Whole-Brain Metabolic Network Monitoring in ALS: A Longitudinal Magnetic Resonance Spectroscopy Imaging Framework
Authors
Husum, Maja Blinge ; Ritterbusch, Ellen Sofie Borup
Term
4. term
Publication year
2026
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that still lacks validated biomarkers for tracking disease progression. This thesis investigates whether whole-brain Magnetic Resonance Spectroscopy Imaging (MRSI) can be used to monitor longitudinal changes in brain metabolism in people living with ALS. Using longitudinal 7T-MRSI data from 5 ALS participants and 12 healthy controls, the authors develop and evaluate an analysis framework in two complementary parts: (1) a change-based z-score method that compares individual regional metabolite changes against normal variability derived from healthy controls, and (2) a network-level analysis based on metabolic similarity matrices to describe reorganization of brain-wide metabolic networks over time. The z-score analysis identified changes exceeding the minimal detectable change threshold in motor and frontal cortical regions, including decreases in tNAA/tCr consistent with progressive upper motor neuron degeneration. The network analysis revealed increasing Frobenius distance from individual baseline across sessions in all ALS participants (p = 0.06), suggesting gradual metabolic reorganization, but no consistent group-level spatial patterns were found, likely reflecting disease heterogeneity and the small sample size. The study demonstrates the feasibility of longitudinal whole-brain MRSI monitoring at both individual and network level and represents an initial step toward more targeted investigations in larger ALS cohorts.
Amyotrofisk lateral sklerose (ALS) er en progressiv neurodegenerativ sygdom uden veldokumenterede biomarkører til at følge sygdomsudviklingen. I dette speciale undersøges, om whole-brain Magnetic Resonance Spectroscopy Imaging (MRSI) kan bruges til at monitorere metaboliske ændringer i hjernen hos personer med ALS over tid. På baggrund af longitudinelle 7T-MRSI-data fra 5 personer med ALS og 12 raske kontroller udvikles og afprøves et analyseframework i to spor: (1) en ændringsbaseret z-score-metode, der sammenligner individuelle, regionale metabolitændringer med normal variationsbredde hos raske kontroller, og (2) en netværksbaseret analyse, hvor metaboliske similarity-matricer anvendes til at beskrive reorganisering af hjernens metaboliske netværk. Z-score-analysen identificerede ændringer, der overskred grænsen for minimal detectable change i motoriske og frontale kortikale områder, herunder fald i tNAA/tCr, som er foreneligt med progressiv øvre motorneurondegeneration. Netværksanalysen viste en stigende Frobenius-distance fra baseline på tværs af målinger hos alle ALS-deltagere (p = 0,06), hvilket indikerer gradvis metabolisk reorganisering, men der sås ikke konsistente rumlige mønstre på gruppeniveau, sandsynligvis på grund af sygdommens heterogenitet og det begrænsede sample. Studiet demonstrerer, at whole-brain MRSI kan anvendes til longitudinel monitorering på både individ- og netværksniveau og udgør et første skridt mod mere målrettede undersøgelser i større ALS-kohorter.
[This abstract has been generated with the help of AI directly from the project full text]