Heike Daldrup

Correlation of dynamic contrast-enhanced magnetic resonance imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media

Background. The endothelial integrity of microvessels is disrupted in malignant tumors. Quantitative assays of tumor microvascular characteristics based on dynamic magnetic resonance imaging (MRI) were correlated with histopathologic grade in mammary soft tissue tumors. Materials and methods. A spectrum of tumors, benign through highly malignant, was induced in 33 female rats by administration of N -ethyl-N -nitrosourea (ENU), a potent carcinogen. Dynamic contrast-enhanced MRI was performed using a small-molecular contrast medium [gadopentetate, MW = 0.5 kDa] and a macromolecular contrast medium [albumin-(Gd-DTPA)30, MW = 92 kDa] at an interval of 1–2 days. Permeability surface area product (PS), as estimated by the corresponding endothelial transfer coefficient (KPS), and fractional plasma volume (fPV) were calculated for each tumor and each contrast agent using a two-compartment bi-directional kinetic model. MRI microvascular characteristics were correlated with histopathologic tumor grade. Results. Tumor permeability to macromolecular contrast medium, characterized by KPS, showed a highly positive correlation with tumor grade (r2 = 0.76, P < 10− 10). KPS values were zero for all benign and some low-grade carcinomas, greater than zero in all other carcinomas, and increased in magnitude with higher tumor grade. A considerably smaller but significantly positive correlation was found between fPV and tumor grade using macromolecular contrast medium (r2 = 0.25, P < 0.003). No correlation between KPS or fPV values and tumor grade was found using gadopentetate (r2 = 0.01, P > 0.95 and r2 = 0.03, P > 0.15, respectively). Conclusion. Quantitative tumor microvascular permeability assays generated with macromolecular MRI contrast medium correlate closely with histologic tumor grade. No significant correlation is found using small-molecular gadopentetate.

High resolution MRI of small joints : Impact of spatial resolution on diagnostic performance and SNR

This study focuses on the spatial resolution required for cartilage imaging. The purposes of this study were (I) to analyze the diagnostic performance in diagnosing artificially produced cartilage lesions in a small joint model using an optimized fat saturated three-dimensional gradient-echo sequence, (II) to relate the lesion size and depth as diagnosed in the magnetic resonance images with the corresponding pathologic findings and (III) to assess signal-to-noise (SNR) ratios for each of the protocols. Twenty-five artificial cartilage lesions were created in the knee joints of 10 rabbits. These specimens and seven specimens without lesions were imaged at 1.5 T using a three-dimensional gradient-echo sequence with varying slice thickness, field of view and matrix. A total of 404 corresponding images were selected, 50% with and 50% without cartilage lesions. Six radiologists scored all images according to five levels of confidence and receiver operating characteristic (ROC) analysis was performed. Lesion size and depth were compared to the corresponding pathological specimen sections. Additionally SNR ratios were calculated. ROC analysis of pooled data from all readers showed the highest area under the ROC curve for the sequence with the highest spatial resolution, while the diagnostic performance was significantly lower in the other sequences (p <0.01). Assessment of the lesion size and depth was correct in 45% and 40% respectively with the highest resolution and in 29% and 23% with the lowest resolution. SNR ratios decreased with increasing spatial resolution. In conclusion this study shows that increasing spatial resolution improves diagnostic performance in cartilage lesions, though SNR decreases substantially. Assessment of correct lesion size and depth still is limited.

Quantitative gadopentetate-enhanced MRI of breast tumors: Testing of different analytic methods

This study assessed several proposed imaging strategies and analytic methods based on gadopentetate‐enhanced MRI to differentiate benign from malignant breast tumors in a blinded experimental animal study. Steady‐state dynamic MRI and first‐pass imaging, performed with either T1‐ or T*2‐ weighted sequences, were compared. Semiquantitative and quantitative analysis methods, based on empirical measures of the data or physiological models, were subsequently applied to the imaging datasets. Comparative measures provided pathologic distinction of benign from malignant tumors, tumor grading, and histologic determination of microvascular density. Of the eight tested methods, only one, an estimate of first‐pass perfusion using T *2‐weighted imaging, showed an almost significant (P = 0.05) difference between benign and malignant tumors and correlated almost significantly (r = .3, P = 0.06) with the tumor grade. All other tests, performed either with steady‐state imaging or with T1‐weighted first‐pass imaging, failed to differentiate benign from malignant tumors. In addition, they yielded poor correlations with tumor grade and microvascular density. Magn Reson Med 44:915–924, 2000.

The choice of region of interest measures in contrast-enhanced magnetic resonance image characterization of experimental breast tumors

Objectives:The objectives of this study were to determine if magnetic resonance (MR) estimates of quantitative tissue microvascular characteristics from regions of interest (ROI) limited to the tumor periphery provided a better correlation with tumor histologic grade than ROI defined for the whole tumor in cross-section. Methods:A metaanalysis was based on 98 quantitative MR image breast tumor characterizations acquired in 3 separate experimental studies using identical methods for tumor induction and contrast enhancement. Results:The endothelial transfer coefficient (KPS) of albumin (Gd-DTPA)30 from the tumor periphery correlated (r = 0.784) significantly more strongly (P < 0.001) with the pathologic tumor grade than KPS derived from the whole tumor (r = 0.604). KPS estimates, either from the tumor periphery or from the whole tumor, correlated significantly more strongly with histologic grade (P < 0.01) than MR image estimates of fractional plasma volume (fPV) from either tumor periphery (r = 0.368) or whole tumor (r = 0.323). Conclusions:KPS estimates from the tumor periphery were the best of these measurable MR image microvascular characteristics for predicting the histologic grade.

Macromolecular contrast media. A new approach for characterising breast tumors with MR-mammography

SummeryThe value of macromolecular contrast agents (MMCM) for the characterization of benign and malignant breast tumors will be demonstrated in this review. Animal studies suggest a high potential of MMCM to increase the specificity of MR-mammography. The concept of tumor differentiation is based on the pathological hyperpermeability of microvessels in malignant tumors. MMCM show a leak into the interstitium of carcinomas, whereas they are confined to the intravascular space in benign tumors. Capabilities and limitations of the MMCM-prototype. Albumin-Gd-DTPA, for breast tumor characterization will be summarized and compared to the standard low molecular weight contrast agent Gd-DTPA. Initial experience with new MMCM, such as Dendrimers, Gd-DTPA-Polylysine and MS-325 will be outlined. The potential of “blood-pool“-iron oxides, such as AMI-227 for the evaluation of tumor microvascular permeabilities will be discussed.ZusammenfassungDiese Übersicht stellt den Stellenwert makromolekularer Kontrastmittel (MMKM) für die MR-tomographische Charakterisierung von benignen und malignen Mammatumoren dar. Aufgrund experimenteller Studien lassen MMKM eine signifikante Verbesserung der Spezifität der dynamischen kontrastmittelunterstützten MR-Mammographie erwarten. Das differentialdiagnostische Konzept beruht auf der pathologischen Hyperpermeabilität von Kapillaren in Karzinomen, die einen MMKM-Austritt in das Tumorinterstitium bedingt, während die intakten Kapillaren benigner Tumoren nicht permeabel für MMKM sind. Diagnostische Möglichkeiten und Grenzen des MMKM-Prototyps, Albumin-Gd-DTPA (92 kD), werden dargestellt und mit dem niedermolekularen Standard-Kontrastmittel Gd-DTPA (500 D) verglichen. Erste Erfahrungen mit neuen, für die klinische Anwendung optimierten MMKM-Präparaten, wie das Kaskadenpolymer, Gd-DTPA-Polylysine und das MS-325 werden vorgestellt. Das Potential von Blood-pool-Eisenoxidpräparaten, z. B. AMI-227, für die Bestimmung von Tumorkapillarpermeabilitäten wird diskutiert.