About fMRI

Functional magnetic resonance imaging – a simplified presentation of its basic principles

Since the early nineties, a new method for non-invasive monitoring of human brain function has been developed besides already established procedures (PET, SPECT, MEG, and EEG). Functional magnetic resonance imaging (fMRI) allows generation of 3-dimensional brain maps of neuronal activity with a spatial resolution much superior to the previous non-invasive procedures. Pioneering work has also been done in Austria (Gomiscek, Beisteiner et al., 1993) and led to foundation of the first dedicated society for functional MRI (www.oegfmrt.org). fMRI allows to map the activated brain areas identified on functional images to the respective anatomic structures identified on anatomical images. While early studies used contrast agents, the functional contrast is nowadays achieved via detection of local blood oxygenation changes which impacts the intensity of the signal. This phenomenon, also known as BOLD (blood-oxygen-level dependent) contrast, was first described by Ogawa et al. (1990). An increase in local neuronal activity increases local inflow of oxygenated blood containing oxygenated hemoglobin. With oxygenated hemoglobin the magnetic properties of the iron of hemoglobin are masked and do not disturb the local magnetic field homogeneity. In contrast, non-activated neuronal tissue is dominated by deoxygenated hemoglobin where the iron atoms have their full magnetic properties and disturb the local magnetic field. This reduction of local magnetic field disturbance in active brain areas increases the MR signal (= BOLD signal increase in activated brain areas). This principle works when more oxygen is transported into the activated area than can be consumed by the local neural tissue. As a consequence, the oxygen level in the capillary bed increases and the proportion between oxygen-rich and oxygen-poor hemoglobin changes. For clinical fMRI it is important to realize that within pathological tissue, perfusion (rCBF) with oxygenated blood sometimes is already maximized. In such tissue a local increase of oxygenated hemoglobin (HB-O2) cannot be generated. Therefore, BOLD fMRI signals (delta S) cannot be detected in such patients.

Dieses als BOLD-Effekt bekannte Phänomen wurde 1990 von Ogawa et al. beschrieben. Dabei macht man sich die unterschiedlichen magnetischen Eigenschaften von oxygeniertem und desoxygeniertem Blut zu nutze. Verantwortlich dafür ist das an Hämoglobin gebundene Eisen. Dieses wird für den Sauerstofftransport oxygeniert und es entsteht Oxyhämoglobin, ein Molekül, in welchem die magnetische Eigenschaft des Eisens weitgehend maskiert ist. Es ist deshalb diamagnetisch. Im Gegensatz dazu steht das Desoxyhämoglobin, dessen Eisenatome ihre volle magnetische Eigenschaft besitzen und somit paramagnetisch sind. Das paramagnetische Desoxyhämoglobin verursacht in seinem unmittelbaren Umfeld Magnetfeldinhomogenitäten und induziert in der Umgebung der Gefäße einen lokalen Magnetfeld-gradienten.

Bei der Stimulation von Kortexarealen kommt es zu einer Steigerung der kortikalen Metabolismusrate (CMRO2) und das aktivierte Areal reagiert mit einem erhöhten regionalen cerebralen Blutfluss (rCBF). Dabei wird mehr Sauerstoff antransportiert als durch die neuronale Aktivität verbraucht werden kann. Auf Grund dessen steigt im venösen Schenkel des Kapillarbettes der Sauerstoffgehalt, und das Verhältnis von Oxyhämoglobin zu Desoxyhämoglobin verschiebt sich zu Gunsten des Oxyhämoglobins. Durch Abnahme des Anteils des paramagnetischen desoxygenierten Blutes, verringern sich auch die in der Umgebung auftretenden Magnetfeldinhomogenitäten. Dies bedeutet eine langsamere Dephasierung der Protonenspins in der angeregten Schicht, was zu einem Signalanstieg im T2* gewichteten Gradientenbild in der aktiven Hirnregion führt.

The BOLD response to a brain stimulus develops in time and is called the hemodynamic response function. This function depends strongly on the conditions of the stimulation and must be taken into account when planning the measurement. Shortly after the onset of the stimulation there is a short decrease of the BOLD signal. In the following, the increased blood flow induced by the stimulation causes an increase of the signal starting about 1-2 seconds after the onset of brain activity. It may well take up to 10 seconds until the maximum of the signal is reached. After cessation of the stimulus, the subsequent signal decrease is also strong and usually undershoots the original signal level for a few seconds. With a field intensity of 1.5 Tesla, the BOLD signal generated by a stimulus has a size of about 3-5%. This means the baseline MR signal is increased by 3-5% due to brain activation. For such small differences, ist is important to repeat stimuli to reduce the influence of artifacts. BOLD signal increases with high field (3 Tesla) or ultra-highfield (7 Tesla) MR systems, but unfortunately also artifacts increase (Geissler et al., 2014). Nowadays several sophisticated data analysis techniques exist to infer the functional status of a brain from fMRI data. These include statistical evaluation of local brain activation, activation of complete brain networks – including the connectivity of the network nodes – as well as multivoxal pattern analysis (Stippich (Ed) 2015).

References:

Gomiscek G, Beisteiner R, Hittmair K, Mueller E, Moser E. A possible role of in-flow effects in functional MR-imaging (1993) MAGMA Magnetic Resonance Materials in Physics, Biology, and Medicine, 1 (3-4), pp. 109-113

Ogawa S, Lee, TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation (1990) Proc. NatI. Acad. Sci. USA, 87, pp. 9868-9872

Geißler A, Matt E, Fischmeister F, Wurnig M, Dymerska B, Knosp E, Feucht M, Trattnig S, Auff E, Fitch WT, Robinson S, Beisteiner R. Differential functional benefits of ultra highfield MR systems within the language network (2014) NeuroImage, 103, pp. 163-170.

Stippich C (Editor). Clinical Functional MRI: Presurgical Functional Neuroimaging (2015) Medical Radiology, Springer Berlin Heidelberg New York, DOI 10.1007/978-3-662-45123-6,  ISBN 978-3-662-45123-6 (eBook )