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Published online before print October 30, 2003, 10.1148/radiol.2293020748
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(Radiology 2003;229:710-717.)
© RSNA, 2003

Musculoskeletal Imaging

Bone Marrow with Diffuse Tumor Infiltration in Patients with Lymphoproliferative Diseases: Dynamic Gadolinium-enhanced MR Imaging1

Alain Rahmouni, MD, Jean-Luc Montazel, MD, Marine Divine, MD, Eric Lepage, MD, Karim Belhadj, MD, Philippe Gaulard, MD, Mohamed Bouanane, MD, Mondher Golli, MD and Hicham Kobeiter, MD

1 From the Departments of Radiology (A.R., J.L.M., M.B., M.G., H.K.), Hematology (M.D., K.B.), Biostatistics (E.L.), and Pathology (P.G.), Centre Hospitalo-Universitaire Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France. Supported by the Association pour la Recherche contre le Cancer. Received June 18, 2002; revision requested August 20; final revision received March 13, 2003; accepted May 20. Address correspondence to A.R. (e-mail: alain.rahmouni@hmn.ap-hop-paris.fr).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate gadolinium enhancement of bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement.

MATERIALS AND METHODS: Dynamic contrast material–enhanced magnetic resonance (MR) imaging of the thoracolumbar spine was performed in 42 patients with histologically proved diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non–Hodgkin lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from enhancement time curves (ETCs). A three-grade system for scoring bone marrow involvement was based on the percentage of neoplastic cells in bone marrow samples. Quantitative ETC values for the 42 patients were compared with ETC values for healthy subjects and with grades of bone marrow involvement by using mean t test comparisons. Receiver operating characteristic (ROC) analysis was conducted by comparing Emax values between patients with and those without bone marrow involvement. Baseline and follow-up MR imaging findings were compared in nine patients.

RESULTS: Significant differences in Emax (P < .001), slope (P < .001), and washout (P = .005) were found between subjects with normal bone marrow and patients with diffuse bone marrow involvement. ROC analysis results showed Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values increased with increasing bone marrow involvement grade. The mean Emax increased from 339% to 737%. Contrast enhancement decreased after treatment in all six patients who responded to treatment but not in two of three patients who did not respond to treatment.

CONCLUSION: Dynamic contrast-enhanced MR images can demonstrate increased bone marrow enhancement in patients with lymphoproliferative diseases and marrow involvement.

© RSNA, 2003

Index terms: Bone marrow, MR, 321.121411, 321.121413, 321.121416, 321.12143 • Bone marrow, neoplasms, 321.342, 321.343, 321.345 • Gadolinium • Hodgkin disease, MR, 321.342 • Lymphoma, MR, 321.343 • Magnetic resonance (MR), contrast enhancement, 321.12143 • Myeloma, 321.345


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
In patients with myeloma or lymphoma, the magnetic resonance (MR) imaging–based identification of focal lesions in axial bone marrow is based on well-defined contours and on lower signal intensity on T1-weighted images and higher signal intensity on T2-weighted images, as compared with the signal intensity of the adjacent, presumed normal bone marrow (1,2). Early during bone marrow infiltration, tumor cells do not displace bone marrow fat cells, the amount of which remains normal (3). Subsequently, diffuse replacement of normal bone marrow by tumor cells leads to a decrease in signal intensity at T1-weighted MR imaging (4,5). The decrease in bone marrow signal intensity at T1-weighted MR imaging can be homogeneous or heterogeneous, yielding a "salt-and-pepper" pattern (5).

It is difficult to distinguish diffuse tumor involvement from the highly variable appearance of normal bone marrow. The gradual change in spinal bone marrow from red to yellow during aging has marked interindividual variability (6). The signal intensity of normal spinal bone marrow is often heterogeneous and often differs from one vertebral body to another (6,7). The appearance of bone marrow on T1- and T2-weighted spin-echo MR images is often normal in patients with early bone marrow invasion by lymphoproliferative diseases and is even normal in up to one-quarter of patients with stage III multiple myeloma (8,9). Interobserver agreement on the visualization of diffuse involvement on T1-weighted MR images is poor (3,5).

Various MR imaging techniques have been developed to improve the detection and quantification of diffuse bone marrow involvement. These techniques include chemical-shift imaging, bulk T1 relaxation time measurement, and hydrogen 1 spectroscopy (5,10–13). All of these methods are used to measure fat content or the water/fat fraction and can help overcome the interobserver variability encountered during visual analysis of spin-echo MR images. However, these quantitative methods have failed to help improve the MR imaging–based detection of diffuse bone marrow involvement (5).

Study results have shown that plasma cells isolated from the bone marrow of patients with myeloma have angiogenic potential (14). The progression of plasma cell tumors is accompanied by an increase in bone marrow vascularization (15). Other lymproliferative diseases, such as B cell non–Hodgkin lymphoma (NHL), also can induce angiogenesis (16). Dynamic contrast material–enhanced MR imaging, which depicts the physiologic features of the microcirculation, has been successfully used in the treatment management of patients with solid malignancies such as breast cancer and osteosarcoma (17–20). The purpose of this study was to evaluate gadolinium enhancement of the bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Study Patients
Between September 1996 and September 2000, 225 patients with newly diagnosed lymphoma (134 with NHL, 91 with Hodgkin disease) and 121 with newly diagnosed myeloma were seen in the hematology department of our institution. We prospectively enrolled the only 42 consecutive patients, among the 225 patients, who had back pain and fulfilled the following criteria: (a) histologically proved bone marrow involvement and (b) no focal bone marrow abnormalities at MR imaging.

The 42 patients ranged in age from 25 to 83 years (mean age, 54 years). Eight of the 42 study patients had NHL; their mean age was 44 years (age range, 27–75 years). Three patients had Hodgkin disease; their mean age was 33 years (age range, 25–44 years). Thirty-one patients had myeloma; their mean age was 58 years (age range, 32–83 years). Of the 31 patients with myeloma, three had stage I; 12, stage II; and 16, stage III tumors, according to the Salmon and Durie classification system (21). The study protocol was approved by our institutional review board, and the patients gave their informed consent.

MR Imaging
The MR imaging protocol was the same as that used in the study by Montazel et al (22). All of the patients underwent MR imaging of the thoracolumbar spine with a 1.5-T magnet (Magnetom SP 63; Siemens, Erlangen, Germany) and a quadrature spine surface coil. The MR imaging protocol was identical for all of the patients and consisted of T1-weighted spin-echo sequences performed with a repetition time msec/echo time msec of 500/15 and T2-weighted spin-echo sequences performed with 2,000/45, 90. These sequences were performed with the following parameters: 256 x 512 matrix, 40-cm field of view, and sagittal, interleaved 4-mm-thick contiguous sections.

Dynamic studies of gadolinium enhancement were performed with a T1-weighted inversion-recovery, centric k-space reordered, turbo fast low-angle shot (FLASH) sequence and the following parameters: 7/3/300 (repetition time msec/echo time msec/inversion time msec), a 10° flip angle, a 128 x 128 matrix, an acquisition time of 1,200 msec, a 40-cm field of view, and a midsagittal, 10-mm section thickness.

A bolus of 0.2 mL of gadoterate meglumine (Dotarem; Laboratoire Guerbet, Aulnay-sous-Bois, France) was manually administered through a catheter inserted into an antecubital vein at an injection rate of approximately 2 mL/sec and followed by a rapid 20-mL saline flush. Turbo FLASH MR sequences were started when half the contrast medium had been injected. The sequences were repeated 30 times at 3-second intervals and lasted 130 seconds. The postcontrast T1-weighted spin-echo sequence was started 4 minutes after the end of the bolus injection of gadoterate meglumine.

Qualitative Analysis
Bone marrow signal intensity was analyzed qualitatively by consensus between two radiologists (A.R., J.L.M.), who were blinded to all clinical data except the patients’ ages. By comparing the signal intensity of the bone marrow with the signal intensity of the extraosseous fat and muscle tissue depicted on T1-weighted spin-echo MR images, the radiologists divided the patients into two groups: The group 1 patients had homogeneous and low fat signal intensity (ie, similar to signal intensity of muscle) with or without isolated focal fat replacement. The group 2 patients had heterogeneous signal intensity with mixed areas of low and high signal intensity, intermediate homogeneous signal intensity (ie, lower than signal intensity of fat and higher than that of muscle), or uniformly high signal intensity (ie, similar to signal intensity of fat). The MR imaging findings in group 1 were considered to be diagnostic of diffuse bone marrow involvement (4,5,9).

Quantitative Analysis
One radiologist (H.K.) quantitatively assessed the bone marrow signal intensity by performing measurements in regions of interest. The regions of interest were placed centrally and anteriorly in the vertebral body to avoid the end plates and possible disk degeneration and to exclude the basivertebral vein plexus and cerebrospinal fluid. The regions of interest were 16 mm in diameter and were at the exact same site on all of the T1-weighted MR images and the exact same site on all of the dynamic turbo FLASH MR images. The regions of interest were placed within a single vertebral body at the center of the coil, where the signal-to-noise ratio is highest. All measurements were performed from the T8 through L3 vertebral body.

The percentage increase in signal intensity, or enhancement (E), on T1-weighted spin-echo MR images was calculated as follows: E = [(SIpost – SIpre) x 100]/SIpre, where SIpre is the signal intensity measurement in the region of interest before contrast medium injection and SIpost is the signal intensity measurement in the region of interest after contrast medium injection. In the dynamic turbo FLASH examinations, SIpre was the region-of-interest signal intensity measurement obtained before the onset of bone marrow enhancement. The percentage increase in signal intensity was graphically plotted against time. A percentage enhancement time curve (ETC) spanning 60 seconds after the onset of aortic enhancement was constructed for each patient by directly plotting the enhancement values. No automated curve fitting was applied.

Histologic Grading of Tumor Involvement
Bone marrow involvement was quantified by analyzing smear samples of iliac crest bone marrow tissue from 26 patients and smear samples of sternal bone marrow tissue from 16 patients with myeloma. The bone marrow involvement in each patient was graded according to the percentage of neoplastic cells in the bone marrow samples: Grade 1 indicated less than 20% of tumor cells in the bone marrow; grade 2, 20%–50%; and grade 3, more than 50%.

Follow-up MR Imaging
Owing to the limited availability of our MR imaging unit, only 17 follow-up examinations could be performed: in nine patients with myeloma, one patient with NHL, and one patient with Hodgkin disease. The follow-up MR examinations were performed an average of 6 months after treatment (range, 1–24 months). Seven patients underwent one, three patients underwent two, and one patient underwent four follow-up MR examinations. The follow-up MR examination and image analysis were the same as those performed before treatment, and image analysis was performed by two radiologists (A.R., H.K.). All 11 of these patients underwent chemotherapy only, without granulocyte colony–stimulating factors. The chemotherapy consisted of monthly courses of vinblastine, melphalan, cyclophosphamide, and steroids in the patients with myeloma. Five of the nine patients with myeloma subsequently underwent high-dose chemotherapy followed by graft placement of stored autologous blood stem cells. The one patient with NHL received an anthracycline-containing regimen (ie, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone). The remaining patient with Hodgkin disease received the MOPP-ABV hybrid regimen (ie, mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine).

At the time of the follow-up MR imaging examinations, the response to treatment in the patients with myeloma was assessed by using the criteria of the Chronic Leukemia-Myeloma Task Force (21,23). Patients were considered to be good responders when the amount of myeloma protein found in their serum or excreted in their urine decreased by 50% or 75%, respectively, and other accompanying conditions (eg, anemia and hypercalcemia) improved after treatment. Patients were considered to be partial responders when the decrease in their serum or urinary myeloma protein level was less than 50% or less than 75%, respectively, and their clinical performance status improved (according to World Health Organization grading system). Patients with a less than 25% decrease in serum myeloma protein level were considered to be nonresponders. One patient with NHL and one patient with Hodgkin disease also underwent iliac crest bone marrow biopsy. Changes in bone marrow enhancement seen on follow-up MR images were interpreted according to the treatment response category determined by two hematologists (M.D., K.B.) in consensus.

Statistical Analyses
Power analysis results demonstrated that 35 patients with bone marrow involvement and 35 control patients should yield 95% power at the overall 5% level (two-sided analysis). In addition to the 42 patients with bone marrow involvement, 71 patients with normal bone marrow (22) also were included in this study for comparison. Differences in age distribution according to sex were assessed by using the {chi}2 test. The following values were calculated for each patient to characterize the ETC (20,24): maximum percentage of enhancement (Emax); time to Emax after the onset of aortic enhancement (Tmax); slope—that is, the rate of enhancement increase between 10% and 90% of Emax; and washout—that is, the value of enhancement at 60 seconds after the onset of aortic enhancement. t test comparisons of the quantitative covariates were performed to assess differences in mean Emax, Tmax, slope, and washout values between the 71 control patients (described in the companion article [22]) and the 42 patients with bone marrow involvement. Emax values were also compared according to grade of bone marrow involvement (22). The nominal significance level for the end points was 5% (P < .05, two-sided analysis).

Receiver operating characteristic curves were constructed from quantitative data by comparing Emax values between the patients with bone marrow involvement and the subjects with normal bone marrow (control group) (22). The areas under the receiver operating characteristic curves were calculated to assess the accuracy of Emax in the diagnosis of bone marrow involvement.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Baseline Results
There was no statistically significant difference in age distribution according to sex (mean age of women, 54.2 years; mean age of men, 54.9 years; P = .39). Qualitative analysis of the T1-weighted spin-echo MR images revealed only 11 patients to have bone marrow involvement.

Mean ETC values for the patients with bone marrow involvement, as compared with those for the control group (22), are shown in Table 1. Differences in Emax, slope, and washout values between the control group and the patients with diffuse bone marrow involvement were significant. Differences in Tmax values between the two groups were not significant.


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  		TABLE 1. Bone Marrow ETC Values for Patients with and Those without Bone Marrow Involvement

 
ETC values determined according to histologic grade of bone marrow involvement are shown in Table 2. Emax, slope, and washout values increased with increasing grade of bone marrow involvement. In Table 3, the ETC values for the control group are compared with those observed in the patients with the three histologic grades of bone marrow involvement. The Emax, slope, and washout values were significantly higher in the patients with limited bone marrow involvement (grade 1) than in the control patients (Table 3, Fig 1), whereas Tmax values did not differ significantly between the groups.


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  		TABLE 2. Bone Marrow ETC Values Determined according to Histologic Grade of Bone Marrow Involvement

 

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  		TABLE 3. P Values for Differences in ETC Measurements among Control Patients and Patients with Different Histologic Bone Marrow Involvement Grades

 


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  		Figure 1a. Sagittal MR images obtained before treatment in 39-year-old man with large cell NHL and 18% of tumor cells in bone marrow (grade 1). (a) Precontrast T1-weighted spin-echo image (500/15) shows heterogeneous signal intensity with mixed areas of low and high signal intensity (group 2). Note the enlarged retroperitoneal lymph node (arrow). (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows subtle bone marrow enhancement. (c) T2-weighted spin-echo image (2,000/90) shows homogeneous normal bone marrow signal intensity. (d) Precontrast turbo FLASH image (7/3, 10° flip angle) and (e) turbo FLASH image obtained 38 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 350%.

 


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  		Figure 1b. Sagittal MR images obtained before treatment in 39-year-old man with large cell NHL and 18% of tumor cells in bone marrow (grade 1). (a) Precontrast T1-weighted spin-echo image (500/15) shows heterogeneous signal intensity with mixed areas of low and high signal intensity (group 2). Note the enlarged retroperitoneal lymph node (arrow). (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows subtle bone marrow enhancement. (c) T2-weighted spin-echo image (2,000/90) shows homogeneous normal bone marrow signal intensity. (d) Precontrast turbo FLASH image (7/3, 10° flip angle) and (e) turbo FLASH image obtained 38 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 350%.

 


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  		Figure 1c. Sagittal MR images obtained before treatment in 39-year-old man with large cell NHL and 18% of tumor cells in bone marrow (grade 1). (a) Precontrast T1-weighted spin-echo image (500/15) shows heterogeneous signal intensity with mixed areas of low and high signal intensity (group 2). Note the enlarged retroperitoneal lymph node (arrow). (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows subtle bone marrow enhancement. (c) T2-weighted spin-echo image (2,000/90) shows homogeneous normal bone marrow signal intensity. (d) Precontrast turbo FLASH image (7/3, 10° flip angle) and (e) turbo FLASH image obtained 38 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 350%.

 


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  		Figure 1d. Sagittal MR images obtained before treatment in 39-year-old man with large cell NHL and 18% of tumor cells in bone marrow (grade 1). (a) Precontrast T1-weighted spin-echo image (500/15) shows heterogeneous signal intensity with mixed areas of low and high signal intensity (group 2). Note the enlarged retroperitoneal lymph node (arrow). (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows subtle bone marrow enhancement. (c) T2-weighted spin-echo image (2,000/90) shows homogeneous normal bone marrow signal intensity. (d) Precontrast turbo FLASH image (7/3, 10° flip angle) and (e) turbo FLASH image obtained 38 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 350%.

 


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  		Figure 1e. Sagittal MR images obtained before treatment in 39-year-old man with large cell NHL and 18% of tumor cells in bone marrow (grade 1). (a) Precontrast T1-weighted spin-echo image (500/15) shows heterogeneous signal intensity with mixed areas of low and high signal intensity (group 2). Note the enlarged retroperitoneal lymph node (arrow). (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows subtle bone marrow enhancement. (c) T2-weighted spin-echo image (2,000/90) shows homogeneous normal bone marrow signal intensity. (d) Precontrast turbo FLASH image (7/3, 10° flip angle) and (e) turbo FLASH image obtained 38 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 350%.

 
No significant difference in ETC values between the patients with grade 1 and those with grade 2 bone marrow involvement were observed. Emax, slope, and washout values were significantly higher in the patients with grade 3 bone marrow involvement than in those with grade 1 involvement (Table 3, Fig 2). Emax and slope values were significantly higher in patients with grade 3 involvement than in those with grade 2 involvement. The accuracy of Emax values in enabling diagnosis of bone marrow involvement was 99% (Fig 2).



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  		Figure 2a. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 


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  		Figure 2b. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 


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  		Figure 2c. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 


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  		Figure 2d. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 


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  		Figure 2e. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 


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  		Figure 2f. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 


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  		Figure 2g. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 


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  		Figure 2h. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 


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  		Figure 2i. (a-e) Sagittal MR images obtained before treatment in 45-year-old woman with myeloma and 60% plasmacytes in bone marrow (grade 3). (a) Precontrast T1-weighted spin-echo image (500/15) shows diffuse low signal intensity consistent with bone marrow involvement. (b) T1-weighted spin-echo image (500/15) obtained 4 minutes after bolus injection of gadoterate meglumine shows bone marrow enhancement. (c) Precontrast turbo FLASH image (7/3, 10° flip angle) and (d) turbo FLASH image obtained 34 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show bone marrow enhancement reached 1,233%. (e) Turbo FLASH image (7/3, 10° flip angle) obtained 80 seconds after enhancement of the aorta shows washout effect: Enhancement decreased to 763%. (f-i) Sagittal MR images obtained in the same patient 4 months after three courses of chemotherapy. This patient was considered to be a good responder to treatment. (f) Precontrast T1-weighted spin-echo image (500/15) shows increase in signal intensity, relative to the signal intensity seen on the pretreatment images, consistent with an increase in fat content. (g) Postcontrast T1-weighted spin-echo image (500/15) shows no enhancement. (h) Precontrast turbo FLASH image (7/3, 10° flip angle) and (i) turbo FLASH image obtained 42 seconds after enhancement of the aorta with bolus injection of gadoterate meglumine show minimal (25%) enhancement.

 
Posttreatment MR Imaging Findings
Emax values normalized in five patients—one with NHL, one with Hodgkin disease, and three with myeloma—at 2–6 months after treatment (Fig 3, Table 4). Bone marrow biopsy results also normalized in the two patients with NHL and Hodgkin disease. Two of the three patients with myeloma were considered to be good responders, while the remaining patient was considered to be a partial responder. Emax values decreased but did not normalize in four other patients. Three of these four patients were partial responders, and one was a nonresponder. Emax values increased in the remaining two patients, both of whom were nonresponders.



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  		Figure 3. Receiver operating characteristic curve constructed from quantitative data depicts sensitivity versus 1 - specificity of Emax for the diagnosis of bone marrow involvement. This analysis was conducted by comparing Emax values between the 42 patients with bone marrow involvement and the 71 control patients (22). Receiver operating characteristic analysis results indicated excellent accuracy of Emax values in the diagnosis of bone marrow involvement.

 

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  		TABLE 4. Posttreatment Follow-up MR Imaging Findings

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
Diffuse bone marrow involvement by lymphoproliferative disease is associated with a homogeneous or heterogeneous decrease in signal intensity at T1-weighted MR imaging (4), which mainly reflects the ratio of fat to nonfat cells. The signal intensity of normal bone marrow at T1-weighted MR imaging is influenced by age-related patterns of cellular and fatty marrow (7), although large interindividual variations exist among subjects of a given age (6). Thus, the normal distribution of cellular and fatty bone marrow can be extremely difficult to distinguish from diffuse marrow infiltration or hypercellular marrow. The signal intensity of bone marrow at T1-weighted MR imaging can also be normal in patients with biopsy-proved marrow infiltration (8,9).

Our study results show that dynamic contrast-enhanced MR imaging can depict the contrast enhancement of bone marrow in patients with bone marrow involvement by lymphoproliferative diseases despite normal signal intensity on the T1-weighted MR images obtained in these patients. In this study, contrast enhancement was also increased in the patients with low plasma cell infiltration. By using spin-echo MR sequences, Stäbler et al (3) observed a mean contrast enhancement of 107% ± 43 (SD) in focal areas of myeloma and found that a signal intensity increase exceeding 40% indicated diffuse infiltration. Moulopoulos et al (4) observed diffuse bone marrow enhancement in seven patients with myeloma and diffuse marrow involvement.

Dynamic contrast-enhanced MR imaging reflects capillary blood flow and permeability and the relative volume of extravascular extracellular space (17). By analyzing ETCs, we found that slope and Emax values increased with the degree of bone marrow involvement. The slope is mainly determined on the basis of tissue vascularization—that is, the number of vessels and the degree of perfusion and capillary permeability (17). Emax is also dependent on the volume of extravascular extracellular space (17).

The described MR imaging technique, with which contrast medium uptake is measured, does not enable measurement of a single specific parameter alone. However, all of these parameters reflect angiogenesis, which increases with lymphoproliferative diseases. A fivefold increase in microvessel surface area has been found in the bone marrow of patients with active myeloma, as compared with the microvessel surface area of the bone marrow in patients who are in complete remission (15,25). Progression of plasma cell tumors is accompanied by an increase in bone marrow neovascularization owing to the increased angiogenic potential of bone marrow plasma cells. Angiogenesis has also been demonstrated in B cell NHL. In two studies, angiogenesis correlated with the B cell NHL grade and was most marked with high-grade NHL (14,16).

We found that contrast medium uptake increased with increasing degree of bone marrow involvement. The sensitivity of dynamic contrast-enhanced MR imaging in the detection of bone marrow involvement may be due to its sensitivity in depicting perfusion and permeability, which is an advantage when measuring tumor malignancy. Previous study (2,26) results have shown that focal lesions of myeloma in untreated patients enhance markedly during the arterial phase of dynamic contrast-enhanced MR imaging. These authors used a turbo FLASH MR imaging technique similar to that used in the present study and applied it only to focal lesions without quantitative measurements (2). It should be noted that turbo FLASH MR images are acceptable for quantitative analysis but not for anatomic analysis because they lack spatial resolution.

More recently, the study results of Moehler et al (27) confirmed that dynamic contrast-enhanced MR imaging can yield evidence of angiogenesis in myeloma. By using color-coded MR images, these authors found that exchange rates and amplitude pharmacokinetic parameters were increased in patients with focal or diffuse multiple myeloma and correlated with microvessel density (assessed at bone marrow biopsies in eight patients) (27). The main dynamic contrast-enhanced MR imaging feature reported to be characteristic of the therapeutic response of focal lesions is a lack of contrast enhancement (26–28). We also found that contrast enhancement decreased in good responders and in patients who were in complete remission, in whom ETC characteristics sometimes returned to normal.

Angiogenesis-inhibiting drugs, such as thalidomide, may be useful for treating cancers that depend on neovascularization, and these agents were recently tried in patients with advanced myeloma (29). We found that conventional chemotherapy also can lead to a decrease in bone marrow contrast medium uptake after as little as 2–4 months. This finding indicates that conventional drugs have direct or indirect effects on angiogenesis. Although our study results show decreased Emax values in the patients who were good responders to treatment, we acknowledge that the number of patients who were followed up with MR imaging was limited.

This study had several limitations. First, tumor angiogenesis was not assessed in the biopsy specimens. Second, although the biopsy specimens studied were probably representative of the overall bone marrow involvement, the specimens were not obtained from the spine segment that was studied by using dynamic contrast-enhanced MR imaging. Third, the degree of contrast enhancement will probably vary according to the MR imaging system and sequence parameters used. With the heavily T1-weighted turbo FLASH MR sequences that we used, Emax reached 1,233% in a patient with grade 3 bone marrow involvement; to our knowledge, this value is higher than any previously reported.

The use of gradient-echo MR sequences adapted for perfusion measurements will further extend the range of Emax values, from 0% to greater than 1,000%—values that are never obtained with conventional spin-echo MR sequences. This will probably be necessary to diagnose bone marrow involvement, determine the grade of bone marrow involvement, and evaluate the response to treatment. Because Emax occurred within the first minute after contrast medium injection in our study and the washout effect increased markedly with increasing grade of bone marrow involvement, we believe that conventional spin-echo MR imaging should be replaced with dynamic contrast-enhanced MR imaging in this setting.

The accuracy of dynamic contrast-enhanced MR imaging in the diagnosis of bone marrow involvement was 99% in our study. However, limited (grade 1) bone marrow involvement will remain difficult to differentiate from normal marrow in young patients because Emax values show major variability, particularly in patients younger than 40 years (22,30). It should also be kept in mind that several nontumorous disorders associated with bone marrow hyperplasia can also cause increased angiogenesis. It should be noted that patients who were treated with granulocyte colony–stimulating factors were not included in this study.

In conclusion, dynamic gadoterate meglumine–enhanced turbo FLASH MR images can demonstrate increased spinal bone marrow enhancement in patients with lymphoproliferative diseases and diffuse bone marrow infiltration. Thus, dynamic contrast-enhanced MR imaging may be helpful in the diagnosis and grading of bone marrow involvement in such patients and for evaluating the treatment response.


   ACKNOWLEDGMENTS
 
We thank David Young for his help in the preparation of the manuscript.


   FOOTNOTES
 
See also the article by Montazel et al in this issue.

Abbreviations: Emax = maximum percentage of enhancement, ETC = enhancement time curve, FLASH = fast low-angle shot, NHL = non–Hodgkin lymphoma, Tmax = time to Emax after onset of aortic enhancement

Author contributions: Guarantors of integrity of entire study, A.R., J.L.M., E.L.; study concepts, A.R., M.D.; study design, A.R., J.L.M.; literature research, K.B., A.R., M.G.; clinical studies, K.B., M.B., A.R., J.L.M.; data acquisition, J.L.M., E.L., M.B.; data analysis/interpretation, P.G., E.L., J.L.M.; statistical analysis, E.L.; manuscript preparation, A.R., H.K.; manuscript definition of intellectual content, J.L.M., H.K., P.G.; manuscript editing, A.R.; manuscript revision/review and final version approval, A.R., E.L.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

  1. Hoane BR, Shields AF, Porter BA, Shulman HM. Detection of lymphomatous bone marrow involvement with magnetic resonance imaging. Blood 1991; 78:728-738.[Abstract/Free Full Text]
  2. Rahmouni A, Divine M, Mathieu D, et al. Detection of multiple myeloma involving the spine: efficacy of fat-suppression and contrast-enhanced MR imaging. AJR Am J Roentgenol 1993; 160:1049-1052.[Abstract/Free Full Text]
  3. Stäbler A, Baur A, Bartl R, Munker R, Lamerz R, Reiser MF. Contrast enhancement and quantitative signal analysis in MR imaging of multiple myeloma: assessment of focal and diffuse growth patterns in marrow correlated with biopsies and survival rates. AJR Am J Roentgenol 1996; 167:1029-1036.[Abstract/Free Full Text]
  4. Moulopoulos LA, Varma DGK, Dimopoulos MA, et al. Multiple myeloma: spinal MR imaging in patients with untreated newly diagnosed disease. Radiology 1992; 185:833-840.[Abstract/Free Full Text]
  5. Vande Berg BC, Lecouvet FE, Michaux L, Ferrant A, Maldague B, Malghem J. Magnetic resonance imaging of the bone marrow in hematological malignancies. Eur Radiol 1998; 87:1335-1344.
  6. Ricci C, Cova M, Kang YS, et al. Normal age-related patterns of cellular and fatty bone marrow distribution in the axial skeleton: MR imaging study. Radiology 1990; 177:83-88.[Abstract/Free Full Text]
  7. Vande Berg BC, Malghem J, Lecouvet FE, Maldague B. Magnetic resonance imaging of normal bone marrow. Eur Radiol 1998; 8:1327-1334.[CrossRef][Medline]
  8. Vande Berg BC, Lecouvet FE, Michaux L, et al. Stage I multiple myeloma: value of MR imaging of the bone marrow in the determination of prognosis. Radiology 1996; 201:243-246.[Abstract/Free Full Text]
  9. Lecouvet FE, Vande Berg BC, Michaux L, et al. Stage III multiple myeloma: clinical and prognostic value of spinal bone marrow MR imaging. Radiology 1998; 209:653-660.[Abstract/Free Full Text]
  10. Ishijima H, Ishikaza H, Horikoshi H, Sakurai M. Water fraction of lumbar vertebral bone marrow estimated from chemical shift misregistration on MR imaging: normal variations with age and sex. AJR Am J Roentgenol 1995; 167:355-358.
  11. Gerard EL, Ferry JA, Amrein PC, et al. Compositional changes in vertebral bone marrow during treatment for acute leukemia: assessment with quantitative chemical shift imaging. Radiology 1992; 183:39-46.[Abstract/Free Full Text]
  12. Vande Berg BC, Schmitz PJ, Scheiff JM, et al. Acute myeloid leukemia: lack of predictive value of sequential quantitative MR imaging during treatment. Radiology 1995; 197:301-305.[Abstract/Free Full Text]
  13. Schick F, Einsele H, Lutz O, Claussen CD. Lipid selective MR imaging and localized 1H spectroscopy of bone marrow during therapy of leukemia. Anticancer Res 1996; 16:1545-1551.[Medline]
  14. Vacca A, Ribatti D, Roncali L, Dammacco F. Angiogenesis in B cell lymphoproliferative diseases: biological and clinical studies. Leuk Lymphoma 1995; 20:27-38.[Medline]
  15. Vacca A, Ribatti D, Presta M, et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood 1999; 93:3064-3073.[Abstract/Free Full Text]
  16. Ribatti D, Vacca A, Nico B, Fanelli M, Roncali L, Dammacco F. Angiogenesis spectrum in the stroma of B-cell non-Hodgkin’s lymphomas: an immunohistochemical and ultrastructural study. Eur J Haematol 1996; 56:45-53.[Medline]
  17. Taylor JS, Tofts PS, Phil D, et al. MR imaging of tumor microcirculation: promise for the new millennium. J Magn Reson Imaging 1999; 10:903-907.[CrossRef][Medline]
  18. Dao T, Rahmouni A, Campana F, Laurent M, Asselain B, Fourquet A. Tumor recurrence versus fibrosis in the irradiated breast: differentiation with dynamic gadolinium-enhanced MR imaging. Radiology 1993; 187:751-755.[Abstract/Free Full Text]
  19. De Baere T, Vanel D, Shapeero LG, Charpentier A, Terrier P, Di Paola M. Osteosarcoma after chemotherapy: evaluation with contrast material-enhanced subtraction MR imaging. Radiology 1992; 185:587-592.[Abstract/Free Full Text]
  20. Verstraete KL, De Deene Y, Roels H, Dierick A, Uyttendaele D, Kunnen M. Benign and malignant musculoskeletal lesions: dynamic contrast-enhanced MR imaging—parametric "first-pass" images depict tissue vascularization and perfusion. Radiology 1994; 192:835-843.[Abstract/Free Full Text]
  21. Salmon SE, Cassady JR. Plasma cell neoplasms. In: De Vita VT, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia, Pa: Lippincott, 1995; 1984-2025.
  22. Montazel JL, Divine M, Lepage E, Kobeiter H, Breil S, Rahmouni A. Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging. Radiology 2003; 229:000-000.
  23. Chronic Leukemia-Myeloma Task Force. Proposed guidelines for protocol studies: plasma cell myeloma. Cancer Treat Rep 1973; 4:145-158.
  24. Parker GJM, Suckling J, Tanner SF, et al. MRIW: parametric analysis software for contrast-enhanced dynamic MR imaging in cancer. RadioGraphics 1998; 18:497-506.[Abstract]
  25. Vacca A, Di Loreto M, Ribatti D, et al. Bone marrow of patients with active multiple myeloma: angiogenesis and plasma cell adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. Am J Hematol 1995; 50:9-14.[Medline]
  26. Rahmouni A, Divine M, Mathieu D, et al. MR appearance of multiple myeloma of the spine before and after treatment. AJR Am J Roentgenol 1993; 160:1053-1057.[Abstract/Free Full Text]
  27. Moehler TM, Hawighorst H, Neben K, et al. Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging. Int J Cancer 2001; 93:862-868.[CrossRef][Medline]
  28. Moulopoulos LA, Dimopoulos MA, Alexanian R, et al. Multiple myeloma: MR patterns of response of treatment. Radiology 1994; 193:441-446.[Abstract/Free Full Text]
  29. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341:1565-1571.[Abstract/Free Full Text]
  30. Baur A, Stäbler A, Bartl R, Lamerz R, Scheidler J, Reiser M. MRI gadolinium enhancement of bone marrow: age-related changes in normals and in diffuse neoplastic infiltration. Skeletal Radiol 1997; 26:414-418.[CrossRef][Medline]



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