{"doi":"10.1002/mrm.29903","title":"Uncertainty propagation in absolute metabolite quantification for in vivo MRS of the human brain","abstract":"Abstract Purpose Absolute spectral quantification is the standard method for deriving estimates of the concentration from metabolite signals measured using in vivo proton MRS ( 1 H‐MRS). This method is often reported with minimum variance estimators, specifically the Cramér‐Rao lower bound (CRLB) of the metabolite signal amplitude's scaling factor from linear combination modeling. This value serves as a proxy for SD and is commonly reported in MRS experiments. Characterizing the uncertainty of absolute quantification, however, depends on more than simply the CRLB. The uncertainties of metabolite‐specific (T 1m , T 2m ), reference‐specific (T 1ref , T 2ref ), and sequence‐specific (T R , T E ) parameters are generally ignored, potentially leading to an overestimation of precision. In this study, the propagation of uncertainty is used to derive a comprehensive estimate of the overall precision of concentrations from an internal reference. Methods The propagated uncertainty is calculated using analytical derivations and Monte Carlo simulations and subsequently analyzed across a set of commonly measured metabolites and macromolecules. The effect of measurement error from experimentally obtained quantification parameters is estimated using published uncertainties and CRLBs from in vivo 1 H‐MRS literature. Results The additive effect of propagated measurement uncertainty from applied quantification correction factors can result in up to a fourfold increase in the concentration estimate's coefficient of variation compared to the CRLB alone. A case study analysis reveals similar multifold increases across both metabolites and macromolecules. Conclusion The precision of absolute metabolite concentrations derived from 1 H‐MRS experiments is systematically overestimated if the uncertainties of commonly applied corrections are neglected as sources of error.","journal":"Magnetic Resonance in Medicine","year":2023,"id":353348,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":385456,"name":"Christoph Juchem","orcid":"0000-0002-1505-201X","position":1,"is_corresponding":false},{"id":1099608,"name":"Ronald Instrella","orcid":"0000-0002-7959-4985","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:12:58.542950Z","pmid":"38029371","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}