Oxygen imaging by MRI: can blood oxygen level-dependent imaging depict the ischemic penumbra?

M apping the ischemic penumbra (ie, the neurophysio-logically silent but still viable ischemic tissue) is increasingly part of routine assessment in suspected acute stroke, although whether this approach is cost-effective is still unclear. 1,2 The penumbra is characterized by both low cerebral blood flow (CBF; Ͻ20 mL ⅐ 100 g Ϫ1 ⅐ min Ϫ1) and elevated oxygen extraction fraction (OEF). 3 The latter is considered a critical marker of tissue viability and is therefore a key imaging target. The penumbra was originally documented in humans using positron emission tomography (PET), 2,3 a validated method to map CBF, OEF and cerebral metabolic rate of oxygen (CMRO 2), 4 but clinical access to PET is scarce. Consequently, MR-based diffusion and perfusion imaging (PWI) and CT-based perfusion imaging are widely used as substitutes. 1 However , both methods have limitations for penumbra imaging 2 and do not directly assess oxygen metabolism. A method combining the advantages of MR and the ability to map OEF would therefore be highly desirable. Blood oxygen level-dependent (BOLD) imaging has recently emerged as a possible candidate for this purpose. However, several BOLD techniques with different levels of validation, accuracy, and clinical applicability are in concurrent development , making the situation somewhat confusing. This review aims to clarify whether BOLD imaging might be of use to map oxygen in the clinical setting. We systematically review and critically discuss all studies published to date in English language, both experimental and clinical, that have applied BOLD in acute stroke. Because our focus is tissue oxygen metabolism, we do not address the T2*-weighted method to visualize leptomeningeal vessels, 5 the mapping of ⌬CMRO 2 during physiological challenges, 6 or the emerging 17 O imaging method. 7 Oxyhemoglobin is diamagnetic, whereas deoxyhemoglobin (DHb) is paramagnetic. Transverse relaxation is sensitive to paramagnetic substances such as DHb, 8 hence the acronym BOLD. Because high OEF results in increased DHb concentration in the end-capillaries and venules, 9 it should be detectable using BOLD. Equation 1 describes the fraction of DHb (␹DHb) in the microvasculature 10 : (1) ␹ DHb ϭ1Ϫs a O 2 ϩm*OEF*s a O 2 where s a O 2 represents the oxygen saturation in arterial blood and m the fraction of oxygen extracted at a given point of the vascular bed. Assuming a linear oxygen extraction along the latter, theoretical maximum average m is 0.5, that is, under extreme ischemic conditions, mϭ0 at …