Study of Diffusion Weighted Imaging Derived Diffusion Parameters as Biomarkers for the Microenvironment in Gliomas

Abstract

ObjectivesTo explore the efficacy of diffusion weighted imaging (DWI)-derived metrics under different models as surrogate indicators for molecular biomarkers and tumor microenvironment in gliomas.MethodsA retrospective study was performed for 41 patients with gliomas. The standard apparent diffusion coefficient (ADCst) and ADC under ultra-high b values (ADCuh) (b values: 2500 to 5000 s/mm2) were calculated based on monoexponential model. The fraction of fast diffusion (f), pseudo ADC (ADCfast) and true ADC (ADCslow) were calculated by bi-exponential model (b values: 0 to 2000 s/mm2). The apparent diffusional kurtosis (Kapp) was derived from the simplified diffusion kurtosis imaging (DKI) model (b values: 200 to 3000 s/mm2). Potential correlations between DWI parameters and immunohistological indices (i.e. Aquaporin (AQP)1, AQP4, AQP9 and Ki-67) were investigated and DWI parameters were compared between high- and low-grade gliomas, and between tumor center and peritumor. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were calculated to determine the performance of independent or combined DWI parameters in grading gliomas.ResultsThe ADCslow and ADCuh at tumor center showed a stronger correlation with Ki-67 than other DWI metrics. The ADCst, ADCslow and ADCuh at tumor center presented correlations with AQP1 and AQP4 while AQP9 did not correlate with any DWI metric. Kapp showed a correlation with Ki-67 while no significant correlation with AQPs. ADCst (p < 0.001) and ADCslow (p = 0.001) were significantly lower while the ADCuh (p = 0.006) and Kapp (p = 0.005) were significantly higher in the high-grade than in the low-grade gliomas. ADCst, f, ADCfast, ADCslow, ADCuh, Kapp at the tumor center had significant differences with those in peritumor when the gliomas grade became high (p < 0.05). Involving ADCuh and Kapp simultaneously into an independent ADCst model (AUC = 0.833) could further improve the grading performance (ADCst+ADCuh+Kapp: AUC = 0.923).ConclusionDifferent DWI metrics fitted within different b-value ranges (low to ultra-high b values) have different efficacies as a surrogate indicator for molecular expression or microstructural complexity in gliomas. Further studies are needed to better explain the biological meanings of these DWI parameters in gliomas.

Quantitative Diffusion-Weighted MR Imaging: Is There a Prognostic Role in Noninvasively Predicting the Histopathologic Type of Uveal Melanomas?

“…Mitotic count is usually higher in epithelioid tumors, whereas it is inconspicuous in spindle cell types [1,17,75] (Figure 5). On the basis of the above, we wondered whether the underlying tissue geometry of the different histopathological types of UM could affect water diffusivity and induce quantitatively measurable changes in ADC values, and, therefore, whether the ADC could represent a surrogate indicator for the microstructural complexity of the tissue microarchitecture [76].…”

“…Probably because of the aforementioned reasons, in our case series, epithelioid tumors showed an ADC value only slightly, but not significantly, higher than that of spindle cells tumors. To this, it must be added that the order of magnitude of DWI measurements is far greater than the cell size, and the ADC value is just an indicator of how much water molecules can spread; furthermore, the ADC value is only one of the DWI-derived metrics [76]. The In our case series, we found no significant difference in the mean ADC value of the histopathologic subtypes, either when assessing the histologic types separately into three distinct groups (p = 0.76) or after dichotomizing the histologic subtypes as epithelioid and non-epithelioid cell type (p = 0.82).…”

“…Probably because of the aforementioned reasons, in our case series, epithelioid tumors showed an ADC value only slightly, but not significantly, higher than that of spindle cells tumors. To this, it must be added that the order of magnitude of DWI measurements is far greater than the cell size, and the ADC value is just an indicator of how much water molecules can spread; furthermore, the ADC value is only one of the DWI-derived metrics [76]. The ADC measurement derived from traditional DW sequences is burdened with some drawbacks, since it is obtained through a monoexponential model and is influenced by microcirculation perfusion.…”

The Concept of «Peritumoral Zone» in Diffuse Low-Grade Gliomas: Oncological and Functional Implications for a Connectome-Guided Therapeutic Attitude

“…A prospective study published in 2017, which compared DKI parameters with perilesional normal-appearing white matter (NAWM) and contralesional NAWM, found some significant differences, namely, higher mean diffusivity and lower kurtosis in the perilesional WM, which were associated with tumor infiltration [14]. Some of the latest studies combining DWI and DKI parameters, despite including DLGG in their cohorts and evaluating the peritumoral area, essentially reinforced the ability of the techniques in differentiating DLGG from HGG but were unable to draw new conclusions regarding the PTZ in DLGG [44,45].…”

Ultra-high b-Value DWI in predicting progression risk of locally advanced rectal cancer: a comparative study with routine DWI

“…Recently, ultra-high b-value DWI (UHBV-DWI) is increasingly explored in relation to the cerebral system [ 15 – 17 ] and prostate cancer [ 18 , 19 ] and has showed considerable potential in tumor grading and detection. In contrast, there is lack of research with respect to the investigation of UHBV-DWI in rectal cancer.…”