Viktor Novikov

Tumor microvascular changes in antiangiogenic treatment: Assessment by magnetic resonance contrast media of different molecular weights

To test magnetic resonance (MR) contrast media of different molecular weights (MWs) for their potential to characterize noninvasively microvascular changes in an experimental tumor treatment model.

MRI monitoring of Avastin antiangiogenesis therapy using B22956/1, a new blood pool contrast agent, in an experimental model of human cancer.

To evaluate the diagnostic and prognostic potential of a new protein‐binding contrast medium, B22956/1, for quantitatively characterizing tumor microvessels by MRI and monitoring response to antiangiogenic therapy.

Tumor microvascular characterization using ultrasmall superparamagnetic iron oxide particles (USPIO) in an experimental breast cancer model

The diagnostic potential of ultrasmall superparamagnetic iron oxide particles (USPIO) for quantitative tumor microvessel characterization was assessed by kinetic analysis of dynamic magnetic resonance imaging (MRI) in a rodent breast cancer model. Microvascular characteristics (transendothelial permeability (KPS) and fractional plasma volume (fPV)) were estimated in 32 female Sprague Dawley rats, bearing breast tumors of varying malignancy. These values were compared to a prototype macromolecular contrast medium standard, albumin‐(GdDTPA)30. Transendothelial permeability (KPS) correlated significantly (P < 0.05) with the tumor grade (Scarff‐Bloom‐Richardson (SBR) score) for the USPIO (r = 0.36), as well as for the reference macromolecule, albumin‐(GdDTPA)30 (r = 0.54). Estimates for the fPV did not show a statistically significant correlation with the tumor grade for either contrast medium. In conclusion, USPIO‐enhanced MRI data were capable to characterize tumor microvessel properties in this breast cancer model: microvascular permeability (determined using USPIO) correlated significantly with tumor grade. Thus, quantitative estimation of microvascular characteristics in tumors could provide a surrogate of new vessel formation (angiogenesis) and thus a further important clinical indication for USPIO, in addition to MR angiography. J. Magn. Reson. Imaging 2001;13:882–888.

Assessment of a rapid clearance blood pool MR contrast medium (P792) for assays of microvascular characteristics in experimental breast tumors with correlations to histopathology

The diagnostic potential of a new rapid clearance blood pool contrast medium (P792; MW = 6.47 kDa) for the MR assessment of microvessel characteristics was assessed in 42 chemically‐induced breast tumors, with comparisons to albumin‐(Gd‐DTPA). Microvessel characteristics, including the transendothelial permeability (KPS) and the fractional blood volume (fPV), were estimated by using dynamic MR data fit to a bidirectional two‐compartment model. The MR‐derived estimates for KPS and fPV using each contrast agent were compared, and assays using each contrast agent were correlated to the histologic tumor grade (SBR score) and the microvascular density (MVD) counts. Using P792‐enhanced data, neither KPS nor fPV showed a statistically significant correlation with the tumor grade or the MVD (P > .05). Conversely, using albumin‐(GdDTPA)30, KPS values correlated significantly with the histologic tumor grade (r = .55; P < .0005) and the MVD (r = .34, P < .05), whereas no correlation was established for fPV. In conclusion, based on P792 data no correlation between tumor microvascular characteristics and histologic markers (SBR score or MVD) was found in this breast tumor model. Our analysis suggests that contrast media of relatively large (on the order of 90 kDa) molecular size, such as albumin‐(GdDTPA)30, are more accurate for the characterization of tumor microvessels. Magn Reson Med 45:880–886, 2001.

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.

Contrast Enhanced MRI of Stunned Myocardium Using Mn-Based MRI Contrast Media

Manganese ions are taken up by myocytes through voltage operated calcium channels (1). Once inside myocytes, manganese ions are retained for several days (2). Previous magnetic resonance studies showed that myocardial uptake of manganese in normal rat heart is attenuated by calcium channel blockers (3). Furthermore, infarcted myocardium is delineated on MR images following addition of either manganese ions (4) or MnDPDP (5), because manganese ion is not retained in the infarcted region. These studies did not evaluate manganese distribution in ischemically injured but viable myocardium. The current study was conducted to determine whether stunned myocardium can be delineated as a contrast defect by differential uptake of manganese ions. Since calcium channels are intimately associated with intracellular calcium release and thereby with contractile response, an abnormal manganese uptake is plausible. There is currently no published method whereby dysfunctional myocardium is defined as a contrast enhanced zone, instead contractile dysfunction is evaluated from differences in ventricular wall thickness at systole and diastole, or by MRI tagging.