A 2-stage simulation method was proposed to estimate the leading contributor to the CEST contrast between disease and normal tissues. First, the proposed method generates a best Bloch-McConnell fit to the MTRasym spectra of the normal brain tissues. Second, it alters only one exchange parameter in the Bloch-McConnell model to fit the MTRasym spectra of disease tissues each time. The candidate parameter that yields the smallest error between simulated and experimental results is identified as the leading contributor to the CEST contrast. The proposed method was validated in numeric phantoms and 9 tuberous sclerosis complex (TSC)-associated epilepsy patients.
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