Dynamic Contrast-Enhanced MRI (DCE-MRI) Analysis

Having set up your input and output images as described in the Introduction, you can now set up the quantification parameters for DCE-MRI. In the DCE-MRI Analysis tool, you will see:

Quantification parameters

• Plasma relaxivity (relaxivity of the contrast agent in blood plasma) and interstitium relaxivity (relaxivity of the contrast agent in the extra-vascular extra-cellular space). Many workers assume that these two relaxivities are the same as each other. If this is the case, then the absolute values are not important, and they can be left at their default values of 1.0. However, if these two relaxivities are known to be different, then their correct values should be entered. Enter the relaxivities in s^-1 mol^-1. If the two relaxivities are different, then entering incorrect values will result in an error in the estimate of v_e (the extracellular space volume fraction).

  Note: the relaxivity is the slope of a plot of R₁ (y-axis) against [Gd] (x-axis).

• Haematocrit. The haematocrit (the fraction of whole blood volume occupied by the red blood cells) in large vessels. Needed for correct estimation of v_e.
• Pulse sequence type. The DCE-MRI tool assumes that you are using a T₁-weighted pulse sequence, and that the signal intensity increases as the contrast agent washes through the tissue. The change in R₁ is assumed to be proportional to the concentration of contrast agent. Choose the type of sequence used:
  • Saturation-recovery. The signal intensity is assumed to be of the form:

    M=M₀ (1-exp^-TR.R1)

    Enter the recovery time (TR) in milliseconds.
  • Inversion-recovery. The signal intensity is assumed to be of the form:

    M=M₀(1-2exp^-TI.R1)

    Enter the inversion time (TI) in milliseconds.
  • Fast Low-Angle SHot (FLASH). The signal intensity is assumed to be of the form:

    M=M₀sin(α)(1-exp^-TR.R1)/ (1-cos(α)exp^-TR.R1)

    Enter the recovery time (TR) in milliseconds, and the flip angle (α) in degrees.
  • Semi quantitative or pre-computed R₁. The concentration of contrast agent is assumed to be proportional to the change in signal intensity. If this option is chosen, then the plasma and interstitium relaxivity values are used as the slope of the plot of signal intensity (y-axis) versus concentration (x-axis). Thus, this option can be regarded as semi-quantitative for many sequences. However, if you pre-compute the R₁ values and use input images that are R₁ images rather than signal intensities, then you can also use this option to give quantitative results. Use this option if you use some other method (outside the DCE-MRI tool) to create pre-computed R₁ images.
  If you choose the Saturation-recovery, Inversion-recovery or FLASH option, then you will also need to select the "M0" image. This is the image that will used for the M₀ values in the expressions above. You set this image either by clicking on the icon, or by typing in the directory and file names.

  

  The M₀ image must have as many slices as there are physical slice locations in your input image(s). For the Saturation-recovery and Inversion-recovery sequence, the M₀ image can be acquired by setting a long recovery time (TR or TI). For the FLASH sequence, the M₀ image can be obtained in one of two ways:
  • Set the flip angle (α) to 90° and acquire an image with a long TR; or
  • Acquire a series of images with different flip angles (α) and use the Image Fitter to estimate M₀ by fitting the expression M=M₀sin(α)(1-exp^-TR.R1)/ (1-cos(α)exp^-TR.R1)
    to the resulting series of images. The fitter will produce images of M₀ and R₁. The R₁ image is not needed by Jim's DCE-MRI analysis, since the pre-contrast R₁ is estimated from the images acquired before contrast arrives in the tissue using the same method as for the post-contrast images.

Arterial Input Function (AIF)

• The time at which contrast agent first appears in the feeding artery. If you cannot see a feeding artery and are measuring the AIF in a draining vein (or by some other means) then this should be the time at which the image first changes in intensity as the contrast arrives in the tissue. By selecting from , you can specify this either as:
  • The time at which contrast first appears (the first image is acquired at t=0).
  • The scan number at which contrast first appears (the first scan is numbered 1).
  Enter one of these. You can graphically confirm the arrival time using the Roaming Response dialog.
• You may optionally enter the time at which the series of images is truncated for the purposes of analysis. Images after this time will not be used as part of dataset for the analysis. Analysis will proceed as if the data after this time point has not been acquired. By selecting from , you can specify this either as:
  • The time at which to truncate the data set, or
  • The scan number at which to truncate the data set. Enter one of these, or leave the field blank to use the whole dataset. you can graphically confirm the time of truncation using the Roaming Response dialog.
• Any lead or lag between the measured arterial input function and the actual arterial feed directly into the tissue. This is specified as a number of frames (time points) of lead or lag. If the measured input function is upstream (proximal) compared to the artery that feeds directly into the tissue, then this can be compensated by setting a positive number of frames for the AIF lead/lag. If the measured input function is actually a venous drain, then this can be compensated by providing a negative number of frames for the AIF lead/lag. Change the AIF lead/lag using the AIF lead/lag spinner.

  

  The text to the left explains the meaning of the lead/lag.
• Choose how you want to obtain the AIF. You can:
  • Manually draw round a feeding artery to produce a region of interest (ROI). In this case you can produce an ROI file that contains just a single ROI drawn on one slice. This same ROI will be used for all time points to obtain the AIF. Alternatively, you can define an ROI at one time point, copy and paste it to the same slice location for all time points, and manually adjust the position to account for patient movement during the scan. If you do this, the tool will expect to find an ROI at every time point, and will given an error if it does not.

    Select the ROI file used for the AIF by pressing the button, or type the name into the text field:

    

    If you have specified the pulse sequence to be saturation-recovery, inversion-recovery or FLASH, then you must also supply an ROI file that contains an ROI drawn on the feeding artery on the M₀ image. Space will be provided in the tool for you to enter the name of this ROI file.

  • Use a predefined AIF. You can read the values of the AIF from a file that contains a list of concentration of contrast agent values. The file must contain two columns of numbers:
    • The first column is ignored, but typically will have the time point at which the [Gd] is measured. You can put in all zeros into this columns if you want.
    • The second column contains the concentration values (moles/L) averaged over the whole blood.
    A space character should separate the two columns. The DCE-MRI tool will output such a file for every analysis it performs, which will give you an example of what is needed. For semi-quantitative analysis you just need values that are proportional to the concentration of contrast agent in the artery. Select the file used for the predefined AIF by pressing the button, or type the name into the text field:

    

• Check the "Show AIF graph" checkbox if you would like a window to pop up showing you the AIF that is being used in the DCE-MRI analysis.

Analysis Type

• Tofts model. Here, the rate of flux of contrast agent from the plasma to the extra-vascular extra-cellular space (EES) is assumed to be proportional to the concentration difference between the plasma and the EES. Within the tissue of interest, the blood plasma is assumed to make a negligible contribution to the overall signal intensity.
• Tofts model with vp term. This is a modified Tofts model that includes a contribution to the signal intensity in the tissue of interest from the blood plasma. An extra term (v_p - the blood plasma volume fraction of the whole tissue) is estimated.

Now choose whether you want to perform pixel-by-pixel analysis, or region of interest (ROI) analysis. You can either:

• Estimate the DCE-MRI parameters for every image pixel, producing output images of these parameters, or
• Estimate the DCE-MRI parameters for a whole ROI, producing single values of these parameters. If you choose this option, you will choose an ROI file which can contain either:
  • A single ROI drawn on one slice. This same ROI will be used for all time points.
  • An ROI at every time point. Each ROI should be the same shape and size (which can be achieved by copying and pasting an ROI to all the desired slices) for all time points, but you can manually adjust the position to account for movement of the tissue of interest. If you choose this option, you will need to supply the name of the ROI file, and also the base name of the AIF output file. This output file will be written with the AIF used in the analysis.
  If you have specified the pulse sequence to be either saturation-recovery, inversion-recovery or FLASH, then you must also supply an ROI file that contains an ROI of the same shape and size as the region to be analysed, positioned on the M₀ image. Space will be provided in the tool for you to enter the name of this ROI file.

DCE-MRI Output Parametric Images

• Ktrans. The volume transfer constant, with units of ml / ml / minute.
• ve. The extra-vascular extra-cellular space volume fraction (as a fraction of the whole tissue volume). Values in this output image will range between 0 and 1.
• vp. The blood plasma volume fraction (as a fraction of the whole tissue volume), produced if you chose the analysis type "Tofts model with vp term". Values in this output image will range between 0 and 1.
• RSq. A measure of the goodness of fit. This is the sum of the squares of the residuals between the fitted curve and the time-series data.