Magnetic Resonance Imaging Reveals Slow-down of Global Cerebral Oxygen Metabolism in Multiple Sclerosis

Multiple sclerosis (MS) is a progressive autoimmune disease with multifactorial etiology involving both environmental and genetic factors (Kemppinen et al, 2011). Due to complex etiology, clinical presentation of MS is also diverse. Conventional magnetic resonance imaging (MRI), including T₁ and T₂-weigthed and fluid attenuated inversion recovery T₂ scans form the backbone of imaging MS patients for diagnosis and treatment monitoring. It has become evident, however, that alternative imaging techniques are needed to reveal subclinical disease (Filippi and Agosta, 2010) for stratification of patients to novel treatment strategies (Menge et al, 2008). At the same token, advanced imaging is expected to gain understanding from MS pathophysiology (Filippi and Agosta, 2010; Paling et al, 2011).

In this issue of Journal of Cerebral Blood Flow & Metabolism, Ge et al (2012) report that global cerebral metabolic rate of O₂ (CMRO₂) is decreased in relapsing-remitting form of MS with a moderate disability score (Ge et al, 2012). Cerebral metabolic rate of O₂ was quantified using MRI from separate measurements of venous oxygen saturation (Y_v) in the sagittal sinus and cerebral blood flow (CBF). Quantification of Y_v in macrovascular blood by means of T₂ mapping was introduced for MRI measurement of oxygen extraction ratio by Oja et al (1999). Ge et al (2012) have developed a more robust and faster MRI technique for quantification of oxygen extraction ratio, dubbed as T2-relaxation-under-spin-tagging (TRUST), and they converted the measured T₂ in the sagittal sinus into Y_v using the in vitro calibration (Zhao et al, 2007). In this respect, the TRUST technique can be regarded as a noninvasive variant of the Kety—Schmidt technique.

The study found a negative correlation between CMRO₂ and T₂ lesion volume, that is, the larger the lesion the lower the CMRO₂, but that the CMRO₂ is independent of the total brain volume (Ge et al, 2012). The study found no significant change in global CBF, however. These observations are potentially interesting in terms of pathology in relapsing-remitting MS, indicating that the disease influences CMRO₂, but not CBF.

The study by Ge et al (2012) is a significant contribution to the MS imaging field underscoring the current trend of imaging physiological parameters in the assessment of brain disorders (Filippi and Agosta, 2010). An early positron emission tomography study showed reduced CMRO₂ and CBF both in white matter and peripheral gray matter in MS (Brooks et al, 1984). A recent MRI perfusion study found a decrease in CBF and blood volume both in white matter and gray matter in relapsing-remitting and primary-progressive forms of MS (Inglese et al, 2008). In addition to hemodynamics, multinuclear MR spectroscopy offers access to cerebral metabolic activity in the MS brain (Hattingen et al, 2011). Hence, focus in MS imaging is shifting from white matter pathology toward global brain and gray matter aspects. Recently, high field MRI has revealed a much larger number of gray matter lesions than conspicuous by conventional MRI at 1.5 T (Filippi and Agosta, 2010). Adding the CMRO₂ to the arsenal of noninvasively obtainable parameters by MRI is a big step forward for a comprehensive assessment of cerebral pathophysiology in MS in clinical settings. Physiological MR imaging data are expected to benefit the clinical management of MS patients in the not too distant future.