1. The Dependence of the Apparent Diffusion Coefficient on Voxel Location and Calculation Method Lars Ewell 1, Naren Vijayakumar 2 2007 Meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO) Los Angeles Convention Center Los Angeles, CA 10/30/07 (1) Department of Radiation Oncology, University of Arizona Health Science Center. (2) Department of Electrical and Computer Engineering, University of Arizona. References 1.Ross, B. D, et al., ‘Evaluation of Cancer Therapy Using Diffusion Magnetic Resonance Imaging’, Molecular Cancer Therapeutics., 2, 581–587, June 2003. 2.Theilmann R, et al, ‘;Changes in Water Mobility Measured by Diffusion MRI Predict Response of Metastatic Breast Cancer to Chemotherapy. Neoplasia 2004;6:831-7. 3. Burdette JH et al. ‘Calculation of Apparent Diffusion Coefficients in Brain Using Two-Point and Six-Point Methods., Journal of Computer Assisted Tomography 1998;22:792-794. 4.Xing D et al., ‘Optimized Diffusion-Weighting for Measurement of Apparent Diffusion Coefficient in Human Brain. Magnetic Resonance Imaging 1997;15:771-784. 5.Ewell L., Watchman C and Wharton K. ‘ Sulci density map to aid in use of apparent diffusion coefficient for therapy evaluation’, Magnetic Resonance Imaging, In Press. a) b) Introduction The application of Diffusion Weighted Magnetic Resonance Imaging (DWMRI) has recently expanded from use mainly in ischemia to radiation oncology (1,2). It is hypothesized that as effective cancer therapy progresses, cellular breakdown leads to increased water mobility, which can be measured/monitored using the Apparent Diffusion Coefficient (ADC). Calculation of the ADC requires at least two T2 weighted images: b=0 and b > 0 s/mm 2. If the ADC is calculated on a pixel by pixel basis, the resultant image is known as an ADC map. In oncology, a Region Of Interest (ROI) containing suspected disease is often chosen, and the ADC of this entire region is longitudinally monitored. While the ADC map can give a qualitative indication of disease progression, an ADC for an ROI can also be quantitatively determined by averaging the pixel intensity in the ADC map for an ROI. However, this is not the same as determining the ADC via averaging the pixel intensity for the ROI in the scans with different b-values. The differences between these two methods are examined. In addition to this distinction, it is possible to utilize more than two b-values in the determination of an ADC. Past studies have found little difference between using two (properly chosen) or more b-values in determining an ADC in the brain(3,4). However, these studies did not compare the brain surface to the brain interior. We have looked at a number of patients and have compared the ADCs of the brain surface, with ADCs of the brain interior. Finally, we have also investigated the density of sulci in the human brain, as it relates to calculation of ADCs (5) Conclusion When determining Apparent Diffusion Coefficients in the human brain, it is likely sufficient to use either ‘Method 1’, or ‘Method 2’ in the calculation. In addition, it is also likely sufficient to use just two b-values. If an extreme lateral area is under consideration, it may be more accurate to use ‘Method 2’ and/or three b-values in the calculation. Methods and Materials In order to determine the ADC, a minimum of two diffusion b-values are needed: 1 non-diffusion, b=0, and another diffusion weighted, b>0. If just two b-values are used, e.g., 0 and 1,000 s/mm 2, the log of the ratio of the pixel intensity as a function of b-value is plotted. The slope of the line is the ADC. This is depicted in Figure 1a. If three values are used, a least squares fit to the three data points is completed. This is depicted in Figure 1b. Figure 1a: Determination of the Apparent Diffusion Coefficient (ADC) using two b-values. The slope of the line is the ADC. Figure 1b: Determination of the ADC using three b- values. The line is a least squares fit to the data. The slope of the line is the ADC. Discussion As can bee seen in Table 1, the ratio of ADC 3 /ADC 2 is approximately 1 (within uncertainty/SD) for both medial and lateral voxels using Method 1 and Method 2. A slight decrease in the ratio is observed for the lateral voxels using Method 1. For some of the most lateral voxels, a significant fraction of the area is background (dark). The ADC calculation in such an area may have ambiguous meaning, resulting in the observed deviation. Abstract Diffusion Weighted Magnetic Resonance Imaging (DWMRI) has the potential to effectively monitor radiation therapy. Utilizing axial DWMRI scans of the human brain, we have calculated Apparent Diffusion Coefficients (ADCs) using a number of different methods. We have utilized an ADC map, as well as averaging the Region Of Interest (ROI) for different diffusion values. Employing the first method, we see a difference in near surface regions of the brain, when using two or three b-values. The second method yields little difference. The differences between all four methods are summarized. Figure 2a: b=0 T2 Weighted image *. Figure 2b: b=850s/mm 2 T2 Weighted image *. Figure 2c: Resultant ADC Map. ADC for ROI can be determined by averaging pixel intensity in ROI. *Note: Image intensities have been rescaled. b=850s/mm 2 darker. ROI Figure 3a: ROI in b=0 T2 Weighted image *. Figure 3b: ROI in b=850s/mm 2 T2 Weighted image *. Figure 3c: The ADC for the ROI is determined by averaging the pixel intensities for different b- values (see text). ADC Calculation When using two b-values (0 and, e.g., 850 s/mm 2 ) the ADC is determined as the log of the ratio of pixel intensities: i.e. ADC = -(1/b)*ln(I i /I o ) with b = b-value for the diffusion weighted scan, I i the pixel intensity in the diffusion weighted scan, and I o the pixel intensity of the non-diffusion weighted (b=0) scan. Since diffusion weighting lowers signal intensity, the ratio in the log argument is less than one, and the ADC is in general >0. If an ADC map has been generated, the ADC for an ROI can be determined by averaging the pixel intensity within the ROI. This is depicted in Figure 2. This is referred to as Method 1. An alternative method of calculating the ADC involves averaging the pixel intensities of the ROI in the non- diffusion weighted scan (b=0), and the diffusion weighted scan ( b=850s/mm 2 ), and then determining the resultant slope. This is depicted in Figure 3. This is referred to as Method 2. Figure 4: Voxel Division Results In five different scan sets, the medial and lateral voxels were separated, and the ratio of ADC using three b-values (0, 520 and 850s/mm 2 ), ADC 3 (as in Figure 1b), to that using two b-values (0 and 850s/mm 2 ), ADC 2 (as in Figure 1a) were compared. The division of the voxels can be seen in Figure 4. The results of the comparisons can be seen in Table 1. Figure 4: Voxel Division Table 1: ADC Calculation Results