Imaging iron‐loaded mouse glioma tumors with bSSFP at 3 T

The poor prognosis for patients with high‐grade glioma is partly due to the invasion of tumor cells into surrounding brain tissue. The goal of the present work was to develop a mouse model of glioma that included the potential to track cell invasion using MRI by labeling GL261 cells with iron oxide contrast agents prior to intracranial injection. Two types of agents were compared with several labeling schemes to balance between labeling with sufficient iron to curb the dilution effect of cell division while avoiding overwhelming signal loss that could prevent adequate visualization of tumor boundaries. The balanced steady‐state free precession (bSSFP) pulse sequence was evaluated for its suitability for imaging glioma tumors and compared to T₂‐weighted two‐dimensional fast spin echo (FSE) and T₁‐weighted spoiled gradient recalled echo (SPGR) at 3 T in terms of signal‐to‐noise ratio and contrast‐to‐noise ratio efficiencies. Ultimately, a three‐dimensional bSSFP protocol consisting of a set of two images with complementary contrasts was developed, allowing excellent tumor visualization with minimal iron contrast when using pulse repetition time = 6 ms and α = 40°, and extremely high sensitivity to iron when using pulse repetition time = 22 ms and α = 20°. Quantitative histologic analysis validated that the strong signal loss seen in balanced steady state free precession pulse sequence images of iron‐loaded tumors correlated well with the presence of iron. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Transverse relaxation time (T2) mapping in the brain with off‐resonance correction using phase‐cycled steady‐state free precession imaging

Purpose

To investigate a new approach for more completely accounting for off‐resonance affects in the DESPOT2 (driven equilibrium single pulse observation of T₂) mapping technique.

Materials and Methods

The DESPOT2 method derives T₂ information from fully balanced steady‐state free precession (bSSFP) images acquired over multiple flip angles. Off‐resonance affects, which present as bands of altered signal intensity throughout the bSSFP images, results in erroneous T₂ values in the corresponding calculated maps. Radiofrequency (RF) phase‐cycling, in which the phase of the RF pulse is incremented along the pulse train, offers a potential method for eliminating these artifacts. In this work we present a general method, referred to as DESPOT2, with full modeling (DESPOT2‐FM), for deriving T₂, as well as off‐resonance frequency, from dual flip angle bSSFP data acquired with two RF phase increments.

Results

The method is demonstrated in vivo through the acquisition of whole‐brain, 1 mm³ isotropic T₂ maps at 3T and shown to provide near artifact‐free maps, even in areas with steep susceptibility‐induced gradients.

Conclusion

DESPOT2‐FM offers an efficient method for acquiring high spatial resolution, whole‐brain T₂ maps at 3T with high precision and free of artifact. J. Magn. Reson. Imaging 2009;30:411–417. © 2009 Wiley‐Liss, Inc.     

An analytical description of balanced steady‐state free precession with finite radio‐frequency excitation

Conceptually, the only flaw in the standard steady‐state free precession theory is the assumption of quasi‐instantaneous radio‐frequency pulses, and 10–20% signal deviations from theory are observed for common balanced steady‐state free precession protocols. This discrepancy in the steady‐state signal can be resolved by a simple T₂ substitution taking into account reduced transverse relaxation effects during finite radio‐frequency excitation. However, finite radio‐frequency effects may also affect the transient phase of balanced steady‐state free precession, its contrast or its spin‐echo nature and thereby have an adverse effect on common steady‐state free precession magnetization preparation methods. As a result, an in‐depth understanding of finite radio‐frequency effects is not only of fundamental theoretical interest but also has direct practical implications. In this article, an analytical solution for balanced steady‐state free precession with finite radio‐frequency pulses is derived for the transient phase (under ideal conditions) and in the steady state demonstrating that balanced steady‐state free precession key features are preserved but revealing an unexpected dependency of finite radio‐frequency effects on relaxation times for the transient decay. Finally, the mathematical framework reveals that finite radio‐frequency theory can be understood as a generalization of alternating repetition time and fluctuating equilibrium steady‐state free precession sequence schemes. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Finite RF pulse correction on DESPOT2

Magnetization transfer and finite radiofrequency (RF) pulses affect the steady state of balanced steady state free precession. As quantification of transverse relaxation (T₂) with driven equilibrium single pulse observation of T₂ is based on two balanced steady state free precession acquisitions, both effects can influence the outcome of this method: a short RF pulse per repetition time (T_RF/TR ? 1) leads to considerable magnetization transfer effects, whereas prolonged RF pulses (T_RF/TR > 0.2) minimize magnetization transfer effects, but lead to increased finite pulse effects. A correction for finite pulse effects is thus implemented in the driven equilibrium single pulse observation of T₂ theory to compensate for reduced transverse relaxation effects during excitation. It is shown that the correction successfully removes the driven equilibrium single pulse observation of T₂ dependency on the RF pulse duration. A reduction of the variation in obtained T₂ from over 50% to less than 10% is achieved. We hereby provide a means of acquiring magnetization transfer‐free balanced steady state free precession images to yield accurate T₂ values using elongated RF pulses. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Small‐tip fast recovery imaging using non‐slice‐selective tailored tip‐up pulses and radiofrequency‐spoiling

Small‐tip fast recovery (STFR) imaging is a new steady‐state imaging sequence that is a potential alternative to balanced steady‐state free precession. Under ideal imaging conditions, STFR may provide comparable signal‐to‐noise ratio and image contrast as balanced steady‐state free precession, but without signal variations due to resonance offset. STFR relies on a tailored “tip‐up,” or “fast recovery,” radiofrequency pulse to align the spins with the longitudinal axis after each data readout segment. The design of the tip‐up pulse is based on the acquisition of a separate off‐resonance (B0) map. Unfortunately, the design of fast (a few ms) slice‐ or slab‐selective radiofrequency pulses that accurately tailor the excitation pattern to the local B0 inhomogeneity over the entire imaging volume remains a challenging and unsolved problem. We introduce a novel implementation of STFR imaging based on “non‐slice‐selective” tip‐up pulses, which simplifies the radiofrequency pulse design problem significantly. Out‐of‐slice magnetization pathways are suppressed using radiofrequency‐spoiling. Brain images obtained with this technique show excellent gray/white matter contrast, and point to the possibility of rapid steady‐state T₂/T₁‐weighted imaging with intrinsic suppression of cerebrospinal fluid, through‐plane vessel signal, and off‐resonance artifacts. In the future, we expect STFR imaging to benefit significantly from parallel excitation hardware and high‐order gradient shim systems. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

On the mechanisms enabling myocardial edema contrast in bSSFP‐based imaging approaches

The biophysical mechanisms influencing balanced steady‐state free precession (bSSFP) based edema imaging in the setting of acute myocardial infarction are not well understood. To assess the various mechanisms that enable the detection of myocardial edema on bSSFP‐based imaging approaches (cine bSSFP and T₂‐prepared bSSFP), experiments were conducted in canine models subjected to ischemia‐reperfusion injury. Results showed that in addition to relaxation effects, the alteration in thermal equilibrium (M₀) (including magnetization transfer) has a significant contribution to the image contrast between edematous and healthy myocardium. The relative signal‐intensity ratios between edematous and healthy myocardium were: 1.51 ± 0.18 (cine bSSFP) and 1.58 ± 0.20 (T₂‐prepared bSSFP); the theoretically estimated relative relaxation and M₀ effects were: 1.17 ± 0.09 and 1.30 ± 0.19, respectively (cine bSSFP), and 1.49 ± 0.23 and 1.06 ± 0.07, respectively (T₂‐prepared bSSFP). There were no significant difference between cine bSSFP and T₂‐prep bSSFP relative signal‐intensity ratios. However, the relative relaxation effect in cine bSSFP was significantly lower than in T₂‐prep bSSFP (P < 0.05), and the M₀ effect in cine bSSFP was significantly higher than in T₂‐prep bSSFP (P < 0.05). Hence the acquisition strategies that wish to maximize myocardial edema contrast in cine bSSFP imaging should take both relaxation and M₀ effects into account. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Influence of MT effects on T2 quantification with 3D balanced steady‐state free precession imaging

Signal from balanced steady‐state free precession is affected by magnetization transfer. To investigate the possible effects on derived T₂ values using variable nutation steady‐state free precession, magnetization transfer‐effects were modulated by varying the radiofrequency pulse duration only or in combination with variable pulse repetition time. Simulations reveal a clear magnetization transfer dependency of T₂ when decreasing radiofrequency pulse duration, reaching maximal deviation of 34.6% underestimation with rectangular pulses of 300 μs duration. The observed T₂ deviation evaluated in the frontal white matter and caudate nucleus shows a larger underestimation than expected by numerical simulations. However, this observed difference between simulation and measurement is also observed in an aqueous probe and can therefore not be attributed to magnetization transfer: it is an unexpected sensitivity of derived T₂ to radiofrequency pulse modulation. As expected, the limit of sufficiently long radiofrequency pulse duration to suppress magnetization transfer‐related signal modulations allows for proper T₂ estimation with variable nutation steady‐state free precession. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Flip angle profile correction for T1 and T2 quantification with look‐locker inversion recovery 2D steady‐state free precession imaging

Fast methods using balanced steady‐state free precession have been developed to reduce the scan time of T₁ and T₂ mapping. However, flip angle (FA) profiles created by the short radiofrequency pulses used in steady‐state free precession deviate substantially from the ideal rectangular profile, causing T₁ and T₂ mapping errors. The purpose of this study was to develop a FA profile correction for T₁ and T₂ mapping with Look‐Locker 2D inversion recovery steady‐state free precession and to validate this method using 2D spin echo as a reference standard. Phantom studies showed consistent improvement in T₁ and T₂ accuracy using profile correction at multiple FAs. Over six human calves, profile correction provided muscle T₁ estimates with mean error ranging from excellent (?0.6%) at repetition time/FA = 18 ms/60° to acceptable (6.8%) at repetition time/FA = 4.9 ms/30°, while muscle T₂ estimates were less accurate with mean errors of 31.2% and 47.9%, respectively. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Fast three‐dimensional proton spectroscopic imaging of the human brain at 3 T by combining spectroscopic missing pulse steady‐state free precession and echo planar spectroscopic imaging

The combination of the principles of two fast spectroscopic imaging (SI) methods, spectroscopic missing pulse steady‐state free precession and echo planar SI (EPSI) is described as an approach toward fast 3D SI. This method, termed missing pulse steady‐state free precession echo planar SI, exhibits a considerably reduced minimum total measurement time T_min, allowing a higher temporal resolution, a larger spatial matrix size, and the use of k‐space weighted averaging and phase cycling, while maintaining all advantages of the original spectroscopic missing pulse steady‐state free precession sequence. The minor signal‐to‐noise ratio loss caused by using oscillating read gradients can be compensated by applying k‐space weighted averaging. The missing pulse steady‐state free precession echo planar SI sequence was implemented on a 3 T head scanner, tested on phantoms and applied to healthy volunteers. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Comparison of wideband steady‐state free precession and T2‐weighted fast spin echo in spine disorder assessment at 1.5 and 3 T

Wideband steady‐state free precession (WB‐SSFP) is a modification of balanced steady‐state free precession utilizing alternating repetition times to reduce susceptibility‐induced balanced steady‐state free precession limitations, allowing its use for high‐resolution myelographic‐contrast spinal imaging. Intertissue contrast and spatial resolution of complete‐spine‐coverage 3D WB‐SSFP were compared with those of 2D T₂‐weighted fast spin echo, currently the standard for spine T₂‐imaging. Six normal subjects were imaged at 1.5 and 3 T. The signal‐to‐noise ratio efficiency (SNR per unit‐time and unit‐volume) of several tissues was measured, along with four intertissue contrast‐to‐noise ratios; nerve‐ganglia:fat, intradural‐nerves:cerebrospinal fluid, nerve‐ganglia:muscle, and muscle:fat. Patients with degenerative and traumatic spine disorders were imaged at both MRI fields to demonstrate WB‐SSFP clinical advantages and disadvantages. At 3 T, WB‐SSFP provided spinal contrast‐to‐noise ratios 3.7–5.2 times that of fast spin echo. At 1.5 T, WB‐SSFP contrast‐to‐noise ratio was 3–3.5 times that of fast spin echo, excluding a 1.7 ratio for intradural‐nerves:cerebrospinal fluid. WB‐SSFP signal‐to‐noise ratio efficiency was also higher. Three‐dimensional WB‐SSFP disadvantages relative to 2D fast spin echo are reduced edema hyperintensity, reduced muscle signal, and higher motion sensitivity. WB‐SSFP's high resolution and contrast‐to‐noise ratio improved visualization of intradural nerve bundles, foraminal nerve roots, and extradural nerve bundles, improving detection of nerve compression in radiculopathy and spinal‐stenosis. WB‐SSFP's high resolution permitted reformatting into orthogonal planes, providing distinct advantages in gauging fine spine pathology. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

High‐resolution 3D radial bSSFP with IDEAL

Radial trajectories facilitate high‐resolution balanced steady state free precession (bSSFP) because the efficient gradients provide more time to extend the trajectory in k‐space. A number of radial bSSFP methods that support fat–water separation have been developed; however, most of these methods require an environment with limited B₀ inhomogeneity. In this work, high‐resolution bSSFP with fat–water separation is achieved in more challenging B₀ environments by combining a 3D radial trajectory with the IDEAL chemical species separation method. A method to maintain very high resolution within the timing constraints of bSSFP and IDEAL is described using a dual‐pass pulse sequence. The sampling of a unique set of radial lines at each echo time is investigated as a means to circumvent the longer scan time that IDEAL incurs as a multiecho acquisition. The manifestation of undersampling artifacts in this trajectory and their effect on chemical species separation are investigated in comparison to the case in which each echo samples the same set of radial lines. This new bSSFP method achieves 0.63 mm isotropic resolution in a 5‐min scan and is demonstrated in difficult in vivo imaging environments, including the breast and a knee with ACL reconstruction hardware at 1.5 T. Magn Reson Med 71:95–104, 2014. © 2013 Wiley Periodicals, Inc.     

Analytical solution to the transient phase of steady‐state free precession sequences

The transient phase of short–TR steady‐state free precession (SSFP) sequences exhibits an often striking complexity and is not only important for nonequilibrium applications (e.g., rapid T₁–measurements), but can also cause severe artifacts in conventional imaging. In both cases, balanced SSFP sequences are practically (with regard to preparation efficiency) and conceptually (concerning the theoretical understanding of the decay) easier to handle their unbalanced counterparts, for which currently no theory is available. Based on a decomposition of coherence pathways into irreducible subpaths, an exact mathematical solution to the transient phase of unbalanced SSFP sequences is presented in this article, which also includes the known results for balanced SSFP and the steady state of arbitrary SSFP sequences as special cases. As an application, it is shown that the familiar Look–Locker expression for the accelerated magnetization recovery in RF‐spoiled sequences is only valid for T₂ → 0. In addition to oscillatory perturbations, systematic deviations from the monoexponential decay are observed for T₂ 0 as a consequence of memory effects. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Brain MR perfusion‐weighted imaging with alternate ascending/descending directional navigation

In this study, a new arterial spin labeling technique that requires no separate spin preparation pulse was developed. Sequential two‐dimensional slices were acquired in ascending and descending orders by turns using balanced steady state free precession for pair‐wise subtraction. Simulation studies showed this new technique, alternate ascending/descending directional navigation (ALADDIN), has high sensitivity to both slow‐ (1–10 cm/sec) and fast‐moving (>10 cm/sec) blood because of the presence of multiple labeling planes proximal to imaging planes and sensitivity of balanced steady state free precession to initial magnetization differences. ALADDIN provided high‐resolution multislice perfusion‐weighted images in ～3 min. About 80–90% of signals in a slice were ascribed to spins saturated in the four prior slices. Three to five edge slices on each side of imaging group were affected by transient magnetization transfer effects and incomplete T₁ recovery between successive acquisitions. ALADDIN signals were dependent on many imaging parameters, implying room for improvement. Sagittal and coronal ALADDIN images demonstrated perfusion direction in gray matter regions was mostly from center to lateral, anterior, or posterior, whereas that in some white matter regions was reversed. ALADDIN is likely useful for many studies requiring perfusion‐weighted imaging with short scan time, insensitiveness to arterial transit time, directional information, high resolution, and/or wide coverage. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Optimization of alternating TR‐SSFP for fat‐suppression in abdominal images at 3T

Magnetic resonance imaging is widely used in the work‐up and monitoring of patients with Crohn's disease. Balanced steady‐state free precession sequences are an important part of the imaging protocol and until now primarily 1.5T scanners have been used in daily clinical practice. This is largely because running balanced steady‐state free precession sequences in 3T magnets has technical problems related to increased B₀ inhomogeneity and specific absorption rate (SAR) deposition. A modified form of alternating repetition time steady‐state free precession sequence is presented to acquire 3D‐isotropic abdominal images with fat‐suppression at 3T within a breath‐hold. The modifications include an adjusted radiofrequency pulse shape, suitable phase‐cycling scheme and TR₁/TR₂ ratio. Results show that the proposed sequence is successful in obtaining high contrast 3D‐isotropic abdominal images within a breath‐hold. Furthermore, the proposed methodology is easy to implement in a clinical setting and does not require any postprocessing steps. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Intrascanner and interscanner variability of magnetization transfer‐sensitized balanced steady‐state free precession imaging

Recently, a new and fast three‐dimensional imaging technique for magnetization transfer ratio (MTR) imaging has been proposed based on a balanced steady‐state free precession protocol with modified radiofrequency pulses. In this study, optimal balanced steady‐state free precession MTR protocol parameters were derived for maximum stability and reproducibility. Variability between scans was assessed within white and gray matter for nine healthy volunteers using two different 1.5 T clinical systems at six different sites. Intrascanner and interscanner MTR measurements were well reproducible (coefficient of variation: c_v < 0.012 and c_v < 0.015, respectively) and results indicate a high stability across sites (c_v < 0.017) for optimal flip angle settings. This study demonstrates that balanced steady‐state free precession MTR not only benefits from short acquisition time and high signal‐to‐noise ratio but also offers excellent reproducibility and low variability, and it is thus proposed for clinical MTR scans at individual sites as well as for multicenter studies. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Assessment of magnetization transfer effects in myocardial tissue using balanced steady‐state free precession (bSSFP) cine MRI

Magnetization transfer imaging (MTI) by means of MRI exploits the mobility of water molecules in tissue and offers an alternative contrast mechanism beyond the more commonly used mechanisms based on relaxation times. A cardiac MTI method was implemented on a commercially available 1.5 T MR imager. It is based on the acquisition of two sets of cardiac‐triggered cine balanced steady‐state free precession (bSSFP) images with different levels of RF power deposition. Reduction of RF power was achieved by lengthening the RF excitation pulses of a cine bSSFP sequence from 0.24 ms to 1.7 ms, while keeping the flip angle constant. Normal volunteers and patients with acute myocardial infarcts were imaged in short and long axis views. Normal myocardium showed an MT ratio (MTR) of 33.0 ± 3.3%. In acute myocardial infarct, MTR was reduced to 24.5 ± 9.2% (P < 0.04), most likely caused by an increase in water content due to edema. The method thus allows detection of acute myocardial infarct without the administration of contrast agents. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Parametric dependence of myocardial blood oxygen level dependent,balanced steady‐state free‐precession imaging at 1.5 T: Theory and experiments

Myocardial blood oxygen level dependent, balanced steady‐state free precession (bSSFP) imaging is a relatively new technique for evaluating myocardial oxygenation changes in the presence of coronary artery stenosis. However, the dependence of myocardial bSSFP blood oxygen level dependent signal on imaging parameters has not been well studied. In this work, modeling capillaries as cylinders that act as magnetic perturbers, the Monte Carlo method was used to simulate spin relaxation via diffusion in a field variation inside and outside blood vessels. bSSFP signal changes at various levels of capillary blood oxygen saturation, for a range of pulse repetition times, flip angle, capillary blood volume fraction, vessel wall permeability, water diffusion coefficient, vessel angle to static magnetic field, and the impact of bulk frequency shifts were studied. The theoretical dependence of bSSFP blood oxygen level dependent contrast on pulse repetition times and flip angle was confirmed by experiments in an animal model with controllable coronary stenosis. Results showed that, with the standard bSSFP acquisition, optimum bSSFP blood oxygen level dependent contrast could be obtained at pulse repetition times = 6.0 ms and flip angle = 70°. Additional technical improvements that preserve the image quality may be necessary to further increase the myocardial bSSFP blood oxygen level dependent sensitivity at 1.5 T through even longer pulse repetition times. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Cartilage morphology at 3.0T: Assessment of three‐dimensional magnetic resonance imaging techniques

Purpose:

To compare six new three‐dimensional (3D) magnetic resonance (MR) methods for evaluating knee cartilage at 3.0T.

Materials and Methods:

We compared: fast‐spin‐echo cube (FSE‐Cube), vastly undersampled isotropic projection reconstruction balanced steady‐state free precession (VIPR‐bSSFP), iterative decomposition of water and fat with echo asymmetry and least‐squares estimation combined with spoiled gradient echo (IDEAL‐SPGR) and gradient echo (IDEAL‐GRASS), multiecho in steady‐state acquisition (MENSA), and coherent oscillatory state acquisition for manipulation of image contrast (COSMIC). Five‐minute sequences were performed twice on 10 healthy volunteers and once on five osteoarthritis (OA) patients. Signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) were measured from the volunteers. Images of the five volunteers and the five OA patients were ranked on tissue contrast, articular surface clarity, reformat quality, and lesion conspicuity. FSE‐Cube and VIPR‐bSSFP were compared to IDEAL‐SPGR for cartilage volume measurements.

Results:

FSE‐Cube had top rankings for lesion conspicuity, overall SNR, and CNR (P < 0.02). VIPR‐bSSFP had top rankings in tissue contrast and articular surface clarity. VIPR and FSE‐Cube tied for best in reformatting ability. FSE‐Cube and VIPR‐bSSFP compared favorably to IDEAL‐SPGR in accuracy and precision of cartilage volume measurements.

Conclusion:

FSE‐Cube and VIPR‐bSSFP produce high image quality with accurate volume measurement of knee cartilage. J. Magn. Reson. Imaging 2010;32:173–183. © 2010 Wiley‐Liss, Inc.