It is shown in the present work that the CEST method for hydroxyl protons can be used to detect changes in glycosaminoglycan (GAG) concentrations in the intervertebral disc. The method, termed gagCEST, was demonstrated ex vivo by correlating the CEST effect with the fixed charge density (FCD) of the nucleus pulposus (NP), as well as, correlating tissue CEST images with their corresponding 23Na images. Incubation of the five NP samples with trypsin produced samples with varying GAG content (N=19), and a good correlation was found between the −OH CEST effect and FCD as well as with the N-acetyl signal amplitude. GagCEST images in vitro further illustrate the amount of detail obtainable from this contrast mechanism when compared to conventional imaging. The large concentration of GAG and the relatively long T1 of water in the NP, make the method sensitive, in particular, for assessing the GAG depletion in this tissue. It is the loss of GAG in the NP that indicates the early stage of disc degeneration.

The results were consistent with manganese-enhanced MRI studies, despite the much lower manganese concentration used for PET (100 mM Mn for MRI compared to ~ 0.05 mM for PET). This indicates that uptake and transport mechanisms are comparable even at low PET doses. This helps establish the use of manganese-based radiotracers in both preclinical and clinical studies to assess anatomy, function, and connectivity.

MRI has been extensively used in neurodegenerative disorders, such as Alzheimer’s disease (AD), frontal-temporal dementia (FTD), mild cognitive impairment (MCI), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). MRI is important for monitoring the neurodegenerative components in other diseases such as epilepsy, stroke and multiple sclerosis (MS). Manganese enhanced MRI (MEMRI) has been used in many preclinical studies to image anatomy and cytoarchitecture, to obtain functional information in areas of the brain and to study neuronal connections. This is due to Mn2+ ability to enter excitable cells through voltage gated calcium channels and be actively transported in an anterograde manner along axons and across synapses. The broad range of information obtained from MEMRI has led to the use of Mn2+ in many animal models of neurodegeneration which has supplied important insight into brain degeneration in preclinical studies. Here we provide a brief review of MEMRI use in neurodegenerative diseases and in diseases with neurodegenerative components in animal studies and discuss the potential translation of MEMRI to clinical use in the future.