced SSFP and Gd-Enhanced FLASH Sequences 
Korean Journal of Radiology  2011;12(6):679-685.
To validate the optimal cardiac phase and appropriate acquisition window for three-dimensional (3D) whole-heart coronary magnetic resonance angiography (MRA) with a steady-state free precession (SSFP) sequence, and to compare image quality between SSFP and Gd-enhanced fast low-angle shot (FLASH) MR techniques at 1.5 Tesla (T).
Materials and Methods
Thirty healthy volunteers (M:F = 25:5; mean age, 35 years; range, 24-54 years) underwent a coronary MRA at 1.5T. 3D whole-heart coronary MRA with an SSFP was performed at three different times: 1) at end-systole with a narrow (120-msec) acquisition window (ESN), 2) mid-diastole with narrow acquisition (MDN); and 3) mid-diastole with wide (170-msec) acquisition (MDW). All volunteers underwent a contrast enhanced coronary MRA after undergoing an unenhanced 3D true fast imaging with steady-state precession (FISP) MRA three times. A contrast enhanced coronary MRA with FLASH was performed during MDN. Visibility of the coronary artery and image quality were evaluated for 11 segments, as suggested by the American Heart Association. Image quality was scored by a five-point scale (1 = not visible to 5 = excellent). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated at the proximal coronary arteries.
The SSFP sequence rendered higher visibility coronary segments, higher image quality, as well as higher SNR and CNR than the Gd-enhanced FLASH technique at 1.5T (p < 0.05). The visibility of coronary segments, image quality, SNR and CNR in the ESN, MDN and MDW with SSFP sequence did not differ significantly.
An SSFP sequence provides an excellent method for the 3D whole-heart coronary MRA at 1.5T. Contrast enhanced coronary MRA using the FLASH sequence does not help improve the visibility of coronary segments, image quality, SNR or CNR on the 3D whole-heart coronary MRA.
PMCID: PMC3194771  PMID: 22043149
Cardiac magnetic resonance; Coronary artery imaging; Steady-state free precession; Fast low-angle shot; Contrast agent; 1.5T
3.  Simultaneous Magnetic Resonance Angiography and Perfusion (MRAP) Measurement: Initial Application in Lower Extremity Skeletal Muscle 
Journal of magnetic resonance imaging : JMRI  2013;38(5):10.1002/jmri.24020.
To obtain a simultaneous 3D MR Angiography and Perfusion (MRAP) using a single acquisition, and to demonstrate MRAP in the lower extremities. A time-resolved contrast-enhanced exam is utilized in MRAP to simultaneously acquire a contrast-enhanced MR angiography (MRA) and dynamic contrast-enhanced (DCE) perfusion, which currently requires separate acquisitions and thus two contrast doses. MRAP can be used to assess large and small vessels in vascular pathologies such as peripheral arterial disease.
Materials and Methods
MRAP was performed on ten volunteers following unilateral plantar flexion exercise (one leg exercised and one rested) on two separate days. Data were acquired after administration of a single dose of contrast agent using an optimized sampling strategy, parallel imaging, and partial-Fourier acquisition to obtain a high spatial resolution, 3D-MRAP frame every four seconds. Two radiologists assessed MRAs for image quality, a signal-to-noise ratio (SNR) analysis was performed, and pharmacokinetic modeling yielded perfusion (Ktrans).
MRA images had high SNR and radiologist-assessed diagnostic quality. Mean Ktrans±standard error were 0.136±0.009, 0.146±0.012, and 0.191±0.012 min−1 in the resting tibialis anterior, gastrocnemius, and soleus, respectively, which significantly increased with exercise to 0.291±0.018, 0.270±0.019, and 0.338±0.022 min−1. Bland-Altman analysis showed good repeatability.
MRAP provides simultaneous high-resolution MRA and quantitative DCE exams to assess large and small vessels with a single contrast dose. Application in skeletal muscle shows quantitative, repeatable perfusion measurements, and the ability to measure physiological differences.
PMCID: PMC3657593  PMID: 23389970
MR Angiography; Dynamic Contrast Enhanced MRI; Perfusion
4.  3.0-T Whole-Heart Coronary Magnetic Resonance Angiography: Comparison of Gadobenate Dimeglumine and Gadofosveset Trisodium 
Gadolinium enhanced coronary magnetic resonance angiography (MRA) at 3 Tesla appears to be superior to non-contrast methods. Gadofosveset is an intravascular contrast agent that may be well suited to this application. The purpose of this study was to perform an intra-individual comparison of gadofosveset and gadobenate for coronary MRA at 3 Tesla.
Materials and Methods
In this prospective randomized study, 22 study subjects [8 (36%) male; 27.9 ± 6 years; BMI = 22.8 ± 2 Kg/m2] underwent two studies using a contrast-enhanced inversion recovery three-dimensional fast low angle shot MRA at 3 Tesla. The order of contrast agent administration was varied randomly, separated by an average of 30 ± 5 days, using either gadobenate dimeglumine (Gd-BOPTA; Bracco, 0.1 mmol/Kg) or gadofosveset trisodium (MS-325; Lantheus Med, 0.03 mmol/Kg). Acquisition time, signal-to-noise ratio (SNR) of coronary vessels and contrast-to-noise ratio (CNR) were evaluated.
Of 308 coronary arteries and veins segment analyzed, overall SNR of coronary arteries and veins segments were not different for the two contrast agents (132 ± 79 for gadofosveset vs 135 ± 78 for gadobenate, p=0.69). Coronary artery CNR was greater for gadofosveset in comparison to gadobenate (73.5 ± 46.9vs. 59.3 ± 75.7 respectively, p=0.03). Gadofosveset-enhanced MRA images displayed better image quality than gadobenate-enhanced MRA images (2.77 ± 0.61 for gadofosveset vs. 2.11 ± 0.51, P<.001). Inter- and intra-reader variability was excellent (ICC > 0.90) for both contrast agents.
Gadofosveset trisodium appears to show slightly better performance for coronary MRA at 3T compared to gadobenate.
PMCID: PMC3702681  PMID: 23515949
Gadofosveset trisodium; gadobenate dimeglumine; coronary MRA
5.  The impact of physiological noise correction on fMRI at 7 T 
Neuroimage  2011;57(1-4):101-112.
Cognitive neuroimaging studies typically require fast whole brain image acquisition with maximal sensitivity to small BOLD signal changes. To increase the sensitivity, higher field strengths are often employed, since they provide an increased image signal-to-noise ratio (SNR). However, as image SNR increases, the relative contribution of physiological noise to the total time series noise will be greater compared to that from thermal noise. At 7 T, we studied how the physiological noise contribution can be best reduced for EPI time series acquired at three different spatial resolutions (1.1 mm × 1.1 mm × 1.8 mm, 2 mm × 2 mm × 2 mm and 3 mm × 3 mm × 3 mm). Applying optimal physiological noise correction methods improved temporal SNR (tSNR) and increased the numbers of significantly activated voxels in fMRI visual activation studies for all sets of acquisition parameters. The most dramatic results were achieved for the lowest spatial resolution, an acquisition parameter combination commonly used in cognitive neuroimaging which requires high functional sensitivity and temporal resolution (i.e. 3 mm isotropic resolution and whole brain image repetition time of 2 s). For this data, physiological noise models based on cardio-respiratory information improved tSNR by approximately 25% in the visual cortex and 35% sub-cortically. When the time series were additionally corrected for the residual effects of head motion after retrospective realignment, the tSNR was increased by around 58% in the visual cortex and 71% sub-cortically, exceeding tSNR ~ 140. In conclusion, optimal physiological noise correction at 7 T increases tSNR significantly, resulting in the highest tSNR per unit time published so far. This tSNR improvement translates into a significant increase in BOLD sensitivity, facilitating the study of even subtle BOLD responses.
► Impact of physiological noise correction on tSNR versus SNR was characterized at 7 T. ► tSNR was improved by 50 to 70% using physiological noise correction in task-free EPI. ► The reported results exceed values for tSNR per unit time published so far. ► tSNR improvements translated into more than 10% increase in BOLD activity in fMRI.
PMCID: PMC3115139  PMID: 21515386
Physiological noise; SNR; Temporal SNR; tSNR; fMRI; 7 T
6.  Vascular Masking for Improved Unfolding in 2D SENSE-Accelerated 3D Contrast-Enhanced MR Angiography 
To describe and evaluate the method we refer to as “vascular masking” for improving signal-to-noise ratio (SNR) retention in SENSE-accelerated contrast-enhanced MR angiography (CE-MRA).
Materials and Methods
Vascular masking is a technique which restricts the SENSE unfolding of an accelerated subtraction angiogram to the voxels within the field of view known to have enhancing signal. This is a more restricted voxel set than that identified with conventional masking which excludes only voxels in the air around the object. Thus, improved retention of SNR is expected. Evaluation was done in phantom and in vivo studies by comparing SNR and the g-factor in results reconstructed using vascular vs. conventional masking. A radiological evaluation was also performed comparing conventional and vascular masking in R = 8 accelerated CE-MRA studies of the thighs (n=21) and calves (n=13).
Images reconstructed with vascular masking showed significant reduction in g-factor and improved retention of SNR vs. those reconstructed with conventional masking. In the radiological evaluation vascular masking consistently provided reduced background noise, improved luminal signal smoothness, and better small vessel conspicuity.
Vascular masking provides improved SNR retention and improved depiction of the vasculature in accelerated, subtraction 3D CE-MRA of the thighs and calves.
PMCID: PMC3818335  PMID: 23897776
Contrast-enhanced MR angiography (CE-MRA); SENSE; masking
7.  Non-Contrast Enhanced MR Angiography (NCE-MRA) of the Calf: A Direct Comparison between Flow-Sensitive Dephasing (FSD) Prepared Steady-State Free Precession (SSFP) and Quiescent-Interval Single-Shot (QISS) in Patients with Diabetes 
PLoS ONE  2015;10(6):e0128786.
To compare the image quality and diagnostic performance of two non-contrast enhanced MR angiography (NCE-MRA) techniques using flow-sensitive dephasing (FSD) prepared steady-state free precession (SSFP) and quiescent-interval single-shot (QISS) for the calf arteries in patients with diabetes.
Materials and Methods
Twenty six patients underwent the two NCE-MRA techniques followed by contrast-enhanced MRA (CE-MRA) of lower extremity on a 1.5T MR system. Image quality scores, arterial stenosis scores, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel sharpness, and diagnostic accuracy for detecting more than 50% arterial stenosis were evaluated and statistically compared using CE-MRA as the reference standard.
All examinations were performed successfully. Of the total 153 calf arterial segments obtained in the 26 patients, FSD and QISS showed no significant difference in the number of diagnostic arterial segments (151 [98%] vs. 147 [96%], respectively, P>0.05). The image quality of FSD was higher than that of QISS in the peroneal artery and posterior tibial artery (P<0.05), but no significant difference in the anterior tibial artery (P>0.05). SNR and CNR of FSD were higher than those of QISS (P<0.01), while FSD showed comparable vessel sharpness compared with QISS (P>0.05). The time efficiency of SNR and CNR between FSD and QISS showed no significant difference when taking into account the times for FSD-related scout scans. There was no difference in sensitivity (95% vs. 93%, P>0.05) and negative predictive value (98% vs. 97%, P>0.05) between FSD and QISS for detecting stenosis greater than 50%. However, FSD showed higher specificities (99% vs. 92%, P<0.05) and diagnostic accuracy (98% vs. 92%, P<0.05) compared to QISS.
Both FSD and QISS had similar high sensitivity and negative predictive value for detecting calf arteries with over 50% stenosis, but FSD showed slightly higher diagnostic specificity and better depiction of arterial lesions due to its isotropic submillimeter spatial resolution. QISS, being an easier to use and less time-consuming technique, could be a method of choice for rapid screening of arterial disease of the lower extremity.
PMCID: PMC4452776  PMID: 26035645
8.  The Feasibility of 350 Micron Spatial Resolution Coronary MRA at 3T in Humans 
Investigative Radiology  2012;47(6):339-345.
The purpose of this study was to (1) develop a high resolution 3T MRA technique with in-plane resolution approximate to that of MDCT and a voxel size of 0.35 × 0.35 × 1.5 mm3 and to (2) investigate the image quality of this technique in healthy subjects and preliminarily in patients with known coronary artery disease (CAD).
Materials and Methods
A 3T coronary MRA technique optimized for an image acquisition voxel as small as 0.35 × 0.35 × 1.5mm3 (HRC) was implemented and the coronary arteries of twenty two subjects were imaged. These included 11 healthy subjects (average age 28.5 years old, five males) and 11 subjects (average age 52.9 years old, five females) with CAD as identified on multidetector coronary computed tomography (MDCT). Additionally, the 11 healthy subjects were imaged using a method with a more common spatial resolution of 0.7×1×3 mm3 (RRC). Qualitative and quantitative comparisons were made between the two MRA techniques.
Normal vessels and CAD lesions were successfully depicted at 350×350μm2 in-plane resolution with adequate signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The CAD findings were consistent among MDCT and HRC. The HRC showed a 47% improvement in sharpness despite a reduction in SNR (reduced by 72%) and CNR (reduced by 86%) compared to the RRC.
This study, as a first step towards substantial improvement in the resolution of coronary MRA, demonstrates the feasibility of obtaining at 3T a spatial resolution that approximates that of MDCT. The acquisition in-plane pixel dimensions are as small as 350μm × 350μm with a 1.5 mm slice thickness. While SNR is lower, the images have improved sharpness resulting in image quality that allowed qualitative identification of disease sites on MRA consistent with MDCT.
PMCID: PMC3349009  PMID: 22551651
9.  Non-Contrast Enhanced MR Angiography of the Foot: Initial Experience of Using Flow Sensitive Dephasing (FSD) Prepared Steady-State Free Precession in Patients with Diabetes 
Radiology  2014;272(3):885-894.
To assess image quality and diagnostic performance of non-contrast enhanced MR angiography (NCE-MRA) using flow-sensitive dephasing (FSD) prepared steady-state free precession (SSFP) for the foot arteries in patients with diabetes.
Materials and Methods
This prospective study was approved by institutional review board and informed consent was obtained from all subjects. Thirty-two healthy volunteers and 38 diabetic patients who had been scheduled for lower extremity contrast-enhanced MRA (CE-MRA) were recruited for the NCE-MRA study on a 1.5T MR system. Image quality and diagnostic accuracy of NCE-MRA for detecting significant arterial stenosis (≥50%) were assessed by two independent reviewers using CE-MRA as reference standard. The difference of the percentage of diagnostic arterial segments on NCE-MRA between healthy volunteers and diabetic patient was evaluated using McNemar test and Generalized Estimating Equation (GEE) for correlated data. Signal-to-noise ratio (SNR) and artery-to-muscle contrast-to-noise ratio (CNR) of pedal arteries were measured and compared between the two MRA techniques using paired t-test.
All subjects successfully underwent NCE-MRA of the foot. NCE-MRA yielded a high percentage of diagnostic arterial segments obtained in both healthy volunteers (303/320=95%) and patients (341/370=92%) and there was no difference in the percentage between the two populations (p=0.195). In patients, the average SNR, and CNR on NCE-MRA was higher than those on CE-MRA (90.7± 38.1 vs. 81.7± 34.7, p=0.023, and 85.2 ± 33.2 vs. 76.6 ± 33.5, p=0.013, respectively.). The average sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of NCE-MRA were 35/40=88%, 107/115=93%, 35/43=81%, 107/112=96%, and 142/155=92%, respectively. Interobserver agreement between the two readers for diagnostic accuracy was good (k = 0.83).
NCE-MRA using FSD-prepared SSFP allows clear depiction of the foot arterial tree and accurate detection of significant arterial stenosis. The technique has the potential to be a safe and reliable screening tool for the assessment of foot arteries in diabetic patients without using gadolinium-based contrast agent.
PMCID: PMC4154940  PMID: 24758556
MR angiography; non-contrast enhanced; diabetes; foot arteries; steady-state free precession; flow-sensitive dephasing
Academic radiology  2005;12(12):1521-1526.
To investigate the magnetic field dependence of the signal-to-noise ratio (SNR) for carotid vessel wall magnetic resonance imaging (MRI) using phased-array (PA) surface coils by comparing images obtained at 1.5 T and 3 T, and to determine to what extent the improved SNR at the higher field can be traded for improved spatial resolution.
Materials and methods
Two pairs of dual-element PA coils were constructed for operation at the two field strengths. The individual elements of each PA were matched to 50 Ω impedance on the neck and tuned at the respective frequencies. The coils were evaluated on a cylindrical phantom positioned with its axis parallel to the main field, and with the coils placed on either side of the phantom parallel to the sagittal plane. In-vivo MR images of the carotid arteries were obtained in five subjects at both field strengths with a fast spin-echo double-inversion black-blood pulse sequence with fat saturation. SNR was measured at both field strengths using standard techniques.
At a depth corresponding to the average location of the carotid arteries in the study subjects, mean phantom SNR for the two coils was higher at 3 T by a factor of 2.5. The greater than linear increase is due to only partial coil loading of these relatively small coils. The practically achievable average SNR gain in vivo was 2.1. The lower in vivo SNR gain is attributed to a reduction in T2 and prolongation of T1 at the higher field strength and, to a lesser extent, the requirement for reduced refocusing pulse flip angle to operate within specific absorption ratio limits. The superior SNR at 3 T appears to provide considerably improved vessel wall delineation.
Carotid artery vessel wall MRI using phased-array surface coils provides a considerable increase in SNR when field strength is raised from 1.5 T to 3 T. This increase can be traded for enhanced in-plane resolution.
PMCID: PMC1343477  PMID: 16321740
high field MRI; 3 T; carotid arteries; phased array coils; SNR
11.  Dual-Echo Arteriovenography Imaging with 7 Tesla MR 
To implement a dual-echo sequence MR imaging technique at 7T for simultaneous acquisition of time-of-flight (TOF) MR angiogram (MRA) and blood oxygenation level-dependent (BOLD) MR venogram (MRV) in a single MR acquisition and to compare the image qualities with those acquired at 3T.
Materials and Methods
We implemented a dual-echo sequence with an echo-specific K-space reordering scheme to uncouple the scan parameter requirements for MRA and MRV at 7T. The MRA and MRV vascular contrast was enhanced by maximally separating the K-space center regions acquired for the MRA and MRV and by adjusting and applying scan parameters compatible between the MRA and MRV. The same imaging sequence was implemented at 3T. Four normal subjects were imaged at both 3T and 7T. MRA and MRV at 7T were reconstructed both with and without phase-mask filtering and were compared with those at 3T with phase-mask filtering quantitatively and qualitatively.
The depiction of small cortical arteries and veins on MRA and MRV at 7T was substantially better than that at 3T, due to about twice higher contrast-to-noise ratio for both arteries (164±57 vs. 77±26) and veins (72±8 vs. 36±6). Even without use of the phase-masking filtering, the venous contrast at 7T (65±7) was higher than that with the filtering at 3T (36±6).
The dual-echo arteriovenography technique we implemented at 7T allows the improved visualization of small vessels in both the MRA and MRV because of the greatly increased SNR and susceptibility contrast, compared to 3T.
PMCID: PMC3713493  PMID: 20027596
High-field MR; MR angiography; time-of-flight; blood-oxygenation-level-dependent venography; susceptibility-weighted imaging; brain imaging; dual-echo technique; CODEA
12.  Signal-to-noise ratio increase in carotid atheroma MRI: a comparison of 1.5 and 3 T 
The British Journal of Radiology  2012;85(1015):937-944.
This study reports quantitative comparisons of signal-to-noise ratio (SNR) at 1.5 and 3 T from images of carotid atheroma obtained using a multicontrast, cardiac-gated, blood-suppressed fast spin echo protocol.
18 subjects, with carotid atherosclerosis (>30% stenosis) confirmed on ultrasound, were imaged on both 1.5 and 3 T systems using phased-array coils with matched hardware specifications. T1 weighted (T1W), T2 weighted (T2W) and proton density-weighted (PDW) images were acquired with identical scan times. Multiple slices were prescribed to encompass both the carotid bifurcation and the plaque. Image quality was quantified using the SNR and contrast-to-noise ratio (CNR). A phantom experiment was also performed to validate the SNR method and confirm the size of the improvement in SNR. Comparisons of the SNR values from the vessel wall with muscle and plaque/lumen CNR measurements were performed at a patient level. To account for the multiple comparisons a Bonferroni correction was applied.
One subject was excluded from the protocol owing to image quality and protocol failure. The mean improvement in SNR in plaque was 1.9, 2.1 and 2.1 in T1W, T2W and PDW images, respectively. All plaque SNR improvements were statistically significant at the p<0.05 level. The phantom experiment reported an improvement in SNR of 2.4 for PDW images.
Significant gains in SNR can be obtained for carotid atheroma imaging at 3 T compared with 1.5 T. There was also a trend towards increased CNR. However, this was not significant after the application of the Bonferroni correction.
PMCID: PMC3474060  PMID: 22294703
13.  Highly Parallel Volumetric Imaging With a 32-Element RF Coil Array 
The improvement of MRI speed with parallel acquisition is ultimately an SNR-limited process. To offset acquisition- and reconstruction-related SNR losses, practical parallel imaging at high accelerations should include the use of a many-element array with a high intrinsic signal-to-noise ratio (SNR) and spatial-encoding capability, and an advantageous imaging paradigm. We present a 32-element receive-coil array and a volumetric paradigm that address the SNR challenge at high accelerations by maximally exploiting multidimensional acceleration in conjunction with noise averaging. Geometric details beyond an initial design concept for the array were determined with the guidance of simulations. Imaging with the support of 32-channel data acquisition systems produced in vivo results with up to 16-fold acceleration, including images from rapid abdominal and MRA studies.
PMCID: PMC2819016  PMID: 15389961
parallel imaging; volumetric imaging; coil design; high acceleration; abdominal imaging; MRA
14.  Accelerating Time-Resolved MRA With Multiecho Acquisition 
A new four-dimensional magnetic resonance angiograpy (MRA) technique called contrast-enhanced angiography with multiecho and radial k-space is introduced, which accelerates the acquisition using multiecho while maintaining a high spatial resolution and increasing the signal-to-noise ratio. An acceleration factor of approximately 2 is achieved without parallel imaging or undersampling by multiecho (i.e., echo-planar imaging) acquisition. SNR is gained from (1) longer pulse repetition times, which allow more time for T1 regrowth; (2) decreased specific absorption rate, which allows use of flip angles that maximize contrast at high field; and (3) minimized effects of a transient contrast bolus signal with a shorter temporal footprint. Simulations, phantom studies, and in vivo scans were performed. Contrast-enhanced angiography with multiecho and radial k-space can be combined with parallel imaging techniques such as Generalized Autocalibrating Partially Parallel Acquisitions to provide additional 2-fold acceleration in addition to higher SNR to trade off for parallel imaging. This technique can be useful in diagnosing vascular lesions where accurate dynamic information is necessary.
PMCID: PMC2879614  PMID: 20512855
multiecho; radial; MRA; time-resolved; 4D; contrast-enhanced; CAMERA
15.  Fast and Tissue-Optimized Mapping of Magnetic Susceptibility and T2* with Multi-Echo and Multi-Shot Spirals 
NeuroImage  2011;59(1):297-305.
Gradient-echo MRI of resonance-frequency shift and T2* values exhibits unique tissue contrast and offers relevant physiological information. However, acquiring 3D-phase images and T2* maps [A1] with the standard spoiled gradient echo (SPGR) sequence is lengthy for routine imaging at high-spatial resolution and whole-brain coverage. In addition, with the standard SPGR sequence, optimal signal-to-noise ratio (SNR) cannot be achieved for every tissue type given their distributed resonance frequency and T2* value. To address these two issues, a SNR optimized multi-echo sequence with a stack-of-spiral acquisition is proposed and implemented for achieving fast and simultaneous acquisition of image phase and T2* maps. The analytical behavior of the phase SNR is derived as a function of resonance frequency, T2* and echo time. This relationship is utilized to achieve tissue optimized SNR by combining phase images with different echo times. Simulations and in vivo experiments were designed to verify the theoretical predictions. Using the multi-echo spiral acquisition, whole-brain coverage with 1 mm isotropic resolution can be achieved within 2.5 minutes, shortening the scan time by a factor of 8. The resulting multi-echo phase map shows similar SNR to that of the standard SPGR. The acquisition can be further accelerated with non-Cartesian parallel imaging. The technique can be readily extended to other multi-shot readout trajectories besides spiral. It may provide a practical acquisition strategy for high resolution and simultaneous 3D mapping of magnetic susceptibility and T2*.
PMCID: PMC3235505  PMID: 21784162
Image phase; susceptibility map; fast imaging; spiral; multiple echoes
16.  Accelerated Isotropic Sub-Millimeter Whole-Heart Coronary MRI: Compressed Sensing versus Parallel Imaging 
To enable accelerated isotropic sub-millimeter whole-heart coronary MRI within a six-minute acquisition, and to compare this with a current state-of-the-art accelerated imaging technique at acceleration rates beyond what is used clinically.
Coronary MRI still faces major challenges, including lengthy acquisition time, low signal-to-noise-ratio (SNR), and suboptimal spatial resolution. Higher spatial resolution in the sub-millimeter (sub-mm) range is desirable, but this results in increased acquisition time and lower SNR, hindering its clinical implementation. In this study, we sought to utilize an advanced B1-weighted compressed sensing (CS) technique for highly-accelerated sub-mm whole-heart coronary MRI, and to compare the results to parallel imaging, the current-state-of-the-art, where both techniques were used at acceleration rates beyond what is used clinically. Two whole-heart coronary MRI datasets were acquired in seven healthy adult subjects (30.3 ± 12.1 yrs; 3 men), using prospective 6-fold acceleration, with random undersampling for the proposed CS technique and with uniform undersampling for SENSE reconstruction. Reconstructed images were qualitatively compared in terms of image scores and perceived SNR on a 4-point scale (1 = poor, 4 = excellent) by an experienced blinded reader.
The proposed technique resulted in images with clear visualization of all coronary branches. Overall image quality and perceived SNR of the CS images were significantly higher than those of parallel imaging (P=0.03 for both), which suffered from noise amplification artifacts due to the reduced SNR.
The proposed CS-based reconstruction and acquisition technique for sub-mm WH coronary MRI provides 6-fold acceleration, where it outperforms parallel imaging with uniform undersampling.
PMCID: PMC3675164  PMID: 23440946
compressed sensing; accelerated imaging; parallel imaging; whole-heart coronary MRI; sub-millimeter; high resolution imaging
17.  Breath-hold imaging of the coronary arteries using Quiescent-Interval Slice-Selective (QISS) magnetic resonance angiography: pilot study at 1.5 Tesla and 3 Tesla 
Coronary magnetic resonance angiography (MRA) is usually obtained with a free-breathing navigator-gated 3D acquisition. Our aim was to develop an alternative breath-hold approach that would allow the coronary arteries to be evaluated in a much shorter time and without risk of degradation by respiratory motion artifacts. For this purpose, we implemented a breath-hold, non-contrast-enhanced, quiescent-interval slice-selective (QISS) 2D technique. Sequence performance was compared at 1.5 and 3 Tesla using both radial and Cartesian k-space trajectories.
The left coronary circulation was imaged in six healthy subjects and two patients with coronary artery disease. Breath-hold QISS was compared with T2-prepared 2D balanced steady-state free-precession (bSSFP) and free-breathing, navigator-gated 3D bSSFP.
Approximately 10 2.1-mm thick slices were acquired in a single ~20-s breath-hold using two-shot QISS. QISS contrast-to-noise ratio (CNR) was 1.5-fold higher at 3 Tesla than at 1.5 Tesla. Cartesian QISS provided the best coronary-to-myocardium CNR, whereas radial QISS provided the sharpest coronary images. QISS image quality exceeded that of free-breathing 3D coronary MRA with few artifacts at either field strength. Compared with T2-prepared 2D bSSFP, multi-slice capability was not restricted by the specific absorption rate at 3 Tesla and pericardial fluid signal was better suppressed. In addition to depicting the coronary arteries, QISS could image intra-cardiac structures, pericardium, and the aortic root in arbitrary slice orientations.
Breath-hold QISS is a simple, versatile, and time-efficient method for coronary MRA that provides excellent image quality at both 1.5 and 3 Tesla. Image quality exceeded that of free-breathing, navigator-gated 3D MRA in a much shorter scan time. QISS also allowed rapid multi-slice bright-blood, diastolic phase imaging of the heart, which may have complementary value to multi-phase cine imaging. We conclude that, with further clinical validation, QISS might provide an efficient alternative to commonly used free-breathing coronary MRA techniques.
PMCID: PMC4655490  PMID: 26597281
Quiescent-interval slice-selective (QISS); Coronary artery; Magnetic resonance angiography; Breath-holding; Navigator; Free-breathing
18.  Accelerated Whole-Heart Coronary MRA Using Motion-Corrected Sensitivity Encoding with Three-Dimensional Projection Reconstruction 
Magnetic resonance in medicine  2014;73(1):284-291.
To achieve whole-heart coronary magnetic resonance angiography (MRA) with (1.0 mm)3 spatial resolution and 5 min of free-breathing scan time.
We used an electrocardiograph-gated, T2-prepared and fat-saturated balanced steady state free precession sequence with 3DPR trajectory for free-breathing data acquisition with 100% gating efficiency. For image reconstruction, we used a self-calibrating iterative SENSE scheme with integrated retrospective motion correction. We performed healthy volunteer study to compare the proposed method with motion-corrected gridding at different retrospective undersampling levels on apparent signal-to-noise ratio (aSNR) and subjective coronary artery (CA) visualization scores.
Compared with gridding, the proposed method significantly improved both image quality metrics for undersampled datasets with 6000, 8000, and 10,000 projections. With as few as 10,000 projections, the proposed method yielded good CA visualization scores (3.02 of 4) and aSNR values comparable to those with 20,000 projections.
Using the proposed method, good image quality was observed for free breathing whole-heart coronary MRA at (1.0 mm)3 resolution with an achievable scan time of 5 min.
PMCID: PMC4101070  PMID: 24435956
coronary MRA; sensitivity encoding; motion correction; 3D radial acquisition
19.  Fast Imaging Technique for fMRI: Consecutive Multishot Echo Planar Imaging Accelerated with GRAPPA Technique 
BioMed Research International  2015;2015:394213.
This study was to evaluate the proposed consecutive multishot echo planar imaging (cmsEPI) combined with a parallel imaging technique in terms of signal-to-noise ratio (SNR) and acceleration for a functional imaging study. We developed cmsEPI sequence using both consecutively acquired multishot EPI segments and variable flip angles to minimize the delay between segments and to maximize the SNR, respectively. We also combined cmsEPI with the generalized autocalibrating partially parallel acquisitions (GRAPPA) method. Temporal SNRs were measured at different acceleration factors and number of segments for functional sensitivity evaluation. We also examined the geometric distortions, which inherently occurred in EPI sequence. The practical acceleration factors, R = 2 or R = 3, of the proposed technique improved the temporal SNR by maximally 18% in phantom test and by averagely 8.2% in in vivo experiment, compared to cmsEPI without parallel imaging. The data collection time was decreased in inverse proportion to the acceleration factor as well. The improved temporal SNR resulted in better statistical power when evaluated on the functional response of the brain. In this study, we demonstrated that the combination of cmsEPI with the parallel imaging technique could provide the improved functional sensitivity for functional imaging study, compensating for the lower SNR by cmsEPI.
PMCID: PMC4564598  PMID: 26413518
20.  Denoising MRI Using Spectral Subtraction 
Improving the signal-to-noise-ratio (SNR) of magnetic resonance imaging (MRI) using denoising techniques could enhance their value, provided that signal statistics and image resolution are not compromised. Here, a new denoising method based on spectral subtraction of the measured noise power from each signal acquisition is presented. Spectral subtraction denoising (SSD) assumes no prior knowledge of the acquired signal and does not increase acquisition time. Whereas conventional denoising/filtering methods are compromised in parallel imaging by spatially dependent noise statistics, SSD is performed on signals acquired from each coil separately, prior to reconstruction. Using numerical simulations, we show that SSD can improve SNR by up to ~45% in MRI reconstructed from both single and array coils, without compromising image resolution. Application of SSD to phantom, human heart, and brain MRI achieved SNR improvements of ~40% compared to conventional reconstruction. Comparison of SSD with anisotropic diffusion filtering showed comparable SNR enhancement at low-SNR levels (SNR = 5–15) but improved accuracy and retention of structural detail at a reduced computational load.
PMCID: PMC4142803  PMID: 23322757
Magnetic resonance imaging (MRI) denoising; parallel imaging; spectral subtraction; SENSE
21.  Compressed sensing to accelerate magnetic resonance spectroscopic imaging: evaluation and application to 23Na-imaging of mouse hearts 
Magnetic Resonance Spectroscopic Imaging (MRSI) has wide applicability for non-invasive biochemical assessment in clinical and pre-clinical applications but suffers from long scan times. Compressed sensing (CS) has been successfully applied to clinical 1H MRSI, however a detailed evaluation of CS for conventional chemical shift imaging is lacking. Here we evaluate the performance of CS accelerated MRSI, and specifically apply it to accelerate 23Na-MRSI on mouse hearts in vivo at 9.4 T.
Synthetic phantom data representing a simplified section across a mouse thorax were used to evaluate the fidelity of the CS reconstruction for varying levels of under-sampling, resolution and signal-to-noise ratios (SNR). The amplitude of signals arising from within a compartment, and signal contamination arising from outside the compartment relative to noise-free Fourier-transformed (FT) data were determined. Simulation results were subsequently verified experimentally in phantoms and in three mouse hearts in vivo.
CS reconstructed MRSI data are scaled linearly relative to absolute signal intensities from the fully-sampled FT reconstructed case (R2 > 0.8, p-value < 0.001). Higher acceleration factors resulted in a denoising of the reconstructed spectra, but also in an increased blurring of compartment boundaries, particularly at lower spatial resolutions. Increasing resolution and SNR decreased cross-compartment contamination and yielded signal amplitudes closer to the FT data. Proof-of-concept high-resolution, 3-fold accelerated 23Na-amplitude maps of murine myocardium could be obtained within ~23 mins.
Relative signal amplitudes (i.e. metabolite ratios) and absolute quantification of metabolite concentrations can be accurately determined with up to 5-fold under-sampled, CS-reconstructed MRSI. Although this work focused on murine cardiac 23Na-MRSI, the results are equally applicable to other nuclei and tissues (e.g. 1H MRSI in brain). Significant reduction in MRSI scan time will reduce the burden on the subject, increase scanner throughput, and may open new avenues for (pre-) clinical metabolic studies.
PMCID: PMC4466859  PMID: 26073300
Compressed sensing; Magnetic resonance spectroscopic imaging; Chemical shift imaging; Mouse; Sodium
22.  MRI-Based Nonrigid Motion Correction in Simultaneous PET/MRI 
Respiratory and cardiac motion is the most serious limitation to whole-body PET, resulting in spatial resolution close to 1 cm. Furthermore, motion-induced inconsistencies in the attenuation measurements often lead to significant artifacts in the reconstructed images. Gating can remove motion artifacts at the cost of increased noise. This paper presents an approach to respiratory motion correction using simultaneous PET/MRI to demonstrate initial results in phantoms, rabbits, and nonhuman primates and discusses the prospects for clinical application.
Studies with a deformable phantom, a free-breathing primate, and rabbits implanted with radioactive beads were performed with simultaneous PET/MRI. Motion fields were estimated from concurrently acquired tagged MR images using 2 B-spline nonrigid image registration methods and incorporated into a PET list-mode ordered-subsets expectation maximization algorithm. Using the measured motion fields to transform both the emission data and the attenuation data, we could use all the coincidence data to reconstruct any phase of the respiratory cycle. We compared the resulting SNR and the channelized Hotelling observer (CHO) detection signal-to-noise ratio (SNR) in the motion-corrected reconstruction with the results obtained from standard gating and uncorrected studies.
Motion correction virtually eliminated motion blur without reducing SNR, yielding images with SNR comparable to those obtained by gating with 5–8 times longer acquisitions in all studies. The CHO study in dynamic phantoms demonstrated a significant improvement (166%–276%) in lesion detection SNR with MRI-based motion correction as compared with gating (P < 0.001). This improvement was 43%–92% for large motion compared with lesion detection without motion correction (P < 0.001). CHO SNR in the rabbit studies confirmed these results.
Tagged MRI motion correction in simultaneous PET/MRI significantly improves lesion detection compared with respiratory gating and no motion correction while reducing radiation dose. In vivo primate and rabbit studies confirmed the improvement in PET image quality and provide the rationale for evaluation in simultaneous whole-body PET/MRI clinical studies.
PMCID: PMC4077320  PMID: 22743250
lesion detection; motion correction; PET/MRI
23.  Noncontrast MR Angiography for Comprehensive Assessment of Abdominopelvic Arteries using Quadruple Inversion-Recovery Preconditioning and 3D balanced Steady-State Free Precession Imaging 
To develop a non-contrast MR angiography (MRA) method for comprehensive evaluation of abdominopelvic arteries in a single 3D acquisition.
Materials and Methods
A non-contrast MRA (NC MRA) pulse sequence was developed using 4 inversion-recovery (IR) pulses and 3D balanced steady-state free precession (b-SSFP) readout to provide arterial imaging from renal to external iliac arteries. Respiratory triggered, high spatial resolution (1.3 × 1.3 × 1.7 mm3) non-contrast angiograms were obtained in seven volunteers and ten patients referred for gadolinium-enhanced MRA (CE MRA). Images were assessed for diagnostic quality by two radiologists. Quantitative measurements of arterial signal contrast were also performed.
NC MRA imaging was successfully completed in all subjects in 7.0 ± 2.3 minutes. In controls, image quality of NC MRA averaged 2.79 ± 0.39 on a scale of 0 to 3, where 3 is maximum. Image quality of NC MRA (2.65 ± 0.41) was comparable to that of CE MRA (2.9 ± 0.32) in all patients. Contrast ratio measurements in patients demonstrated that NC MRA provides arterial contrast comparable to source CE MRA images with adequate venous and excellent background tissue suppression.
The proposed non-contrast MRA pulse sequence provides high quality visualization of abdominopelvic arteries within clinically feasible scan times.
PMCID: PMC3097061  PMID: 21591013
non-contrast MRA; abdominal MRA; bSSFP
24.  Combined Low-Dose Contrast-Enhanced MR Angiography and Perfusion for Acute Ischemic Stroke at 3T: A More Efficient Stroke Protocol 
There is need to improve image acquisition speed for MR imaging in evaluation of patients with acute ischemic stroke. The purpose of this study was to evaluate the feasibility of a 3T MR stroke protocol that combines low-dose contrast-enhanced MRA and dynamic susceptibility contrast perfusion, without additional contrast.
Thirty patients with acute stroke who underwent 3T MR imaging followed by DSA were retrospectively enrolled. TOF-MRA of the neck and brain and 3D contrast-enhanced MRA of the craniocervical arteries were obtained. A total of 0.1 mmol/kg of gadolinium was used for both contrast-enhanced MRA (0.05 mmol/kg) and dynamic susceptibility contrast perfusion (0.05 mmol/kg) (referred to as half-dose). An age-matched control stroke population underwent TOF-MRA and full-dose (0.1 mmol/kg) dynamic susceptibility contrast perfusion. The cervicocranial arteries were divided into 25 segments. Degree of arterial stenosis on contrast-enhanced MRA and TOF-MRA was compared with DSA. Time-to-maximum maps (>6 seconds) were evaluated for image quality and hypoperfusion. Quantitative analysis of arterial input function curves, SNR, and maximum T2* effects were compared between half- and full-dose groups.
The intermodality agreements (k) for arterial stenosis were 0.89 for DSA/contrast-enhanced MRA and 0.63 for DSA/TOF-MRA. Detection specificity of >50% arterial stenosis was lower for TOF-MRA (89%) versus contrast-enhanced MRA (97%) as the result of overestimation of 10% (39/410) of segments by TOF-MRA. The DWI-perfusion mismatch was identified in both groups with high interobserver agreement (r = 1). There was no significant difference between full width at half maximum of the arterial input function curves (P = .14) or the SNR values (0.6) between the half-dose and full-dose groups.
In patients with acute stroke, combined low-dose contrast-enhanced MRA and dynamic susceptibility contrast perfusion at 3T is feasible and results in significant scan time and contrast dose reductions.
PMCID: PMC4159142  PMID: 24503557
25.  High-resolution motion compensated MRA in patients with congenital heart disease using extracellular contrast agent at 3 Tesla 
Using first-pass MRA (FP-MRA) spatial resolution is limited by breath-hold duration. In addition, image quality may be hampered by respiratory and cardiac motion artefacts. In order to overcome these limitations an ECG- and navigator-gated high-resolution-MRA sequence (HR-MRA) with slow infusion of extracellular contrast agent was implemented at 3 Tesla for the assessment of congenital heart disease and compared to standard first-pass-MRA (FP-MRA).
34 patients (median age: 13 years) with congenital heart disease (CHD) were prospectively examined on a 3 Tesla system. The CMR-protocol comprised functional imaging, FP- and HR-MRA, and viability imaging. After the acquisition of the FP-MRA sequence using a single dose of extracellular contrast agent the motion compensated HR-MRA sequence with isotropic resolution was acquired while injecting the second single dose, utilizing the timeframe before viability imaging. Qualitative scores for image quality (two independent reviewers) as well as quantitative measurements of vessel sharpness and relative contrast were compared using the Wilcoxon signed-rank test. Quantitative measurements of vessel diameters were compared using the Bland-Altman test.
The mean image quality score revealed significantly better image quality of the HR-MRA sequence compared to the FP-MRA sequence in all vessels of interest (ascending aorta (AA), left pulmonary artery (LPA), left superior pulmonary vein (LSPV), coronary sinus (CS), and coronary ostia (CO); all p < 0.0001). In comparison to FP-MRA, HR-MRA revealed significantly better vessel sharpness for all considered vessels (AA, LSPV and LPA; all p < 0.0001). The relative contrast of the HR-MRA sequence was less compared to the FP-MRA sequence (AA: p <0.028, main pulmonary artery: p <0.004, LSPV: p <0.005). Both, the results of the intra- and interobserver measurements of the vessel diameters revealed closer correlation and closer 95 % limits of agreement for the HR-MRA. HR-MRA revealed one additional clinical finding, missed by FP-MRA.
An ECG- and navigator-gated HR-MRA-protocol with infusion of extracellular contrast agent at 3 Tesla is feasible. HR-MRA delivers significantly better image quality and vessel sharpness compared to FP-MRA. It may be integrated into a standard CMR-protocol for patients with CHD without the need for additional contrast agent injection and without any additional examination time.
PMCID: PMC3552711  PMID: 23107424
Congenital heart disease; Magnetic resonance angiography; 3 Tesla; High-resolution; Thoracic vasculature; Extracellular contrast agent; ECG-gated; Navigator-gated; Gadobutrol

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