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Osteogenic and Ewing Sarcomas: Estimation of Necrotic Fraction during Induction Chemotherapy with Dynamic Contrast-enhanced MR Imaging¹

¹ From the Department of Radiology (J.P.D., D.M.P, L.H.S., D.B.), Weill Medical College of Cornell University, 1300 York Ave, Box 234, New York, NY 10021-4885; Departments of Radiology (D.M.P., L.H.S., J.A.K., D.B.), Surgery (J.H.H.), Pediatrics (P.A.M., R.G.), Pathology (A.G.H.), Biostatistics (H.T.T.), Medical Physics (J.A.K., D.B.), and Medicine (J.A.K.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Institute of Neurology, University College London, England (P.S.T.). Received October 9, 2001; revision requested January 2, 2002; final revision received October 16; accepted November 6. Supported in part by National Institutes of Health grants R01HL50139, CA05826-038A1, and RO1CA62556. Address correspondence to J.P.D. (e-mail: jpd2001@med.cornell.edu).

View larger version (86K): [in a new window]   Figure 1a. (a) Sagittal fast multiplanar spoiled gradient-echo MR image (9/2, 256 x 256 matrix, 24-cm field of view, 12-mm section thickness) obtained 4 minutes after administration of gadopentetate dimeglumine in a patient with osteosarcoma, 30% response (grade 1). Regions of interest are placed on regions of muscle (1), vessel (2), necrotic tumor (3), and tumor (4). (b) Representative time-intensity curves from various regions exhibit differences in initial slope time and maximum enhancement. Typical muscular uptake (1) shows a gradual increase in intensity without a noticeable plateau during this imaging period. The popliteal artery (2) has four to five time points characterizing the initial arrival of contrast material into the vessel. Necrotic tumor (3) is characterized by a lesser degree of enhancement than that of muscle. Viable tumor (4) shows an enhancement and slope greater that of muscle but less than that of vessel. At pathologic examination, the patient was confirmed to be a grade I responder to chemotherapy, exhibiting 30% necrosis at single-slice pathologic examination.

View larger version (21K): [in a new window]   Figure 1b. (a) Sagittal fast multiplanar spoiled gradient-echo MR image (9/2, 256 x 256 matrix, 24-cm field of view, 12-mm section thickness) obtained 4 minutes after administration of gadopentetate dimeglumine in a patient with osteosarcoma, 30% response (grade 1). Regions of interest are placed on regions of muscle (1), vessel (2), necrotic tumor (3), and tumor (4). (b) Representative time-intensity curves from various regions exhibit differences in initial slope time and maximum enhancement. Typical muscular uptake (1) shows a gradual increase in intensity without a noticeable plateau during this imaging period. The popliteal artery (2) has four to five time points characterizing the initial arrival of contrast material into the vessel. Necrotic tumor (3) is characterized by a lesser degree of enhancement than that of muscle. Viable tumor (4) shows an enhancement and slope greater that of muscle but less than that of vessel. At pathologic examination, the patient was confirmed to be a grade I responder to chemotherapy, exhibiting 30% necrosis at single-slice pathologic examination.

View larger version (28K): [in a new window]   Figure 2. Representative compartmental model fits of tumor regions of interest for two patients with different chemotherapy responses, with respective model parameters. The amplitude of the model fit is greater for more viable tumor. The transfer coefficient between the vascular and extracellular spaces (kep) is also greater for the grade II responder.

View larger version (55K): [in a new window]   Figure 3. Osteosarcoma grade I (10% necrosis) response at time of definitive surgery. A, Sagittal T1-weighted MR image (24-cm field of view, 256 x 256 matrix, 12-mm section thickness) from the last time point after contrast material administration. B, Parametric image contains the slope of each voxel of the tumor region of interest. A lack of uptake in the central osseous component of the tumor is evident (arrow). C, Parametric model amplitude image of Akep displays a deficit in enhancement in the same region as in B. Static contrast-enhanced T1-weighted MR image (fast multiplanar spoiled gradient-echo sequence: 9/2, 256 x 256 matrix, 24-cm field of view, 12-mm section thickness) displayed a fairly uniform pattern of contrast material distribution. However, a greater degree of enhancement is seen in the soft-tissue component of the tumor (arrow) than in the intraosseous region on both parametric images.

View larger version (25K): [in a new window]   Figure 4. Initial slope histograms normalized to the total number of tumor voxels for two responders to chemotherapy. The histogram distributions contain the slope values for each voxel in the tumor region of interest. Each distribution was fit with the function shown in Equation (3), and the amplitude, mean, and width were determined. The percentage necrosis was inversely proportional to the distribution width and mean. The amplitude of the distribution was directly proportional to the percentage necrosis.

View larger version (16K): [in a new window]   Figure 5a. (a) Correlation between histogram amplitude of the initial slope and pathologically determined necrotic fraction (n = 28). A cutoff value of 1.3 for the histogram amplitude was chosen directly from the receiver operating characteristic curve. (b) Correlation between the histogram amplitude of the model parameter Akep and the pathologically determined necrotic fraction (n = 29). A cutoff value of 2.3 for the histogram amplitude was chosen directly from the receiver operating characteristic curve.

View larger version (17K): [in a new window]   Figure 5b. (a) Correlation between histogram amplitude of the initial slope and pathologically determined necrotic fraction (n = 28). A cutoff value of 1.3 for the histogram amplitude was chosen directly from the receiver operating characteristic curve. (b) Correlation between the histogram amplitude of the model parameter Akep and the pathologically determined necrotic fraction (n = 29). A cutoff value of 2.3 for the histogram amplitude was chosen directly from the receiver operating characteristic curve.

View larger version (18K): [in a new window]   Figure 6. Receiver operating characteristic curves for initial slope and two-compartment model methods, showing areas under the curves of 86% and 91%, respectively.