Bjørn A. Graff

Assessment of tumor blood perfusion by high-resolution dynamic contrast-enhanced MRI: A preclinical study of human melanoma xenografts

A noninvasive method to obtain high‐resolution images of tumor blood perfusion is needed for individualized cancer treatments. In this study we investigated the potential usefulness of dynamic contrast‐enhanced MRI (DCE‐MRI), using human melanoma xenografts as models of human cancer. Gadopentetate dimeglumine (Gd‐DTPA) was used as the contrast agent, and DCE‐MRI was performed at a voxel size of 0.5 × 0.2 × 2.0 mm3 with spoiled gradient‐recalled sequences. We obtained images of E · F (where E is the extraction fraction, and F is perfusion) by subjecting DCE‐MR images to Kety analysis. We obtained highly reproducible E · F images, which we verified by imaging heterogeneous tumors twice. We hypothesized that the extraction fraction of Gd‐DTPA would be high and would not vary significantly in tumor tissue, implying that E · F should be a well‐suited parameter for describing tumor blood perfusion. Observations consistent with this hypothesis were made by comparison of E · F‐images with immunostained histological preparations from the imaged sections. The E · F images mirrored the histological appearance of the tumor tissue perfectly. Quantitative studies showed that E · F was highest in nonhypoxic tissue with high microvascular density, second highest in nonhypoxic tissue with low microvascular density, third highest in hypoxic tissue, and lowest in necrotic tissue. Moreover, the radial heterogeneity in E · F was almost identical to that in the blood supply, as assessed by the use of Na99mTcO4 as a perfusion tracer. Taken together, our observations show that high‐resolution images reflecting tumor blood perfusion can be obtained by DCE‐MRI. Magn Reson Med 52:269–276, 2004.

Comparison of tumor blood perfusion assessed by dynamic contrast-enhanced MRI with tumor blood supply assessed by invasive imaging

To evaluate the potential of Gd‐DTPA‐based dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) for providing high‐resolution tumor blood perfusion images.

Intratumor heterogeneity in blood perfusion in orthotopic human melanoma xenografts assessed by dynamic contrast-enhanced magnetic resonance imaging

To determine the intratumor heterogeneity in blood perfusion of orthotopic human melanoma xenografts by use of gadopentetate dimeglumine (Gd‐DTPA)‐based dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI).

Quantitative assessment of uptake and distribution of iron oxide particles (NC100150) in human melanoma xenografts by contrast-enhanced MRI

The intratumor heterogeneity in uptake of iron oxide particles (NC100150) in human melanoma xenografts was studied by MRI and the uptake was related to the blood volume fraction, BV, and the permeability surface area product, PS, in an attempt to identify transport barriers limiting the delivery of large macromolecular therapeutic agents to tumors. Dynamic MRI was performed by using spoiled gradient recalled sequences and the extravascular uptake of NC100150, BV, and PS were calculated for each tumor voxel by using a two‐compartment tissue model. The uptake of NC100150 and BV were low in the tumor center and increased gradually towards the tumor periphery, whereas there was no radial gradient in PS. Significant correlations were found between the voxel values of the parameters. Thus, PS was inversely correlated to BV, and this correlation was stronger in the center than in the periphery of the tumors. The uptake of NC100150 was positively correlated to PS and this correlation was strong in the tumor periphery, where the blood perfusion is high, and weak in the tumor center, where the blood perfusion is low. In contrast, the uptake of NC100150 was not correlated to BV in any tumor region. These observations suggest that the extravascular uptake of NC100150 was limited primarily by the microvascular permeability in the tumor periphery and primarily by the blood perfusion in the tumor center. Magn Reson Med 51:727–735, 2004.

Analysis of diffusion tensor imaging metrics for gliomas grading at 3 T

OBJECTIVES To assess the diagnostic accuracy of axial diffusivity (AD), radial diffusivity (RD), apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values derived from DTI for grading of glial tumors, and to estimate the correlation between DTI parameters and tumor grades. METHODS Seventy-eight patients with glial tumors underwent DTI. AD, RD, ADC and FA values of tumor, peritumoral edema and contralateral normal-appearing white matter (NAWM) and AD, RD, ADC and FA ratios: lowest average AD, RD, ADC and FA values in tumor or peritumoral edema to AD, RD, ADC and FA of NAWM were calculated. DTI parameters and tumor grades were analyzed statistically and with Pearson correlation. Receiver operating characteristic (ROC) curve analysis was also performed. RESULTS The differences in ADC, AD and RD tumor values, and ADC and RD tumor ratios were statistically significant between grades II and III, grades II and IV, and between grades II and III-IV. The AD tumor ratio differed significantly among all tumor grades. Tumor ADC, AD, RD and glial tumor grades were strongly correlated. In the ROC curve analysis, the area under the curve (AUC) of the parameter tumor ADC was the largest for distinguishing grade II from grades III to IV (98.5%), grade II from grade IV (98.9%) and grade II from grade III (97.0%). CONCLUSION ADC, RD and AD are useful DTI parameters for differentiation between low- and high-grade gliomas with a diagnostic accuracy of more than 90%. Our study revealed a good inverse correlation between ADC, RD, AD and WHO grades II-IV astrocytic tumors.

Enhancement characteristics of lymphomatous lymph nodes of the neck

Background: Previous studies of computed tomography (CT) enhancement of lymphomatous lymph nodes suggest that these nodes might have lower post contrast attenuation values than normal lymph nodes. We have previously found that the contrast medium enhancement curves of lymphomatous lymph nodes of the neck had significantly lower enhancement than those of presumably normal lymph nodes. Purpose: To prospectively compare CT contrast medium enhancement curves of a homogeneous population of 28 patients with lymphomatous lymph nodes of the neck with 20 controls; to compare enhancement curves before and after successful treatment and to compare nodes with Hodgkin lymphoma (HL) and nodes with non-Hodgkin lymphoma (NHL). Material and Methods: Twenty-eight consecutive patients (12 with HL) with lymphomatous lymph nodes of the neck and 20 control patients with sarcomas and presumably normal neck nodes underwent dynamic CT examinations. Seventeen of the patients in complete remission after lymphoma treatment were also examined. Results: The lymphomatous lymph nodes had significantly lower mean enhancement values than those of the control group (mean HU value at 90 s 77.9±10.5 HU and 93.4±15.3 HU, respectively, sensitivity 91% for values <92 HU at 90 s). Late enhancement values in the treated patients were significantly higher than those in the untreated patients. Patients with HL and patients with NHL had similar enhancement curves except that those with NHL had higher values at 7 min. No significant difference in mean percentage loss of enhancement was found between normal nodes and lymph nodes with HL before treatment, but there was a slightly significant difference between normal nodes and lymph nodes with NHL. No significant difference in percentage loss of enhancement was found between normal nodes and lymphomatous lymph nodes after treatment. Conclusion: Dynamic CT examinations showed that lymphomatous lymph nodes had significantly lower mean enhancement values than those of the control group and confirmed the findings from a pilot study. Before treatment the mean enhancement values of HL were significantly higher than those of NHL at 7 min. There was no significant difference between the curves after treatment.

Enhancement characteristics of lymphomatous lymph nodes of the mediastinum.

Background Previous studies of CT enhancement of lymphomatous lymph nodes (LLN) of the neck showed that the LLN had lower enhancement values than normal lymph nodes. Purpose To elucidate the contrast medium enhancement curves of LLN in the mediastinum by comparing the curves of LLN with those of normal lymph nodes, and to compare the present enhancement curves of LLN of the mediastinum with the curves of LLN of the neck from a previous similar investigation. Material and Methods Twenty-four consecutive patients with LLN in the mediastinum (9 with Hodgkins lymphoma [HL]) and 23 control patients with sarcomas and thus presumably normal mediastinal nodes underwent dynamic CT examinations. The previous, similar investigation of lymph nodes of the neck comprised 28 patients with LLN and 20 control patients. Results The enhancement curves of the mediastinal LLN had significantly lower values than those of the mediastinal control nodes. The LLN of the mediastinum had lower mean peak contrast values than the corresponding nodes of the neck from a previous investigation. Conclusion The comparison of enhancement curves of mediastinal LLN with mediastinal control nodes showed a marked similarity with and substantiates our previous findings in lymph nodes of the neck.

Enhancement characteristics of retroperitoneal lymphomatous lymph nodes

Background Previous studies of CT enhancement of lymphomatous lymph nodes (LLN) of the neck and the mediastinum showed that the LLN had lower enhancement values than normal lymph nodes. Purpose To elucidate the contrast medium enhancement curves of LLN in the retroperitoneum by comparing the curves of LLN with those of normal lymph nodes, to test whether differences between these curves could be of diagnostic value, and to compare the present enhancement curves of LLN of the retroperitoneum with the curves of LLN of the neck and the mediastinum from previous similar investigations. Material and Methods Twenty-eight consecutive patients with LLN of the retroperitoneum (three with Hodgkins lymphoma [HL]) and 21 control patients with sarcomas and thus presumably normal retroperitoneal nodes underwent dynamic CT examinations. The previous, similar investigation of lymph nodes of the neck comprised 28 patients with LLN and the investigation of mediastinal lymph nodes comprised 24 patients with LLN. Results The enhancement curves of the retroperitoneal LLN had significantly lower attenuation than those of the retroperitoneal control nodes. A combination of peak contrast value and time to peak adjusted to total body weight yielded a diagnostic accuracy which at the best showed a sensitivity of 90.5% with a specificity of 82.6%. The LLN of the retroperitoneum had higher attenuation values than corresponding nodes of the mediastinum but no significant difference was found between LLN of the retroperitoneum and LLN of the neck in previous similar investigations. Conclusion The comparison of enhancement curves of retroperitoneal LLN with retroperitoneal control nodes showed a marked similarity with and substantiates our previous findings in lymph nodes of the neck and of the mediastinum. The best diagnostic accuracy was achieved by combining the parameters peak contrast value and time to peak and adjusting these values to the body weight. Peak enhancement of the retroperitoneal LLN was higher and arrived earlier than that of the mediastinal nodes from the previous investigation.