Pharmacokinetic analysis of glioma compartments with dynamic Gd-DTPA-enhanced magnetic resonance imaging

Dynamic contrast-enhanced magnetic resonance imaging (MRI) is widely used for measuring perfusion and blood volume, especially cerebral blood volume (CBV). In case of blood-brain barrier (BBB) disruption, the conventional techniques only partially determine the pharmacokinetic parameters of contrast medium (CM) exchange between different compartments. Here a modified pharmacokinetic model is applied, which is based on the bidirectional CM exchange between blood and two interstitial compartments in terms of the fractional volumes of the compartments and the vessel permeabilities between them. The evaluation technique using this model allows one to quantify the fractional volumes of the different compartments (blood, cells, slowly and fast enhancing interstitium) as well as the vessel permeabilities and cerebral blood flow (CBF) with a single T1-weighted dynamic MRI measurement. The method has been successfully applied in 25 glioma patients for generating maps of all of these parameters. The fractional volume maps allow for the differentiation of glioma vascularization types. The maps show a good correlation with the histological grading of these tumors. Furthermore, regions with enhanced interstitial volumes are found in high-grade gliomas. Differences in permeability maps of Gd-DTPA apart from BBB disruption do not exist between different tissue types. CBF measured in high-grade glioma is less pronounced than it would be expected from their blood volume. Therefore pharmacokinetic imaging provides an additional tool for glioma characterization.     

Comparison of dual-echo DSC-MRI- and DCE-MRI-derived contrast agent kinetic parameters

The application of dynamic susceptibility contrast (DSC) MRI methods to assess brain tumors is often confounded by the extravasation of contrast agent (CA). Disruption of the blood-brain barrier allows CA to leak out of the vasculature leading to additional T(1), T(2) and T(2) relaxation effects in the extravascular space, thereby affecting the signal intensity time course in a complex manner. The goal of this study was to validate a dual-echo DSC-MRI approach that separates and quantifies the T(1) and T(2) contributions to the acquired signal and enables the estimation of the volume transfer constant, K(trans), and the volume fraction of the extravascular extracellular space, v(e). To test the validity of this approach, DSC-MRI- and dynamic contrast enhanced (DCE) MRI-derived K(trans) and v(e) estimates were spatially compared in both 9L and C6 rat brain tumor models. A high degree of correlation (concordance correlation coefficients >0.83, Pearson's r>0.84) and agreement was found between the DSC-MRI- and DCE-MRI-derived measurements. These results indicate that dual-echo DSC-MRI can be used to simultaneously extract reliable DCE-MRI kinetic parameters in brain tumors in addition to conventional blood volume and blood flow metrics.     

Investigating brain tumor differentiation with diffusion and perfusion metrics at 3T MRI using pattern recognition techniques

The aim of this study was to evaluate the contribution of diffusion and perfusion MR metrics in the discrimination of intracranial brain lesions at 3T MRI, and to investigate the potential diagnostic and predictive value that pattern recognition techniques may provide in tumor characterization using these metrics as classification features. Conventional MRI, diffusion weighted imaging (DWI), diffusion tensor imaging (DTI) and dynamic-susceptibility contrast imaging (DSCI) were performed on 115 patients with newly diagnosed intracranial tumors (low-and- high grade gliomas, meningiomas, solitary metastases). The Mann–Whitney U test was employed in order to identify statistical differences of the diffusion and perfusion parameters for different tumor comparisons in the intra-and peritumoral region. To assess the diagnostic contribution of these parameters, two different methods were used; the commonly used receiver operating characteristic (ROC) analysis and the more sophisticated SVM classification, and accuracy, sensitivity and specificity levels were obtained for both cases. The combination of all metrics provided the optimum diagnostic outcome. The highest predictive outcome was obtained using the SVM classification, although ROC analysis yielded high accuracies as well. It is evident that DWI/DTI and DSCI are useful techniques for tumor grading. Nevertheless, cellularity and vascularity are factors closely correlated in a non-linear way and thus difficult to evaluate and interpret through conventional methods of analysis. Hence, the combination of diffusion and perfusion metrics into a sophisticated classification scheme may provide the optimum diagnostic outcome. In conclusion, machine learning techniques may be used as an adjunctive diagnostic tool, which can be implemented into the clinical routine to optimize decision making.     

Quantitative assessment of intracranial tumor response to dexamethasone using diffusion, perfusion and permeability magnetic resonance imaging

There is increasing interest in obtaining quantitative imaging parameters to aid in the assessment of tumor responses to treatment. In this study, the feasibility of performing integrated diffusion, perfusion and permeability magnetic resonance imaging (MRI) for characterizing responses to dexamethasone in intracranial tumors was assessed. Eight patients with glioblastoma, five with meningioma and three with metastatic carcinoma underwent MRI prior to and 48-72 h following dexamethasone administration. The MRI protocol enabled quantification of the volume transfer constant (K(trans)), extracellular space volume fraction (nu(e)), plasma volume fraction (nu(p)), regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), longitudinal relaxation time (T(1)) and mean diffusivity (D(av)). All subjects successfully completed the imaging protocol for the presteroid and poststeroid scans. Significant reductions were observed after the treatment for K(trans), nu(e) and nu(p) in enhancing tumor as well as for T(1) and D(av) in the edematous brain in glioblastoma; on the other hand, for meningioma, significant differences were seen only in edematous brain T(1) and D(av). No significant difference was observed for any parameter in metastatic carcinoma, most likely due to the small sample size. In addition, no significant difference was observed for enhancing tumor rCBF and rCBV in any of the tumor types, although the general trend was for rCBV to be reduced and for rCBF to be more variable. The yielded parameters provide a wealth of physiologic information and contribute to the understanding of dexamethasone actions on different types of intracranial tumors.     

Effect of magnetic field gradients induced by microvasculature on NMR measurements of molecular self-diffusion in biological tissues

Presence of induced mesoscopic gradients of magnetic field in magnetically heterogeneous samples affects the measured value of apparent diffusion coefficient. This effect is investigated theoretically in the context of diffusion measurements in perfused biological tissues with blood as the paramagnetic compartment. It is shown that the apparent diffusion coefficient is sensitive to mutual correlations in vessel positions. Neglect of these correlations results in a failure of the commonly used model of microvasculature in which vessels are described as independently placed cylinders. The model is modified to account for intervessel correlations. The results indicate an underestimation of apparent diffusion coefficient in proportion to the magnetic susceptibility of intravascular compartment in agreement with published experimental data. The proportionality coefficient depends on the microvascular architecture. Comparison with experimental data yields a numerical value for a new model parameter that characterises the correlation in mutual positions of blood vessels.     

Conventional MR imaging with simultaneous measurements of cerebral blood volume and vascular permeability in ganglioglioma

The conventional MR imaging appearance of gangliogliomas is often variable and nonspecific. Conventional MR images, relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) measurements were reviewed in 20 patients with pathologically proven grade 1 and 2 gangliogliomas (n = 20) and compared to a group of grade 2 low-grade gliomas (n = 30). The conventional MRI findings demonstrated an average lesion size of 4.1 cm, contrast enhancement (n = 19), variable degree of edema, variable mass effect, necrosis/cystic areas (n = 8), well defined (n = 12), signal heterogeneity (n = 9), calcification (n = 4). The mean rCBV was 3.66 +/- 2.20 (mean +/- std) for grade 1 and 2 gangliogliomas. The mean rCBV in a comparative group of low-grade gliomas (n = 30), was 2.14 +/- 1.67. p Value < 0.05 compared with grade 1 and 2 ganglioglioma. The mean K(trans) was 0.0018 +/- 0.0035. The mean K(trans) in a comparative group of low-grade gliomas (n = 30), was 0.0005 +/- 0.001. p Value = 0.14 compared with grade 1 and 2 ganglioglioma. The rCBV measurements of grade 1 and 2 gangliogliomas are elevated compared with other low-grade gliomas. The K(trans), however, did not demonstrate a significant difference. Gangliogliomas demonstrate higher cerebral blood volume compared with other low-grade gliomas, but the degree of vascular permeability in gangliogliomas is similar to other low-grade gliomas. Higher cerebral blood volume measurements can help differentiate gangliogliomas from other low-grade gliomas.     

Macroscopic tumor volume of malignant glioma determined by contrast-enhanced magnetic resonance imaging with and without magnetization transfer contrast

The purposes of this study were to compare the conspicuity and lesion volume of contrast-enhancing macroscopic malignant glioma determined by postcontrast magnetic resonance (MR) imaging with and without magnetization transfer (MT) saturation, and to discuss possible implications for radiotherapy planning. Nineteen patients (age 24–60 years) with histologically proven malignant glioma were prospectively examined by MR imaging. After the administration of gadolinium dimeglumine (0.1 mmol/kg body weight), the lesions were imaged with an MT-weighted FLASH (fast, low-angle shot) pulse sequence and with a conventional T₁-weighted spin-echo (SE) sequence without MT saturation. The mean tumor volumes of gliomas measured on MT-weighted FLASH images were significantly (p < .01) larger than those obtained from T₁-weighted SE images (45 ± 15 cm³ vs. 33 ± 10 cm³). The mean contrast-to-noise ratio of enhancing lesions on MT-weighted FLASH was 48 ± 14 compared with 30 ± 14 on SE images, representing a significant (p < .01) improvement. We conclude that the volume of contrast enhancement of malignant glioma identified on MT-weighted FLASH images represents the area of disrupted blood-brain barrier. If this volume of subtle contrast enhancement is caused by tumor infiltration and represents the boost target volume for stereotactic radiosurgery or brachytherapy, MT-weighted FLASH images would be better than T₁-weighted SE images to define these volumes. These improved delineation of areas at highest risk for recurrence following radiation therapy should enhance the efficacy of treatment planning for high-boost therapy.     

Magnetic resonance imaging measurements of vascular permeability and extracellular volume fraction of breast tumors by dynamic Gd-DTPA-enhanced relaxometry

Vascular permeability (k(ep), min(-1)) and extracellular volume fraction (v(e)) are tissue parameters of great interest to characterize malignant tumor lesions. Indeed, it is well known that tumors with high blood supply better respond to therapy than poorly vascularized tumors, and tumors with large extracellular volume tend to be more malignant than tumors showing lower extracellular volume. Furthermore, the transport of therapeutic agents depends on both extracellular volume fraction and vessel permeability. Thus, before treatment, these tissue parameters may prove useful to evaluate tumor aggressiveness and to predict responsiveness to therapy and variations during cytotoxic therapies could allow to assess treatment efficacy and early modified therapy schedules in case of poor responsiveness. As a consequence, there is a need to develop methods that could be routinely used to determine these tissue parameters. In this work, blood-tissue permeability and extracellular volume fraction information were derived from magnetic resonance imaging dynamic longitudinal relaxation rate (R(1)) mapping obtained after an intravenous bolus injection of Gd-DTPA in a group of 92 female patients with breast lesions, 68 of these being histologically proven to be with carcinoma. For the sake of comparison, 24 benign lesions were studied. The measurement protocol based on two-dimensional gradient echo sequences and a monoexponential plasma kinetic model was that validated in the occasion of previous animal experiments. As a consequence of neoangiogenesis, results showed a higher permeability in malignant than in benign lesions, whereas the extracellular volume fraction value did not allow any discrimination between benign and malignant lesions. The method, which can be easily implemented whatever the imaging system used, could advantageously be used to quantify lesion parameters (k(ep) and v(e)) in routine clinical imaging. Because of its large reproducibility, the method could be useful for intersite comparisons and follow-up studies.     

Complimentary aspects of diffusion imaging and fMRI: II. Elucidating contributions to the fMRI signal with diffusion sensitization

Tissue water molecules reside in different biophysical compartments. For example, water molecules in the vasculature reside for variable periods of time within arteries, arterioles, capillaries, venuoles and veins, and may be within blood cells or blood plasma. Water molecules outside of the vasculature, in the extravascular space, reside, for a time, either within cells or within the interstitial space between cells. Within these different compartments, different types of microscopic motion that water molecules may experience have been identified and discussed. These range from Brownian diffusion to more coherent flow over the time scales relevant to functional magnetic resonance imaging (fMRI) experiments, on the order of several 10s of milliseconds. How these different types of motion are reflected in magnetic resonance imaging (MRI) methods developed for "diffusion" imaging studies has been an ongoing and active area of research. Here we briefly review the ideas that have developed regarding these motions within the context of modern "diffusion" imaging techniques and, in particular, how they have been accessed in attempts to further our understanding of the various contributions to the fMRI signal changes sought in studies of human brain activation.     

Assessment of a combined spin- and gradient-echo (SAGE) DSC-MRI method for preclinical neuroimaging

The goal of this study was to optimize and validate a combined spin- and gradient-echo (SAGE) sequence for dynamic susceptibility-contrast magnetic resonance imaging to obtain hemodynamic parameters in a preclinical setting. The SAGE EPI sequence was applied in phantoms and in vivo rat brain (normal, tumor, and stroke tissue). Partial and full Fourier encoding schemes were implemented and characterized. Maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), vessel size index (VSI), volume transfer constant (K^trans), and volume fraction of the extravascular extracellular space (v_e) were obtained. Partial Fourier encoding provided shortened echo times with acceptable signal-to-noise ratio and temporal stability, thus enabling reliable characterization of T₂, T₂^? and T₁ in both phantoms and rat brain. The hemodynamic parameters CBV, CBF, and MTT for gradient-echo and spin-echo contrast were determined in tumor and stroke; VSI, K^trans, and v_e were also computed in tumor tissue. The SAGE EPI sequence allows the acquisition of multiple gradient- and spin-echoes, from which measures of perfusion, permeability, and vessel size can be obtained in a preclinical setting. Partial Fourier encoding can be used to minimize SAGE echo times and reliably quantify dynamic T₂ and T₂^? changes. This acquisition provides a more comprehensive assessment of hemodynamic status in brain tissue with vascular and perfusion abnormalities.     

Improved T(1)-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma

Dynamic contrast-enhanced (DCE) T(1)-weighted magnetic resonance imaging (MRI) is a powerful tool capable of providing quantitative assessment of contrast uptake and characterization of microvascular structure in human gliomas. The kinetics of the bolus injection doped with increasing concentrations of gadopentate dimeglumine (Gd-DTPA) depends on tissue as well as pulse sequence parameters. A simple method is described that overcomes the limitation of relative signal increase measurement and may lead to improved accuracy in quantification of perfusion indices of glioma. Based on an analysis of the contrast behavior of spoiled gradient-recalled echo sequence; a parameter K with arbitrary unit 5.0 is introduced, which provides a better approximation to the differential T(1) relaxation rate. DCE-MRI measurements of relative cerebral blood volume (rCBV) and cerebral blood flow (rCBF) were calculated in 25 patients with brain tumors (15=high-grade glioma, 10=low-grade glioma). The mean rCBV was 6.46 +/- 2.45 in high-grade glioma and 2.89 +/- 1.47 in the low-grade glioma. The rCBF was 3.94 +/- 1.47 in high-grade glioma while 2.25 +/- 0.87 in low-grade glioma. A significant difference in rCBF and rCBV was found between high- and low-grade gliomas. This simple and robust technique reveals the complexity of tumor vasculature and heterogeneity that may aid in therapeutic management especially in nonenhancing high-grade gliomas. We conclude that the precontrast medium steady-state residue parameter K may be useful in improved quantification of perfusion indices in human glioma using T(1)-weighted DCE-MRI.     

The effect of dexamethasone on tissue water distribution and proton relaxation in Panc02 tumors

The present experiments were conducted to determine the effects of dexamethasone mediated changes in tumor water distribution on proton relaxation times (T1, T2) in a murine pancreatic adenocarcinoma (Panc02). Spin lattice (T1) and spin-spin (T2) relaxation times were determined by ex vivo methods (10MHz) and by in vivo imaging techniques (6.25 MHz) at various intervals after single or multiple dexamethasone treatments. In complementary studies, dexamethasone mediated changes in tumor capillary permeability, tumor water distribution, relative tumor blood flow and tumor cell proliferation were also determined.

Proton spin lattice (T1) and spin-spin (T2 relaxation times for Panc02 tumors shortened within two hours of a single dexamethasone treatment. The time course and magnitude of this response was dexamethasone dose dependent. The time dependent changes in T1 and T2 after dexamethasone were similar at 10 MHz (ex vivo) and 6.25 MHz (in vivo imaging). Although dexamethasone produced little or no change in total tumor water content and tumor cell proliferation, transient changes in the physiologic distribution of tumor water were clearly demonstrated.

The data supports the idea that dexamethasone induced changes in the distribution of tumor water were mediated by changes in capillary permeability and tumor blood flow. These physiologic responses produced serial changes in tumor extracellular extravascular water content that were consistent with the observed changes in tumor T1 and T2. The results from these experiments might imply that therapy associated changes in tumor proton relaxation times may not only reflect changes in tissue water content, but may also reflect physiologic responses which alter the distribution of tissue water and solute.     

MRI of human tumor xenografts in vivo: Proton relaxation times and extracellular tumor volume

Proton T₁ and T₂ differ substantially between tumors, but the tumor properties causing heterogeneity in T₁ and T₂ have not been fully recognized. The purpose of the study reported here was to investigate whether differences in T₁ and T₂ between tumors are mainly a consequence of differences in the fractional volume of the extracellular compartment. The study was performed using a single human tumor xenograft line showing large naturally occurring intratumor heterogeneity in the size of the extracellular compartment. The size of the extracellular compartment was calculated from the volume and the density of the tumor cells. Cell volume was measured by an electronic particle counter. Cell density was determined by stereological analysis of histological preparations. T₁ and T₂ were measured by MRI in vivo both in the absence and presence of Gd-DTPA. Two spin-echo pulse sequences were used, one with a repetition time (TR) of 600 ms and echo times (TEs) of 20, 40, 60, and 80 ms and the other with a TR of 2,000 ms and TEs of 20, 40, 60, and 80 ms. Measurements of T₁ and T₂ in the presence of Gd-DTPA were performed in a state of semi-equilibrium between uptake and clearance of Gd-DTPA. MR-images and histological preparations of tumor subregions homogeneous in extracellular volume were analysed in pairs. The extracellular volume differed between tumor subregions from 5 to 70%. T₁ and T₂ measured in the absence of Gd-DTPA differed between tumor subregions by a factor of approximately 1.5 and increased with increasing extracellular volume. The relative decrease in T₁ caused by Gd-DTPA, represented by $\text{(T}{}_{\mathrm{<mtext>1\; control</mtext>}}\text{−T}{}_{\mathrm{<mtext>1\; Gd-DTPA</mtext>}}\text{)}\text{T}{}_{\mathrm{<mtext>1\; control</mtext>}}$, also increased with increasing extracellular volume. The relative decrease in T₂ did not change significantly as the extracellular volume increased. These observations strongly suggest that the size of the extra-cellular compartment is a major determinant of proton T₁s and T₂s of tumors, possibly because the ratios of free to structured and free to bound water increase with increasing extracellular tumor volume.     

(1)H-MRS metabolic patterns for distinguishing between meningiomas and other brain tumors

Yet meningiomas have characteristic neuroimaging features, some other lesions are still confusing with meningiomas. The aim of this study was trying to find the typical (1)H-MRS metabolic factors of histologic subtyped meningiomas, schwannomas, metastases, and other brain tumors for differential diagnosis among them. (1)H-MRS using STEAM (TE/30 ms, TR/2 sec) and PRESS (TE/288 ms, TR/2 sec) sequences were performed on 44 untreated brain tumors. Obtained metabolic patterns from the typical spectra of meningioma, schwannoma, metastasis were compared with each other or other brain tumors to evaluate the usefulness for diagnosis between them. Alanine(Ala) was observed in 15 cases of the 19 meningiomas with a little variation to three histologic subtypes, while minimal lipids were observed in every 19 meningiomas. Elevated glutamate/glutamine(Glx) was detected in 12 cases of the meniningiomas. Increased myo-inositol(mI) was detected in 11 cases of the 13 schwannomas. Dominant lipids signals as well as long-T2 lipids were detected in every metastasis in conjunction with elevated choline (Cho). Enhanced Glx was observed in 4 cases of the 8 metastases without correlation of primary tumor site or types. Hemangiopericytoma showed different spectral patterns from typical meningiomas: only dominant Cho, minimal lipids and absence of Ala or Glx signals. These metabolic patterns in typical tumors may provide a basis for differential diagnosis (average value of chi(2) = 23.33, p < 0.01) between meningiomas and schwannomas as well as metastases. However proton spectral distinction among the different histologic subtypes of meningiomas was not definite.     

Dynamic contrast-enhanced MRI of Implanted VX2 tumors in rabbit muscle: comparison of Gd-DTPA and NMS60

We studied the dynamics of injected contrast enhancement in implanted VX2 tumors in rabbit thigh muscle. We compared two contrast agents Gd-DTPA and NMS60, a novel gadolinium containing trimer of molecular weight 2.1 kd. T1-weighted spin echo images were acquired preinjection and at 5-60 min after i.v. injection of 0.1 mmol/kg of agent. Dynamic T1-weighted SPGR images (1.9 s/image) were acquired during the bolus injection. Male NZW rabbits (n = 13) were implanted with approximately 2 x 10(6) VX2 tumor cells and grew tumors of 28+/-27 mL over 12 to 21 days. NMS60 showed significantly greater peak enhancement in muscle, tumor rim, and core compared to DTPA in both T1-weighted and SPGR images. NMS60 also showed delayed peak enhancement in the dynamic scans (compared to Gd-DTPA) and significantly reduced leakage rate constant into the extravascular space for tumor rim (K21 = 5.1 min(-1) vs. 11.5 min(-1) based on a 2 compartment kinetic model). The intermediate weight contrast agent NMS60 offers greater tumor enhancement than Gd-DTPA and may offer improved regional differentiation on the basis of vascular permeability in tumors.     

Assessment of T1 time course changes and tissue-blood ratios after Gd-DTPA administration in brain tumors

Sequential T1 changes in brain tumor tissue after Gd-DTPA administration were investigated in 10 patients, including 4 meningiomas, 2 gliomas, 3 metastatic cerebral tumors and 1 brain abscess. T1 values were measured serially for 60 minutes following Gd-DTPA injection using a magnetic focusing technique. In vitro T1 of the whole blood samples was also comparatively examined. Time processes in the tissue-blood ratio (TBR) were calculated from two-point relaxation rates at 5 and 30 minutes. The obtained ratios of TBR were ranged from 1.0 to 3.0, probably depending on histological types of brain tumor (the value of 1.0 to 1.5 for meningioma and 1.5 to 3.0 for glioma and metastatic tumor). No significant changes in the T1 value were observed in the examined normal tissue and peritumoral edema. These results indicate that Gd-DTPA plays an important role not only as an image enhancer for tumor tissue but also as an indicator for estimating the blood-brain barrier function.     

Quantitative pharmacokinetic analysis of DCE-MRI data without an arterial input function: a reference region model

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumor perfusion, microvascular vessel wall permeability and extravascular-extracellular volume fraction. Analysis of DCE-MRI data is usually based on indicator dilution theory that requires knowledge of the concentration of the contrast agent in the blood plasma, the arterial input function (AIF). A method is presented that compares the tissues of interest (TOI) curve shape to that of a reference region (RR), thereby eliminating the need for direct AIF measurement. By assigning literature values for Ktrans (the blood perfusion-vessel permeability product) and v(e) (extravascular-extracellular volume fraction) in a reference tissue, it is possible to extract the Ktrans and v(e) values for a TOI without knowledge of the AIF. The operational RR equation for DCE-MRI analysis is derived, and its sensitivity to noise and incorrect assignment of the RR parameters is tested via simulations. The method is robust at noise levels of 10%, returning accurate (+/-20% in the worst case) and precise (+/-15% in the worst case) values. Errors in the TOI Ktrans and v(e) values scale approximately linearly with the errors in the assigned RR Ktrans and v(e) values. The methodology is then applied to a Lewis Lung Carcinoma mouse tumor model. A slowly enhancing TOI yielded Ktrans=0.039+/-0.002 min-1 and v(e)=0.46+/-0.01, while a rapidly enhancing region yielded Ktrans=0.35+/-0.05 min-1 and v(e)=0.31+/-0.01. Parametric Ktrans and v(e) mappings manifested a tumor periphery with elevated Ktrans (>0.30 min-1) and v(e) (>0.30) values. The main advantage of the RR approach is that it allows for quantitative assessment of tissue properties without having to obtain high temporal resolution images to characterize an AIF. This allows for acquiring images with higher spatial resolution and/or SNR, and therefore, increased ability to probe tissue heterogeneity.     

Dynamic Contrast-Enhanced Imaging and Analysis at High Spatial Resolution of MCF7 Human Breast Tumors

High resolution, dynamic GdDTPA-enhanced images of MCF7 human breast tumors in immunodeficient mice were analyzed at pixel resolution. The analysis, based on a physiological model, was performed by applying a nonlinear least-square algorithm using a color coded scale. The final output mapped at pixel resolution capillary permeability times surface area and fraction of extracellular volume, for each tumor slice. In addition, the output included assessment of the fit to the model by determining the proportion of variability (R²) for each pixel. The spatial variation in theR²values served to identify regions where the predominant mechanism of enhancement was leakage from the intravascular volume to the extracellular volume (R²close to 1). In regions with lowR²other mechanisms of enhancement appear to be dominating presumably diffusion within the extracellular space. As expected, in necrotic regions lacking microcapillaries and identified by analyzingT₂-weighted images of the same tumors, the model failed to fit the dynamic contrast enhanced data. The heterogeneous distribution of the determined pathophysiological features demonstrates the importance of recording and analyzing breast tumor images at high spatial resolution.     

Islet cell tumor of the pancreas associated with tumor thrombus in the portal vein.

We report the MR findings of a 70-year-old man with an islet cell tumor that diffusely involved the body of the pancreas associated with enhancing portal vein tumor thrombus and cavernous transformation. The diffusely infiltrative tumor mass was best shown on early post gadolinium spoiled gradient echo. The tumor thrombus enhanced intensely on early post gadolinium images and was also well shown on true FISP (Fast Imaging with Steady State Precession) images. The extent of liver metastases was best shown on fat suppressed T2-weighted images. The most unusual finding was tumor thrombus involving the SMV and portal vein.