Monitoring Bevacizumab-Induced Tumor Vascular Normalization by Intravoxel Incoherent Motion Diffusion-Weighted MRI.
Accurate monitoring of tumor blood vessel normalization progression is beneficial to accurate treatment of patients. At present, there is a lack of safe and noninvasive monitoring methods.
To serial monitor the vascular normalization time window of tumor antiangiogenesis treatment through intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and histopathological methods.
Exploratory animal study.
Sixty rat C6 glioma models were randomly and equally divided into the control groups (N = 30) and bevacizumab treatment groups (N = 30). Twenty-five for magnetic resonance imaging (MRI) and five for electron microscope testing in each group.
T1-weighted imaging (T1WI), T2WI with a fast spin echo sequence and IVIM-DWI with a spin-echo echo-planar imaging sequence at 3 T.
IVIM-DWI quantitative parameters (f, D, D*, and fD*) were obtained on days 0, 2, 4, 6, and 8 after bevacizumab treatment. After MRI, the microvessel density (MVD), pericyte coverage, and hypoxia-inducible factor-1α (HIF-1α) were assessed. Electron microscope observation was performed at each time point.
One-way analysis of variance and Student's t-tests were used to compare differences within and between groups. Spearman's correlation coefficient (r) assess the correlation between IVIM and pathological parameters. The intragroup correlation coefficient was determined to assess the repeatability of each IVIM parameter.
The IVIM-DWI perfusion parameters (f and fD*) of the treated group were higher than the control group on days 2 and 4. Compared to the control group, MVD decreased on days 2 and pericyte coverage increased on days 4 in the treatment group. Electron microscopy showed that the tight junctions of the treatment group were prolonged on days 2-4. In the control group, f had the highest correlation with MVD (r = 0.689). In the treated group, f had a good correlation with pericyte coverage (r = 0.557), HIF-1α had a moderately positive correlation with f (r = 0.480) and fD*(r = 0.447).
The vascular normalization time window of bevacizumab treatment of glioma was days 2-4 after antiangiogenesis treatment, which could be monitored noninvasively by IVIM-DWI.
2 TECHNICAL EFFICACY: Stage 3.
Li B
，Xu D
，Zhou J
，Wang SC
，Cai YX
，Li H
，Xu HB
... -
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Application of Intravoxel Incoherent Motion Diffusion-Weighted Imaging in Predicting and Monitoring Early Efficacy of Anti-Angiogenic Therapy in the C6 Glioma Rat Model.
To investigate the feasibility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in evaluating early effects of anti-angiogenic therapy in the C6 glioma rat model.
Twenty-six rats of the C6 glioma model were randomly divided into a treatment group (received bevacizumab) and a control group (physiological saline). IVIM-DWI was performed on days 0, 1, 3, 5, and 7 after anti-angiogenic therapy and tumor growth and IVIM-DWI parameters were dynamically observed. Hematoxylin and eosin, CD34 microvessel density (MVD), proliferation of cell nuclear antigen (PCNA), and Hif-α staining were performed on day 7. One-way ANOVA was used to compare intra-group differences and an independent-samples t-test was used to compare inter-group differences of MRI parameters. Correlations between IVIM-DWI parameters, tumor size, and pathological results were analyzed.
The relative change in tumor volume (ΔVolume) in the two groups differed significantly on days 5 and 7 (p = 0.038 and p < 0.001). The perfusion-related parameters D*- and f-values decreased in the treatment group and demonstrated significant differences compared with the control group on days 3, 5, and 7 (p = 0.033, p < 0.001, and p < 0.001, respectively). The diffusion-related parameters ADC and D-values increased in the treatment group and were found to be significantly differently different from the control group on days 5 and 7 (both p < 0.001). The initial D-value showed a negative correlation with ΔVolume (γ = -0.744, p < 0.001), whereas the initial D*-value and relative change of D-value had a positive correlation with ΔVolume (γ = 0.718, p < 0.001 and γ = 0.800, p < 0.001, respectively). MVD was strongly positively correlated with D*-value (r = 0.886, p = 0.019), PCNA was negatively correlated with ADC- and D-values (r = -0.848, p = 0.033; and r = -0.928 p = 0.008, respectively), and Hif-1α was strongly negatively correlated with D*-value (r = -0.879, p = 0.010).
IVIM-DWI was sensitive and accurate in predicting and monitoring the effects of early anti-angiogenesis therapy in a C6 glioma rat model.
Hou W
，Xue Y
，Qian Y
，Pan H
，Xu M
，Shen Y
，Li X
，Yu Y
... -
《Frontiers in Oncology》
Intravoxel Incoherent Motion and Dynamic Contrast-Enhanced Magnetic Resonance Imaging to Early Detect Tissue Injury and Microcirculation Alteration in Hepatic Injury Induced by Intestinal Ischemia-Reperfusion in a Rat Model.
Intravoxel incoherent motion (IVIM) can provide quantitative information about water diffusion and perfusion that can be used to evaluate hepatic injury, but it has not been studied in hepatic injury induced by intestinal ischemia-reperfusion (IIR). Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) can provide perfusion data, but it is unclear whether it can provide useful information for assessing hepatic injury induced by IIR.
To examine whether IVIM and DCE-MRI can detect early IIR-induced hepatic changes, and to evaluate the relationship between IVIM and DCE-derived parameters and biochemical indicators and histological scores.
Prospective pre-clinical study.
Forty-two male Sprague-Dawley rats.
IVIM-diffusion-weighted imaging (DWI) using diffusion-weighted echo-planar imaging sequence and DCE-MRI using fast spoiled gradient recalled-based sequence at 3.0 T.
All rats were randomly divided into the control group (Sham), the simple ischemia group, the ischemia-reperfusion (IR) group (IR1h, IR2h, IR3h, and IR4h) in a model of secondary hepatic injury caused by IIR, and IIR was induced by clamping the superior mesenteric artery for 60 minutes and then removing the vascular clamp. Advanced Workstation (AW) 4.6 was used to calculate the imaging parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], perfusion-related diffusion [D* ] and volume fraction [f]) of IVIM. OmniKinetics (OK) software was used to calculate the DCE imaging parameters (Ktrans , Kep , and Ve ). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed with an automatic biochemical analyzer. Superoxide dismutase (SOD) activity was assessed using the nitro-blue tetrazolium method. Malondialdehyde (MDA) was determined by thiobarbituric acid colorimetry. Histopathology was performed with hematoxylin and eosin staining.
One-way analysis of variance (ANOVA) and Bonferroni post-hoc tests were used to analyze the imaging parameters and biochemical indicators among the different groups. Pearson correlation analysis was applied to determine the correlation between imaging parameters and biochemical indicators or histological score.
ALT and MDA reached peak levels at IR4h, while SOD reached the minimum level at IR4h (all P < 0.05). ADC, D, D* , and f gradually decreased as reperfusion continued, and Ktrans and Ve gradually increased (all P < 0.05). The degrees of change for f and Ve were greater than those of other imaging parameters at IR1h (all P < 0.05). All groups showed good correlation between imaging parameters and SOD and MDA (r[ADC] = 0.615, -0.666, r[D] = 0.493, -0.612, r[D* ] = 0.607, -0.647, r[f] = 0.637, -0.682, r[Ktrans ] = -0.522, 0.500, r[Ve ] = -0.590, 0.665, respectively; all P < 0.05). However, the IR groups showed poor or no correlation between the imaging parameters and SOD and MDA (P [Ktrans and MDA] = 0.050, P [D and SOD] = 0.125, P [the remaining imaging parameters] < 0.05). All groups showed a positive correlation between histological score and Ktrans and Ve (r = 0.775, 0.874, all P < 0.05), and a negative correlation between histological score and ADC, D, f, and D* (r = -0.739, -0.821, -0.868, -0.841, respectively; all P < 0.05). For the IR groups, there was a positive correlation between histological score and Ktrans and Ve (r = 0.747, 0.802, all P < 0.05), and a negative correlation between histological score and ADC, D, f, and D* (r = -0.567, -0.712, -0.715, -0.779, respectively; all P < 0.05).
The combined application of IVIM and DCE-MRI has the potential to be used as an imaging tool for monitoring IIR-induced hepatic histopathology.
1 TECHNICAL EFFICACY STAGE: 2.
Yang J
，Meng M
，Pan C
，Qian L
，Sun Y
，Shi H
，Shen Y
，Dou W
... -
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ResearchGate
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