Masafumi Harada: “Usefulness of Quantitative Metabolic Biomarkers Observed by Clinical 3T MRI Instrument”
CiNet 1F Conference Room
Department of Radiology and Radiation Oncology
Graduate School of Biomedical Sciences
Host : Yoshichika Yoshioka (PI)
MR spectroscopy (MRS) is a unique and attractive technique, and offers many kinds of biological parameters reflecting concentration and relaxation time of metabolites. However, the observed metabolites are still limited only in major high concentrated ones such as n-acetyl aspartate, creatine, choline and myo-inositol, because the routine measurements are usually conducted only by conventional PRESS or STEAM technique in clinical instruments. To increase the possibility of MRS, we developed MEGA-editing sequences and applied it to several clinical patients. We have already reported the decrease of GABA concentration in Schizophrenia, OCD and autistic patient etc. Glutathione and lactate are also discriminated by this technique. It is recently known that mutant IDH-1 and -2 are correlated with the prognosis of patients with glioma and induce 2-hydroxy glutarate (2-HG), which can be measured by proton MRS. 2-HG is now focused on the topics of proton MRS for the clinical diagnosis of brain tumors. It is considered that MEGA-editing technique can be used to observe 2-HG with high sensitivity and specificity.
The metabolites existed in the lower frequency field from the protons of H2O (left side) have not been used in clinical proton MRS, but there are several interesting metabolites observed in this frequency field. For example, NAD+ is one of the important metabolites appeared in the lower frequency field from H2O and we are now trying to observe NAD+ signal using the clinical apparatus.
Chemical exchange saturation transfer (CEST) method can be used to observe chemical substances which have not been evaluated by routine MRI and MRS, such as amide proton. CEST technique usually uses asymmetry of Magnetization Transfer (MT) rate by transforming to Z-spectrum. We analyzed Z-spectrum by multi-parametric curve fitting in a multi-pool model, and separated magnetization transfer (MT) and nuclear Overhauser effect (NOE) from CEST. Because we considered that amide-proton will be one component of macromolecules, we compared extracted CEST, MT and NOE indices with quantitative values of macromolecules observed by proton MRS in brain tumors. As the results, CEST index showed the inverted correlation with MT and NOE indices, and only NOE index demonstrated moderate inverted correlation with the amount of macromolecules. This result may imply that the decrease of NOE induces accelerated visibility of macromolecules by proton MRS in malignant tumors.
In our conclusion, editing and CEST techniques added to conventional MRS will noninvasively offer variable interesting information for biochemical metabolites in the pathological and functional disorders in the brain. The development of the robust measurement method for minor metabolites will bring us new important insight to clinical diagnosis and therapeutic perspection.