Evaluation of the DTI-ALPS Index as a Biomarker of the Glymphatic System at 1.5T

The glymphatic system is a waste clearance pathway within the brain that relies on the flow of cerebrospinal fluid facilitated by astrocytes. It has been proposed that this glymphatic system can be observed using Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS). Yet, all observations have been made at 3.0T while most clinical scanners worldwide operate at 1.5T. The change in magnetic field strength is significant, as it affects signal-to-noise ratio, spatial resolution, and the minimum echo time achievable for the same diffusion weighting, which implies different diffusion times embedded in the observations. The question remains on the usefulness of this index at 1.5T for the observation of pathologies, particularly those related to glial cells. This study aimed to evaluate the usability of the DTI-ALPS index as a biomarker for the glymphatic system using 1.5T MRI, focusing on reproducibility among different users and its capacity to distinguish pathological values in glioma patients.

A retrospective study included 44 glioma patients and 10 healthy volunteers, with DTI sequences acquired using a 1.5T MRI scanner. Patients whose structural anatomy at the level of the lateral ventricle was significantly modified by the tumor were excluded. Reproducibility between sessions and different users was evaluated on 16 healthy subjects from a public dataset. The ALPS index was calculated based on diffusivity measurements in the projection and association fibers. Four neuroradiologists independently placed regions of interest for ALPS index calculation. Statistical analyses included Intraclass Correlation Coefficients (ICC) to assess inter-rater reliability and linear regression models to analyze the relationship between ALPS index values and patient characteristics.

In the data from healthy subjects, the inter-rater reliability was low (ICC = 0.34), indicating high variability among users. A negative correlation between the ALPS index and age was observed. In glioma patients, the ALPS index showed significant differences between ipsilateral and contralateral hemispheres (1.46 ± 0.24 vs. 1.31 ± 0.22, respectively), with the contralateral side exhibiting values closer to those of healthy subjects (1.65 ± 0.20).

The reproducibility of the DTI-ALPS index is significantly affected by user variability. Further research is needed to standardize ROI placement and improve image processing techniques to enhance the reliability of the ALPS index in clinical practice.

Being easily implemented, the DTI-ALPS index demonstrates some potential as a non-invasive biomarker for glymphatic system function, particularly in identifying pathological changes in glioma patients, considering evaluation in ipsi- and contralateral hemispheres.