A comparison study between the saturation-recovery-T1 and CASL MRI methods for quantitative CBF imaging

The saturation-recovery (SR)-T₁ MRI method for quantitatively imaging cerebral blood flow (CBF) change (ΔCBF) concurrently with the blood oxygenation level dependence (BOLD) alteration has been recently developed and validated by simultaneous measurement of relative CBF change using laser Doppler flowmetry (LDF) in rats at 9.4T. In this study, ΔCBF induced by mildly transient hypercapnia and measured by the SR-T₁ MRI method was rigorously compared with an established perfusion MRI method—continuous arterial spin labeling (CASL) approach in normal and preclinical middle cerebral artery occlusion (MCAo) rat models. The results show an excellent agreement between ΔCBF values measured with these two imaging methods. Moreover, the intrinsic longitudinal relaxation rate (R₁^int) was experimentally determined in vivo in normal rat brains at 9.4T by comparing two independent measures of the apparent longitudinal relaxation rate (R₁^app) and CBF measured by the CSAL approach across a wide range of perfusion. In turn, the R₁^int constant can be employed to calculate the CBF value based on the R₁^app measurement in healthy brain. This comparison study validates the fundamental relationship for linking brain tissue water R₁^app and cerebral perfusion, demonstrates the feasibility of imaging and quantifying both CBF and its change using the SR-T₁ MRI method in vivo.     

Improving cerebral blood flow quantification for arterial spin labeled perfusion MRI by removing residual motion artifacts and global signal fluctuations

Denoising is critical to improving the quality and stability of cerebral blood flow (CBF) quantification in arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) due to the intrinsic low signal-to-noise-ratio (SNR) of ASL data. Previous studies have been focused on reducing the spatial or temporal noise using standard filtering techniques, and less attention has been paid to two global nuisance effects, the residual motion artifacts and the global signal fluctuations. Since both nuisances affect the whole brain, removing them in advance should enhance the CBF quantification quality for ASL MRI. The purpose of this paper was to assess this potential benefit. Three methods were proposed to suppress each or both of the two global nuisances. Their performances for CBF quantification were validated using ASL data acquired from 13 subjects. Evaluation results showed that covarying out both global nuisances significantly improved temporal SNR and test-retest stability of CBF measurement. Although the concept of removing both nuisances is not technically novel per se, this paper clearly showed the benefits for ASL CBF quantification. Dissemination of the proposed methods in a free ASL data processing toolbox should be of interest to a broad range of ASL users.     

Image correction during large and rapid B0 variations in an open MRI system with permanent magnets using navigator echoes and phase compensation

An open permanent magnet system with vertical B₀ field and without self-shielding can be quite susceptible to perturbations from external magnetic sources. B₀ variation in such a system located close to a subway station was measured to be greater than 0.7 μT by both MRI and a fluxgate magnetometer. This B₀ variation caused image artifacts. A navigator echo approach that monitored and compensated the view-to-view variation in magnetic resonance signal phase was developed to correct for image artifacts. Human brain imaging experiments using a multislice gradient-echo sequence demonstrated that the ghosting and blurring artifacts associated with B₀ variations were effectively removed using the navigator method.     

Comparison of pulsed arterial spin labeling encoding schemes and absolute perfusion quantification

Arterial spin labeling (ASL) using magnetic resonance imaging (MRI) is a powerful noninvasive technique to investigate the physiological status of brain tissue by measuring cerebral blood flow (CBF). ASL assesses the inflow of magnetically labeled arterial blood into an imaging voxel. In the last 2 decades, various ASL sequences have been proposed which differ in their ease of implementation and their sensitivity to artifacts. In addition, several quantification methods have been developed to determine the absolute value of CBF from ASL magnetization difference images. In this study, we evaluated three pulsed ASL sequences and three absolute quantification schemes. It was found that FAIR-QUIPSSII implementation of ASL yields 10–20% higher signal-to-noise ratio (SNR) and 18% higher CBF as compared with PICORE-Q2TIPS (with FOCI pulses) and PICORE-QUIPSSII (with BASSI pulses). In addition, quantification schemes employed can give rise to up to a 35% difference in CBF values. We conclude that, although all quantitative ASL sequences and CBF calibration methods should in principle result in the similar CBF values and image quality, substantial differences in CBF values and SNR were found. Thus, comparing studies using different ASL sequences and analysis algorithms is likely to result in erroneous intra- and intergroup differences. Therefore, (i) the same quantification schemes should consistently be used, and (ii) quantification using local tissue proton density should yield the most accurate CBF values because, although still requiring definitive demonstration in future studies, the proton density of blood is assumed to be very similar to the value of gray matter.     

On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow

Arterial-spin-labeling (ASL) magnetic resonance imaging (MRI) provides a noninvasive tool to measure cerebral blood flow (CBF) and is increasingly used as a surrogate for baseline neural activity. However, the power of ASL MRI in detecting CBF differences between patient and control subjects is hampered by inter-subject variations in global CBF, which are associated with non-neural factors and may contribute to the noise in the across-group comparison. Here, we investigated the sensitivity of this technique and proposed a normalization strategy to better detect such a difference. A “model” situation was employed in which two visual stimuli (i.e. cross fixation and flashing checkerboard) were presented to two groups of subjects to mimic “control” and “patient” groups (N=7 for each group), respectively. It was found that absolute CBF (aCBF) in the occipital lobe in the checkerboard group was 26.0% greater compared to the fixation group, but the level of significance was modest (P=.03). In contrast, when normalizing the CBF with whole-brain CBF or CBF in a reference region [termed relative CBF (rCBF)], the statistical significance was improved considerably (P<.003). For voxel-based analysis, the rCBF indices correctly detected CBF differences in the occipital lobe in the across-group comparison, while aCBF failed to detect any significant cluster using the same statistical threshold. We also performed Monte Carlo simulation to confirm the experimental findings and found that the power improvement was most pronounced when signal-to-noise-ratio is moderate and the underlying CBF difference was small. The simulation also showed that, with the proposed normalization, a detection power of 80% can be achieved using a sample size of about 20. In summary, rCBF is a more sensitive index to detect small differences in CBF, rather than the much-sought-after aCBF, since it reduces data noise caused by inter-subject variations in global CBF.     

Effects of blood ΔR2* non-linearity on absolute perfusion quantification using DSC-MRI: Comparison with Xe-133 SPECT

Purpose

To evaluate whether a non-linear blood ΔR₂*-versus-concentration relationship improves quantitative cerebral blood flow (CBF) estimates obtained by dynamic susceptibility contrast (DSC) MRI in a comparison with Xe-133 SPECT CBF in healthy volunteers.

Material and Methods

Linear as well as non-linear relationships between ΔR₂* and contrast agent concentration in blood were applied to the arterial input function (AIF) and the venous output function (VOF) from DSC-MRI. To reduce partial volume effects in the AIF, the arterial time integral was rescaled using a corrected VOF scheme.

Results

Under the assumption of proportionality between the two modalities, the relationship CBF(MRI) = 0.58CBF(SPECT) (r = 0.64) was observed using the linear relationship and CBF(MRI) = 0.51CBF(SPECT) (r = 0.71) using the non-linear relationship.

Discussion

A smaller ratio of the VOF time integral to the AIF time integral and a somewhat better correlation between global DSC-MRI and Xe-133 SPECT CBF estimates were observed using the non-linear relationship. The results did not, however, confirm the superiority of one model over the other, potentially because realistic AIF signal data may well originate from a combination of blood and surrounding tissue.     

Denoising arterial spin labeling perfusion MRI with deep machine learning

PurposeArterial spin labeling (ASL) perfusion MRI is a noninvasive technique for measuring cerebral blood flow (CBF) in a quantitative manner. A technical challenge in ASL MRI is data processing because of the inherently low signal-to-noise-ratio (SNR). Deep learning (DL) is an emerging machine learning technique that can learn a nonlinear transform from acquired data without using any explicit hypothesis. Such a high flexibility may be particularly beneficial for ASL denoising. In this paper, we proposed and validated a DL-based ASL MRI denoising algorithm (DL-ASL).MethodsThe DL-ASL network was constructed using convolutional neural networks (CNNs) with dilated convolution and wide activation residual blocks to explicitly take the inter-voxel correlations into account, and preserve spatial resolution of input image during model learning.ResultsDL-ASL substantially improved the quality of ASL CBF in terms of SNR. Based on retrospective analyses, DL-ASL showed a high potential of reducing 75% of the original acquisition time without sacrificing CBF measurement quality.ConclusionDL-ASL achieved improved denoising performance for ASL MRI as compared with current routine methods in terms of higher PSNR, SSIM and Radiologic scores. With the help of DL-ASL, much fewer repetitions may be prescribed in ASL MRI, resulting in a great reduction of the total acquisition time.     

Absolute quantification of cerebral blood flow: correlation between dynamic susceptibility contrast MRI and model-free arterial spin labeling

Purpose

To compare absolute cerebral blood flow (CBF) estimates obtained by model-free arterial spin labeling (ASL) and dynamic susceptibility contrast MRI (DSC-MRI), corrected for partial volume effects (PVEs).

Methods

CBF was measured using DSC-MRI and model-free ASL (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) at 3 T in 15 subjects with brain tumor, and the two modalities were compared with regard to CBF estimates in normal gray matter (GM) and DSC-to-ASL CBF ratios in selected tumor regions. The DSC-MRI CBF maps were calculated using a global arterial input function (AIF) from the sylvian-fissure region, but, in order to minimize PVEs, the AIF time integral was rescaled by a venous output function time integral obtained from the sagittal sinus.

Results

In GM, the average DSC-MRI CBF estimate was 150±45 ml/(min 100 g) (mean±SD) while the corresponding ASL CBF was 44±10 ml/(min 100 g). The linear correlation between GM CBF estimates obtained by DSC-MRI and ASL was r=.89, and observed DSC-to-ASL CBF ratios differed by less than 3% between GM and tumor regions.

Conclusions

A satisfactory positive linear correlation between the CBF estimates obtained by model-free ASL and DSC-MRI was observed, and DSC-to-ASL CBF ratios showed no obvious tissue dependence.     

Reliability and reproducibility of perfusion MRI in cognitively normal subjects

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is becoming a popular method for measuring perfusion due to its ability of generating perfusion maps noninvasively. This allows for frequent repeat scanning, which is especially useful for follow-up studies. However, limited information is available regarding the reliability and reproducibility of ASL perfusion measurements. Here, the reliability and reproducibility of pulsed ASL was investigated in an elderly population to determine the variation in perfusion among cognitively normal individuals in different brain structures. Intraclass correlation coefficients (ICC) and within-subject variation coefficients (wsCV) were used to estimate reliability and reproducibility over a period of 1 year. Twelve cognitively normal subjects (75.5±5.3 years old, six male and six female) were scanned four times (at 0, 3, 6 and 12 months). No significant difference in cerebral blood flow (CBF) was found over this period. CBF values ranged from 46 to 53 ml/100 g per minute in the medial frontal gyrus (MFG) and from 40 to 44 ml/100 g per minute over all gray matter regions in the superior part of the brain. Data obtained from the first two scans were processed by two readers and showed high reliability (ICC >0.97) and reproducibility (wsCV <6%). However, over the total period of 1 year, reliability reduced to a moderate level (ICC=0.63–0.74) with wsCVs of gray matter, left MFG, right MFG of 13.5%, 12.3%, and 15.4%, respectively. In conclusion, measurement of CBF with pulsed ASL provided good agreement between inter-raters. A moderate level of reliability was obtained over a 1-year period, which was attributed to variance in slice positioning and coregistration. As such pulsed ASL has the potential to be used for CBF comparison in longitudinal studies.     

Effects of variable blast pressures on blood flow and oxygen saturation in rat brain as evidenced using MRI

It has been recognized that primary blast waves may result in neurotrauma in soldiers in theater. A new type of contrast used in magnetic resonance imaging (MRI), susceptibility-weighted imaging (SWI), has been developed that is based on the different susceptibility levels in diverse tissues and can detect decreases in cerebral blood flow (CBF) using inferred oxygen saturation changes in tissue. In addition, a continuous arterial spin-labeled (ASL) MRI sequence was used as a direct measure of regional CBF within the brain tissue. Animals were subjected to whole-body blast exposures of various overpressures within a gas-driven shock tube. When exposed to low levels of overpressure, most rats demonstrated no obvious changes between pre- and postexposure in the conventional MR images. CBF changes measured by SWI and ASL were significantly higher for the overpressure exposed groups as compared to the sham group and tended to increase with pressure increases at the highest two pressures. In the hippocampus, all blast animals had a reduction in the CBF consistently in the range of 0-27%. In summary, low levels of primary blast pressure exposure demonstrated a significant physiologic effect to the brain up to 72 h postexposure.     

Robust estimation of the cerebral blood flow in arterial spin labelling

The introduction of arterial spin labelling (ASL) techniques in magnetic resonance imaging (MRI) has made feasible a non-invasive measurement of the cerebral blood flow (CBF). However, to date, the low signal-to-noise ratio of ASL gives us no option but to repeat the acquisition to accumulate enough data in order to get a reliable signal. The perfusion signal is then usually extracted by averaging across the repetitions. But the sample mean is very sensitive to outliers. A single incorrect observation can therefore be the source of strong detrimental effects on the perfusion-weighted image estimated with the sample mean.     

Quantification of cerebral blood flow in nonhuman primates using arterial spin labeling and a two-compartment model

Noninvasive absolute quantification of cerebral blood flow (CBF) with high spatial resolution is still a challenging task. Arterial spin labeling (ASL) is a promising magnetic resonance imaging (MRI) method for accurate perfusion quantification. However, modeling of ASL data is far from being standardized and has not been investigated in great detail. In this study, two-compartment modeling of monkey ASL data in three physiological conditions (baseline, sensory activated and globally elevated CBF) is reported. Absolute perfusion and arterial transit times were derived for gray matter (GM) and white matter (WM) separately. The uncertainties of the model's result were determined by Monte Carlo simulations. The fitted CBF values for GM were 133 ml/min/100 ml at baseline condition, 165 ml/min/100 ml during visual stimulation and 234 ml/min/100 ml for globally elevated CBF after intravenous injection of acetazolamide. The ratio of GM to WM CBF was 2.5 at baseline and was found to decrease to 1.6 after application of acetazolamide. The corresponding arterial transit times decreased from 742 to 607 ms in GM and from 985 to 875 ms in WM. Monte Carlo simulations showed that absolute CBF values can be determined with an error of 11-15%, while the arterial transit time values have a coefficient of variation of 25-31%. With an alternative acquisition scheme, the precision of the arterial transit times can be improved significantly. The CBF values in the occipital lobe of the monkey brain quantified with ASL are higher than previously reported in positron emission tomography studies.     

Validation study of a pulsed arterial spin labeling technique by comparison to perfusion computed tomography

Abnormalities in cerebral blood flow (CBF) are believed to play a significant role in the development of major neonatal neuropathologies. One approach that would appear ideal for measuring CBF in this fragile age group is arterial spin labeling (ASL) since ASL techniques are noninvasive and quantitative. The purpose of this study was to assess the accuracy of a pulsed ASL method implemented on a 3-T scanner dedicated to neonatal imaging. Cerebral blood flow was measured in nine neonatal piglets, the ASL–CBF measurements were acquired at two inversion times (TI) (1200 and 1700 ms), and CBF was measured by perfusion computed tomography (pCT) for validation. Perfusion CT also provided images of cerebral blood volume, which were used to identify large blood vessels, and contrast arrival time, which were used to assess differences in arterial transit times between gray and white matter. Good agreement was found between gray matter CBF values from pCT (76±1 ml/min per 100 g) and ASL at TI=1700 ms (73±1 ml/min per 100 g). At TI=1200 ms, ASL overestimated CBF (91±2 ml/min per 100 g), which was attributed to substantial intravascular signal. No significant differences in white matter CBF from pCT and ASL were observed (average CBF=60±1 ml/min per 100 g), nor was there any difference in contrast arrival times for gray and white matter (0.95±0.04 and 0.99±0.03 s, respectively), which suggests that the arterial transit times for ASL were the same in this animal model. This study verified the accuracy of the implemented ASL technique and showed the value of using pCT to study other factors that can affect ASL–CBF measurements.     

Abnormalities of cerebral blood flow in multiple sclerosis: A pseudocontinuous arterial spin labeling MRI study

Arterial spin labeling (ASL) is a noninvasive technique that can measure cerebral blood flow (CBF). To our knowledge, there is no study that examined regional CBF of multiple sclerosis (MS) patients by using this technique. The present study assessed the relationship between clinical presentations and functional imaging data in MS using pseudocontinuous arterial spin labeling (pCASL). Twenty-seven patients with MS and 24 healthy volunteers underwent magnetic resonance imaging and pCASL to assess CBF. Differences in CBF between the two groups and the relationships of CBF values with the T2-hyperintense volume were evaluated. Compared to the healthy volunteers, reduced CBF was found in the bilateral thalami and right frontal region of the MS patients. The volume of the T2-hyperintense lesion was negatively correlated with regional CBF in some areas, such as both thalami. Our results suggest that demyelinated lesions in MS mainly have a remote effect on the thalamus and that the measurement of CBF using ASL could be an objective marker for monitoring disease activity in MS.     

Tagging of the Magnetization with the Transition Zones of 360° Rotations Generated by a Tandem of Two Adiabatic DANTE Inversion Sequences

A new technique is presented for generating myocardial tagging using the signal intensity minima of the transition zones between the bands of 0° and 360° rotations, induced by a tandem of two adiabatic delays alternating with nutations for tailored excitation (DANTE) inversion sequences. With this approach, the underlying matrix corresponds to magnetization that has experienced 0° or 360° rotations. The DANTE sequences were implemented from adiabatic parent pulses for insensitivity of the underlying matrix to B₁ inhomogeneity. The performance of the proposed tagging technique is demonstrated theoretically with computer simulations and experimentally on phantom and on the canine heart, using a surface coil for both RF transmission and signal reception. The simulations and the experimental data demonstrated uniform grid contrast and sharp tagging profiles over a twofold variation of the B₁ field magnitude.     

Intracranial vascular feature changes in time of flight MR angiography in patients undergoing carotid revascularization surgery

PurposeTo characterize the intracranial vascular features extracted from time of flight (TOF) images and their changes from baseline to follow-up in patients undergoing carotid revascularization, using arterial spin labeling (ASL) cerebral blood flow (CBF) measurement as a reference.MethodsIn this retrospective study, brain TOF and ASL images of 99 subjects, acquired before, within 48 h, and/or 6 months after, carotid revascularization surgery were analyzed. TOF images were analyzed using a custom software (iCafe) to quantify intracranial vascular features, including total vessel length, total vessel volume, and number of branches. Mean whole-brain CBF was calculated from ASL images. ASL scans showing low ASL signal in the entire flow territory of an internal carotid artery (ICA), which may be caused by labeling failure, were excluded. Changes and correlations between time points were analyzed separately for TOF intracranial vascular features and ASL CBF.ResultsSimilar to ASL CBF, TOF vascular features (i.e. total vessel length, total vessel volume and number of branches) increased dramatically from baseline to post-surgery, then returned to a level slightly higher than the baseline in long-term follow-up (All P < 0.05). Correlation between time points was observed for all three TOF vascular features but not for ASL CBF.ConclusionIntracranial vascular features, including total vessel length, total vessel volume and number of branches, extracted from TOF images are useful in detecting brain blood flow changes induced by carotid revascularization surgery.     

Utility of a diffusion-weighted arterial spin labeling (DW-ASL) technique for evaluating the progression of brain white matter lesions

PurposeTo investigate the utility of diffusion-weighted arterial spin labeling (DW-ASL) for detecting the progression of brain white matter lesions.Materials and methodsA total of 492 regions of interest (ROIs) in 41 patients were prospectively analyzed. DW-ASL was performed using the diffusion gradient prepulse of five b-values (0, 25, 60, 102, and 189) before the ASL readout. We calculated the water exchange rate (K_w) with post-processing using the ASL signal information for each b-value. The cerebral blood flow (CBF) was also calculated using b0 images. Using the signal information in FLAIR (fluid-attenuated inversion recovery) images, we classified the severity of white matter lesions into three grades: non-lesion, moderate, and severe. In addition, the normal K_w level was measured from DW-ASL data of 60 ROIs in five control subjects. The degree of variance of the K_w values (K_w-var) was calculated by squaring the value of the difference between each K_w value and the normal K_w level. All patient's ROIs were divided into non-progressive and progressive white matter lesions by comparing the present FLAIR images with those obtained 2 years before this acquisition.ResultsCompared to the non-progressive group, the progressive group had significantly lower CBF, significantly higher severity grades in FLAIR, and significantly greater K_w-var values. In a receiver operator characteristic curve analysis, a high area under the curve (AUC) of 0.89 was obtained with the use of K_w-var. In contrast, the AUCs of 0.59 for CBF and 0.72 for severity grades in FLAIR were obtained.ConclusionsThe DW-ASL technique can be useful to detect the progression of brain white matter lesions. This technique will become a clinical tool for patients with various degrees of white matter lesions.     

Quantification of superparamagnetic iron oxide using inversion recovery balanced steady-state free precession

Cellular and molecular MRI trafficking studies using superparamagnetic iron oxide (SPIO) have greatly improved non-invasive investigations of disease progression and drug efficacy, but thus far, these studies have largely been restricted to qualitative assessment of hypo- or hyperintense areas near SPIO. In this work, SPIO quantification using inversion recovery balanced steady-state free precession (IR-bSSFP) was demonstrated at 3 T by extracting R₂ values from a monoexponential model (P. Schmitt et al., 2004). A low flip angle was shown to reduce the apparent recovery rate of the IR-bSSFP time course, thus extending the dynamic range of quantification. However, low flip angle acquisitions preclude the use of traditional methods for combining RF phase-cycled images to reduce banding artifacts arising from off-resonance due to B₀ inhomogeneity. To achieve R₂ quantification of SPIO, we present a new algorithm applicable to low flip angle IR-bSSFP acquisitions that is specifically designed to identify on-resonance acquisitions. We demonstrate in this work, using both theoretical and empirical methods, that the smallest estimated R₂ from multiple RF phase-cycled acquisitions correspond well to the on-resonance time course. Using this novel minimum R₂ algorithm, homogeneous R₂ maps and linear R₂ calibration curves were created up to 100 μg(Fe)/mL with 20° flip angles, despite substantial B₀ inhomogeneity. In addition, we have shown this technique to be feasible for pre-clinical research: the minimum R₂ algorithm was resistant to off-resonance in a single slice mouse R₂ map, whereas maximum intensity projection resulted in banding artifacts and overestimated R₂ values. With the application of recent advances in accelerated acquisitions, IR-bSSFP has the potential to quantify SPIO in vivo, thus providing important information for oncology, immunology, and regenerative medicine MRI studies.     

Current-density imaging using ultra-low-field MRI with adiabatic pulses

Magnetic resonance imaging (MRI) allows measurement of electric current density in an object. The measurement is based on observing how the magnetic field of the current density affects the associated spins. However, as high-field MRI is sensitive to static magnetic field variations of only the field component along the main field direction, object rotations are typically needed to image three-dimensional current densities. Ultra-low-field (ULF) MRI, on the other hand, with B₀ on the order of 10–100 μT, allows novel MRI sequences. We present a rotation-free method for imaging static magnetic fields and current densities using ULF MRI. The method utilizes prepolarization pulses with adiabatic switch-off ramps. The technique is designed to reveal complete field and current-density information without the need to rotate the object. The method may find applications, e.g., in conductivity imaging. We present simulation results showing the feasibility of the sequence.     

Evaluation of preprocessing steps to compensate for magnetic field distortions due to body movements in BOLD fMRI

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is currently the dominant technique for non-invasive investigation of brain functions. One of the challenges with BOLD fMRI, particularly at high fields, is compensation for the effects of spatiotemporally varying magnetic field inhomogeneities (ΔB₀) caused by normal subject respiration and, in some studies, movement of the subject during the scan to perform tasks related to the functional paradigm. The presence of ΔB₀ during data acquisition distorts reconstructed images and introduces extraneous fluctuations in the fMRI time series that decrease the BOLD contrast-to-noise ratio. Optimization of the fMRI data-processing pipeline to compensate for geometric distortions is of paramount importance to ensure high quality of fMRI data. To investigate ΔB₀ caused by subject movement, echo-planar imaging scans were collected with and without concurrent motion of a phantom arm. The phantom arm was constructed and moved by the experimenter to emulate forearm motions while subjects remained still and observed a visual stimulation paradigm. These data were then subjected to eight different combinations of preprocessing steps. The best preprocessing pipeline included navigator correction, a complex phase regressor and spatial smoothing. The synergy between navigator correction and phase regression reduced geometric distortions better than either step in isolation and preconditioned the data to make them more amenable to the benefits of spatial smoothing. The combination of these steps provided a 10% increase in t-statistics compared to only navigator correction and spatial smoothing and reduced the noise and false activations in regions where no legitimate effects would occur.