Abstract
The beginning and the end of the vascular normalization window are not clear in response to anti-angiogenic therapies. We used dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion MRI (IVIM-MRI) to noninvasively evaluate the vascular normalization window. MRI was performed five times: before treatment and on the second, fourth, sixth and eighth days of treatment. Quantitative perfusion parameters were calculated at each time point, including the volume transfer coefficient (Ktrans), reverse transfer constant (Kep), pseudodiffusion coefficient (D*) and perfusion fraction (f). Tumors were evaluated for changes by immunohistochemistry. An increase in Ktrans and Kep was observed after bevacizumab treatment on days 2 and 4. Similar trends were observed for D* and f on days 2 and 4. However, the parameters of Ktrans, Kep, D* and f were decreased on days 6 and 8. A significant increase of the vessel maturity index between the treatment and control groups was measured on days 2 and 4, but this increase abated by days 6 and 8. IVIM and DCE-MRI are helpful when quantifying the tumor perfusion and evaluating the vascular normalization window after anti-vessel therapy. IVIM and DCE-MRI can outline the important period after anti-vessel treatment.
Highlights
In normal physiological processes, such as the menstrual cycle and wound healing, angiogenesis is tightly regulated and creates a balance between pro- and anti-angiogenic factors
Established rat C6 gliomas were divided into a bevacizumab treatment group (n=32) and a control group (n=8) approximately 10 days after tumor cell injection, when tumors were approximately 49.25±1.10 and 49.00±1.38 mm3 (P=0.749)
We have shown that functional magnetic resonance (MR) imaging parameters can predict the vascular normalization window of an orthotopic glioma model in rats after anti-angiogenic therapy
Summary
In normal physiological processes, such as the menstrual cycle and wound healing, angiogenesis is tightly regulated and creates a balance between pro- and anti-angiogenic factors. In tumors, especially malignant tumors, the balance is tilted to promote angiogenesis, causing the development of architecturally and functionally abnormal vasculature [1, 2]. Tumor growth relies mainly on angiogenesis, and the newly formed tumor vessels provide oxygen and nutrients for the growth of tumors. The tumor vasculature is structurally irregular, characterized as being more tortuous, fragile, dilated and disorganized [3, 4]. Intravascular fluid and plasma proteins extravasate, leading to an increase in interstitial fluid pressure (IFP). Abnormal blood supply and interstitial hypertension interfere with the delivery of therapeutics to solid tumors. Hypoxia renders tumor cells resistant to both radiation and a variety of cytotoxic chemotherapy drugs [4]. Drug delivery to tumors is inefficient, reducing chemotherapeutic efficacy
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