Evaluation of alterations in interstitial fluid dynamics in cases of whole‐brain radiation using the diffusion‐weighted image analysis along the perivascular space method

Abstract

In the current study, we assessed changes in interstitial fluid dynamics resulting after whole‐brain radiotherapy using the diffusion‐weighted image analysis along the perivascular space (DWI‐ALPS) method, which is a simplified variation of the diffusion tensor image ALPS (DTI‐ALPS) method using diffusion‐weighted imaging (DWI) with orthogonal motion‐probing gradients (MPGs). This retrospective study included 47 image sets from 22 patients who underwent whole‐brain radiotherapy for brain tumors. The data for the normal control group comprised 105 image sets from 105 participants with no pathological changes. DWI was performed with the three MPGs applied in an orthogonal direction to the imaging plane, and apparent diffusion coefficient images for the x‐, y‐, and z‐axes were retrospectively generated. The ALPS index was calculated to quantify interstitial fluid dynamics. The independent t‐test was used to compare the ALPS index between normal controls and patients who underwent whole‐brain radiotherapy. Patients were compared in all age groups and individual age groups (20–39, 40–59, and 60–84 years). We also examined the correlation between biologically equivalent doses (BEDs) and the ALPS index, as well as the correlation between white matter hyperintensity and the ALPS index. In the comparison of all age groups, the ALPS index was significantly lower (p < 0.001) in the postradiation group (1.32 ± 0.16) than in the control group (1.44 ± 0.17), suggesting that interstitial fluid dynamics were altered in patients following whole‐brain radiotherapy. Significant age group differences were found (40–59 years: p < 0.01; 60–84 years: p < 0.001), along with a weak negative correlation between BEDs (r = −0.19) and significant correlations between white matter hyperintensity and the ALPS index (r = −0.46 for periventricular white matter, r = −0.38 for deep white matter). It was concluded that the ALPS method using DWI with orthogonal MPGs suggest alteration in interstitial fluid dynamics in patients after whole‐brain radiotherapy. Further systematic prospective studies are required to investigate their association with cognitive symptoms.

Radiation-induced glymphatic dysfunction in patients with nasopharyngeal carcinoma: a study using diffusion tensor image analysis along the perivascular space

“…Compared with patients in the pre-RT group, those in the post-RT group had a significantly lower DTI-ALPS index. This finding is consistent with that of a recent diffusion-weighted imaging study in which the diffusion-weighted imaging-ALPS index was significantly lower in the post-radiation group than in the control group (Taoka et al, 2023). A decreased DTI-ALPS index may thus indicate glymphatic system insufficiency in patients with NPC following RT.…”

“…Our findings of significant negative correlations between the MDRT and the DTI-ALPS index indicate that a higher ipsilateral maximum RT dosage is associated with a lower DTI-ALPS index. This expected finding implies that glymphatic functional impairments are mainly induced by RT, and is in line with one recent whole-brain radiation study showing that the ALPS index has a weak negative correlation with biologically equivalent RT doses (Taoka et al, 2023). Moreover, using rat models, several studies have reported that increased single or total radiation doses result in elevated inflammatory factors (such as tumor necrosis factor-α, interferon-γ, and interleukin-1β), cellular debris, and BBB permeability, and have a negative effect on perivascular astrocyte survival (Chiang et al, 1993;Raju et al, 2000;Yuan et al, 2003;Yang et al, 2017).…”

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

“…There was a weak negative correlation between ALPS and irradiation dose. 91 When performing the DWI-ALPS method, it is important to note that, unlike the DTI method, the positional relationship between white matter fibers and the ROI cannot be adjusted in post-processing, so the transverse section must be perpendicular to the projection fiber at the time of imaging.…”

“…A number of studies using the DTI-ALPS method have evaluated the association between age and ALPSindex. 4,17,18,[27][28][29]36,43,56,61,70,74,78,[80][81][82][83][84][85][86][87][88][89][90][91][92] Among these reports, a number of them showed negative correlations between age and ALPS-index. McKnight et al showed a negative correlation between the ALPS-index and age in a group of subjects with PD or essential tremor aged approximately 40−80 years, with a correlated Spearman's rank correlation coefficient of −0.203.…”