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Diffusion-Weighted MRI in the Body: Applications and Challenges in Oncology

¹ Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
² Academic Department of Radiology, Royal Marsden Hospital, Downs Rd., Sutton, Surrey SM2 5PT, United Kingdom.

View larger version (40K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —Diffusion of water molecules. Restricted diffusion: cellularity and intact cell membranes. Drawing represents 1 voxel of tissue evaluated by diffusion-weighted imaging (DWI) containing cells and blood vessel. Note water molecules (black circles with arrows) within extracellular space, intracellular space, and intravascular space, all of which contribute to measured MR signal. In this highly cellular environment, water diffusion is restricted because of reduced extracellular space and by cell membranes, which act as barrier to water movement.

View larger version (22K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —Diffusion of water molecules. Free diffusion: low cellularity and defective cell membranes. In less cellular environment, relative increase in extracellular space allows freer water diffusion than more cellular environment would. Defective cell membranes also allow movement of water molecules between extracellular and intracellular spaces.

View larger version (15K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2 —Measuring water diffusion. Stejskal and Tanner [10] adopted T2-weighted spin-echo sequence for measuring water diffusion. They applied symmetric diffusion-sensitizing gradient around 180° refocusing pulse. On this schematic drawing, stationary molecules are unaffected by gradients and measured signal intensity is preserved. By contrast, moving water molecules acquire phase information from first gradient, which is not entirely rephased by second gradient, thereby leading to signal loss. Hence, water diffusion is detected as attenuation of measured MR signal intensity. RF = radiofrequency pulse.

View larger version (110K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A —Tissue characterization by diffusion-weighted images. Diffusion-weighted MR images in 55-year-old man with liver metastasis obtained at different b values show large heterogeneous metastasis within right lobe of liver. Necrotic center of metastasis (squares) shows attenuation of signal intensity with increasing b values, indicating less restricted diffusion. By comparison, rim of tumor (rectangles) is more cellular and shows little signal attenuation with increasing b value.

View larger version (114K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B —Tissue characterization by diffusion-weighted images. Diffusion-weighted MR images in 55-year-old man with liver metastasis obtained at different b values show large heterogeneous metastasis within right lobe of liver. Necrotic center of metastasis (squares) shows attenuation of signal intensity with increasing b values, indicating less restricted diffusion. By comparison, rim of tumor (rectangles) is more cellular and shows little signal attenuation with increasing b value.

View larger version (98K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3C —Tissue characterization by diffusion-weighted images. Diffusion-weighted MR images in 55-year-old man with liver metastasis obtained at different b values show large heterogeneous metastasis within right lobe of liver. Necrotic center of metastasis (squares) shows attenuation of signal intensity with increasing b values, indicating less restricted diffusion. By comparison, rim of tumor (rectangles) is more cellular and shows little signal attenuation with increasing b value.

View larger version (120K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A —T2 shine-through. Diffusion-weighted images of liver in 62-year-old man with liver metastasis obtained at different b values show ill-defined high-signal-intensity metastasis in right lobe of liver (arrow, C). However, note gallbladder (arrowhead, C) also shows high signal intensity, even on image obtained with b value of 500 s/mm2. In this case, high signal intensity of gallbladder is not due to restricted water diffusion but to T2 shine-through. Note intrinsic high signal intensity of gallbladder on T2-weighted (b = 0 s/mm2) image (A) due to its long T2 relaxation time.

View larger version (109K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B —T2 shine-through. Diffusion-weighted images of liver in 62-year-old man with liver metastasis obtained at different b values show ill-defined high-signal-intensity metastasis in right lobe of liver (arrow, C). However, note gallbladder (arrowhead, C) also shows high signal intensity, even on image obtained with b value of 500 s/mm2. In this case, high signal intensity of gallbladder is not due to restricted water diffusion but to T2 shine-through. Note intrinsic high signal intensity of gallbladder on T2-weighted (b = 0 s/mm2) image (A) due to its long T2 relaxation time.

View larger version (123K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4C —T2 shine-through. Diffusion-weighted images of liver in 62-year-old man with liver metastasis obtained at different b values show ill-defined high-signal-intensity metastasis in right lobe of liver (arrow, C). However, note gallbladder (arrowhead, C) also shows high signal intensity, even on image obtained with b value of 500 s/mm2. In this case, high signal intensity of gallbladder is not due to restricted water diffusion but to T2 shine-through. Note intrinsic high signal intensity of gallbladder on T2-weighted (b = 0 s/mm2) image (A) due to its long T2 relaxation time.

View larger version (10K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5A —Apparent diffusion coefficient (ADC). Simplified schematic shows derivation of ADC. Logarithm of relative signal intensity is plotted on y-axis against values on x-axis. Slope of line fitted through plots is ADC. In this example, slope of line (ADC) is smaller for tumor (gray line) than for normal liver (black line).

View larger version (119K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5B —Apparent diffusion coefficient (ADC). Tumor area with low ADC (gray outline) is darker than normal liver with higher ADC (black outline). Note contrast on ADC map is opposite that seen on diffusion-weighted image. On diffusion-weighted image, tumor showed less signal attenuation and appeared higher signal intensity than normal liver. B and C obtained in 45-year-old man with liver metastasis.

View larger version (152K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5C —Apparent diffusion coefficient (ADC). Tumor area with low ADC (gray outline) is darker than normal liver with higher ADC (black outline). Note contrast on ADC map is opposite that seen on diffusion-weighted image. On diffusion-weighted image, tumor showed less signal attenuation and appeared higher signal intensity than normal liver. B and C obtained in 45-year-old man with liver metastasis.

View larger version (14K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6 —Diffusion-weighted imaging in liver. Graph shows signal attenuation of normal liver with increasing b values (thin dashed line). Note there is initial rapid attenuation of signal intensity with small increase in b value from zero. This is due to nulling of signal contribution from capillary perfusion. Slope of line (thick dashed line) fitted through all b values describes apparent diffusion coefficient (ADC). However, slope of line (thick solid line) fitted through only higher b values (e.g., 150–500 mm2/s) can be used to describe perfusion-insensitive ADC. Error bars show 95% CI of pixel values.

View larger version (136K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7A —Diffusion-weighted imaging (DWI) performed during free-breathing of 65-year-old man with rectal cancer. Thin-partition DWI can be achieved using free-breathing technique. In this example, axial image with b value of 750 s/mm2 (B) is displayed using inverted gray scale; image shows areas of restricted diffusion corresponding to area of rectal tumor (arrows) and 4-mm mesorectal lymph node (circles). Thinner slice partition allows multiplanar reformats for anatomic localization. Addition perirectal nodes (arrowheads, D) are also visible on sagittal reformatted image (D). Note corresponding features on T2-weighted MRI (A).

View larger version (78K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7B —Diffusion-weighted imaging (DWI) performed during free-breathing of 65-year-old man with rectal cancer. Thin-partition DWI can be achieved using free-breathing technique. In this example, axial image with b value of 750 s/mm2 (B) is displayed using inverted gray scale; image shows areas of restricted diffusion corresponding to area of rectal tumor (arrows) and 4-mm mesorectal lymph node (circles). Thinner slice partition allows multiplanar reformats for anatomic localization. Addition perirectal nodes (arrowheads, D) are also visible on sagittal reformatted image (D). Note corresponding features on T2-weighted MRI (A).

View larger version (67K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7C —Diffusion-weighted imaging (DWI) performed during free-breathing of 65-year-old man with rectal cancer. Thin-partition DWI can be achieved using free-breathing technique. In this example, axial image with b value of 750 s/mm2 (B) is displayed using inverted gray scale; image shows areas of restricted diffusion corresponding to area of rectal tumor (arrows) and 4-mm mesorectal lymph node (circles). Thinner slice partition allows multiplanar reformats for anatomic localization. Addition perirectal nodes (arrowheads, D) are also visible on sagittal reformatted image (D). Note corresponding features on T2-weighted MRI (A).

View larger version (84K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7D —Diffusion-weighted imaging (DWI) performed during free-breathing of 65-year-old man with rectal cancer. Thin-partition DWI can be achieved using free-breathing technique. In this example, axial image with b value of 750 s/mm2 (B) is displayed using inverted gray scale; image shows areas of restricted diffusion corresponding to area of rectal tumor (arrows) and 4-mm mesorectal lymph node (circles). Thinner slice partition allows multiplanar reformats for anatomic localization. Addition perirectal nodes (arrowheads, D) are also visible on sagittal reformatted image (D). Note corresponding features on T2-weighted MRI (A).

View larger version (91K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8A —Lesion detection in 58-year-old woman with metastatic disease. Diffusion-weighted images show small hyperintense metastasis in right lobe of liver (arrowhead, C). Lesion is not easily seen on unenhanced T1- and T2-weighted images (A and B). At diffusion-weighted imaging (DWI), high signal (arrow, C) from intrahepatic vessels is suppressed by application of diffusion gradient (arrow, D) on image obtained with b value of 150 s/mm2. Such black-blood DW images can facilitate lesion detection. However, note also susceptibility and cardiac motion artifacts (black lines) over left lobe on images obtained with b values of 150 (D) and 500 (E) s/mm2.

View larger version (111K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8B —Lesion detection in 58-year-old woman with metastatic disease. Diffusion-weighted images show small hyperintense metastasis in right lobe of liver (arrowhead, C). Lesion is not easily seen on unenhanced T1- and T2-weighted images (A and B). At diffusion-weighted imaging (DWI), high signal (arrow, C) from intrahepatic vessels is suppressed by application of diffusion gradient (arrow, D) on image obtained with b value of 150 s/mm2. Such black-blood DW images can facilitate lesion detection. However, note also susceptibility and cardiac motion artifacts (black lines) over left lobe on images obtained with b values of 150 (D) and 500 (E) s/mm2.

View larger version (113K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8C —Lesion detection in 58-year-old woman with metastatic disease. Diffusion-weighted images show small hyperintense metastasis in right lobe of liver (arrowhead, C). Lesion is not easily seen on unenhanced T1- and T2-weighted images (A and B). At diffusion-weighted imaging (DWI), high signal (arrow, C) from intrahepatic vessels is suppressed by application of diffusion gradient (arrow, D) on image obtained with b value of 150 s/mm2. Such black-blood DW images can facilitate lesion detection. However, note also susceptibility and cardiac motion artifacts (black lines) over left lobe on images obtained with b values of 150 (D) and 500 (E) s/mm2.

View larger version (100K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8D —Lesion detection in 58-year-old woman with metastatic disease. Diffusion-weighted images show small hyperintense metastasis in right lobe of liver (arrowhead, C). Lesion is not easily seen on unenhanced T1- and T2-weighted images (A and B). At diffusion-weighted imaging (DWI), high signal (arrow, C) from intrahepatic vessels is suppressed by application of diffusion gradient (arrow, D) on image obtained with b value of 150 s/mm2. Such black-blood DW images can facilitate lesion detection. However, note also susceptibility and cardiac motion artifacts (black lines) over left lobe on images obtained with b values of 150 (D) and 500 (E) s/mm2.

View larger version (101K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8E —Lesion detection in 58-year-old woman with metastatic disease. Diffusion-weighted images show small hyperintense metastasis in right lobe of liver (arrowhead, C). Lesion is not easily seen on unenhanced T1- and T2-weighted images (A and B). At diffusion-weighted imaging (DWI), high signal (arrow, C) from intrahepatic vessels is suppressed by application of diffusion gradient (arrow, D) on image obtained with b value of 150 s/mm2. Such black-blood DW images can facilitate lesion detection. However, note also susceptibility and cardiac motion artifacts (black lines) over left lobe on images obtained with b values of 150 (D) and 500 (E) s/mm2.

View larger version (118K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9A —Lesion characterization in 48-year-old man with liver cancer. Diffusion-weighted images show cyst (arrow, A) and metastasis (asterisk, A) in right lobe of liver. Signal from cyst is attenuated with increasing b value, whereas cellular tumor maintains high signal intensity.

View larger version (112K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9B —Lesion characterization in 48-year-old man with liver cancer. Diffusion-weighted images show cyst (arrow, A) and metastasis (asterisk, A) in right lobe of liver. Signal from cyst is attenuated with increasing b value, whereas cellular tumor maintains high signal intensity.

View larger version (130K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9C —Lesion characterization in 48-year-old man with liver cancer. Diffusion-weighted images show cyst (arrow, A) and metastasis (asterisk, A) in right lobe of liver. Signal from cyst is attenuated with increasing b value, whereas cellular tumor maintains high signal intensity.

View larger version (175K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9D —Lesion characterization in 48-year-old man with liver cancer. Other solid lesions can mimic appearance of metastasis. Hemangioma (circle, D) shows restricted diffusion on image obtained with b value of 500 s/mm2. However, note typical high T2 signal intensity of lesion. Hence, it is useful to interpret diffusion-weighted imaging sequences with other imaging sequences.

View larger version (145K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9E —Lesion characterization in 48-year-old man with liver cancer. Other solid lesions can mimic appearance of metastasis. Hemangioma (circle, D) shows restricted diffusion on image obtained with b value of 500 s/mm2. However, note typical high T2 signal intensity of lesion. Hence, it is useful to interpret diffusion-weighted imaging sequences with other imaging sequences.

View larger version (177K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9F —Lesion characterization in 48-year-old man with liver cancer. Other solid lesions can mimic appearance of metastasis. Hemangioma (circle, D) shows restricted diffusion on image obtained with b value of 500 s/mm2. However, note typical high T2 signal intensity of lesion. Hence, it is useful to interpret diffusion-weighted imaging sequences with other imaging sequences.

View larger version (25K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 10 —Schematic diagram shows variation in tumor apparent diffusion coefficient (ADC) with treatment. Soon after initiation of chemotherapy or radiation therapy, cell swelling occurs, which can lead to decrease in tumor ADC. This is followed by cell necrosis and lysis, resulting in rise in ADC. Treatment can also induce tumor apoptosis, resulting in cell shrinkage and increased ADC. These apoptotic tumor cells may also undergo secondary lysis (dotted arrow). After completion of treatment, there is process of reequilibrium with resorption of extracellular fluid, leading to decrease in ADC. Tumor regrowth (black curved arrow) can also result in decreased ADC. (Schematic adapted from Moffat et al. [59])

View larger version (200K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 11A —T2-weighted and segment of whole-body diffusion-weighted images. T2-weighted image (A) and diffusion-weighted inverted gray-scale maximum-intensity-projection (b = 1,000 s/mm2) image (B) of pelvis show nodal disease along both pelvic sidewalls in 63-year-old man with colon cancer. By performing imaging at multiple stations, whole-body diffusion map can be constructed.

View larger version (109K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 11B —T2-weighted and segment of whole-body diffusion-weighted images. T2-weighted image (A) and diffusion-weighted inverted gray-scale maximum-intensity-projection (b = 1,000 s/mm2) image (B) of pelvis show nodal disease along both pelvic sidewalls in 63-year-old man with colon cancer. By performing imaging at multiple stations, whole-body diffusion map can be constructed.

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