Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS): Revisiting the Meaning and Significance of the Method

Abstract

More than 5 years have passed since the Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) method was proposed with the intention of evaluating the glymphatic system. This method is handy due to its noninvasiveness, provision of a simple index in a straightforward formula, and the possibility of retrospective analysis. Therefore, the ALPS method was adopted to evaluate the glymphatic system for many disorders in many studies. The purpose of this review is to look back and discuss the ALPS method at this moment.The ALPS-index was found to be an indicator of a number of conditions related to the glymphatic system. Thus, although this was expected in the original report, the results of the ALPS method are often interpreted as uniquely corresponding to the function of the glymphatic system. However, a number of subsequent studies have pointed out the problems on the data interpretation. As they rightly point out, a higher ALPS-index indicates predominant Brownian motion of water molecules in the radial direction at the lateral ventricular body level, no more and no less. Fortunately, the term "ALPS-index" has become common and is now known as a common term by many researchers. Therefore, the ALPS-index should simply be expressed as high or low, and whether it reflects a glymphatic system is better to be discussed carefully. In other words, when a decreased ALPS-index is observed, it should be expressed as "decreased ALPS-index" and not directly as "glymphatic dysfunction". Recently, various methods have been proposed to evaluate the glymphatic system. It has become clear that these methods also do not seem to reflect the entirety of the extremely complex glymphatic system. This means that it would be desirable to use various methods in combination to evaluate the glymphatic system in a comprehensive manner.

DTI-ALPS index decreased in patients with Type 2 Diabetes Mellitus

“…Research has corroborated that this waste clearance network performs a multitude of functions across different areas. Clearly, the phenomena detectable through ALPS represent just a fraction of these diverse activities ( Taoka et al, 2024 ). The DTI-ALPS index probably cannot differentiate between perivascular water diffusion and other forms of directed water movement, like diffusion alongside fiber pathways, which are also included in the region of interest.…”

Evaluating the glymphatic system via magnetic resonance diffusion tensor imaging along the perivascular spaces in brain tumor patients

“…Therefore, even if the DTI-ALPS appears as a technique to evaluate the GS, those indices might not reflect brain waste clearance directly. Hence, changes in the DTI-ALPS index should be interpreted with caution [37,52,53].…”

Perivascular and Parenchymal Brain Fluid Diffusivity in Patients With a Recent Small Subcortical Infarct

“…(3) Novel non-invasive techniques based on MRI diffusion methods enable the assessment of tissue microstructure such as water content and diffusion in the brain. The analysis of diffusion parameters along the perivascular spaces (ALPS) estimates molecular diffusion that occurs parallel to the PVS, (4,5) and the analysis of the fraction of free water (FW) in the extracellular space (6) provides estimations of the ISF movement in the PVS and its fractional extracellular volume, respectively. Recently, some authors proposed a combined evaluation of PVS appearance, FW, and ALPS measures to estimate the function of brain uid at different points of the pathway according to the glymphatic model (Fig.…”