HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rahmouni, A. Articles by Vasile, N. Search for Related Content PubMed PubMed Citation Articles by Rahmouni, A. Articles by Vasile, N.

Mediastinal Lymphoma: Quantitative Changes in Gadolinium Enhancement at MR Imaging after Treatment¹

¹ From the Departments of Radiology (A.R., N.J., M.G., N.V.), Hematology (M.D., K.B., F.R.), Biostatistics (E.L.), and Pathology (P.G.), Centre Hospitalo–Universitaire Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. Received April 7, 2000; revision requested June 1; final revision received November 1; accepted November 20. Supported by the Association pour la Recherche contre le Cancer. 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 compare changes in gadolinium enhancement at magnetic resonance (MR) imaging with outcome in mediastinal lymphoma after treatment.

MATERIALS AND METHODS: Thirty-one patients with bulky mediastinal lymphoma (17 with Hodgkin disease, 14 with non–Hodgkin lymphoma) underwent serial MR imaging before and up to 50 months after treatment, with routine follow-up (including computed tomography). Signal intensity ratios between masses and muscle were calculated on T1-weighted, T2-weighted, and contrast material–enhanced T1-weighted spin-echo MR images. The percentage enhancement and signal intensity ratios of mediastinal masses on T2-weighted MR images were calculated at diagnosis and during and after treatment.

RESULTS: Twenty-one patients with persistent complete remission had a mean percentage enhancement of residual masses (4%; range, -26% to 40%) that was significantly lower than that of initial masses (78%; range, 41%–124%). Although the mean signal intensity ratio of residual masses on T2-weighted images was significantly lower than that of initial masses, an increase in this ratio was observed in four patients after treatment. In seven patients with relapse, the percentage enhancement value of the residual mass was as high as that of the initial mass.

CONCLUSION: Gadolinium enhancement of lymphomatous masses of the mediastinum decreased markedly after treatment in patients in continuous complete remission but not in patients with relapse.

Index terms: Gadolinium • Hodgkin disease, MR, 67.121411, 67.12143, 67.342 • Lymphoma, MR, 67.121411, 67.12143, 67.343 • Magnetic resonance (MR), contrast enhancement, 67.12143 • Magnetic resonance (MR), tissue characterization, 67.121411 • Mediastinum, neoplasms, 67.342, 67.343

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
The signal intensity of lymphoma at magnetic resonance (MR) imaging changes during the course of the disease. The theoretic basis of signal changes is as follows: Active, untreated tumor tissue contains an excess of free water, which increases the signal intensity on T2-weighted images. With successful treatment, cellular elements and the water content of the tumor are reduced, while the collagen and fibrotic stroma of the original tumor account for the main component of the signal. These factors reduce the signal intensity of the residual mass on T2-weighted images (1–3). In previous studies (4–5), active versus inactive residual masses were identified on the basis of signal intensity patterns, as determined by means of optical reference to the appearance of muscle and fat on T1- and T2-weighted images. This method has yielded various degrees of success in monitoring disease activity (4–10).

The sensitivity of MR imaging in the prediction of relapse in a residual mass ranges from 45% to 90%, with a specificity of 80%–90%, in the different studies (5–7). Active tumor foci may be found within a residual mass with low signal intensity on T2-weighted images. Necrosis, immature fibrotic tissue, edema, and inflammation associated with responding disease can simulate the high signal intensity of a viable tumor, particularly within the first 6 months after therapy (3–5,10,11). In malignancies other than lymphoma, such as osteosarcoma, breast cancer, and myeloma, gadolinium-enhanced MR imaging is used to differentiate active tumors from inactive residual tissue (10,12–14). The aim of this study was to determine the changes in gadolinium enhancement of lymphomatous masses between diagnosis, treatment, and follow-up in patients with lymphoma of the mediastinum and to determine whether the pattern of change reflects the nature of residual masses in this setting.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Patients
Between January 1990 and February 1996, we prospectively enrolled 31 consecutive patients who fulfilled the following inclusion criteria: (a) an initial manifestation of bulky mediastinal disease and (b) follow-up including at least two MR examinations. The mediastinal bulk was defined, by using chest radiographs, as a ratio of the maximum transverse mass diameter to the internal thoracic diameter at the T5-6 level equal to 0.33 (15). All patients were recruited from the department of hematology at our institution.

During the same period, 283 patients with lymphoma (117 with Hodgkin disease, 166 with diffuse large-cell non-Hodgkin lymphoma) were seen in the department of hematology, and 54 of these 283 patients had bulky involvement of the mediastinum. Although they had bulky mediastinal involvement, 23 of these 54 patients could not undergo MR imaging follow-up in our department of radiology because of limited availibility of MR imaging (21 patients) and claustrophobia (two patients). Among the 31 patients examined, 17 patients had Hodgkin disease, and 14 had diffuse large B-cell non-Hodgkin lymphoma. The characteristics of the patients, including age at diagnosis, Ann Arbor clinical stage of disease, treatment, and outcome are listed in Table 1. This study protocol had institutional review board approval (Committee for the Protection of Patients in Biomedical Research). All the patients provided informed consent.

In addition, all nodal masses had to show a decrease in the product of the two largest diameters of more than 75% on CT images (16). Relapse was defined by an increase in the size of the residual mass or the onset of new lesions that led to biopsy and histologic examination, if necessary. At the cutoff date for this analysis (June 1999), the median clinical follow-up of survivors was 81 months (range, 29–113 months) since diagnosis. Event-free survival was measured as the interval between the starting date of chemotherapy and the date of progression, relapse, death, or last follow-up when treatment was ongoing (Table 1).

MR Imaging Technique
Twenty-three patients underwent MR imaging at diagnosis, before initiation of therapy, and eight patients underwent MR imaging after induction chemotherapy. The necessity of rapid treatment did not allow MR examination before treatment in these eight patients due to limited availibility of MR imaging in our institution. MR imaging was repeated as close as possible to the dates of CT for the response to treatment and follow-up when a residual mass was present. MR imaging follow-up ranged from 2 to 50 months (median, 9 months) after baseline MR examination. The total number of MR examinations was 105, with a median of three per patient (range, two to eight examinations).

MR imaging was performed with a 1.5-T unit (Magnetom SP63; Siemens, Erlangen, Germany) and a body coil. All examinations were performed with electrocardiographic gating, and presaturation bands were used above and below the transverse sections. T1- and T2-weighted transverse spin-echo sequences were obtained with the following parameters: 7-mm-thick sections, 300–350-mm field of view, two signals acquired, 256 x 192 matrix for the T2-weighted sequence, and 512 x 200 matrix for the T1-weighted sequence. For T1-weighted sequences, the repetition time was equivalent to the R-R interval (620–930 msec), while T2-weighted sequences were gated to every second or third heart beat. The echo time for T1-weighted sequences was 15 msec. T2-weighted sequences were performed with double-echo acquisitions with echo times of 20 and 80 msec. The T1-weighted sequence was repeated 4 minutes after intravenous administration of gadolinium–tetraazacyclododecanetetraacetic acid (Dotarem, Guerbet, France; 0.1 mmol per kilogram of body weight). Imaging time per patient varied from 25 to 30 minutes.

Image Analysis
Analysis of MR images stored on optical disks was retrospectively performed by two radiologists (A.R., N.J.) who were unaware of the clinical status of the patients. The signal intensity of lymphomatous masses was measured in the regions of interest (ROIs). For all MR examinations in the same patient, the ROI measurement was made at the same section level and encompassed the same region of the mass on T1- and T2-weighted images. Thus, the section level containing the ROI used to measure the residual mass served as the reference section level for measuring the ROI of the initial lymphomatous mass. The selected section level was free of recent biopsy sites and had no partial volume averaging with adjacent tissues. ROIs were always placed outside areas of necrotic or cystic tissue (defined as areas of high signal intensity on the T2-weighted image that did not enhance after administration of contrast material). On the same section level as that chosen for the ROI measurement of the mass, an ROI of paraspinal muscle was selected in the phase-encoding direction. Areas containing motion artifacts and fat-containing regions of the residual masses or muscles were avoided when the ROI was placed. We did not measure fat tissue, which can be too thin in the mediastinum or chest wall for accurate measurements. The ROI area was always larger than 1 cm² and encompassed at least 50 pixels. The ROI area varied from 20% to 90%, according to the area of the residual mass. The ROI area varied from 1 to 2 cm² within the paraspinal muscle.

Signal intensity ratios were calculated between tumor and muscle on T1-weighted, T2-weighted, and contrast material–enhanced T1-weighted images. The percentage of enhancement of lymphomatous masses E was obtained as follows: E = (SIR after - SIR before)/SIR before, where SIR is the signal intensity ratio, SIR before is the ratio measured on the nonenhanced T1-weighted image, and SIR after is the ratio measured on the contrast-enhanced T1-weighted image.

The signal intensity ratio on T2-weighted images and enhancement values of the residual mass at the end of induction chemotherapy were compared with those measured at diagnosis. In patients with relapse, values measured at relapse were compared with baseline values and also with values measured before relapse. Individual signal intensity and enhancement values were plotted against time for all the patients with complete remission. The posttreatment enhancement values were also expressed as ratios of the pretreatment values, which were also plotted against time: A value of 1 was assigned to the pretreatment enhancement values.

Nonlinear regression models were used to fit the data with the Marquardt iterative method (17). The Weibull family model was particularly useful because it summarizes a wild type of nonlinear models, including the exponential. The equation of the cumulative distribution function is F(t) = 1 - e^-AtG. If G = 1, the model is equivalent to the exponential distribution. Model parameters A and G were estimated for signal intensity and enhancement values. Then, the entire set of models was plotted against time. The 95% CI was computed by using the asymptotic standard error for the estimate of the parameters. Comparisons were tested with the Wilcoxon rank sum test. We used a two-tailed formulation to test the null hypothesis that gadolinium enhancement of mediastinal masses does not change with time. These analyses were performed by using statistical analysis software (SAS; SAS Institute, Cary, NC).

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
On the basis of clinical and CT findings obtained within 3 weeks following the day of treatment completion, 29 of the 31 patients were in complete remission, although all had a residual mass. In the remaining two patients, the residual mass in one patient with Hodgkin disease increased in size from 25 to 36 cm² 4 months after completion of treatment, which comprised chemotherapy and radiation therapy of the mediastinum. The mass was removed surgically. It contained normal thymic and fibrotic tissue with no residual tumor, and the size increase was considered to be due to a thymic rebound. The other patient with non-Hodgkin lymphoma was considered to have progressive disease, as a cervical mass appeared during induction chemotherapy, although the size of the mediastinal mass had decreased. Despite salvage treatment, including autologous bone marrow grafting, the patient died of acute respiratory distress syndrome. Autopsy showed a mediastinal fibrotic mass, but there was no tumor at histologic examination.

At the cutoff date, continuous complete remission persisted in 21 patients. Nine patients were considered to have a relapse on the basis of clinical and CT findings. Of these nine patients, five with non-Hodgkin lymphoma had relapse within 12 months after treatment initiation. The remaining four patients who had Hodgkin disease relapsed within 17–54 months. Five of the patients who had relapse died of disease progression. Salvage therapy was successful in the remaining four patients.

Before treatment, the mean size of the initial masses was 51 cm² (range, 24–144 cm²). The signal intensity ratio of the initial masses on T2-weighted images was always higher than that of muscle and ranged from 2.3 to 10.0 (mean, 4.0). The initial masses always enhanced more strongly than muscle, and enhancement values ranged from 41% to 124% (mean, 78%).

After treatment, a residual mass larger than 1 cm² was always present on follow-up MR images. The residual mass was always smaller than the initial mass, even in patients with relapse.

In the 21 patients with persistent complete remission, the median time between the last follow-up MR examination and the cutoff date was 73 months (range, 50–102 months). The changes in signal intensity ratio and enhancement values over time are shown in Figure 1. After induction treatment, the mean enhancement value was 4% (range, -26% to 40%) in all 21 patients. For the 15 patients who underwent MR examination before treatment, the mean enhancement value was 6% (range, -20% to 40%), which was significantly lower than the mean initial enhancement value (P < .05); for the remaining six patients not undergoing these examinations, the mean value was 1% (range, -26% to 15%).

View larger version (17K): [in this window] [in a new window] [Download PPT slide]   Figure 1a. (a) Graph shows changes in enhancement values of residual masses in 21 patients in continuous complete remission over time. Gadolinium enhancement of mediastinal masses decreased to the same level as that of muscle. All enhancement values are plotted against the exponential decrease in the mean enhancement values; interval boundaries represent 95% CIs. (b) Graph shows changes in the signal intensity ratio on T2-weighted MR images in 21 patients in continuous complete remission over time. Although it decreases, the ratio in residual masses on T2-weighted MR images remains higher than that of muscle.

View larger version (18K): [in this window] [in a new window] [Download PPT slide]   Figure 1b. (a) Graph shows changes in enhancement values of residual masses in 21 patients in continuous complete remission over time. Gadolinium enhancement of mediastinal masses decreased to the same level as that of muscle. All enhancement values are plotted against the exponential decrease in the mean enhancement values; interval boundaries represent 95% CIs. (b) Graph shows changes in the signal intensity ratio on T2-weighted MR images in 21 patients in continuous complete remission over time. Although it decreases, the ratio in residual masses on T2-weighted MR images remains higher than that of muscle.

View larger version (19K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Graph shows changes in the enhancement of the residual masses, expressed as a ratio, compared with that of the initial mass. A value of 1 is assigned to the pretreatment value. No enhancement higher than that obtained before treatment was measured in residual masses.

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. Diffuse large-cell lymphoma in a 42-year-old woman. All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,200/80, repetition time msec/echo time msec) shows an anterior mediastinal mass (large arrows) of high signal intensity relative to that of muscle, bilateral axillary lymph nodes (arrowheads), and left respiratory artifacts (small arrows) due to limited pleural effusion. (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo (730/15) images demonstrate marked enhancement of the mass (arrows). Note bilateral axillary lymph nodes with the same signal intensity as that of the mediastinal mass (arrowheads). A left pleural effusion is present, although it is not well shown on the images. MR follow-up was performed 4 months later after induction chemotherapy. (d) T2-weighted spin-echo image (2,220/80) shows that the mediastinal mass (large arrows) is decreased in size, but its signal intensity is unchanged. A left pleural effusion is seen (small arrows), but axillary lymph nodes are almost not visible (arrowheads). (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (740/15) show that enhancement of the residual mass (large arrows) is lower than that of muscle, which is consistent with an inactive mass, although a left pleural effusion is still present (small arrows in e). Further MR follow-up confirmed a residual inactive mass. This patient was still in complete remission 8 years after the completion of treatment.

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. Diffuse large-cell lymphoma in a 42-year-old woman. All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,200/80, repetition time msec/echo time msec) shows an anterior mediastinal mass (large arrows) of high signal intensity relative to that of muscle, bilateral axillary lymph nodes (arrowheads), and left respiratory artifacts (small arrows) due to limited pleural effusion. (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo (730/15) images demonstrate marked enhancement of the mass (arrows). Note bilateral axillary lymph nodes with the same signal intensity as that of the mediastinal mass (arrowheads). A left pleural effusion is present, although it is not well shown on the images. MR follow-up was performed 4 months later after induction chemotherapy. (d) T2-weighted spin-echo image (2,220/80) shows that the mediastinal mass (large arrows) is decreased in size, but its signal intensity is unchanged. A left pleural effusion is seen (small arrows), but axillary lymph nodes are almost not visible (arrowheads). (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (740/15) show that enhancement of the residual mass (large arrows) is lower than that of muscle, which is consistent with an inactive mass, although a left pleural effusion is still present (small arrows in e). Further MR follow-up confirmed a residual inactive mass. This patient was still in complete remission 8 years after the completion of treatment.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 3c. Diffuse large-cell lymphoma in a 42-year-old woman. All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,200/80, repetition time msec/echo time msec) shows an anterior mediastinal mass (large arrows) of high signal intensity relative to that of muscle, bilateral axillary lymph nodes (arrowheads), and left respiratory artifacts (small arrows) due to limited pleural effusion. (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo (730/15) images demonstrate marked enhancement of the mass (arrows). Note bilateral axillary lymph nodes with the same signal intensity as that of the mediastinal mass (arrowheads). A left pleural effusion is present, although it is not well shown on the images. MR follow-up was performed 4 months later after induction chemotherapy. (d) T2-weighted spin-echo image (2,220/80) shows that the mediastinal mass (large arrows) is decreased in size, but its signal intensity is unchanged. A left pleural effusion is seen (small arrows), but axillary lymph nodes are almost not visible (arrowheads). (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (740/15) show that enhancement of the residual mass (large arrows) is lower than that of muscle, which is consistent with an inactive mass, although a left pleural effusion is still present (small arrows in e). Further MR follow-up confirmed a residual inactive mass. This patient was still in complete remission 8 years after the completion of treatment.

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 3d. Diffuse large-cell lymphoma in a 42-year-old woman. All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,200/80, repetition time msec/echo time msec) shows an anterior mediastinal mass (large arrows) of high signal intensity relative to that of muscle, bilateral axillary lymph nodes (arrowheads), and left respiratory artifacts (small arrows) due to limited pleural effusion. (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo (730/15) images demonstrate marked enhancement of the mass (arrows). Note bilateral axillary lymph nodes with the same signal intensity as that of the mediastinal mass (arrowheads). A left pleural effusion is present, although it is not well shown on the images. MR follow-up was performed 4 months later after induction chemotherapy. (d) T2-weighted spin-echo image (2,220/80) shows that the mediastinal mass (large arrows) is decreased in size, but its signal intensity is unchanged. A left pleural effusion is seen (small arrows), but axillary lymph nodes are almost not visible (arrowheads). (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (740/15) show that enhancement of the residual mass (large arrows) is lower than that of muscle, which is consistent with an inactive mass, although a left pleural effusion is still present (small arrows in e). Further MR follow-up confirmed a residual inactive mass. This patient was still in complete remission 8 years after the completion of treatment.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 3e. Diffuse large-cell lymphoma in a 42-year-old woman. All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,200/80, repetition time msec/echo time msec) shows an anterior mediastinal mass (large arrows) of high signal intensity relative to that of muscle, bilateral axillary lymph nodes (arrowheads), and left respiratory artifacts (small arrows) due to limited pleural effusion. (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo (730/15) images demonstrate marked enhancement of the mass (arrows). Note bilateral axillary lymph nodes with the same signal intensity as that of the mediastinal mass (arrowheads). A left pleural effusion is present, although it is not well shown on the images. MR follow-up was performed 4 months later after induction chemotherapy. (d) T2-weighted spin-echo image (2,220/80) shows that the mediastinal mass (large arrows) is decreased in size, but its signal intensity is unchanged. A left pleural effusion is seen (small arrows), but axillary lymph nodes are almost not visible (arrowheads). (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (740/15) show that enhancement of the residual mass (large arrows) is lower than that of muscle, which is consistent with an inactive mass, although a left pleural effusion is still present (small arrows in e). Further MR follow-up confirmed a residual inactive mass. This patient was still in complete remission 8 years after the completion of treatment.

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 3f. Diffuse large-cell lymphoma in a 42-year-old woman. All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,200/80, repetition time msec/echo time msec) shows an anterior mediastinal mass (large arrows) of high signal intensity relative to that of muscle, bilateral axillary lymph nodes (arrowheads), and left respiratory artifacts (small arrows) due to limited pleural effusion. (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo (730/15) images demonstrate marked enhancement of the mass (arrows). Note bilateral axillary lymph nodes with the same signal intensity as that of the mediastinal mass (arrowheads). A left pleural effusion is present, although it is not well shown on the images. MR follow-up was performed 4 months later after induction chemotherapy. (d) T2-weighted spin-echo image (2,220/80) shows that the mediastinal mass (large arrows) is decreased in size, but its signal intensity is unchanged. A left pleural effusion is seen (small arrows), but axillary lymph nodes are almost not visible (arrowheads). (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (740/15) show that enhancement of the residual mass (large arrows) is lower than that of muscle, which is consistent with an inactive mass, although a left pleural effusion is still present (small arrows in e). Further MR follow-up confirmed a residual inactive mass. This patient was still in complete remission 8 years after the completion of treatment.

Seven of the nine patients with relapse had assessable serial MR images. Two patients did not undergo MR imaging at the time of relapse. One of these two patients (both of whom had Hodgkin disease) had relapse in the abdomen 27 months after diagnosis, with no increase in the residual mediastinal mass at CT. The other patient had a mediastinal relapse that occurred 24 months after the last follow-up MR examination. The seven patients with assessable images had a mediastinal relapse characterized with marked gadolinium enhancement of the residual mass (Table 2) (Figs 4, 5). In five of them, the enhancement value of the residual mass at relapse was at least equal to that obtained in three patients before treatment and in two patients after induction chemotherapy. In the remaining two patients (patients 1, 2), the enhancement value at relapse was lower than that before treatment, but it was higher than the mean enhancement value (4%) in the 21 patients with persistent complete remission. Two of these seven patients with relapse (patients 2, 4) had undergone MR imaging less than 6 months before the relapse. These images showed strong enhancement of the residual mass, although the residual mass had shrunk by more than 75% relative to the mass at diagnosis (Fig 4). The signal intensity ratio of the residual mass on T2-weighted images at relapse was at least equal to that at baseline in two of the six patients, and it was lower in three (T2-weighted images were not obtained in one patient).

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 4a. Diffuse large-cell lymphoma in a 38-year-old woman (patient 2 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,040/80) shows an anterior mediastinal mass (arrows) with high signal intensity relative to that of muscle and a left pleural effusion (*). (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo images (680/15) demonstrate marked enhancement of the mass (arrows). MR follow-up was performed 6 months later. Treatment included high-dose chemotherapy and autologous bone marrow transplantation. (d) T2-weighted spin-echo image (2,392/80) obtained after completion of treatment shows that the mediastinal mass (arrows) is decreased in size, but its signal intensity is still higher than that of muscle. Note the absence of pleural effusion. (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (792/15) show marked enhancement of the residual mass consistent with active disease (arrows). A round nonenhancing area (arrowheads in f) corresponding to a high-signal-intensity area on the T2-weighted image is present within the mass and could correspond to necrosis. (g) T2-weighted spin-echo image (2,229/80) obtained 4 months later confirms that the residual mass (arrows) is active by showing an increase in its size. Note a recurrent left pleural effusion (*).

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 4b. Diffuse large-cell lymphoma in a 38-year-old woman (patient 2 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,040/80) shows an anterior mediastinal mass (arrows) with high signal intensity relative to that of muscle and a left pleural effusion (*). (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo images (680/15) demonstrate marked enhancement of the mass (arrows). MR follow-up was performed 6 months later. Treatment included high-dose chemotherapy and autologous bone marrow transplantation. (d) T2-weighted spin-echo image (2,392/80) obtained after completion of treatment shows that the mediastinal mass (arrows) is decreased in size, but its signal intensity is still higher than that of muscle. Note the absence of pleural effusion. (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (792/15) show marked enhancement of the residual mass consistent with active disease (arrows). A round nonenhancing area (arrowheads in f) corresponding to a high-signal-intensity area on the T2-weighted image is present within the mass and could correspond to necrosis. (g) T2-weighted spin-echo image (2,229/80) obtained 4 months later confirms that the residual mass (arrows) is active by showing an increase in its size. Note a recurrent left pleural effusion (*).

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 4c. Diffuse large-cell lymphoma in a 38-year-old woman (patient 2 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,040/80) shows an anterior mediastinal mass (arrows) with high signal intensity relative to that of muscle and a left pleural effusion (*). (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo images (680/15) demonstrate marked enhancement of the mass (arrows). MR follow-up was performed 6 months later. Treatment included high-dose chemotherapy and autologous bone marrow transplantation. (d) T2-weighted spin-echo image (2,392/80) obtained after completion of treatment shows that the mediastinal mass (arrows) is decreased in size, but its signal intensity is still higher than that of muscle. Note the absence of pleural effusion. (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (792/15) show marked enhancement of the residual mass consistent with active disease (arrows). A round nonenhancing area (arrowheads in f) corresponding to a high-signal-intensity area on the T2-weighted image is present within the mass and could correspond to necrosis. (g) T2-weighted spin-echo image (2,229/80) obtained 4 months later confirms that the residual mass (arrows) is active by showing an increase in its size. Note a recurrent left pleural effusion (*).

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 4d. Diffuse large-cell lymphoma in a 38-year-old woman (patient 2 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,040/80) shows an anterior mediastinal mass (arrows) with high signal intensity relative to that of muscle and a left pleural effusion (*). (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo images (680/15) demonstrate marked enhancement of the mass (arrows). MR follow-up was performed 6 months later. Treatment included high-dose chemotherapy and autologous bone marrow transplantation. (d) T2-weighted spin-echo image (2,392/80) obtained after completion of treatment shows that the mediastinal mass (arrows) is decreased in size, but its signal intensity is still higher than that of muscle. Note the absence of pleural effusion. (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (792/15) show marked enhancement of the residual mass consistent with active disease (arrows). A round nonenhancing area (arrowheads in f) corresponding to a high-signal-intensity area on the T2-weighted image is present within the mass and could correspond to necrosis. (g) T2-weighted spin-echo image (2,229/80) obtained 4 months later confirms that the residual mass (arrows) is active by showing an increase in its size. Note a recurrent left pleural effusion (*).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 4e. Diffuse large-cell lymphoma in a 38-year-old woman (patient 2 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,040/80) shows an anterior mediastinal mass (arrows) with high signal intensity relative to that of muscle and a left pleural effusion (*). (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo images (680/15) demonstrate marked enhancement of the mass (arrows). MR follow-up was performed 6 months later. Treatment included high-dose chemotherapy and autologous bone marrow transplantation. (d) T2-weighted spin-echo image (2,392/80) obtained after completion of treatment shows that the mediastinal mass (arrows) is decreased in size, but its signal intensity is still higher than that of muscle. Note the absence of pleural effusion. (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (792/15) show marked enhancement of the residual mass consistent with active disease (arrows). A round nonenhancing area (arrowheads in f) corresponding to a high-signal-intensity area on the T2-weighted image is present within the mass and could correspond to necrosis. (g) T2-weighted spin-echo image (2,229/80) obtained 4 months later confirms that the residual mass (arrows) is active by showing an increase in its size. Note a recurrent left pleural effusion (*).

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 4f. Diffuse large-cell lymphoma in a 38-year-old woman (patient 2 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,040/80) shows an anterior mediastinal mass (arrows) with high signal intensity relative to that of muscle and a left pleural effusion (*). (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo images (680/15) demonstrate marked enhancement of the mass (arrows). MR follow-up was performed 6 months later. Treatment included high-dose chemotherapy and autologous bone marrow transplantation. (d) T2-weighted spin-echo image (2,392/80) obtained after completion of treatment shows that the mediastinal mass (arrows) is decreased in size, but its signal intensity is still higher than that of muscle. Note the absence of pleural effusion. (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (792/15) show marked enhancement of the residual mass consistent with active disease (arrows). A round nonenhancing area (arrowheads in f) corresponding to a high-signal-intensity area on the T2-weighted image is present within the mass and could correspond to necrosis. (g) T2-weighted spin-echo image (2,229/80) obtained 4 months later confirms that the residual mass (arrows) is active by showing an increase in its size. Note a recurrent left pleural effusion (*).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 4g. Diffuse large-cell lymphoma in a 38-year-old woman (patient 2 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. (a) Before treatment, T2-weighted spin-echo image (2,040/80) shows an anterior mediastinal mass (arrows) with high signal intensity relative to that of muscle and a left pleural effusion (*). (b) Nonenhanced and (c) gadolinium-enhanced T1-weighted spin-echo images (680/15) demonstrate marked enhancement of the mass (arrows). MR follow-up was performed 6 months later. Treatment included high-dose chemotherapy and autologous bone marrow transplantation. (d) T2-weighted spin-echo image (2,392/80) obtained after completion of treatment shows that the mediastinal mass (arrows) is decreased in size, but its signal intensity is still higher than that of muscle. Note the absence of pleural effusion. (e) Nonenhanced and (f) gadolinium-enhanced T1-weighted spin-echo images (792/15) show marked enhancement of the residual mass consistent with active disease (arrows). A round nonenhancing area (arrowheads in f) corresponding to a high-signal-intensity area on the T2-weighted image is present within the mass and could correspond to necrosis. (g) T2-weighted spin-echo image (2,229/80) obtained 4 months later confirms that the residual mass (arrows) is active by showing an increase in its size. Note a recurrent left pleural effusion (*).

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 5a. Diffuse large-cell lymphoma in a 38-year-old woman (patient 6 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. MR images were obtained 4 months after treatment, including chemotherapy. On the basis of clinical and CT analysis, the patient was considered to be in complete remission. (a) Nonenhanced and (b) gadolinium-enhanced T1-weighted spin-echo images (715/15) show that enhancement of the residual mass was lower than that of muscle, except for a 1-cm-diameter enhancing area (arrow) close to the main pulmonary artery. This small area was consistent with active disease, although the mass (arrowheads in b) is mainly inactive. (c) Nonenhanced and (d) gadolinium-enhanced T1-weighted spin-echo images (780/15) obtained 4 months later demonstrate that relapse occurred in the left part of the mediastinum, although the remaining residual mass in front of the aorta decreased in size. Enhancement of the active part of the residual mass (arrows) is higher than that of muscle. In d, the inactive area of the residual mass (arrowheads) has a signal intensity lower than that of muscle.

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 5b. Diffuse large-cell lymphoma in a 38-year-old woman (patient 6 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. MR images were obtained 4 months after treatment, including chemotherapy. On the basis of clinical and CT analysis, the patient was considered to be in complete remission. (a) Nonenhanced and (b) gadolinium-enhanced T1-weighted spin-echo images (715/15) show that enhancement of the residual mass was lower than that of muscle, except for a 1-cm-diameter enhancing area (arrow) close to the main pulmonary artery. This small area was consistent with active disease, although the mass (arrowheads in b) is mainly inactive. (c) Nonenhanced and (d) gadolinium-enhanced T1-weighted spin-echo images (780/15) obtained 4 months later demonstrate that relapse occurred in the left part of the mediastinum, although the remaining residual mass in front of the aorta decreased in size. Enhancement of the active part of the residual mass (arrows) is higher than that of muscle. In d, the inactive area of the residual mass (arrowheads) has a signal intensity lower than that of muscle.

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 5c. Diffuse large-cell lymphoma in a 38-year-old woman (patient 6 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. MR images were obtained 4 months after treatment, including chemotherapy. On the basis of clinical and CT analysis, the patient was considered to be in complete remission. (a) Nonenhanced and (b) gadolinium-enhanced T1-weighted spin-echo images (715/15) show that enhancement of the residual mass was lower than that of muscle, except for a 1-cm-diameter enhancing area (arrow) close to the main pulmonary artery. This small area was consistent with active disease, although the mass (arrowheads in b) is mainly inactive. (c) Nonenhanced and (d) gadolinium-enhanced T1-weighted spin-echo images (780/15) obtained 4 months later demonstrate that relapse occurred in the left part of the mediastinum, although the remaining residual mass in front of the aorta decreased in size. Enhancement of the active part of the residual mass (arrows) is higher than that of muscle. In d, the inactive area of the residual mass (arrowheads) has a signal intensity lower than that of muscle.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 5d. Diffuse large-cell lymphoma in a 38-year-old woman (patient 6 in Table 2). All of these transverse MR images were obtained with electrocardiographic gating. MR images were obtained 4 months after treatment, including chemotherapy. On the basis of clinical and CT analysis, the patient was considered to be in complete remission. (a) Nonenhanced and (b) gadolinium-enhanced T1-weighted spin-echo images (715/15) show that enhancement of the residual mass was lower than that of muscle, except for a 1-cm-diameter enhancing area (arrow) close to the main pulmonary artery. This small area was consistent with active disease, although the mass (arrowheads in b) is mainly inactive. (c) Nonenhanced and (d) gadolinium-enhanced T1-weighted spin-echo images (780/15) obtained 4 months later demonstrate that relapse occurred in the left part of the mediastinum, although the remaining residual mass in front of the aorta decreased in size. Enhancement of the active part of the residual mass (arrows) is higher than that of muscle. In d, the inactive area of the residual mass (arrowheads) has a signal intensity lower than that of muscle.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

At diagnosis, enhancement varied among our patients. Well-known pathologic differences among initial masses could explain these differences in enhancement, including different vessel density and different amounts and types of fibrosis (immature vs mature) (2,21). However, the effect of these pathologic features on gadolinium enhancement could not be assessed, as the initial diagnosis of lymphoma was obtained mainly by means of peripheral lymph node biopsy in our study. The weakest enhancement at diagnosis (41%) was close to the highest value (40%) after induction chemotherapy in the patients with inactive residual masses. However, there was no overlap in individual patients because enhancement of the residual mass was always weaker than that of the initial mass (Fig 2). Thus, the results of quantitative contrast-enhanced MR imaging of residual masses must be compared with pretreatment results for accurate assessment.

Our results also confirm that the mean signal intensity of lymphoma on T2-weighted images decreases after treatment (22). The signal intensity ratios on T2-weighted images before and after treatment had quantitative values similar to those obtained by Nyman et al (1). However, most other previous investigators used pattern signal analysis based on visual comparison of signal intensities between the mass and fatty tissue on T1- and T2-weighted images. The main reason for qualitative analysis was the inhomogeneous MR aspect of lymphomatous masses at diagnosis and after treatment (4–11). This inhomogeneity is mainly due to necrotic areas, which are best shown on contrast-enhanced T1-weighted images (23). In our study, ROI measurements readily excluded gross necrotic areas, as we compared T2- and nonenhanced and contrast-enhanced T1-weighted images. Rehn et al (23) showed that patients with pronounced tumor inhomogeneity on MR images at diagnosis had a poor prognosis. This prognostic information cannot be used to predict in situ relapse, but represents another reason for performing a baseline pretreatment gadolinium-enhanced MR examination before treatment. When we assessed the nature of a residual mass, our results showed that signal intensity on T2-weighted images was less reliable than enhancement, as the signal can sometimes increase in successfully treated patients, particularly during the 1st year of follow-up, as reported in previous studies (1,4,5,11). Pathologic analyses in previous studies (4) showed that inflammation, with or without necrosis, was responsible for this high signal intensity on T2-weighted images.

A disadvantage of visual qualitative analysis of signal intensity on T2-weighted images is the problem of assessing whether the residual mass has a signal intensity that is higher or lower than that of fat, because (a) the fat tissue within the chest wall can be thin; (b) the magnetic field and/or coil inhomogeneities increase at the periphery of the image, and the fat signal can be different in different regions of the chest wall or axilla; and (c) the signal of the tumor can be close to the signal of fat, with a tumor-to-fat signal intensity ratio ranging from 0.6 to 1.3 before treatment, according to Nyman et al (1). A statistically significant decrease in the tumor-to-fat signal, ranging from 0.2–1.3 in inactive residual masses, was observed by these authors, but signal intensity on T2-weighted images can sometimes remain close to that of fat, presumably because of necrosis (1). Thus, areas of necrosis within residual masses make it difficult to identify tumor foci (4,5).

Among our 31 patients with residual masses, seven (23%) had relapse within the mediastinum. A patient can be considered a partial or incomplete responder when a residual mass persists, even if it is "sterilized." Such patients may wrongly receive additional treatment, or a wait-and-see policy may delay necessary additional treatment, depending on the interval between follow-up imaging procedures. A persistent residual mass is usually found after treatment of lymphoma, particularly in patients who initially have bulky lymphomatous masses in the mediastinum (21,24). Studies aimed at analyzing the effectiveness of chemotherapy, alone or combined with bone marrow transplantation or radiation therapy, require methods to assess the viability of residual lymphomatous masses. As shown in this and previous studies, a decrease in the size of the lymphomatous mass does not rule out an active persistent tumor. However, our results show that persistent active tumors are associated with strong gadolinium enhancement.

Gallium imaging, and more recently 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), have also been shown to provide better information on the viability of residual masses than CT-based assessment of size changes. However, no gallium uptake is seen in about 20% of lymphomatous masses at diagnosis, and studies (5,25) in which MR and gallium imaging were compared showed no superiority of the latter in the prediction of relapses. Increased glycolysis, a biochemical feature of malignant cells, explains FDG uptake by lymphomatous masses at PET. This complex technique offers results at least equivalent to those of CT in the detection of lymphoma during initial staging (26–28). It may also permit identification of patients requiring intensification after completion of chemotherapy (29). Promising results have also recently been obtained in the detection of residual disease (30).

Our findings suggests that MR images that show persistent strong contrast enhancement of lymphomatous masses may be an additional tool in the detection of relapse in situ. Although an increase in the size of a residual mass remains one of the most important markers of relapse, our findings show that size alone is not sufficient to enable detection of early relapse. A previous study (4) based on pattern analysis showed divergent changes in size and signal intensity on T2-weighted images. For our part, we observed divergent changes in size and gadolinium enhancement in relapsing patients (Fig 4). On the other hand, a moderate increase in a residual anterior mediastinal mass after treatment does not necessarily reflect the presence of viable tumor, as in one of our patients who had thymic hyperplasia following treatment (31).

Several limitations of our study prevent us from drawing firm conclusions: (a) With spin-echo sequences, enhancement values reflect several parameters, including blood flow and volume characteristics (perfusion), microvascular permeability, and increased fractional volume of the extracellular compartment. Dugdale et al (32) and Stroszcynski et al (33) showed that perfusion values measured at CT decreased when lymphoma masses became inactive. First-pass dynamic contrast-enhanced MR imaging should then provide better results. (b) Use of a dedicated thoracic coil, use of thinner sections, and decreased motion artifacts with breath-hold sequences may enable better analysis of the enhancement characteristics of lymphomatous masses of the mediastinum. (c) Our quantitative analysis did not encompass the whole initial tumor or the entire residual mass, as only the section level corresponding to the location of the residual mass was measured. (d) Viable tumor cells can remain in a small part of an otherwise fibrotic residual mass. Active tumor foci may thus be too small for morphologic detection, as in one of our patients who had an in situ relapse 24 months after the last follow-up MR examination.

In conclusion, we found that MR evaluation of residual lymphomatous masses requires a pretreatment baseline MR study for comparison, and it can be done not only with T2 weighting but also with gadolinium enhancement. Further studies of imaging with more recent MR techniques of perfusion analysis of lymphomatous masses before and after treatment are required for comparison with FDG PET.

	ACKNOWLEDGMENTS

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

	FOOTNOTES

 
Abbreviations: FDG = 2-[fluorine-18]fluoro-2-deoxy-D-glucose, ROI = region of interest

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

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 

1. Nyman RS, Rehn SM, Glimelius BLG, Hagberg HE, Hemmingsson AL, Sundstrom CJ. Residual mediastinal masses in Hodgkin disease: prediction of size with MR imaging. Radiology 1989; 170:435-440.[Abstract/Free Full Text]
2. Lee JKT, Glazer HS. Controversy in the MR imaging appearance of fibrosis. Radiology 1990; 177:21-22.[Free Full Text]
3. Webb WR. MR imaging of treated mediastinal Hodgkin disease. Radiology 1989; 170:315-316.[Free Full Text]
4. Rahmouni A, Tempany C, Jone R, Mann R, Yang A, Zerhouni E. Lymphoma: monitoring tumor size and signal intensity with MR imaging. Radiology 1993; 188:445-451.[Abstract/Free Full Text]
5. Hill M, Cunningham D, MacVicar D, et al. Role of magnetic resonance imaging in predicting relapse in residual masses after treatment of lymphoma. J Clin Oncol 1993; 11:2273-2278.[Abstract/Free Full Text]
6. Gasparini MD, Balzarini L, Castellani MR, et al. Current role of Gallium scan and magnetic resonance imaging in the management of mediastinal Hodgkin lymphoma. Cancer 1993; 72:577-582.[Medline]
7. Devizzi L, Maffioli L, Bonfante V, et al. Comparison of gallium scan, computed tomography, and magnetic resonance in patients with mediastinal Hodgkin’s disease. Ann Oncol 1997; 8(suppl 1):S53-S56.
8. Zinzani PL, Zompatori M, Bendandi M, et al. Monitoring bulky mediastinal disease with gallium-67, CT scan, and magnetic resonance imaging in Hodgkin’s disease and high-grade non-Hodgkin’s lymphoma. Leuk Lymphoma 1996; 22:131-135.[Medline]
9. Foss Abrahamsen A, Lien HH, Aas M, et al. Magnetic resonance imaging and 67 gallium scan in mediastinal malignant lymphoma: a prospective pilot study. Ann Oncol 1994; 5:433-436.[Abstract/Free Full Text]
10. Husband JES. Mackenzie Davidson memorial lecture 1994: imaging of treated cancer. Br J Radiol 1995; 68:1-12.[Medline]
11. Spiers ASD, Husband JES, MacVicar AD. Treated thymic lymphoma: comparison of MR imaging with CT. Radioloy 1997; 203:369-376.
12. 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]
13. Dao TH, 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]
14. 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]
15. Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol 1989; 7:1630-1636.[Abstract]
16. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol 1999; 17:1244-1253.[Abstract/Free Full Text]
17. Marquardt DW. An algorithm for least square estimation of non-linear parameters. J Soc Ind Appl Math 1963; 11:431-441.
18. Forsgren G, Nyman R, Glimelius B, Hagberg H, Rehn S, Hemmingsson A. Gd-DTPA-enhanced MR imaging in mediastinal Hodgkin’s disease. Acta Radiol 1994; 35:564-569.[Medline]
19. Ribatti D, Vacca A, Nico M, 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]
20. 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.[Medline]
21. Cazals-Hatem D, Lepage E, Brice P, et al. Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA ("Groupe d’Etude des Lymphomes de l’Adulte") study. Am J Surg Pathol 1996; 20:877-88.[Medline]
22. Nyman R, Forsgren G, Glimelius B. Long-term follow-up of residual mediastinal masses in treated Hodgkin’s disease using MR imaging. Acta Radiol 1996; 37:323-326.[Medline]
23. Rehn SM, Rodriguez M, Bergström SR, Nyman RS, Glimelius BLG. Tumour inhomogeneities on magnetic resonance imaging, a new factor with prognostic information in non-Hodgkin’s lymphomas. Leuk Lymphoma 1997; 24:501-511.[Medline]
24. North LB, Fuller LM, Sullivan Halley JA, et al. Regression of mediastinal Hodgkin disease after therapy: evaluation of time interval. Radiology 1987; 164:599-602.[Abstract/Free Full Text]
25. Van Amsterdam JAG, Kluin-Nelemans JC, Van Eck-Smit BLF, Pauwels EKJ. Role of 67Ga scintigraphy in localization of lymphoma. Ann Hematol 1996; 72:202-207.[Medline]
26. Moog F, Bangarter M, Diederichs CG, et al. Lymphoma: role of whole-body 2-deoxy-2-(F-18)-fluoro-D-glucose (FDG) PET in nodal staging. Radiology 1997; 203:795-800.[Abstract/Free Full Text]
27. Jerusalem G, Warland V, Najjar F, et al. Whole-body 18F-FDG PET for the evaluation of patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Nucl Med Commun 1999; 20:13-20.[Medline]
28. Delbeke D. Oncological applications of FDG PET imaging: brain tumors, colorectal cancer, lymphoma and melanoma. J Nucl Med 1999; 40:591-603.[Abstract/Free Full Text]
29. Jerusalem G, Beguin Y, Fassotte MF, et al. Whole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin’s disease and non-Hodgkin’s lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 1999; 94:429-433.[Abstract/Free Full Text]
30. Cremerius U, Fabry U, Neuerburg J, Zimmy M, Osieka R, Buell U. Positron emission tomography with 18F-FDG to detect residual disease after therapy for malignant lymphoma. Nucl Med Commun 1998; 19:1055-1063.[Medline]
31. Carmosino L, Di Benedetto A, Feffer S. Thymic hyperplasia following successful chemotherapy. Cancer 1985; 56:1526- 1528.[Medline]
32. Dugdale PE, Miles KA, Kelley BB, Leggett DA. CT measurement of perfusion and permeability within lymphoma masses and its ability to assess grade, activity, and chemotherapeutic response. J Comput Assist Tomogr 1999; 23:540-547.[Medline]
33. Stroszcynski CR, Hosten N, Oellinger JJ, Spahn G, Amthauer HW, Felix R. Value of MR imaging for the staging and monitoring of patients with lymphoma and bulky disease (abstr). Radiology 1998; 209(P):401.

This article has been cited by other articles:

				T. Inaoka, K. Takahashi, M. Mineta, T. Yamada, N. Shuke, A. Okizaki, K. Nagasawa, H. Sugimori, and T. Aburano Thymic Hyperplasia and Thymus Gland Tumors: Differentiation with Chemical Shift MR Imaging Radiology, June 1, 2007; 243(3): 869 - 876. [Abstract] [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF)