ReviewThe great brain versus vein debate
Section snippets
The technologies
As detailed elsewhere in this issue, the efforts to produce images due to task induced changes in BOLD signal in humans were initially being pursued by at least 3 different groups (Bandettini et al., 1992a, Kwong et al., 1992, Ogawa et al., 1992) using two very distinct technologies. In terms of the MRI technology of the day, these two approaches were as different as night and day, but they shaped the research directions that these 3 groups followed for many years. The groups at MCW and MGH
First light
When one examines the images and time series in those first three papers with the benefit of 20 years of hindsight, some interesting patterns emerge. One is struck by how similar the SNR in these images was, as well as how similar the ratio of fractional BOLD signal change (ΔS/S) to the baseline fluctuations of the time course was (functional contrast-to-noise or fCNR). It is likely that the low tip angle used in FLASH was compensated by the higher SNR afforded by 4 T, such that the SNR in all
In defense of FLASH
The use of FLASH allowed the acquisition of higher resolution BOLD images that could be superimposed on anatomic images with no uncertainty due to susceptibility distortion differences between EPI and anatomic imaging sequences. This turned out to be a very important advantage in understanding some of the fundamental physics of the BOLD effect. Although all 3 groups published 64 × 64 resolution images in their first papers, only the Minnesota group presented high-resolution anatomic images that
Where does the signal come from?
In those early days, there were two approaches to determining the vascular contributions to the BOLD signal. The first was to examine the relative changes seen in the spin-echo and gradient-echo sequences. There was some elegant theory around this, developed by the MGH group (more for the interpretation of iron oxide and Gd contrast agent changes) (Fisel et al., 1991, Weisskoff et al., 1994) and by the Minnesota group for BOLD (Ogawa et al., 1993). Peter Bandettini also had some beautiful work
How does the signal depend on field strength?
A couple of years later, I had set up my own lab at the Robarts Research Institute at the University of Western Ontario, and purchased a modern 4 T system. Although SISCo no longer existed, I persuaded Varian and Siemens to cooperate and they produced a fantastic 4 T machine that stood us in good stead for a decade. Along with Brian Rutt and his motivated student Joe Gati, we set about designing a study that would once and for all show the field dependence of the BOLD effect without having to
Brain versus vein
Why was this distinction of capillary versus vein so important ? Theoretically, if one were sensitive only to 1 mm or larger veins, then the spatial resolution of fMRI was doomed to be of the order of a half to 1 cm, since that is the rough spatial separation between such vessels. For many years a debate raged in the MRI and neuroscience communities as to the merits of higher fields and the importance of the signal source. Some argued that whether one was sensitive to veins or microvasculature
Don't shoot the messenger
This may seem obvious now, but when I gave the Monday morning plenary lecture at the August 1993 Society of Magnetic Resonance in Medicine meeting in New York, it most certainly was not. With the exuberance of someone who was probably the youngest plenary speaker in the society's history (I had just turned 30), I launched a full broadside salvo about the physics of BOLD. Just over one year after the publication of the first papers, there still weren't too many groups pursuing fMRI but I had
The two faces of phase
Although the progression to 7 T had increased sensitivity to microvascular BOLD signal, veins still dominated the fractional changes. Spin echo EPI has not yet become commonly utilized, perhaps due to some of the challenges of working at ultra high fields. Pondering this some time in 2001, I went back to some of the work of Song Lai and Mark Haacke (Lai et al., 1996). They had shown that subtraction of the magnitude of a low pass filtered complex image from a low pass filtered magnitude image
Epilog
The story is not over yet, though it has not evolved dramatically in the past decade. By one metric, the work I've referenced (during and post-Minnesota) has had huge impact, in that it has been cited thousands of times and been the subject of a few brawls at international meetings. But if one steps back and examines the real impact, it has been in the adoption of higher magnetic fields. I firmly believe that we could not have 3 T as a clinical field strength now if it hadn't been for the
References (21)
- et al.
Human ocular dominance columns as revealed by high-field functional magnetic resonance imaging
Neuron
(2001) - et al.
Functional magnetic resonance imaging using RASER
Neuroimage
(2011) - et al.
Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model
Biophys. J.
(1993) - et al.
Single-shot diffusion imaging at 2.0 Tesla
J. Magn. Reson.
(1990) - et al.
Time course EPI of human brain function during task activation
Magn. Reson. Med.
(1992) - et al.
Quantification of changes in relaxation rates R2* and R2 in activated brain tissue
- et al.
Retinotopic organization in human visual cortex and the spatial precision of functional MRI
Cereb. Cortex
(1997) - et al.
MR contrast due to microscopically heterogeneous magnetic susceptibility: numerical simulations and applications to cerebral physiology
Magn. Reson. Med.
(1991) - et al.
Experimental determination of the BOLD field strength dependence in vessels and tissue
Magn. Reson. Med.
(1997) - et al.
High-resolution mapping of iso-orientation columns by fMRI
Nat. Neurosci.
(2000)
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Determining laminar neuronal activity from BOLD fMRI using a generative model
2021, Progress in NeurobiologyCitation Excerpt :It has long been recognized that the spatial profile of the GE-BOLD signal ((Koopmans et al., 2010; Uludağ and Blinder, 2018), and references therein) typically does not resemble what is expected from a cortical microcircuit model (Bastos et al., 2012; Douglas and Martin, 1991). This issue has been coined in the standard resolution fMRI studies as the “brain vs vein” debate (Menon, 2012), as often the largest BOLD signal changes are detected in pial veins remote from the actual locus of the neuronal activation (Turner, 2002). In laminar fMRI studies, intracortical ascending veins can lead to a similar phenomenon.
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2021, Seminars in Ultrasound, CT and MRIEffects of phase regression on high-resolution functional MRI of the primary visual cortex
2021, NeuroImageCitation Excerpt :More study is needed to assess whether the phase regression effects reduce the orientation dependence of GE-EPI which is driven by pial vessels (Viessmann et al., 2019). One additional area of interest would be the inclusion of phase regression into laminar modelling (Havlicek and Uludag, 2019; Markuerkiaga et al., 2016) as these methods focus on removal of penetrating vasculature and not correction for vessels on the pial surface. Finally, extension of phase regression to other GE sequences such as 3D-EPI could allow for wider adoption of this technique (Hendriks et al., 2020).
One cranium, two brains not yet introduced: Distinct but complementary views of the social brain
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