ABSTRACT: 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 T(1)- 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 T(1)-weighted first-pass imaging, failed to differentiate benign from malignant tumors. In addition, they yielded poor correlations with tumor grade and microvascular density.
Magnetic Resonance in Medicine 01/2001; 44(6):915-24. · 2.96 Impact Factor
ABSTRACT: This study compared gadopentetate dimeglumine (molecular weight, 0.5 kD), a standard contrast medium, and Gadomer-17 (apparent molecular weight, approximately 35 kD), a new, clinically applicable, large-molecular contrast medium, with respect to their microvascular characterizations of experimentally induced breast tumors at magnetic resonance (MR) imaging.
A spectrum of breast tumors, benign through highly malignant, was induced in Sprague-Dawley rats (n = 30) by intraperitoneal administration of N-ethyl-N-nitrosourea (ENU), a potent carcinogen. All animals underwent three-dimensional spoiled gradient-recalled MR imaging, with precontrast imaging and dynamic postcontrast imaging after injection of gadopentetate dimeglumine (0.1 mmol/kg) and Gadomer-17 (0.03 mmol/kg), administered in a random order at a 24-hour interval. Several microvascular parameters were compared: the endothelial transfer coefficient (K(PS)), a measure of microvascular permeability; the fractional plasma volume (fPV), and the plasma equivalent volume. Each MR imaging parameter was correlated with histopathologic findings.
With Gadomer-17, the mean values for K(PS) and fPV were significantly greater in carcinomas than in fibroadenomas (P < .004 and .04, respectively). With gadopentetate dimeglumine, the mean values for fPV and PEV were significantly greater in carcinomas (P <. 004 and .02, respectively). Because of the high variability within both fibroadenoma and carcinoma groups, however, there were no significant correlations between K(PS), fPV, or PEV and histopathologic tumor grade as indicated by the Scarff-Bloom-Richardson score, for either agent.
Although the K(PS) and fPV estimates obtained from dynamic MR imaging data with Gadomer-17 enhancement offer some potential for characterizing breast tumors, none of the quantitative microvascular parameters derived with either agent were significantly correlated with histopathologic tumor grade.
Academic Radiology 11/2000; 7(11):934-44. · 1.69 Impact Factor
ABSTRACT: Magnetic resonance imaging enhanced with macromolecular contrast medium was used to monitor effects of angiogenesis inhibition on tumor microvascular permeability and ascites volume in an athymic rat model of human ovarian cancer.
Groups of 6 athymic rats implanted intraperitoneally with SKOV-3, a human ovarian cancer cell line, were treated through a 14-day course with antibody to vascular endothelial growth factor or with saline solution for control animals. Dynamic magnetic resonance imaging was performed with a 92,000-d contrast agent, albumin-(gadolinium-diethylenetriaminepentaacetic acid)(30). Vascular permeability was estimated from dynamic enhancement data that were analyzed with a unidirectional 2-compartment kinetic model.
Animals treated with vascular endothelial growth factor antibody accumulated significantly smaller volumes of peritoneal ascites (P <.05) and showed significantly lower magnetic resonance imaging-assayed tumor microvascular permeabilities (P <.05) than did control animals.
Magnetic resonance imaging enhanced with a macromolecular contrast agent in an athymic rat model of human ovarian cancer treated with anti-vascular endothelial growth factor antibody can be used to measure a reduction in tumor microvascular permeability, corresponding to a reduction in ascites production.
American Journal of Obstetrics and Gynecology 10/2000; 183(4):956-63. · 3.47 Impact Factor
ABSTRACT: To differentiate prostate cancers of different histopathologic grades with dynamic gadolinium-enhanced magnetic resonance (MR) imaging. Results with a conventional small-molecular contrast medium (CM) were compared to those with a prototypic macromolecular CM.
High- and low-grade tumors, sublines of the Dunning R3327 rat prostate cancer line, were subcutaneously implanted into the flanks of 12 male Copenhagen rats. Dynamic contrast material-enhanced MR imaging was performed with small-molecular CM and macromolecular CM at an interval of 1 day. Microvascular permeability, as estimated with the endothelial transfer coefficient, and fractional plasma volume were calculated for each tumor and each CM by means of a two-compartmental, bidirectional kinetic model.
Mean endothelial transfer coefficient values for both macromolecular CM and small-molecular CM were significantly different between the two tumor sublines (P = .0004 and P = .01, respectively). For the high- and low-grade tumors, no overlap of values was seen with macromolecular CM, but a broad overlap was seen with small-molecular CM despite a significant difference in mean values.
Dynamic contrast-enhanced MR imaging permits differentiation of histopathologic prostatic tumor types. Quantitative microvascular permeability characteristics estimated from macromolecular CM-enhanced data were significantly superior to those derived from small-molecular CM-enhanced data.
Radiology 11/1999; 213(1):265-72. · 5.73 Impact Factor
ABSTRACT: The 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.
Der Radiologe 10/1997; 37(9):733-40. · 0.61 Impact Factor
ABSTRACT: The 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.
Diese 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.
Der Radiologe 04/1997; 37(9):733-740. · 0.61 Impact Factor