Abstract
BackgroundDiffusion weighted magnetic resonance imaging (DW-MRI) holds great potential for monitoring treatment response in cancer patients shortly after initiation of radiotherapy. It is hypothesized that a decrease in cellular density of irradiated cancerous tissue will lead to an increase in quantitative apparent diffusion coefficient (ADC) values. DW-MRI can therefore serve as a non-invasive marker of cell death and apoptosis in response to treatment. In the present study, we aimed to investigate the applicability of DW-MRI in preclinical models to monitor radiation-induced treatment response. In addition, we compared DW-MRI with ex vivo measures of cell density, cell death and apoptosis.MethodsDW-MRI was tested in two different syngeneic mouse models, a colorectal cancer (CT26) and a breast cancer (4 T1). ADC values were compared with quantitative determinations of apoptosis and cell death by flow cytometry. Furthermore, ADC-values were also compared to histological measurement of cell density on tumor sections.ResultsWe found a significant correlation between ADC-values and apoptotic state in the CT26 model (P = 0.0031). A strong correlation between the two measurements of ADC-value and apoptotic state was found in both models, which were also present when comparing ADC-values to cell densities.ConclusionsOur findings demonstrate that DW-MRI can be used for non-invasive monitoring of radiation-induced changes in cell state during cancer therapy. ADC values reflect ex vivo cell density and correlates well with apoptotic state, and can hereby be described as a marker for the cell state after therapy and used as a non-invasive response marker.
Highlights
Diffusion weighted magnetic resonance imaging (DW-MRI) holds great potential for monitoring treatment response in cancer patients shortly after initiation of radiotherapy
Monitoring of treatment response in cancer patients is of huge clinical importance to optimize therapeutic interventions, and the general approach based on morphology is described by the RECIST guidelines which were last updated in 2009 [1]
The size at day 4 of the treated groups were approximately 55% lower for the 10 Gy group and 60% lower for the 15 Gy group, than in the apparent diffusion coefficient (ADC)-values on the DW-MRI scans made on day 0, 1, 2, 3, and 4 increased for treatment groups compared to control group for both models (Fig. 1c and d)
Summary
Diffusion weighted magnetic resonance imaging (DW-MRI) holds great potential for monitoring treatment response in cancer patients shortly after initiation of radiotherapy. It is hypothesized that a decrease in cellular density of irradiated cancerous tissue will lead to an increase in quantitative apparent diffusion coefficient (ADC) values. Non-invasive measures of functional changes in the tumor, e.g. induction One such potential imaging modality is diffusion weighted magnetic resonance imaging (DW-MRI). This technique was focused on neuroimaging due to the limited motion in the brain and hereby a decreased number of pitfalls and artifact shortcomings [2]. DW-MRI is based on the brownian motion within tissues, and molecule-movement being restricted by cellular structures in high-density tissue e.g. solid. It has been shown that there is an inverse correlation between cellular density and ADC, describing a high cellular density as a low ADC-value due to high restriction in tissue and hereby decreased water movement [9,10,11]
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