1. Diffusion MR Imaging for Monitoring of Treatment Response
Anwar R. Padhani, MBBS, FRCP, FRCR, Dow-Mu Koh, MD, MRCP, FRCR 
Magnetic Resonance Imaging Clinics 
Volume 19, Issue 1, Pages (February 2011)
DOI: /j.mric
Copyright © 2011 Elsevier Inc. Terms and Conditions

2. Fig. 1
DW-MR imaging relationships with bone marrow cellularity and water content. An abundance of fatty cells and low water content causes low signal intensity on high b-value images and low ADC values. Increasing bone marrow cellularity with replacement of fat cells and increases in water content causes initial increases in signal intensity and ADC values. Once fat cells are eliminated, increasing cell density may cause lowering of ADC values; however, persistent increases in signal intensity on high b-value images are seen.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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3. Fig. 2
Disease progression in multiple myeloma with lowering of ADC values. A 62-year-old man with multiple myeloma being treated with bortezomib (proteosome inhibitor). Two examinations performed 3 months apart are shown. Whole body DW-MR imaging (inverted gray scale, b800 s/mm2) show disease progression with increasing signal intensity and extent of the bony marrow disease. Extraosseous disease is also visible. ADC value decreases are seen in the sacrum and iliac bone. Please see Fig. 8 for details regarding the degree of ADC reductions in the sacrum and iliac bones. Tx, therapy.
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4. Fig. 3
Progressive disease in metastatic breast cancer with increasing ADC values. A 49-year-old woman with metastatic breast cancer. Two examinations performed 3 months apart are shown; whole body DW-MR imaging (inverted gray scale, b800 s/mm2) shows disease progression with increasing signal intensity and extent of the bony marrow disease. ADC increases are seen in the sacrum and iliac bones. The ADC of the right sacrum increased from 870 μm2/s to 990 μm2/s.
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5. Fig. 4
Monitoring response to chemotherapy after ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) for Hodgkin disease. A 29-year-old man with Hodgkin disease before and at day 8 after starting ABVD chemotherapy. The whole body DW-MR imaging (inverted scale, b800 s/mm2) shows dramatic reduction in the signal intensity at all disease sites and corresponding increases in ADC values are seen in the nodal disease in the lower neck and upper abdomen (arrows). There are minor changes in tumor size at this early time point after commencing therapy.
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6. Fig. 5
T2 shine-through caused by radiotherapy for a multiple myeloma deposit. A 69-year-old man with multiple myeloma deposit in the L3 vertebral body before (A) and 5 months later after radiotherapy (B). b0, ADC map, coronal b800 reconstruction, and T1-weighted images are shown. Before therapy (A) the deposit shows the typical appearance of a high-cellularity lesion with high signal intensity on b800 images (arrow) and low ADC values; spinal canal narrowing is noted. Following radiotherapy (B), the lesion is a little smaller with no compromise of the thecal sac; yellow bone marrow atrophy is also noted on the T1-weighted image. ADC values have increased but the lesion remains bright on the b800 image (arrow; T2 shine-through). T2 shine-through suggests inactive disease.
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7. Fig. 6
Bone marrow hyperplasia following G-CSF therapy. A 63-year-old woman with a locally advanced left breast cancer with axillary nodal disease (arrowhead) before (left panel) and during neoadjuvant chemotherapy (right panel). The patient received FEC chemotherapy (5-fluorouracil, epirubicin, cyclophosphamide) (×3 cycles) and then taxotere (2 cycles with G-CSF therapy). (A) Diffuse increases in the bone marrow signal intensity are observable on the whole-body DW-MR imaging images (inverted scale, b800 s/mm2 images) in normal red bone marrow areas (spine, pectoral and pelvic girdles). Increased signal intensity is also noted in yellow marrow areas (arrows). A good response to treatment is seen in the primary breast cancer and nodal disease, although residual active disease is still visible (arrowhead). (B) Sagittal T1- and T2-weighted images with spectral fat saturation show increased bone marrow cellularity in the normal spinal bone marrow on the T1-weighted images. (C) Diffuse increases in signal intensity of the sacral bone marrow on b800 images with corresponding decreases in ADC values after treatment (bottom row).
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8. Fig. 6
Bone marrow hyperplasia following G-CSF therapy. A 63-year-old woman with a locally advanced left breast cancer with axillary nodal disease (arrowhead) before (left panel) and during neoadjuvant chemotherapy (right panel). The patient received FEC chemotherapy (5-fluorouracil, epirubicin, cyclophosphamide) (×3 cycles) and then taxotere (2 cycles with G-CSF therapy). (A) Diffuse increases in the bone marrow signal intensity are observable on the whole-body DW-MR imaging images (inverted scale, b800 s/mm2 images) in normal red bone marrow areas (spine, pectoral and pelvic girdles). Increased signal intensity is also noted in yellow marrow areas (arrows). A good response to treatment is seen in the primary breast cancer and nodal disease, although residual active disease is still visible (arrowhead). (B) Sagittal T1- and T2-weighted images with spectral fat saturation show increased bone marrow cellularity in the normal spinal bone marrow on the T1-weighted images. (C) Diffuse increases in signal intensity of the sacral bone marrow on b800 images with corresponding decreases in ADC values after treatment (bottom row).
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9. Fig. 7
DW-MR imaging changes of primary breast cancer treated with chemotherapy. A 42-year-old woman with a locally advanced left breast cancer treated with FEC chemotherapy. Examinations were performed before and after 3 cycles. (A) Axial T2-weighted (T2W) and short-tau inversion recovery (STIR) images show that there has been little change in tumor size (top row, pretherapy; bottom row, after 3 cycles of treatment). (B) b800 and ADC maps before and after therapy at the same time points shows some reduction in signal intensity on b800 images, but marked increases in global ADC values are noted. (C) Volume-rendered images shows that the tumor volume increases from mL (designated as PRIOR) to mL (designated as CURRENT). Histograms show increases in ADC values (mean 1450 μm2/s to 1779 μm2/s) with a greater proportion of pixels having ADC values greater than 2000 μm2/s. The mastectomy specimen showed tumor necrosis with macroscopic areas of invasive cancer.
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10. Fig. 7
DW-MR imaging changes of primary breast cancer treated with chemotherapy. A 42-year-old woman with a locally advanced left breast cancer treated with FEC chemotherapy. Examinations were performed before and after 3 cycles. (A) Axial T2-weighted (T2W) and short-tau inversion recovery (STIR) images show that there has been little change in tumor size (top row, pretherapy; bottom row, after 3 cycles of treatment). (B) b800 and ADC maps before and after therapy at the same time points shows some reduction in signal intensity on b800 images, but marked increases in global ADC values are noted. (C) Volume-rendered images shows that the tumor volume increases from mL (designated as PRIOR) to mL (designated as CURRENT). Histograms show increases in ADC values (mean 1450 μm2/s to 1779 μm2/s) with a greater proportion of pixels having ADC values greater than 2000 μm2/s. The mastectomy specimen showed tumor necrosis with macroscopic areas of invasive cancer.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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11. Fig. 8
Disease progression in multiple myeloma depicted by parametric response maps. Same patient as illustrated in Fig. 2. A 62-year-old man with multiple myeloma progressing on bortezomib (proteosome inhibitor) therapy. Two examinations performed 3 months apart are shown. (A) Top row: ADC maps before (left, designated as PRIOR) and after therapy (right, designated as CURRENT); the 2 examinations have been spatially coregistered. Middle row: Colored ADC maps before and after therapy within identical-sized regions of interest (ROIs) placed on left iliac bone and left sacrum. Reductions in mean ADC values are seen on visual inspection of the parametric maps and on combined ROI histogram on the bottom row. Mean ADC 896 μm2/s pretreatment to 724 μm2/s posttreatment. (B) Same ROIs used in (A) with parametric response maps of ADC (PRMADC) also called functional diffusion maps (fDM), where voxel-by-voxel differences between the 2 examinations shown in (A) are classified as decreased (blue), unchanged (green), or increased (red). The percentage of changed voxels is highly dependent on the ADC threshold that has been set. The thresholds used for illustration were 100, 200, 300, and 400 μm2/s. Voxel-by-voxel differences can be illustrated as ADC change histograms (see 100 and 300 μm2/s plots) or as scatter plots (see 200 and 400 μm2/s plots). The greater the change in threshold used, the fewer are the pixels classified as unchanged (green).
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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12. Fig. 8
Disease progression in multiple myeloma depicted by parametric response maps. Same patient as illustrated in Fig. 2. A 62-year-old man with multiple myeloma progressing on bortezomib (proteosome inhibitor) therapy. Two examinations performed 3 months apart are shown. (A) Top row: ADC maps before (left, designated as PRIOR) and after therapy (right, designated as CURRENT); the 2 examinations have been spatially coregistered. Middle row: Colored ADC maps before and after therapy within identical-sized regions of interest (ROIs) placed on left iliac bone and left sacrum. Reductions in mean ADC values are seen on visual inspection of the parametric maps and on combined ROI histogram on the bottom row. Mean ADC 896 μm2/s pretreatment to 724 μm2/s posttreatment. (B) Same ROIs used in (A) with parametric response maps of ADC (PRMADC) also called functional diffusion maps (fDM), where voxel-by-voxel differences between the 2 examinations shown in (A) are classified as decreased (blue), unchanged (green), or increased (red). The percentage of changed voxels is highly dependent on the ADC threshold that has been set. The thresholds used for illustration were 100, 200, 300, and 400 μm2/s. Voxel-by-voxel differences can be illustrated as ADC change histograms (see 100 and 300 μm2/s plots) or as scatter plots (see 200 and 400 μm2/s plots). The greater the change in threshold used, the fewer are the pixels classified as unchanged (green).
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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13. Fig. 9
High ADC values before therapy predict for poor response in metastatic colorectal cancer. A 62-year-old man undergoing examinations before (top rows) and after (bottom rows) chemotherapy for metastatic colorectal cancer. Two liver metastases are shown that are of high signal intensity on the T2-weighted images (A) and are of high signal intensity on ADC maps (B). Both lesions were shown to be metastases on contrast-enhanced scans (not shown). Neither the large nor the small (arrowhead) lesions show evidence of response after therapy.
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14. Fig. 10
Response of cervix carcinoma to chemoradiation. A 30-year-old woman undergoing examinations before and after chemoradiation for locally advanced squamous carcinoma of the cervix. (A) Anatomic T1- and T2-weighted images before (top row) and 6 months after therapy (bottom row). The tumor has responded well to therapy with a reduction in tumor size (arrowhead). There are new edematous changes in the pelvic fat and pelvic side walls (arrows) consistent with microvessel leakage and inflammation occurring after radiotherapy. Radiation-induced fatty marrow atrophy also appears. (B) Corresponding b800 and ADC images show a marked increase in ADC values in the cervical stroma and in the pelvic fatty tissues (arrows). However, persistent increases on high b-value images associated with decreased ADC values are seen at the edge of the excavated cervix tumor (arrowhead), raising the suspicion of residual active disease.
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15. Fig. 11
Differential response of metastatic bone disease. A 41-year-old woman with metastatic breast cancer being treated with chemotherapy and bisphosphonates. Images show T1-weighted, T2-weighted, b800, and ADC maps of the sacrum before therapy (A) in April, during therapy (B) in June, and in September (C). Corresponding ADC spread plots from the left (D) and right sacrum (E) are also illustrated. These images should be studied bearing in mind Fig. 1. The left sacral metastasis has higher signal intensity on the b800 image in April (A) compared with the right sacrum. By June this metastasis shows increasing ADC values (B) which remain elevated in September (C). Note lowering of signal intensity on b800 images by September. These changes in ADC values are consistent with therapy response. The right sacrum is relatively normal on the T1-weighted image in April but shows mild increase in signal intensity on b800 images. By June there are increases in ADC values of the right sacrum with increases in signal intensity on b800 images. These DW-MR imaging findings with lowering of the signal intensity on T1-weighted image are consistent with new metastatic infiltration (no G-CSF therapy given). By September, the right sacrum shows lowering of signal intensity on T1-weighted images with lowering of ADC values. This appearance is consistent with increasing bone marrow infiltration.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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16. Fig. 11
Differential response of metastatic bone disease. A 41-year-old woman with metastatic breast cancer being treated with chemotherapy and bisphosphonates. Images show T1-weighted, T2-weighted, b800, and ADC maps of the sacrum before therapy (A) in April, during therapy (B) in June, and in September (C). Corresponding ADC spread plots from the left (D) and right sacrum (E) are also illustrated. These images should be studied bearing in mind Fig. 1. The left sacral metastasis has higher signal intensity on the b800 image in April (A) compared with the right sacrum. By June this metastasis shows increasing ADC values (B) which remain elevated in September (C). Note lowering of signal intensity on b800 images by September. These changes in ADC values are consistent with therapy response. The right sacrum is relatively normal on the T1-weighted image in April but shows mild increase in signal intensity on b800 images. By June there are increases in ADC values of the right sacrum with increases in signal intensity on b800 images. These DW-MR imaging findings with lowering of the signal intensity on T1-weighted image are consistent with new metastatic infiltration (no G-CSF therapy given). By September, the right sacrum shows lowering of signal intensity on T1-weighted images with lowering of ADC values. This appearance is consistent with increasing bone marrow infiltration.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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17. Fig. 12
Serial changes in metastatic prostate cancer responding to abiraterone acetate. A 69 year-old-man with advanced metastatic prostate cancer that was hormone refractory. The patient received abiraterone acetate, an inhibitor of 17α-hydroxylase that reduces testosterone production by both the testes and adrenal glands. (A) Serial changes on T1-weighted spinal images over 17 months. Gradual increases in signal intensity are seen consistent with tumor cell replacement by fatty bone marrow. Residual areas of lowed signal intensity represent areas of secondary myelofibrosis and sclerotic bone. (B) Serial changes on b800 (top row) and ADC maps (bottom row) of the sacrum on coronal reconstructions over the same time period. Note initial patchy increases in signal intensity on b800 images (arrows) with diffuse increases in ADC values. After February 2009, gradual decreases in signal intensity on b800 images and ADC values are observed, consistent with a healing response to treatment.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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18. Fig. 13
Radiation atrophy of the bone marrow. A 56-year-old woman with metastatic breast cancer. Whole body DW-MR imaging scan (inverted scale, b800 s/mm2) shows focal areas of increased signal intensity in the bone marrow of the spine and pelvis consistent with bony metastases. Focus on the left upper chest. Note that the left upper ribs, left clavicle, and scapular bone are not visible. The brachial plexus remains visible. This effect is caused by yellow marrow atrophy due to radiation, initially to the chest wall and then to the left supraclavicular fossa, for recurrent nodal disease that is not visible.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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19. Fig. 14
T2 shine-through following chemotherapy for multiple myeloma. (A) 18F-Fluorodexyglucose PET scan (left) and whole body DW-MR imaging image (inverted scale, b800 s/mm2) on a 55-year-old man with multiple myeloma treated with chemotherapy alone. No areas of abnormal hypermetabolism are seen on the PET scan but 2 areas of increased signal intensity are seen on the DW-MR imaging image (right lower rib [arrowhead] and right iliac bone [arrow]). (B) Axial STIR, CT scan, b800 image, and ADC map through the rib lesion. The lesion is of high signal intensity on both the b800 image and the ADC map, indicating T2 shine-through. This appearance suggests inactive disease. Note low signal intensity of the liver on the b800 image and ADC map, consistent with iron overload.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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20. Fig. 15
41 year old female with metastatic renal cancer. Effect of antiangiogenic therapy on renal carcinoma metastasis. (A) Axial CT scans of the liver in the arterial and portal phases of enhancement before (top row) and 6 weeks after commencing sorafenib therapy (bottom row). A modest reduction in tumor size is seen with marked reduction in enhancement, and CT density of large liver metastasis is noted (arrowhead). (B) b800 and ADC images at the same time points showing reduction in tumor size, but persistent high signal is visible on b800 images. There is a minimal increase in ADC values from 1410 μm2/s to 1460 μm2/s.
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21. Fig. 16
66 year old male with prostate cancer. Multiparametric imaging of primary prostate cancer treated with androgen deprivation. Locally advanced prostate cancer being treated with the antiandrogen goserelin acetate. Images were obtained 6 months apart. (A) Pretherapy T2-weighted (T2W), b800, and proton MR spectroscopic imaging (MRSI) images with selected spectra from normal peripheral zone (PZ) and tumor (T) depicted in separate panels; the spectra are scaled to the maximum peak (citrate) on the spectra. Dynamic-enhanced MR imaging curves from the region of the tumor and PZ are also shown. (B) Following therapy the gland is smaller (pretherapy gland volume 20.2 mL; posttreatment 10.6 ml) with poorer zonal differentiation on T2-weighted images, consistent with glandular atrophy. Reductions in citrate peaks are seen in tumor and PZ, also consistent with glandular atrophy. High choline levels indicate ongoing active disease in the tumor. Vascular shutdown in the tumor region is known to occur with androgen deprivation. There is no change in the b800 signal intensity. Curved artifact (arrowhead) does not interfere with the assessment of the prostate signal intensity appearances. (C) ADC histograms of the whole prostate showing reductions in number of pixels with ADC values greater than 1500 μm2/s. The whole prostate ADC shows a minimal decrease from 1395 μm2/s to 1322 μm2/s.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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22. Fig. 16
66 year old male with prostate cancer. Multiparametric imaging of primary prostate cancer treated with androgen deprivation. Locally advanced prostate cancer being treated with the antiandrogen goserelin acetate. Images were obtained 6 months apart. (A) Pretherapy T2-weighted (T2W), b800, and proton MR spectroscopic imaging (MRSI) images with selected spectra from normal peripheral zone (PZ) and tumor (T) depicted in separate panels; the spectra are scaled to the maximum peak (citrate) on the spectra. Dynamic-enhanced MR imaging curves from the region of the tumor and PZ are also shown. (B) Following therapy the gland is smaller (pretherapy gland volume 20.2 mL; posttreatment 10.6 ml) with poorer zonal differentiation on T2-weighted images, consistent with glandular atrophy. Reductions in citrate peaks are seen in tumor and PZ, also consistent with glandular atrophy. High choline levels indicate ongoing active disease in the tumor. Vascular shutdown in the tumor region is known to occur with androgen deprivation. There is no change in the b800 signal intensity. Curved artifact (arrowhead) does not interfere with the assessment of the prostate signal intensity appearances. (C) ADC histograms of the whole prostate showing reductions in number of pixels with ADC values greater than 1500 μm2/s. The whole prostate ADC shows a minimal decrease from 1395 μm2/s to 1322 μm2/s.
Magnetic Resonance Imaging Clinics  , DOI: ( /j.mric )
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