Elsevier

NeuroImage

Volume 62, Issue 2, 15 August 2012, Pages 970-974
NeuroImage

Review
The great brain versus vein debate

https://doi.org/10.1016/j.neuroimage.2011.09.005Get rights and content

Abstract

From the earliest fMRI experiments, it was quickly appreciated by those working with BOLD at high field that the signal change originated from visible veins whose spatial localization was relatively coarse (“the macrovasculature”), and smaller vessels (“the microvasculature”) that were not individually visible in BOLD images. It was expected that a functional brain imaging technique that was predominantly sensitive to the macrovasculature would not have the same effective resolution as one sensitive to the microvasculature. Elimination of the venous signal and enhancement of the microvascular one offered the tantalizing ability to image columnar and lamellar structures in the brain and distinguished fMRI from its predecessor techniques. This article reviews a brief history of how these signal sources were first identified and separated and some of the controversy associated with the “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

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