MR methods have been proposed to estimate blood oxygen saturation in cerebral tissues by exploiting the magnetic susceptibility difference between oxy and deoxyhemoglobin. These models neglect the contribution of extravascular susceptibility sources leading to inaccurate measurements. Recent approaches combined quantitative BOLD and QSM methods, but these models neglected the impact of the geometrical arrangements of extravascular sources on signal decay. Consequently, we propose a new model to unravel the magnitude and phase of MRI gradient echo sequence signal contributions of intravascular and extravascular compartments to produce blood-oxygen saturation and non-vascular susceptibility maps. This new model and previous MRI approaches are implemented in rat data acquired in healthy and stroke settings. The results are compared across anatomical regions of interest characterized by different extravascular magnetic susceptibilities. Results obtained with the new model improved estimations in myelin-rich white matter regions and delineated oxygen saturation decrease in stroke lesions after 60 min of middle cerebral artery occlusion. Characterization of extravascular susceptibility sources improved the overall results, highlighting its critical role in the translation toward pathological applications.
ChristenTBouzatPPannetierN, et al. Tissue oxygen saturation mapping with magnetic resonance imaging. J Cereb Blood Flow Metab2014; 34: 1550–1557.
2.
BiondettiEChoJLeeH.Cerebral oxygen metabolism from MRI susceptibility. Neuroimage2023; 276: 120189.
3.
BaronJCBousserMGComarD, et al. Noninvasive tomographic study of cerebral blood flow and oxygen metabolism in vivo. Eur Neurol1981; 20: 273–284.
4.
JainVAbdulmalikOJoy PropertK, et al. Investigating the magnetic susceptibility properties of fresh human blood for noninvasive oxygen saturation quantification. Magn Reson Med2012; 68: 863–867.
5.
HeXYablonskiyDA.Quantitative BOLD: mapping of human cerebral deoxygenated blood volume and oxygen extraction fraction: default state. Magn Reson Med2007; 57: 115–126.
6.
ChristenTLemassonBPannetierN, et al. Evaluation of a quantitative blood oxygenation level-dependent (qBOLD) approach to map local blood oxygen saturation. NMR Biomed2011; 24: 393–403.
7.
YablonskiyDAHaackeEM.Theory of NMR signal behavior in magnetically inhomogeneous tissues: the static dephasing regime. Magn Reson Med1994; 32: 749–763.
8.
FanAPBilgicBGagnonL, et al. Quantitative oxygenation venography from MRI phase. Magn Reson Med2014; 72: 149–159.
9.
ZhangJLiuTGuptaA, et al. Quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) using quantitative susceptibility mapping (QSM). Magn Reson Med2015; 74: 945–952.
10.
ChristenTSchmiedeskampHStrakaM, et al. Measuring brain oxygenation in humans using a multiparametric quantitative blood oxygenation level dependent MRI approach. Magn Reson Med2012; 68: 905–911.
11.
GelmanNGorellJMBarkerPB, et al. MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content. Radiology1999; 210(3): 759–767.
12.
ChenWGauthierSAGuptaA, et al. Quantitative susceptibility mapping of multiple sclerosis lesions at various ages. Radiology2014; 271: 183–192.
13.
KrafftPRBaileyELLekicT, et al. Etiology of stroke and choice of models. Int J Stroke2012; 7: 398–406.
14.
ChoJKeeYSpincemailleP, et al. Cerebral metabolic rate of oxygen (CMRO2) mapping by combining quantitative susceptibility mapping (QSM) and quantitative blood oxygenation level-dependent imaging (qBOLD). Magn Reson Med2018; 80: 1595–1604.
15.
ShinH-GLeeJYunYH, et al. χ-Separation: magnetic susceptibility source separation toward iron and myelin mapping in the brain. Neuroimage2021; 240: 118371.
16.
DimovAVGillenKMNguyenTD, et al. Magnetic susceptibility source separation solely from gradient echo data: histological validation. Tomography2022; 8: 1544–1551.
17.
LiZFengRLiuQ, et al. APART-QSM: an improved sub-voxel quantitative susceptibility mapping for susceptibility source separation using an iterative data fitting method. Neuroimage2023; 274: 120148.
18.
BroisatALemassonBAhmadiM, et al. Mapping of brain tissue hematocrit in glioma and acute stroke using a dual autoradiography approach. Sci Rep2018; 8: 9878.
Van RossumGDrakeFLJr.Python reference manual. Amsterdam: Centrum voor Wiskunde en Informatica, 1995.
21.
BarrièreDAMagalhãesRNovaisA, et al. The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization. Nat Commun2019; 10: 5699.
22.
JenkinsonMSmithS.A global optimisation method for robust affine registration of brain images. Med Image Anal2001; 5: 143–156.
23.
JenkinsonMBannisterPBradyM, et al. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage2002; 17: 825–841.
24.
BrossardCMontigonOBouxF, et al. MP3: medical software for processing multi-parametric images pipelines. Front Neuroinform2020; 14: 594799.
25.
PeiMNguyenTDThimmappaND, et al. An algorithm for fast mono-exponential fitting based on auto-regression on linear operations (ARLO) of data. Magn Reson Med2015; 73: 843–850.
26.
LiuTWisnieffCLouM, et al. Nonlinear formulation of the magnetic field to source relationship for robust quantitative susceptibility mapping. Magn Reson Med2013; 69: 467–476.
WangYLiuT.Quantitative susceptibility mapping (QSM): decoding MRI data for a tissue magnetic biomarker. Magn Reson Med2015; 73: 82–101.
29.
WuBLiWGuidonA, et al. Whole brain susceptibility mapping using compressed sensing. Magn Reson Med2012; 67: 137–147.
30.
WeiHDibbRZhouY, et al. Streaking artifact reduction for quantitative susceptibility mapping of sources with large dynamic range. NMR Biomed2015; 28: 1294–1303.
31.
BouzatPMilletABoueY, et al. Changes in brain tissue oxygenation after treatment of diffuse traumatic brain injury by erythropoietin. Crit Care Med2013; 41: 1316.
32.
ChakhoyanACorroyer-DulmontALeblondMM, et al. Carbogen-induced increases in tumor oxygenation depend on the vascular status of the tumor: a multiparametric MRI study in two rat glioblastoma models. J Cereb Blood Flow Metab2017; 37: 2270–2282.
33.
ChristenTLemassonBPannetierN, et al. Is T2* enough to assess oxygenation? Quantitative blood oxygen level–dependent analysis in brain tumor. Radiology2012; 262: 495–502.
34.
CoqueryNFrancoisOLemassonB, et al. Microvascular MRI and unsupervised clustering yields histology-resembling images in two rat models of glioma. J Cereb Blood Flow Metab2014; 34: 1354–1362.
35.
Julien-DolbecCTropresIMontigonO, et al. Regional response of cerebral blood volume to graded hypoxic hypoxia in rat brain. Br J Anaesth2002; 89: 287–293.
36.
LemassonBChristenTSerducR, et al. Evaluation of the relationship between MR estimates of blood oxygen saturation and hypoxia: effect of an antiangiogenic treatment on a gliosarcoma model. Radiology2012; 265: 743–752.
37.
LemassonBBouchetAMaisinC, et al. Multiparametric MRI as an early biomarker of individual therapy effects during concomitant treatment of brain tumours. NMR Biomed2015; 28: 1163–1173.
38.
SchilteCBouzatPMilletA, et al. Mannitol improves brain tissue oxygenation in a model of diffuse traumatic brain injury. Crit Care Med2015; 43: 2212–2218.
39.
ValableSCorroyer-DulmontAChakhoyanA, et al. Imaging of brain oxygenation with magnetic resonance imaging: a validation with positron emission tomography in the healthy and tumoural brain. J Cereb Blood Flow Metab2017; 37: 2584–2597.
40.
ValableSToutainJDivouxD, et al. Magnetic resonance imaging of hypoxia in acute stroke compared with fluorine-18 fluoromisonidazole-positron emission tomography: a cross-validation study?NMR Biomed2023; 36: e4858.
41.
WatabeTShimosegawaEWatabeH, et al. Quantitative evaluation of cerebral blood flow and oxygen metabolism in normal anesthetized rats: 15O-labeled gas inhalation PET with MRI fusion. J Nucl Med2013; 54: 283–290.
42.
TemmaTKoshinoKMoriguchiT, et al. PET quantification of cerebral oxygen metabolism in small animals. Sci World J2014; 2014: 159103.
43.
KatoHKanaiYWatabeT, et al. Quantitative measurement of regional cerebral blood flow and oxygen metabolism in a rat model of cerebral hypoperfusion. Brain Res2019; 1719: 208–216.
44.
MacaisaCMWatabeTLiuY, et al. Preserved cerebral oxygen metabolism in astrocytic dysfunction: a combination study of 15O-gas PET with 14C-acetate autoradiography. Brain Sci2019; 9: 101.
45.
ShimochiSIhalainenJParikkaV, et al. Small animal PET with spontaneous inhalation of 15O-labelled oxygen gases: longitudinal assessment of cerebral oxygen metabolism in a rat model of neonatal hypoxic–ischaemic encephalopathy. J Cereb Blood Flow Metab2024; 44: 1024–1038.
46.
BradleyWG.MR appearance of hemorrhage in the brain. Radiology1993; 189: 15–26.
47.
WangZLuoWZhouF, et al. Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex. J Biomed Opt2012; 17: 125001.
48.
WatchmakerJMJuttukondaMRDavisLT, et al. Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients. J Cereb Blood Flow Metab2018; 38: 1618–1630.
49.
YablonskiyDASukstanskiiALHeX.Blood oxygenation level-dependent (BOLD)-based techniques for the quantification of brain hemodynamic and metabolic properties—theoretical models and experimental approaches. NMR Biomed2013; 26: 963–986.
50.
OmaeTIbayashiSKusudaK, et al. Effects of high atmospheric pressure and oxygen on middle cerebral blood flow velocity in humans measured by transcranial Doppler. Stroke1998; 29: 94–97.
51.
LiHYinJLiL, et al. Isoflurane postconditioning reduces ischemia-induced nuclear factor-κB activation and interleukin 1β production to provide neuroprotection in rats and mice. Neurobiol Dis2013; 54: 216–224.
52.
SakaiHShengHYatesRB, et al. Isoflurane provides long-term protection against focal cerebral ischemia in the rat. Anesthesiology2007; 106: 92–99.
53.
Welniak-KaminskaMFiedorowiczMOrzelJ, et al. Volumes of brain structures in captive wild-type and laboratory rats: 7T magnetic resonance in vivo automatic atlas-based study. PLoS One2019; 14: e0215348.
54.
YablonskiyDASukstanskiiALLuoJ, et al. Voxel spread function method for correction of magnetic field inhomogeneity effects in quantitative gradient-echo-based MRI. Magn Reson Med2013; 70: 1283–1292.
55.
UchidaYKanHInoueH, et al. Penumbra detection with oxygen extraction fraction using magnetic susceptibility in patients with acute ischemic stroke. Front Neurol2022; 13: 752450.
56.
UchidaYKanHKanoY, et al. Longitudinal changes in iron and myelination within ischemic lesions associate with neurological outcomes: a pilot study. Stroke2024; 55(4): 1041–1050.
57.
LeeHWehrliFW.Whole-brain 3D mapping of oxygen metabolism using constrained quantitative BOLD. Neuroimage2022; 250: 118952.
58.
DelphinABouxFBrossardC, et al. Enhancing MR vascular fingerprinting with realistic microvascular geometries. Imaging Neurosci2024; 2: 1–13.
59.
CoudertTDelphinABarrierA, et al. MR fingerprinting for imaging brain hemodynamics and oxygenation. J Magn Reson Imaging. Epub ahead of print 15 May 2025. DOI: 10.1002/ jmri.29812.
ChenJGongN-JChaimKT, et al. Decompose quantitative susceptibility mapping (QSM) to sub-voxel diamagnetic and paramagnetic components based on gradient-echo MRI data. Neuroimage2021; 242: 118477.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
