Combined ¹H and ³¹P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis

Abstract

(1)H MRSI has evolved as an important tool to study the onset and progression of brain damage in multiple sclerosis. Abnormal increases in total creatine, total choline and myoinositol have been noted in multiple sclerosis. However, the pathobiochemical mechanisms related to these changes are still largely unclear. The combination of (1)H MRSI and (1)H-decoupled (31)P MRSI can specify to what extent phosphorylated components of total creatine and total choline contribute to this increase. Combined (1)H and (31)P MRSI data were obtained at 3 T in 22 patients with multiple sclerosis and in 23 healthy controls, and aligned with structural MRI to allow for correction for partial volume effects caused by cerebrospinal fluid and lesion load. A significant increase in total creatine was found in multiple sclerosis, and this was attributed to equal changes in the phosphorylated and unphosphorylated components. The concentrations of the putative glial markers total creatine and myoinositol in lesion-free (1)H MRSI voxels correlated with the global lesion load. We conclude that changes in total creatine are not related to altered energy metabolism, but rather indicate gliosis. Together with the increase in myoinositol, total creatine can be considered as a biomarker for disease severity. A significant total choline increase was mainly a result of choline components not visible by (31)P MRS. The origin of this residual choline fraction remains to be investigated.

Adenosine Triphosphate Metabolism Measured by Phosphorus Magnetic Resonance Spectroscopy: A Potential Biomarker for Multiple Sclerosis Severity

“…The latter events can be translated as a decrease in PCr levels in MS lesions as previously seen in one study [8] and was also correlated with disease severity in another study [9]. However, in our work, PCr did not correlate with EDSS, which is in line with 2 recent studies [12,13]. This might be due to the fact that our analysis was exclusively performed on NAWM and not MS plaques.…”

“…The increase in PCr in NAWM of MS patients is in agreement with previous studies [9,10,11,12,13]. In a normal state, PCr diffuses into astrocytic processes to build up ATP by brain cytosolic creatine kinase isoform (CK-BB), and this transcription is dependent of cyclic adenosine monophosphate (cAMP) [21].…”

“…Previous works showed increased PCr in the normal appearing white matter (NAWM) of MS patients compared to healthy controls [10,11,12,13]. Although NAWM ATP might be used as a biomarker of disease severity, the relationship between ATP metabolites and Expanded Disability Status Scale (EDSS) remains unclear in RRMS and SPMS.…”

Metabolic gray matter changes of adolescents with anorexia nervosa in combined MR proton and phosphorus spectroscopy

“…The MRSI protocol was similar to the one previously described by Hattingen et al [55]. Figure 1 shows the target region at the level of the centrum semiovale including the ACC, which was covered by 2D 1 H MRSI with an axial slice of 12 mm thickness (TR 0 1,500 ms; TE030 ms; two acquisitions).…”

Metabolic Changes in Patients with Aneurysmal Subarachnoid Hemorrhage Apart from Perfusion Deficits: Neuronal Mitochondrial Injury?

“…7 1 H-MR spectroscopy allows noninvasive in vivo measurement of metabolic changes that are able to detect brain damage even in normal-appearing brain tissue. [8][9][10] Cerebral metabolite changes could also be measured by 1 H-MR spectroscopy after SAH, even on morphologically normal MR imaging. 1,7,11,12 Furthermore, Macmillan et al 1 found chronic metabolic changes in patients after aSAH that might be compatible with the neurologic sequelae in patients with SAH.…”