PT3 Chapter 5: more advanced applications of EPI RF sequences

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PT3 Chapter 5: more advanced applications of EPI RF sequences

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5.01 BOLD and fMRI Outline

 BOLD (Blood-Oxygen-Level Dependent contrast imaging) and fMRI (functional MRI)  

The color coded fMRI projected on a T1w serie. Courtesy: Siemens.





BOLD-contrast imaging, is a method used in fMRI to observe different areas of the brain or other organs, which are found to be active in time so the change of blood oxygenation could be detected with MRI and the contrast gives information on the overall deoxy hemoglobin (dHb) content in a voxel. In the brain, this is determined by two parameters:

  • The dHb concentration in blood, which is directly proportional to the CMRO2/CBF (cerebral metabolic rate of oxygen consumption/cerebral blood flow) ratio: the rate at which oxygen is consumed compared to its rate of delivery;
  • The total amount of dHb containing blood volume in a given volume of brain tissue.

The contrast behavior includes a T2*, different to the T2 contrast. It is thought that the dominant mechanism in BOLD fMRI is the increased decay rate of the MR signal in the presence of field in-homogeneities produced by dHb. So it is ideal that the GRE-EPI RF sequence is sensitive to such local variations.

Note: magnetic field in-homogeneities generated in and around blood vessels, because of the presence of the para-magnetic dHb, depends on vessel diameter. This means that blood vessels play a critical role in the coupling between variations in neuronal activity and MR measurable signals. The MR detectable signals also depend on parameters other than physiology, specifically magnetic field strength and the type of RF pulse sequence used. So there is a difference in sensitivity to vessel diameter in Perfusion imaging using SE or GRE-EPI RF sequences.


From Stimulus to BOLD

5.02 fMRI  introduction       

Cortical activation, also called arousal in psychology is the stimulation of the cerebral cortex into a state of general wakefulness, or attention. EEG (Electroencephalography) measures the degree of arousal.


The Brain Before fMRI (1957)


Courtesy: Polyak, in Savoy, 2001, Acta Psychologica.


The Cerebrum: The cerebrum or cortex is the largest part of the human brain, associated with higher brain function such as thought and action. The cerebral cortex is divided into four sections, called “lobes”: the frontal lobe, parietal lobe, occipital lobe, and temporal lobe.

Both conventional and fMRI are intended to highlight the detection of neural activity (function) as opposed to anatomy (structure).



This is how we started with fMRI: finger tapping on both sides


In this simple fMRI experiment a person alternates between periods of doing a particular task and a control (rest) state, such as 30sec blocks looking at a visual stimulus alternating with 30sec blocks with eyes closed. The fMRI data is analyzed to identify brain areas in which the MR signal has a matching pattern of changes, and these areas are thought to be activated by the stimulus (shown: the visual cortex at the back of the head).

fMRI is based on the idea that blood carrying oxygen from the lungs behaves differently in a magnetic field than blood that has already released its oxygen to the cells. So, oxygen-rich blood and oxygen-poor blood have a different magnetic resonance.

fMRI is a functional neuro imaging procedure using MRI technology that measures brain activity by detecting associated changes in blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled.

fMRI creates the images or brain maps of brain functioning in such a way that increased blood flow to the activated areas of the brain shows up on the MRI scans. But it does not actually detect blood flow or other metabolic processes.


What is needed for an fMRI exam?

The protocol is important (preferable a EPI single shot), clear instructions, paradigms (with on-off activation patterns) maybe with visual display, external devices (e.g. button response boxes) time-course viewing (real time imaging), with activation detection. All this needs to be synchronized. In addition, analysis and registration tools. fMRI is event-related. It has a paradigm- or block design.

For the fMRI acquisitions: a strong T2* (or susceptibility) weighting, a long (TE40 – 60 ms), long TR (1 – 3 sec), a matrix 64 – 96 or even 128 but with a high temporal resolution!

Advantages of single shot techniques over multi-shot in fMRI:

  • The ability to cover the whole brain rapidly;
  • Partially suppress temporal signal fluctuations in fMRI time series (like blood vessel pulsation (vaso-motion)), respiration, and spontaneous neuronal activity,
  • At higher field strength, it is necessary to acquire single shot images faster, because the MR signal disappears faster after the excitation (the T2* is shorter) due to increased magnetic field in-homogeneities. The parallel imaging technique improved the method used a lot.


5.02a New developments

The understanding of MR measurable functional signals in the brain has improved a lot over the years since the development of the method. Also the advances and refinements in instrumentation, as mentioned before, such as the introduction of ultrahigh field MRI systems and data acquisition and image analysis methods, have a lot of impact on the IQ. Thanks to all of this mapping of cortical columns, layer specific activation or brain reading can be developed using field strength up to 11.7 T, as planned for the NeuroSpin Laboratory in France for example.

Two recent developments with fMRI involve the use of multivariate machine learning algorithms to decode brain activity patterns and a strategy that’s called as encoding. (Naselaris et al. 2011).

Also note the new coming techniques like the Multiband/multi-slice, the CAIPIRINHA varieties as it has been incorporated into the SSFP RF sequence (Stab et al. 2011) and radial acquisitions (Yutzy et al. 2011).

With these instruments and methods as the ever improving data analysis methods, fMRI may be performed in short future with totally different approaches and provide much better information than the already available great techniques today.

The RF pulse sequence showing the regular EPI and Multiplexed EPI (M-EPI) RF sequences and images obtained with Multiplexed EPI images. Courtesy: Kâmil Uğurbil.


As mentioned before, EPI RF pulse sequence generates a single slice image during each readout train, which is repeated by the number of slices to scan the whole brain. The single slice RF pulse is replaced by  (MB) Multi-Band RF pulses to excite several slices simultaneously, and then un-aliasing them using multi (array) coils for the Multi-Band technique (mentioned in the GRE RF sequence module). Multiplexed-EPI (M-EPI) RF pulse sequence combines the SIR approach with the MB technique: SIR repeatedly excites 3 slices (as shown in the RF pulse sequence diagram with pulses in red, blue and green) and acquires them in a single echo train (single shot). The example shows 4 slices from 2 mm isotropic resolution, of the 60 slices in total of the whole brain on a 3 Tesla, data set obtained with the M-EPI technique are shown including the acceleration factors. (Adapted from Feinberg et al. 2010; Moeller et al. 2010).


5.02b Specific effects to pay extra attention to

The GRE BOLD effect comes from both extra-vascular and intra-vascular blood. The blood contribution to fMRI signals can be the dominant source of functional maps at lower fields. This blood effect happens at all levels of the vasculature. Its presence in capillaries and small veins is not a problem for spatial specificity; however, the functional signals associated with blood in large veins degrade the reliability between regions of different neuronal activity and the fMRI maps. This mis-perception is diminished at ultrahigh fields as blood T2* decreases (Duong et al. 2003; Uludag et al. 2009) and becomes much shorter than tissue values of this parameter.

The large vessel effects that persist in GRE-EPI fMRI can be suppressed with SE-EPI fMRI at ultrahigh-, but not at low magnetic fields. SE-EPI fMRI responds to apparent T2 changes both in the extra-vascular space around micro-vasculature (capillaries and small post-capillary venules) and in blood itself (van Zijl et al. 1998; Ugurbil et al. 1999; Ugurbil et al. 2000; Uludag et al. 2009). The spatially inaccurate intra-vascular effects in veins are suppressed at ultrahigh fields, because the apparent T2 of venous blood decreases precipitously with increasing magnetic field magnitude (see Duong et al. 2003; Uludag et al. 2009 and references therein); it is diminished from ~180 ms at 1.5 Tesla (Barth and Moser 1997) to ~6 ms at 9.4 Tesla (Lee et al. 1999), significantly smaller than brain tissue T2; thus, at TE values that correspond approximately to grey matter T2, which would be optimal for detection of functional mapping signals associated with parenchyma at such field strengths, the blood signal would be significantly diminished, and even undetectable. At 3T, ~50% of the SE-EPI fMRI signals were shown to arise from blood (Norris et al. 2002). But at 7T, the blood contribution was estimated to be less than 10% at echo times matching grey matter T2 (Duong et al.)

So be aware that all vessel types containing dHb, ranging from capillaries to large veins contribute to the T2* GRE fMRI, the main technique used in fMRI. However, the large vein contribution dominates GRE fMRI at all magnetic field strengths. Thus, GRE fMRI suffers from inaccuracies in functional mapping, because of large vessel contributions.


5.02c Clinical Applications


fMRI in the spine. Courtesy: Academic Hospital Maastricht, department of Radiology


The application of fMRI is extending very fast and is also used a lot by psychiatrists. As mentioned before, we started with finger tapping, language, visual stimuli etc etc.

Some websites about fMRI including anatomy:

5.03 Questions


After this introduction of MORE ADVANCED APPLICATIONS of EPI RF Sequences and at the end of the module you should be able:    


  • To understand the acronyms and abbreviations in this part of the module and from those EPI RF sequences.
  • To have an in depth knowledge of the behavior, contrast and special effects of those BOLD and fMRI EPI RF sequences.
  • To understand the indication and techniques of those BOLD and fMRI EPI RF sequences.
  • To describe various applications for the use of those BOLD and fMRI EPI RF sequences.

At the end of this module you should have the skills to design imaging protocols for MRI exams, choosing the best method and contrast of those EPI RF sequences discussed in this part of the module.



Answer the questions and statements so you can jump to the LAST part!