BOLD Pulse Sequences

What is the best pulse sequence to use for BOLD fMRI?  

Neuronal activity creates a hemodynamic response that locally alters local brain concentrations of deoxy- and oxy-hemoglobin. This process, in turn, produces time-dependent alterations in T2- and T2*- relaxation times forming the basis of the BOLD signal. A BOLD pulse sequence should therefore have the following characteristics: 1) sensitivity to T2 and/or T2* changes; 2) ability to detect the intrinsically low BOLD signal, often just a few percent different than baseline; and 3) sufficient spatial and temporal resolution to cover the entire brain at multiple closely spaced time points.  

At fields of 3.0 T or below, T2*-weighted gradient echo (GRE) sequences are the most commonly used BOLD sequences. At 7.0T and higher, T2-weighted spin echo (SE) techniques are generally preferred. The parameter choices discussed below apply primarily to 3.0T imaging. Most choices are largely empirical and based on a trade-off between signal-to-noise, spatial resolution, temporal resolution, and motion artifacts. (Additional methods for 7.0T imaging and newer techniques for all field strengths can be found in the Advanced Discussion.)

fMRI axial images are generally aligned parallel to the anterior commissure (AC) — posterior commissure (PC) line

• Plane of imaging. Choice is usually oblique axial, parallel to the anterior commissure-posterior commissure (AC-PC) line with whole-brain coverage. For evaluating some anatomy (like the hippocampus) oblique coronal imaging perpendicular to the structure or the AC-PC line may be used.
• Echo time (TE). The BOLD effect is maximized on GRE imaging when TE ≈ T2* of tissue. However, longer TE's produce more susceptibility artifacts and signal dropout on GRE-EPI images. Post-processing field mapping corrections may be required. At 3.0T a reasonable compromise value is TE ≈ 30−35 ms.

• Repetition time (TR). Should be less than the hemodynamic response function (HRF) time course. Values of 1−​4 sec are typical. Short TR's (≤ 1.5 s) provide better estimation of the HRF and more statistical power, but other parameters such as flip angle must be changed to avoid saturation effects and blood inflow signal.
• Slice thickness. This is a trade-off between low signal-to-noise (too thin) versus partial volume averaging (too thick). Values of 2−4 mm are typical.
• Slice order. Interleaved acquisition (1,3,5,...2,4,6..) generally selected to reduce slice cross-talk artifacts.
• In-plane resolution. Increasing matrix size to achieve higher in-plane spatial resolution increases imaging time (thus impairing temporal resolution), lengthens readout time (producing more artifacts), and reduces signal-to-noise. A trade-off exists, with base resolution matrices of 64x64 − 128x128 (or 2x2 − 3x3 mm in-plane resolution) being typical choices.
• Total imaging time. For maximal subject compliance overall imaging time should not exceed the 45-60 minute range, with no more than 10-12 minutes per individual experiment.
• Parallel imaging. Generally advised to decrease acquisition time, increase temporal resolution, and reduce susceptibility artifacts. Only low acceleration factors (R ≈ 2) recommended so as not to impair signal-to-noise ratio (SNR) too severely. Multiband techniques are becoming more popular, allowing simultaneous acquisition of 2-3 slices in the z-direction without SNR penalty.

Advanced Discussion (show/hide)»

Advanced Techniques and Options

Distortion Correction. Pre-acquisition field-mapping has long been employed to minimize susceptibility-induced spatial distortions in fMRI, but this carries with it a significant time penalty. A quick shimming procedure may be performed to improve homogeneity as a more widely used alternative, especially in non-research centers.

3D Methods. 3D acquisition offers potential advantages for fMRI including reduction in image dropout and contiguous acquisition without gaps or need to performe slice-time correction. Implementation has been difficult as TR and readout time may be prolonged and hence unacceptable for many applications. Segmented 3D methods with parallel imaging in two directions may help alleviate these problems. A technique known as z-shimming may also be used which involves applying a compensating gradient along the slab-encode (z)-axis that ensures the k-space trajectory has returned to the origin at time TE.

Multiplexed Acquisition. The use of "multi-band" techniques to excite several slices simultaneously is now possible, albeit at the expense of lengthening the EPI readout train.

PRESTO (Principle of Echo Shifting with a Train of Observations. The PRESTO technique employs a clever particular pattern of slice-selection gradients with equal rephasing areas to delay the appearance of the signal generated by the first RF-pulse until a second RF-pulse has been applied. This method is the subject of a separate Q&A and is offered as a commercial product by Philips for both ASL and fMRI.

Other Non-GRE Pulse Sequences. Techniques using fast (turbo) spin echo have been investigated for fMRI in that it offers high signal-to-noise and reduced geometric distortion. However, FSE/TSE sequences produce T2-weighting, and some modification (such as introducing echo shifting delays or echo parity corrections) must be introduced to impart the needed T2* sensitivity required for fMRI at 3T and below. The hybrid GRASE method (with alternating gradient- and spin-echoes may offer a solution, but has not been widely explored at present. At 7T and above the need for T2*-weighting may not be so great, as pure T2-changes in the fMRI signal may better reflect the locus of neuronal activity. At ultra-high fields, therefore, spin echo and SSFP methods may be used and enjoy certain advantages.

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References
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     Glover GH. 3D z-shim method for reduction of susceptibility effects in BOLD fMRI. Magn Reson Med 1999; 42:290-299.
     Gonzalez-Castillo J, Roopchansingh V, Bandettini PA, Bodurka J. Physiological noise effects on the flip angle selection in BOLD fMRI. NeuroImage 2011; 54:2764-2778.
     Inglis B. A checklist for fMRI acquisition methods reporting in the literature. From thewinnower.com (downloaded 7/16, an more modern list expanding on the 2008 paper of Poldrack)
     Poldrack RA, Fletcher PC, Henson RN, et al. Guidelines for reporting an fMRI study. NeuroImage 2008; 40:409-414.
      Preibisch C, Wallenhorst T, Heidemann R, et al. Comparison of parallel acquisition techniques Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) and Modified Sensitivity Encoding (mSENSE) in functional MRI (fMRI) at 3T. J Magn Reson Imaging 2008; 27:590-598.
     van Gelderen P, Duyn JH, Ramsey NF, Liu G, Moonen CTW. The PRESTO technique for fMRI. NeuroImage 2012; 62:676-681.
     Weiskopf N, Hutton C, Josephs O, Deichmann R. Optimal EPI parameters for reduction of susceptibility-induced BOLD senstiivty losses: a whole-brain analysis at 3 T and 1.5 T. NeuroImage 2006; 33:493-504.

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