Commonly, malignant tumors, whether they are primary tumors or metastases, are characterized by neovascularization and increased angiogenic activity. As a consequence, tumors may have a higher proportion of immature, and thus hyperpermeable, vessels. There is need for non-invasive methods to assess tumor biology in vivo preceeding and following therapy. Dynamic contrast-enhanced MRI has been utilized successfully to quantify the microvascular characteristics of tumors based on the fractional blood volume and microvascular permeability. In human gliomas, estimates of the microvascular permeability have shown to be predictive of the pathological grade [1,2], and to correlate with the mitotic activity of a tumor [2]. Given the linear relationship between the density changes and contrast agent concentration and the lack of confounding sensitivity to flow, CT based quantifications potentially are a more accurate representation of the tissue microvasculature compared to MRI. Combined with a high spatial resolution and no susceptibility artifacts, CT may be used for non-invasive assessment of tumor malignancy and for monitoring of treatment effects. Since these quantifications probe angiogenic activity, they lend themselves towards development of surrogate measures for the treatment efficacy of anti-angiogenic treatment. |
Case study
A 71-year old patient status post Gamma knife therapy for three melanoma metastatic foci to the brain presents with a seizure to the Emergency Department, where a CT scan of the brain is ordered. The non-contrast CT scan showed, unchanged compared to a prior MRI (not shown), a focus compatible with the patient's history of metastatic disease to the brain, located in the left posterior superior parietal lobe (Fig. 1a). High density indicated hemor-rhage in the tumor. This lesion was scanned with a dynamic contrast-enhanced series on the Lightspeed QX/i CT scanner. The scan consisted of a single location data acquisition of two slices using the following parameters: 80kV, 190 mA, matrix 512x512, standard algorithm. Images were acquired after bolus injection of 100cc non-ionic contrast agent, every 2 secs for the first 80 seconds, and consequently every 20 seconds for a total data acquisition duration of 5.5 mins. Density changes in blood and tissue were kinetically analyzed using the CT Perfusion 2 software, which yields parameter maps of fractional tissue blood volume (CBV [ml/100g], blood flow [ml/100g*min] and microvascular permeability surface area product, PS, [ml/100g*min], based on arterial deconvolution and a distributed parameter model. The tumors demonstrates a strong enhancement both on early (Fig. 1b) and late (Fig. 1c) postcontrast images. Regions of interest in the tumor and the contralateral tissue (Fig. 2a) reveal the higher initial density compared to the contralateral normal tissue, due to hemorrhage (Fig. 2b). The contrast agent peak is higher in the tumor, and the decline to baseline smaller than in the tumor, given by the higher blood volume and by the microvascular permeability. |
High resolution maps of CBV, CBF and PS were obtained (Fig. 3). Compared to normal grey matter, the tumors demonstrated a subtly increased CBV (Fig. 3a, arrow) and normal CBF (Fig. 3b), whereas the surrounding edematous tissue demonstrated decreased values of CBV and CBF. Microvascular permeability, PS (Fig. 3c, arrow), however, was particularly characteristic in the tumor (>10 ml/100g*min) compared to normal brain tissue with approximately zero permeability (Fig. 3c). |
ConclusionThere is a need for non-invasive methods to assess tumor biology in vivo preceeding and following therapy. Dynamic contrastenhanced CT allows a non-invasive determination of the tumor blood volume, blood flow and microvascular permeability, and may serve as a surrogate outcome measure for anti-angiogenic treatment.
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