BOLD contrast

In magnetic resonance tomography (MRT), the BOLD contrast (from English blood oxygenation level dependent , ie "dependent on the blood oxygen content") is the dependence of the (image) signal on the oxygen content in the red blood cells . The main application of the BOLD contrast is the functional MRI (fMRI) to display brain activity. The acronym BOLD is also used synonymously for blood oxygen level dependent or (more rarely) blood oxygen (ation) level dependence / dependency .

historical development

Linus Pauling discovered as early as 1935 that the magnetic properties of the protein hemoglobin in the red blood cells change depending on the degree of oxygenation . In 1982 Keith Thulborn and co-workers showed that hemoglobin in blood samples exhibits different MRI signals depending on the oxygenation status. The same effect is observed in 1990 Seiji Ogawa and employees in vivo in laboratory animals; They also coined the term “blood oxygenation level dependent (BOLD)” - contrast. Ogawa also recognized the potential that BOLD contrast would have for functional MRI. The first results, which showed the brain activity of test subjects after visual stimulation using the BOLD contrast, were published in 1992 by John W. Belliveau and colleagues. In 2001, Nikos Logothetis and colleagues showed that the BOLD response measured in this way is directly related to neural activity.

Physical basics

Change in transverse relaxation of blood as a function of the concentration of paramagnetic deoxygenated hemoglobin (data for rat blood at 4.3 Tesla).

Deoxygenated hemoglobin (desHb) contains (due to the ionic bond of the iron atom) four unpaired electrons per heme group and is therefore paramagnetic . In hemoglobin oxygenated with oxygen (oxyHb), however, the iron bond becomes covalent and there are no unpaired electrons; oxygenated hemoglobin is therefore diamagnetic .

In addition to the proton (density) distribution, MRT images also show the relaxation behavior of the hydrogen nuclei in the sample (which differs for liquids and different tissues) as a contrast. The strong magnetic dipole field of the paramagnetic deoxygenated hemoglobin leads to local magnetic field inhomogeneities and, via the intermolecular dipole-dipole relaxation mechanism , leads to the dephasing of the initially coherently precessing nuclear spins. This dephasing is observed as a shortened (transversal) relaxation time in the vicinity of the desHb and thus changes - depending on the desHb concentration - the contrast of the image. As shown in the adjacent figure, the relaxation rate changes linearly with the square of the desHb concentration; as the desHB concentration increases, the relaxation rate increases and the relaxation time decreases. The oxygenation-dependent change of on which the contrast in gradient echo recordings is based is even more pronounced than the change in. The change in BOLD contrast due to the changed time is therefore particularly clear in these ; to a lesser extent, however, it can also be observed in spin echo recordings due to the oxygenation-dependent time. ${\displaystyle R_{2}}$ ${\displaystyle R_{2}}$ ${\displaystyle T_{2}}$ ${\displaystyle R_{2}}$ ${\displaystyle R_{2}^{*}}$ ${\displaystyle T_{2}^{*}}$ ${\displaystyle T_{2}}$

Mathematically, the changes in the relaxation rates can be described as

${\displaystyle R_{2}=R_{2,0}+\alpha \,p_{\text{Hb}}+\beta \,p_{\text{Hb}}^{2}}$ and

${\displaystyle R_{2}^{*}=R_{2,0}^{*}+\alpha ^{*}p_{\text{Hb}}+\beta ^{*}p_{\text{Hb}}^{2}}$,

where and are the relaxation rates of (diamagnetic) oxygenated hemoglobin and the proportion of deoxygenated hemoglobin. varies between 0 (exclusively oxygenated hemoglobin) and 1 = 100% (exclusively deoxygenated hemoglobin). Often you will also find a description depending on the blood oxygenation ("saturation")  that you get when you bet. ${\displaystyle R_{2,0}}$ ${\displaystyle R_{2,0}^{*}}$ ${\displaystyle p_{\text{Hb}}}$ ${\displaystyle p_{\text{Hb}}}$ ${\displaystyle Y}$ ${\displaystyle p_{\text{Hb}}=1-Y}$

Measured values ​​of the quantities and in the magnetic field  are: ${\displaystyle R_{2,0}^{(*)},\alpha ^{(*)}}$ ${\displaystyle \beta ^{(*)}}$ ${\displaystyle B_{0}}$

sample	${\displaystyle B_{0}}$	${\displaystyle R_{2,0}/\mathrm {s} ^{-1}}$	${\displaystyle \alpha /\mathrm {s} ^{-1}}$	${\displaystyle \beta /\mathrm {s} ^{-1}}$	${\displaystyle R_{2,0}^{*}/\mathrm {s} ^{-1}}$	${\displaystyle \alpha ^{*}/\mathrm {s} ^{-1}}$	${\displaystyle \beta ^{*}/\mathrm {s} ^{-1}}$	source
human Blood, in vitro	1.5 T				7th	1	35
Pig blood, in vivo	1.5 T				2	14th	22nd
Pig blood, in vivo	1.5 T				2	12	19th
Bovine blood, in vitro	1.5 T	5	0	21st	7th	0	25th
Bovine blood, in vitro	4.7 T	15th	0	254	41	0	319

(In the measurements listed last, the coefficients were set to 0, since the determination of and can influence each other and thus lead to unreliable results.) ${\displaystyle \alpha ^{(*)}}$ ${\displaystyle \alpha ^{(*)}}$ ${\displaystyle \beta ^{(*)}}$

Applications of the BOLD effect

• The BOLD effect can be used to measure neuronal activity using fMRI. A signal increase in the activated brain areas in weighted (or weighted) MRI images is observed . This is explained by the fact that the neuronal activity leads to an increased consumption of oxygen and thus initially to more deoxygenated hemoglobin; however, this effect is overcompensated by an increased cerebral blood flow with inflowing oxygenated hemoglobin (“ neurovascular coupling ”), so that finally the desHb concentration in activated brain areas decreases and thus the transverse relaxation time (and the observed signal) increases. ${\displaystyle T_{2}^{*}}$ ${\displaystyle T_{2}}$
• The BOLD effect allows MR venographs to be created using susceptibility-weighted imaging (SWI). The SWI procedure was initially called BOLD, which was then replaced by the more general term "susceptibility-weighted", since BOLD-based venographs are only one application for this procedure.

• Another application is in BOLD kidney imaging to measure intrarenal oxygenation; in particular the change in oxygenation due to the administration of substances such as furosemide (Lasix ^® ) can be investigated in this way. The subject of research is the use of BOLD contrast to study the oxygenation of tumors .

literature

• E. Mark Haacke, Robert W. Brown, Michael R. Thompson, Ramesh Venkatesan: Magnetic resonance imaging: physical principles and sequence design . 1st edition. J. Wiley & Sons, New York 1999, ISBN 0-471-35128-8 , Chapters 25.5-25.6, pp. 765-779 .
• B. Derntl, U. Habel, F. Schneider: Functional magnetic resonance tomography in psychiatry and psychotherapy . In: The neurologist . tape 81 , no. 1 , p. 16-23 , doi : 10.1007 / s00115-009-2827-9 , PMID 20057981 .
• Scott H. Faro, Feroze B. Mohamed (Eds.): BOLD fMRI: A Guide to Functional Imaging for Neuroscientists . Springer, New York 2010, ISBN 978-1-4419-1328-9 ( limited preview in Google Book Search).

Individual evidence

1. ^ L Pauling: The oxygen equilibrium of hemoglobin and its structural interpretation . In: Proc Natl Acad Sci USA . tape 21 , no. 4 , 1935, pp. 186-191 , PMID 16587956 .
2. ↑ ^{a b c} KR Thulborn, JC Waterton, PM Matthews, GK Radda: Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field . In: Biochim Biophys Acta . tape 714 , no. 2 , 1982, p. 265-270 , doi : 10.1016 / 0304-4165 (82) 90333-6 , PMID 6275909 .
3. ^ S Ogawa , TM Lee, AR Kay, DW Tank : Brain magnetic resonance imaging with contrast dependent on blood oxygenation . In: Proc Natl Acad Sci USA . tape 87 , no. 24 , 1990, pp. 9868-9872 , PMID 2124706 .
4. ↑ ^{a b} S Ogawa, TM Lee, AS Nayak, P Glynn: Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields . In: Magn Reson Med . tape 14 , no. 1 , 1990, p. 68-78 , doi : 10.1002 / mrm.1910140108 , PMID 2161986 .
5. ↑ JW Belliveau, DN Kennedy, RC McKinstry, BR Buchbinder, RM Weisskoff, MS Cohen, JM Vevea, TJ Brady, BR Rosen: Functional mapping of the human visual cortex by magnetic resonance imaging . In: Science . tape 254 , 1991, pp. 716-719 , doi : 10.1126 / science.1948051 , PMID 1948051 .
6. ↑ NK Logothetis, J Pauls, M Augath, T Trinath, A Oeltermann: Neurophysiological investigation of the basis of the fMRI signal . In: Nature . tape 412 , p. 150-157 , doi : 10.1038 / 35084005 , PMID 11449264 .
7. ↑ M Zborowski, GR Ostera, LR Moore, S Milliron, JJ Chalmers, AN Schechter: Red blood cell magnetophoresis . In: Biophys J . tape 84 , no. 4 , 2003, p. 2638-2645 , doi : 10.1016 / S0006-3495 (03) 75069-3 , PMID 12668472 .
8. ↑ ^{a b} D Li, Y Wang, DJ Waight: Blood oxygen saturation assessment in vivo using T2 * estimation . In: Magn Reson Med . tape 39 , no. 5 , 1998, pp. 685-690 , doi : 10.1002 / mrm.1910390503 , PMID 9581597 .
9. ^ D Li, Y Wang, DJ Waight: In vivo correlation between blood T2 * and oxygen saturation . In: J Magn Reson Imaging . tape 8 , no. 6 (Nov – Dec), 1998, pp. 1236-1239 , doi : 10.1002 / jmri.1880080609 , PMID 9848734 .
10. ↑ ^{a b c} MJ Silvennoinen, CS Clingman, X Golay, RA Kauppinen, PC van Zijl: Comparison of the dependence of blood R2 and R2 * on oxygen saturation at 1.5 and 4.7 Tesla . In: Magn Reson Med . tape 49 , no. 1 , 2003, p. 47-60 , doi : 10.1002 / mrm.10355 , PMID 12509819 .
11. ^ JR Reichenbach, EM Haacke: High-resolution BOLD venographic imaging: a window into brain function . In: NMR Biomed . tape 14 , no. 7–8 , 2001, pp. 453-67 , doi : 10.1002 / nbm.722 , PMID 11746938 .
12. ^ Li LP, Halter S, Prasad PV: Blood oxygen level-dependent MR imaging of the kidneys . In: Magn Reson Imaging Clin N Am . tape 16 , no. 4 , 2008, p. 613-625 , doi : 10.1016 / j.mric.2008.07.008 , PMID 18926426 .
13. ↑ AR Padhani, KA Krohn, JS Lewis, M Alber: Imaging oxygenation of human tumors . In: Eur Radiol . tape 17 , no. 4 , 2007, p. 861-872 , doi : 10.1007 / s00330-006-0431-y , PMID 17043737 .