Visualization of free radical reactions in an aqueous sample irradiated by 290 MeV carbon beam

The detection of free radical reactions in a gelatin sample irradiated by a heavy‐ion beam was tested using electron paramagnetic resonance (EPR) spectroscopic and MRI methods. Geometry and the amount of free radical generation in a sample are described. A reaction mixture containing glutathione and a nitroxyl radical, TEMPOL, was caked with gelatin, and then irradiated with a 290 MeV carbon beam. The amount of free radical generation in a solid sample was almost flat from the surface to the beam end, except for a small peak, the peak radioactivation profile, and then steeply decreased approaching the beam end. Total free radical reactions obtained with carbon‐beam irradiation were expected to be less than one‐third of X‐ray irradiation, when the same dose for a deeper target was considered. Both EPR and MRI are useful tools to visualize free radical generation in samples irradiated by a heavy‐ion beam. The EPR‐based method is more sensitive and quantitative than the MRI‐based method; however, the MRI method can achieve high spatial resolution. This study gives the rationale for a redox regulation trial using antioxidant drugs to reduce the side effects on normal tissues in carbon‐beam therapy. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Fast gated EPR imaging of the beating heart: Spatiotemporally resolved 3D imaging of free‐radical distribution during the cardiac cycle

In vivo or ex vivo electron paramagnetic resonance imaging (EPRI) is a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. However, applications of EPRI have been limited by long projection acquisition times and the consequent fact that rapid gated EPRI was not possible. Hence in vivo EPRI typically provided only time‐averaged information. In order to achieve direct gated EPRI, a fast EPR acquisition scheme was developed to decrease EPR projection acquisition time down to 10–20 ms, along with corresponding software and instrumentation to achieve fast gated EPRI of the isolated beating heart with submillimeter spatial resolution in as little as 2–3 min. Reconstructed images display temporal and spatial variations of the free‐radical distribution, anatomical structure, and contractile function within the rat heart during the cardiac cycle. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Three-dimensional spatial EPR imaging of the rat heart

While instrumentation capable of performing three-dimensional EPR imaging of free radicals in whole tissues and isolated organs has been developed at L-band, important questions remain regarding the resolution and image quality that can be obtained in practice using the presently available free radical labels. Therefore, studies were performed applying three-dimensional spatial EPR imaging at L-band to image the distribution of free radical labels in the isolated heart and in phantoms of similar size. With nitroxide labels the obtainable resolution is limited by the presence of hyperfine structure in the EPR absorption function that in turn limits the maximum applicable gradient. The authors observed that with the nitroxide labels, resolutions in the range of 1–2 mm are possible, while with a single line glucose char label, resolutions of 0.2 mm are obtained. With the nitroxides, images were of sufficient resolution to resolve the overall global shape of the heart and the location of the left and right ventricular cavities; however, finer structures could not be resolved. With the glucose char much finer resolution could be obtained enabling visualization of the ventricles, aortic root, and proximal coronary arteries.     

Evaluation of the dose distribution gradient in the close vicinity of brachytherapy seeds using electron paramagnetic resonance imaging

Electron paramagnetic resonance (EPR) spectroscopy has been successfully employed to determine radiation dose using alanine. The EPR signal intensity reflects the number of stable free radicals produced, and provides a quantitative measurement of the absorbed dose. The aim of the present study was to explore whether this principle can be extended to provide information on spatial dose distribution using EPR imaging (EPRI). Lithium formate was selected because irradiation induces a single EPR line, a characteristic that is particularly convenient for imaging purposes. ¹²⁵I‐brachytherapy seeds were inserted in tablets made of lithium formate. Images were acquired at 1.1 GHz. Monte Carlo (MC) calculations were used for comparison. The dose gradient can be determined using two‐dimensional (2D) EPR images. Quantitative data correlated with the dose estimated by the MC simulations, although differences were observed. This study provides a first proof‐of‐concept that EPRI can be used to estimate the gradient dose distribution in phantoms after irradiation. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Proton electron double resonance imaging (PEDRI) of the isolated beating rat heart.

Proton electron double resonance imaging (PEDRI) is a double resonance technique where proton MRI is performed with irradiation of a paramagnetic solute. A low-field PEDRI system was developed at 20.1 mT suitable for imaging free radicals in biological samples. With a new small dual resonator, PEDRI was applied to image nitroxide free radicals in isolated beating rat hearts. Experiments with phantoms showed maximum image enhancement factors (IEF) of 42 or 28 with TEMPONE radical concentrations of 2-3 mM at EPR irradiation powers of 12W or 6W, respectively. In the latter case, image resolution better than 0.5 mm and radical sensitivity of 5 microM was obtained. For isolated heart studies, EPR irradiation power of 6W provided optimal compromise of modest sample heating with good SNR. Only a small increase in temperature of about 1 degrees C was observed, while cardiac function remained within 10% of control values. With infusion of 3 mM TEMPONE an IEF of 15 was observed enabling 2D or 3D images to be obtained in 27 sec or 4.5 min, respectively. These images visualized the change in radical distribution within the heart during infusion and clearance. Thus, PEDRI enables rapid and high-quality imaging of free radical uptake and clearance in perfused hearts and provides a useful technique for studying cardiac radical metabolism.     

Three-Dimensional gated EPR imaging of the beating heart: Time-resolved measurements of free radical distribution during the cardiac contractile cycle

In vivo or ex vivo EPR imaging, EPRI, has been established as a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. While instrumentation capable of performing EPR imaging of free radicals in whole tissues and isolated organs has been previously reported, it was not possible to image rapidly moving organs such as the beating heart Therefore instrumentation was developed to enable the performance of gated-spectroscopy and imaging on isolated beating rat hearts at L-band. A synchronized pulsing and timing system capable of gated acquisitions of up to 256 images per cycle, with rates of up to 16 Hz was developed. The temporal and spatial accuracy of this instrumentation was verified using a specially designed beating heart-shaped isovolumic phantom with electromechanically driven sinusoidal motion at a cycle rate of 5 Hz. Gated EPR imaging was performed on a series of isolated rat hearts perfused with nitroxide spin labels. These hearts were paced at a rate of 6 Hz with either 16 or 32 gated images acquired per cardiac contractile cycle. The images enabled visualization of the time-dependent alterations in the free radical distribution and anatomical structure of the heart that occur during the cardiac cycle.     

Advantageous application of a surface coil to EPR irradiation in overhauser‐enhanced MRI

The present study describes the advantageous application of a surface coil to electron paramagnetic resonance (EPR) irradiation in Overhauser‐enhanced MRI (OMRI). OMRI is a double‐resonance method for imaging free radicals based on the Overhauser effect. Proton NMR images are recorded without and with EPR irradiation of the free radical resonance, which results in a difference proton image that shows signal enhancement in spatial regions that contain the free radical. To obtain good signal enhancement in OMRI, very high RF power and a long EPR irradiation time are required. To improve sensitivity and shorten the image acquisition time, especially for localized (and topical) applications, we developed and tested a surface‐coil‐type EPR irradiation coil. Theoretical calculations and experimental data showed that EPR irradiation through the surface coil could ameliorate the localized Overhauser enhancement, which was related to the ratio of B₁ surface coil/B₁ volume coil in the region of interest (ROI), as expected. The increased sensitivity could also be converted into a shortened EPR irradiation time, resulting in fast data acquisition. For biomedical applications, the use of a surface coil (as opposed to a conventional volume coil) could decrease the total RF power deposition in the sample required to obtain the same Overhauser enhancement in the ROI. Magn Reson Med 57:806–811, 2007. © 2007 Wiley‐Liss, Inc.     

EPR/NMR co-imaging for anatomic registration of free-radical images.

While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals in the whole body of small animals, it solely visualizes the free-radical distribution and does not typically provide anatomic visualization of the body. However, anatomic registration is often required for meaningful interpretation of the EPRI-derived free-radical images. An approach is reported for whole-body, EPRI-based, free-radical imaging along with proton MRI in mice. EPRI instrumentation with a 750-MHz narrow band microwave bridge and transverse oriented electric field reentrant resonator, with automatic coupling control and automatic tuning control capability, was used to map the spatial distribution of nitroxide free radicals in phantoms and in living mice, while low-field proton MRI at 16 MHz was used to define the anatomic structure to register the EPR images. Small capillary tubes containing an aqueous radical label were used as markers to enable image superimposition. With this coregistration technique, the EPRI free-radical images were precisely registered, enabling assignment of the location of the observed free-radical distribution within the organs of the mice. This technique enabled differentiation of the distribution and metabolism of nitroxide radicals within the major organs and body sites of living mice.     

Development of a hybrid EPR/NMR coimaging system.

Electron paramagnetic resonance imaging (EPRI) is a powerful technique that enables spatial mapping of free radicals or other paramagnetic compounds; however, it does not in itself provide anatomic visualization of the body. Proton magnetic resonance imaging (MRI) is well suited to provide anatomical visualization. A hybrid EPR/NMR coimaging instrument was constructed that utilizes the complementary capabilities of both techniques, superimposing EPR and proton-MR images to provide the distribution of paramagnetic species in the body. A common magnet and field gradient system is utilized along with a dual EPR and proton-NMR resonator assembly, enabling coimaging without the need to move the sample. EPRI is performed at approximately 1.2 GHz/ approximately 40 mT and proton MRI is performed at 16.18 MHz/ approximately 380 mT; hence the method is suitable for whole-body coimaging of living mice. The gradient system used is calibrated and controlled in such a manner that the spatial geometry of the two acquired images is matched, enabling their superposition without additional postprocessing or marker registration. The performance of the system was tested in a series of phantoms and in vivo applications by mapping the location of a paramagnetic probe in the gastrointestinal (GI) tract of mice. This hybrid EPR/NMR coimaging instrument enables imaging of paramagnetic molecules along with their anatomic localization in the body.     

In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy

Imaging of free radicals by electron paramagnetic resonance (EPR) spectroscopy using time domain acquisition as in nuclear magnetic resonance (NMR) has not been attempted because of the short spin-spin relaxation times, typically under 1 μs, of most biologically relevant paramagnetic species. Recent advances in radiofrequency (RF) electronics have enabled the generation of pulses of the order of 10–50 ns. Such short pulses provide adequate spectral coverage for EPR studies at 300 MHz resonant frequency. Acquisition of free induction decays (FID) of paramagnetic species possessing inhomogenously broadened narrow lines after pulsed excitation is feasible with an appropriate digitizer/averager. This report describes the use of time-domain RF EPR spectrometry and imaging for in vivo applications. FID responses were collected from a water-soluble, narrow line width spin probe within phantom samples in solution and also when infused intravenously in an anesthetized mouse. Using static magnetic field gradients and back-projection methods of image reconstruction, two-dimensional images of the spin-probe distribution were obtained in phantom samples as well as in a mouse. The resolution in the images was better than 0.7 mm and devoid of motional artifacts in the in vivo study. Results from this study suggest a potential use for pulsed RF EPR imaging (EPRI) for three-dimensional spatial and spectral-spatial imaging applications. In particular, pulsed EPRI may find use in in vivo studies to minimize motional artifacts from cardiac and lung motion that cause significant problems in frequency-domain spectral acquisition, such as in continuous wave (cw) EPR techniques.     

High spatial and temporal resolution cardiac cine MRI from retrospective reconstruction of data acquired in real time using motion correction and resorting

Cine MRI is used for assessing cardiac function and flow and is typically based on a breath‐held, segmented data acquisition. Breath holding is particularly difficult for patients with congestive heart failure or in pediatric cases. Real‐time imaging may be used without breath holding or ECG triggering. However, despite the use of rapid imaging sequences and accelerated parallel imaging, real‐time imaging typically has compromised spatial and temporal resolution compared with gated, segmented breath‐held studies. A new method is proposed that produces a cardiac cine across the full cycle, with both high spatial and temporal resolution from a retrospective reconstruction of data acquired over multiple heartbeats during free breathing. The proposed method was compared with conventional cine images in 10 subjects. The resultant image quality for the proposed method (4.2 ± 0.4) without breath holding or gating was comparable to the conventional cine (4.4 ± 0.5) on a five‐point scale (P = n.s.). Motion‐corrected averaging of real‐time acquired cardiac images provides a means of attaining high‐quality cine images with many of the benefits of real‐time imaging, such as free‐breathing acquisition and tolerance to arrhythmias. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Modulated repetition time look‐locker (MORTLL): A method for rapid high resolution three‐dimensional T1 mapping

Purpose

To demonstrate a modification of the Look‐Locker (LL) technique that enables rapid high resolution T1 mapping over the physiologic range of intracranial T1 values, ranging from white matter to cerebrospinal fluid (CSF). This is achieved by use of a three‐dimensional (3D) balanced steady‐state free precession (b‐SSFP) acquisition (for high signal‐to‐noise and resolution) along with variable repetition time to allow effective full recovery of longitudinal magnetization.

Materials and Methods

Two modifications to the Look‐Locker technique were made to realize high resolution imaging in a clinically reasonable scan time. The 3D b‐SSFP acquisition after an initial inversion pulse was followed by a variable repetition time. This technique makes it possible to image a volume of thin contiguous slices with high resolution and accuracy using a simple fitting procedure and is particularly useful for imaging long T1 species such as CSF. The total scan time is directly proportional to the number of slices to be acquired. The scan time was reduced by almost half when the repetition time was modified using a predesigned smooth function. Phantoms and volunteers were imaged at different resolutions on a 3 Tesla scanner. Results were compared with other accepted techniques.

Results

T1 values in the brain corresponded well with full repetition time imaging as well as inversion recovery spin echo imaging. T1 values for white matter, gray matter, and CSF were measured to be 755 ± 10 ms, 1202 ± 9 ms, and 4482 ± 71 ms, respectively. Scan times were reduced by approximately half over full repetition time measurements.

Conclusion

High resolution T1 maps can be obtained rapidly and with a relatively simple postprocessing method. The technique is particularly well suited for long T1 species. For example, changes in the composition of proteins in CSF are linked to various pathologies. The T1 values showed excellent agreement with values obtained from inversion recovery spin‐echo imaging. J. Magn. Reson. Imaging 2009. © 2009 Wiley‐Liss, Inc.     

Slice-selective images of free radicals in mice with modulated field gradient electron paramagnetic resonance (EPR) imaging.

Continuous wave (CW) electron paramagnetic resonance (EPR) imaging can be used to obtain slice-selective images of free radicals without measuring three-dimensional (3D) projection data. A method that incorporated a modulated magnetic field gradient (MFG) was combined with polar field gradients to select a slice in the subject noninvasively. The slice-selective in vivo EPR imaging of triarylmethyl radicals in the heads of live mice is reported. 3D surface-rendered images were successfully obtained from slice-selective images. In the experiment in mice, a slice thickness of 1.8 mm was achieved.     

Effects of respiratory cycle and body position on quantitative pulmonary perfusion by MRI

Purpose:

To evaluate the performance of lung perfusion imaging using two‐dimensional (2D) first pass perfusion MRI and a quantitation program based on model‐independent deconvolution algorithm.

Materials and Methods:

In eight healthy volunteers 2D first pass lung perfusion was imaged in coronal planes using a partial Fourier saturation recovery stead state free precession (SSFP) technique with a temporal resolution of 160 ms per slice acquisition. The dynamic signal in the lung was measured over time and absolute perfusion calculated based on a model‐independent deconvolution program.

Results:

In the supine position mean pulmonary perfusion was 287 ± 106 mL/min/100 mL during held expiration. It was significantly reduced to 129 ± 68 mL/min/100 mL during held inspiration. Similar differences due to respiration were observed in prone position with lung perfusion much greater during expiration than during inspiration (271 ± 101 versus 99 ± 38 mL/min/100 mL (P < 0.01)). There was a linear increase in pulmonary perfusion from anterior to posterior lung fields in supine position. The perfusion gradient reversed in the prone position with the highest perfusion in anterior lung and the lowest in posterior lung fields.

Conclusion:

Lung perfusion imaging using a 2D saturation recovery SSFP perfusion MRI coupled with a model‐independent deconvolution algorithm demonstrated physiologically consistent dynamic heterogeneity of lung perfusion distribution. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Feasibility and assessment of non-invasive in vivo redox status using electron paramagnetic resonance imaging

Purpose:
To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox-sensitive paramagnetic contrast agents. Material and Methods:
Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor-bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor-bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. Results:
Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluated in vivo. EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. Conclusion:
Using redox-sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors.     

Novel reconstruction method for three‐dimensional axial continuously moving table whole‐body magnetic resonance imaging featuring autocalibrated parallel imaging GRAPPA

Continuously moving table MR imaging has been successfully evaluated for whole‐body tumor staging and metastasis screening. In previous studies it was demonstrated that three‐dimensional (3D) slab‐selective excitation with lateral readout can provide very efficient k‐space coverage when the longitudinal field of view (FOV) is limited. To reduce respiratory artifacts, data acquisition in the thoracoabdominal region of the patient typically must be performed during one single breath hold. This consequently restricts acquisition time and thus spatial resolution. In this work, a novel reconstruction method is introduced for axial 3D moving table data acquisition with lateral readout. The method features table position correction completely in k‐space and is compatible with autocalibrated parallel imaging (GRAPPA). Parallel imaging can be applied to increase spatial resolution while maintaining the breath‐holding time. A sophisticated protocol for whole‐body moving table MRI was developed. The impact of gradient nonlinearity on the featured imaging method was evaluated in phantom and volunteer experiments. Finally, the protocol was optimized toward minimizing residual artifacts. Moving table whole‐body MRI with lateral readout was performed in 5 healthy volunteers and was compared with lateral readout data acquired with a GRAPPA accelerated protocol providing increased spatial resolution. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Motion artifact correction in free‐breathing abdominal MRI using overlapping partial samples to recover image deformations

This article presents a method to reconstruct liver MRI data acquired continuously during free breathing, without any external sensor or navigator measurements. When the deformations associated with k‐space data are known, generalized matrix inversion reconstruction has been shown to be effective in reducing the ghosting and blurring artifacts of motion. This article describes a novel method to obtain these nonrigid deformations. A breathing model is built from a fast dynamic series: low spatial resolution images are registered and their deformations parameterized by overall superior–inferior displacement. The correct deformation for each subset of the subsequent imaging data is then found by comparing a few lines of k‐space with the equivalent lines from a deformed reference image while varying the deformation over the model parameter. This procedure is known as image deformation recovery using overlapping partial samples (iDROPS). Simulations using 10 rapid dynamic studies from volunteers showed the average error in iDROPS‐derived deformations within the liver to be 1.43 mm. A further four volunteers were imaged at higher spatial resolution. The complete reconstruction process using data from throughout several breathing cycles was shown to reduce blurring and ghosting in the liver. Retrospective respiratory gating was also demonstrated using the iDROPS parameterization. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

In vivo proton electron double resonance imaging of mice with fast spin echo pulse sequence

Purpose:

To develop and evaluate a two‐dimensional (2D) fast spin echo (FSE) pulse sequence for enhancing temporal resolution and reducing tissue heating for in vivo proton electron double resonance imaging (PEDRI) of mice.

Materials and Methods:

A four‐compartment phantom containing 2 mM TEMPONE was imaged at 20.1 mT using 2D FSE‐PEDRI and regular gradient echo (GRE)‐PEDRI pulse sequences. Control mice were infused with TEMPONE over ～1 min followed by time‐course imaging using the 2D FSE‐PEDRI sequence at intervals of 10–30 s between image acquisitions. The average signal intensity from the time‐course images was analyzed using a first‐order kinetics model.

Results:

Phantom experiments demonstrated that EPR power deposition can be greatly reduced using the FSE‐PEDRI pulse sequence compared with the conventional gradient echo pulse sequence. High temporal resolution was achieved at ～4 s per image acquisition using the FSE‐PEDRI sequence with a good image SNR in the range of 233–266 in the phantom study. The TEMPONE half‐life measured in vivo was ～72 s.

Conclusion:

Thus, the FSE‐PEDRI pulse sequence enables fast in vivo functional imaging of free radical probes in small animals greatly reducing EPR irradiation time with decreased power deposition and provides increased temporal resolution. J. Magn. Reson. Imaging 2012;471‐475. © 2011 Wiley Periodicals, Inc.     

In vivo imaging of spin-trapped nitric oxide in rats with septic shock: MRI spin trapping.

This paper reports the first in vivo NMR image of the distribution of NO using the "MRI spin-trapping" technique. NO was complexed with the Fe(II)-chelate spin trap, N-methyl-D-glucamine dithiocarbamate (MGD), verified as (MGD)(2)-Fe(II)-NO by EPR, and the radical distribution was "visualized" by MR images. In rats, the (MGD)(2)-Fe(II)-NO complex was concentrated in the liver displaying significantly enhanced contrast in the vascular structure such as hepatic vein and inferior vena cava. Nitric oxide synthase was verified as the source of NO in rats with septic shock by pre-administration of the competitive inhibitor N-monomethyl-L-arginine, resulting in reduced enhancement. The NO complex was more stable in vivo and a more effective MRI contrast agent than other stable nitrogen containing radicals, such as nitroxides. The MRI spin-trapping method should be a powerful tool for visualizing spatial distributions of free radicals in pathologic organs and tissues when combined with the appropriate radical complexing agent, such as (MGD)(2)-Fe(II) used in these studies. Magn Reson Med 42:235-239, 1999.     

3D diffusion tensor MRI with isotropic resolution using a steady‐state radial acquisition

Purpose

To obtain diffusion tensor images (DTI) over a large image volume rapidly with 3D isotropic spatial resolution, minimal spatial distortions, and reduced motion artifacts, a diffusion‐weighted steady‐state 3D projection (SS 3DPR) pulse sequence was developed.

Materials and Methods

A diffusion gradient was inserted in a SS 3DPR pulse sequence. The acquisition was synchronized to the cardiac cycle, linear phase errors were corrected along the readout direction, and each projection was weighted by measures of consistency with other data. A new iterative parallel imaging reconstruction method was also implemented for removing off‐resonance and undersampling artifacts simultaneously.

Results

The contrast and appearance of both the fractional anisotropy and eigenvector color maps were substantially improved after all correction techniques were applied. True 3D DTI datasets were obtained in vivo over the whole brain (240 mm field of view in all directions) with 1.87 mm isotropic spatial resolution, six diffusion encoding directions in under 19 minutes.

Conclusion

A true 3D DTI pulse sequence with high isotropic spatial resolution was developed for whole brain imaging in under 20 minutes. To minimize the effects of brain motion, a cardiac synchronized, multiecho, DW‐SSFP pulse sequence was implemented. Motion artifacts were further reduced by a combination of linear phase correction, corrupt projection detection and rejection, sampling density reweighting, and parallel imaging reconstruction. The combination of these methods greatly improved the quality of 3D DTI in the brain. J. Magn. Reson. Imaging 2009;29:1175–1184. © 2009 Wiley‐Liss, Inc.