Model Free Quantification

Perhaps the simplest method for providing reliable and reproducible information that has a bearing on the kinetics of contrast agent accumulation is an integration of the concentration of the agent observed in the tissue of interest over time [the initial area under curve (IAUC), unit mmol] (Evelhoch 1999). The value of IAUC obtained in a tumour is dependent on the period over which integration is performed; typically this will be from the time point representing contrast agent administration or arrival in the tissue to a time t, typically 60-120 s after the start time. IAUCt may then be defined as t

where [CA](t') represents the concentration of contrast agent measured in the tissue at time t'. Figure 6.1 shows an example of IAUC60 calculated in a liver metastasis, and clearly indicates spatial

Fig. 6.1. Multiplanar map of IAUC60 defined in a liver metastasis (orthogonal coronal sagittal and axial views). Note ring pattern indicating a higher degree of contrast agent arrival in the tumour periphery than the tumour core, which shows near zero IAUC, indicating a severely hypoperfused area. Red crosshairs indicate point of intersection of three orthogonal planes

Fig. 6.1. Multiplanar map of IAUC60 defined in a liver metastasis (orthogonal coronal sagittal and axial views). Note ring pattern indicating a higher degree of contrast agent arrival in the tumour periphery than the tumour core, which shows near zero IAUC, indicating a severely hypoperfused area. Red crosshairs indicate point of intersection of three orthogonal planes heterogeneity in the vascular characteristics of this tumour.

Other approaches to quantification of the general shape of the contrast agent concentration time course include measurement of the peak concentration, gradient of concentration increase, time of contrast agent arrival, and time to maximum enhancement. Whilst some of these parameters are perhaps simpler still to estimate than IAUC, they are in general more prone to the effects of data noise, and are therefore considered to be less reproducible than IAUC.

Most model-free measurements of contrast agent delivery to tissues are dependent upon the arterial input function (AIF) to the tumour of interest, which may be difficult to measure. This has led to attempts to normalise against reference measurements obtained from normal tissues. For example, IAUC measurements in tumours have been made using a reference IAUC obtained from muscle (Evelhoch 1999; Evelhoch et al. 2002). However, in situations where the effects of intervention are to be monitored using DCE-MRI, care must be taken to ensure that the normalisation tissue is unaffected by the procedure (e.g. due to the action of a blood flow altering pharmaceutical or the spatially extended effects of a radiotherapy field). An alternative method to minimise the influence of variable AIFs is to use a power injector or other highly reproducible contrast agent administration protocol (Parker et al. 2003b).

Model-free quantification methods aim to provide indices related to contrast agent accumulation that are easy to derive and relatively reproducible. The major disadvantage in using such parameters is the difficulty in their interpretation. For example, whilst IAUC could be defined as 'a measure of the amount of contrast agent delivered to and retained within the tumour within the stated time period', such a definition is imprecise, and does not tell us anything specifically about potentially useful tissue properties, such as blood flow and microvascular endothelial permeability. In general (although the relative contributions are dependent upon the integration time period) IAUC reflects contrast agent kinetics determined by a combination of blood flow, blood volume, endothelial permeability, and the extracellular extravascular space volume. Similarly, measures such as the gradient of contrast agent uptake, and the peak concentration during the time course are influenced by each of these parameters in generally intractable proportions.

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