Characterizing brain metabolism in ALS with GlucoCEST MRI: A novel radiation-free imaging technique that can contribute to improved diagnostics and precision medicine for neurodegenerative disorders

Background: Amyotrophic lateral sclerosis (ALS) is a fatal disorder with heterogeneous clinical expression.

While overt morphological findings are often preceded by hypometabolism in ALS, FDG-PET is sparsely used in routine clinical practice due to costs and a somewhat uncertain diagnostic/predictive value.

Meanwhile, GlucoCEST MRI is a novel radiation-free method for imaging metabolism that has yet to be applied in ALS.Aim: To evaluate the feasibility and accuracy of GlucoCEST MRI for assessing brain metabolism in ALS and study its diagnostic and predictive value.Methods: A prospective study with 120 persons with ALS and 60 matched controls will be conducted at Karolinska University Hospital using a second-generation clinical 7 Tesla MRI scanner.

GlucoCEST will be processed and analyzed using advanced post-processing techniques and compared to the gold-standard, FDG-PET imaging, in patients.

Patients will be longitudinally followed comprehensively over up to 4-years.Significance: GlucoCEST can integrate metabolic and structural information from a single scan to detect early neurodegeneration at a lower cost and with less patient risk and -burden than FDG-PET.

As a radiation-free technique, the method is especially suitable for precision medicine approaches since it can track disease progression over time to advance our understanding of neurodegenerative disease processes and monitor the efficacy of emerging disease-modifying treatments in clinical trials.