We describe a standard set of quantity names and symbols related to the estimation of kinetic parameters from dynamic contrast-enhanced T 1 -weighted magnetic resonance imaging data, using diffusable agents such as gadopentetate dimeglumine (Gd-DTPA). These include a) the volume transfer constant K trans (min ؊1 ); b) the volume of extravascular extracellular space (EES) per unit volume of tissue v e (0 F v e F 1); and c) the flux rate constant between EES and plasma k ep (min ؊1 ). The rate constant is the ratio of the transfer constant to the EES (k ep ‫؍‬ K trans / v e ). Under flow-limited conditions K trans equals the blood plasma flow per unit volume of tissue; under permeability-limited conditions K trans equals the permeability surface area product per unit volume of tissue. We relate these quantities to previously published work from our groups; our future publications will refer to these standardized terms, and we propose that these be adopted as international standards.

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The purpose of this study was to quantify microcirculation and microvasculature in breast lesions by pharmacokinetic analysis of Gd-DTPA-enhanced MRI series. Strongly T 1 -weighted MR images were acquired in 18 patients with breast lesions using a saturation-recovery-TurboFLASH sequence. Concentrationtime courses were determined for blood, pectoral muscle, and breast masses and subsequently analyzed by a two-compartment model to estimate plasma flow and the capillary transfer coefficient per unit of plasma volume (F/V P , K PS /V P ) as well as fractional volumes of the plasma and interstitial space (f P , f I ). Breast cancer represents the most common malignancy in females, constituting a major health problem, particularly in developed countries. Conventional X-ray mammography, supplemented by sonography, has been proven to be the primary modality for breast imaging. However, despite the important role played by X-ray mammography as a diagnostic and screening tool, it suffers especially from a limited specificity and thus leads to unnecessary breast biopsies. Therefore, new noninvasive imaging strategies are required for discriminating between benign and malignant breast masses in women with equivocal findings in conventional breast imaging or women with breast implants, previous therapy, or predisposing mutations of tumor suppressor genes. Besides positron emission tomography (PET), dynamic contrast-enhanced MRI is the most promising approach providing information on tumor pathophysiology for improved diagnosis and management of breast lesions.As summarized in recent review articles on dynamic MR mammography (1-3), the kinetics of signal variation in breast lesions after injection of a paramagnetic contrast medium (CM) represents an important criterion for the detection and differentiation of suspicious breast masses. According to the analysis presented by Kuhl et al. (4), a persisting (accumulating) enhancement pattern or a washout phenomenon over a period of time of about 5-6 min after the initial perfusion phase is a strong indicator for benign and malignant lesions, respectively.Although the histopathological basis of the different enhancement patterns in breast masses is not yet fully understood, it is well known that angiogenesis, i.e., the formation of new vessels, is an important aspect (5,6). Microvessels in solid tumors exhibit a series of severe structural and functional abnormalities: They are often dilated, tortuous, elongated, and saccular and show an incomplete or even missing endothelial lining and an interrupted basement membrane. Moreover, there is an anarchic vascular organization of microvessels accompanied by significant arterio-venous shunt flow (6).To gain further insight into contrast enhancement in breast lesions and its histopathological basis, it is necessary to study tumor microvasculature and microcirculation in more detail in vivo. To this end, various MR studies were performed to quantify different aspects of contrast enhancement using either simple compartment models or princip...

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A dynamic contrast-enhanced MRI technique for whole breast examinations is presented. The fast kinetics of tissue response during and after constant-rate intravenous infusion of gadolinium diethylenetriaminopentaacetic acid was resolved using a strongly T1-weighted saturation recovery TurboFLASH sequence that makes it possible to acquire signal-time courses sequentially from 15 adjacent slices with a temporal sampling rate of 21 s. On the basis of the mathematically established and experimentally verified linear relationship between the measured saturation recovery TurboFLASH signal variation and the gadolinium diethylenetriaminopentaacetic acid concentration in the tissue, the signal-time courses were analyzed within the framework of pharmacokinetic modeling. In our study, the tissue response was parameterized adequately using an open linear two-compartment model. With this approach, the tissue specific information contained in the signal-time course can be described using only two parameters: an amplitude A, reflecting the degree of MR signal enhancement, and an exchange parameter k21, characterizing vascular permeability and perfusion of the tissue. A clearly arranged representation of the large amount of data (480 saturation recovery TurboFLASH breast images/examination) was accomplished by means of color coding of the computed parameters, resulting in one color-coded pharmacokinetic parameter map/cross-section.

The combination of target-specific drugs like bevacizumab with chemotherapeutics has improved treatment efficacy in advanced colorectal cancer (CRC). However, the clinical prognosis of metastatic CRCs is still poor, and novel drugs are currently assessed with respect to their efficacies in patients with CRCs. In a phase III study, the multikinase inhibitor regorafenib has recently been shown to prolong survival of patients with CRCs after standard therapies failed. In the present study, the activity of regorafenib was investigated in comparison with the angiogenesis inhibitor DC101 in the highly aggressive, murine CT26 metastatic colon cancer model. While a treatment for 10 days with DC101 given at a dose of 34 mg/kg every third day significantly delayed tumor growth compared with vehicle-treated animals, regorafenib completely suppressed tumor growth at a daily oral dose of 30 mg/kg. Regorafenib also induced a stronger reduction in tumor vascularization, as longitudinally assessed in vivo by dynamic contrast-enhanced MRI (DCE-MRI) and confirmed by immunohistochemistry. In addition, regorafenib inhibited the angiogenic activity more strongly and induced a three times higher apoptosis rate than DC101. Even more important, regorafenib completely prevented the formation of liver metastases, whereas in DC101-treated animals, the metastatic rate was only reduced by 33% compared with the vehicle group. In addition, regorafenib significantly reduced the amount of infiltrating macrophages. These data show that the multikinase inhibitor regorafenib exerts strong antiangiogenic, antitumorigenic, and even antimetastatic effects on highly aggressive colon carcinomas indicative for its high potential in the treatment of advanced CRCs.

Sequential computed tomographic scanning was performed in patients with neck tumors after contrast material administration. For data analysis, a pharmacokinetic two-compartment model was employed that takes into account both capillary blood supply and bidirectional diffusion of the contrast agent across the capillary wall. This approach offers the possibility to quantitatively characterize tissue microcirculation with regional blood flow, capillary permeability, and relative compartmental volumes.