Realistic phantoms to characterize dosimetry in pediatric CT.

BACKGROUND: The estimation of organ doses and effective doses for children receiving CT examinations is of high interest. Newer, more realistic anthropomorphic body models can provide information on individual organ doses and improved estimates of effective dose. MATERIALS AND METHODS: Previously developed body models representing 50th-percentile individuals at reference ages (newborn, 1, 5, 10 and 15 years) were modified to represent 10th, 25th, 75th and 90th height percentiles for both genders and an expanded range of ages (3, 8 and 13 years). We calculated doses for 80 pediatric reference phantoms from simulated chest-abdomen-pelvis exams on a model of a Philips Brilliance 64 CT scanner. Individual organ and effective doses were normalized to dose-length product (DLP) and fit as a function of body diameter. RESULTS: We calculated organ and effective doses for 80 reference phantoms and plotted them against body diameter. The data were well fit with an exponential function. We found DLP-normalized organ dose to correlate strongly with body diameter (R2>0.95 for most organs). Similarly, we found a very strong correlation with body diameter for DLP-normalized effective dose (R2>0.99). Our results were compared to other studies and we found average agreement of approximately 10%. CONCLUSION: We provide organ and effective doses for a total of 80 reference phantoms representing normal-stature children ranging in age and body size. This information will be valuable in replacing the types of vendor-reported doses available. These data will also permit the recording and tracking of individual patient doses. Moreover, this comprehensive dose database will facilitate patient matching and the ability to predict patient-individualized dose prior to examination.

Patient-specific dose calculations for pediatric CT of the chest, abdomen and pelvis.

BACKGROUND: Organ dose is essential for accurate estimates of patient dose from CT. OBJECTIVE: To determine organ doses from a broad range of pediatric patients undergoing diagnostic chest-abdomen-pelvis CT and investigate how these relate to patient size. MATERIALS AND METHODS: We used a previously validated Monte Carlo simulation model of a Philips Brilliance 64 multi-detector CT scanner (Philips Healthcare, Best, The Netherlands) to calculate organ doses for 40 pediatric patients (M:F = 21:19; range 0.6-17 years). Organ volumes and positions were determined from the images using standard segmentation techniques. Non-linear regression was performed to determine the relationship between volume CT dose index (CTDIvol)-normalized organ doses and abdominopelvic diameter. We then compared results with values obtained from independent studies. RESULTS: We found that CTDIvol-normalized organ dose correlated strongly with exponentially decreasing abdominopelvic diameter (R(2) > 0.8 for most organs). A similar relationship was determined for effective dose when normalized by dose-length product (R(2) = 0.95). Our results agreed with previous studies within 12% using similar scan parameters (e.g., bowtie filter size, beam collimation); however results varied up to 25% when compared to studies using different bowtie filters. CONCLUSION: Our study determined that organ doses can be estimated from measurements of patient size, namely body diameter, and CTDIvol prior to CT examination. This information provides an improved method for patient dose estimation.

In-line phase shift tomosynthesis.

PURPOSE: The purpose of this work is to (1) demonstrate laboratory measurements of phase shift images derived from in-line phase-contrast radiographs using the attenuation-partition based algorithm (APBA) of Yan et al. [Opt. Express 18(15), 16074-16089 (2010)], (2) verify that the APBA reconstructed images obey the linearity principle, and (3) reconstruct tomosynthesis phase shift images from a collection of angularly sampled planar phase shift images. METHODS: An unmodified, commercially available cabinet x-ray system (Faxitron LX-60) was used in this experiment. This system contains a tungsten anode x-ray tube with a nominal focal spot size of 10 µm. The digital detector uses CsI∕CMOS with a pixel size of 50×50 µm. The phantoms used consisted of one acrylic plate, two polystyrene plates, and a habanero pepper. Tomosynthesis images were reconstructed from 51 images acquired over a ±25° arc. All phase shift images were reconstructed using the APBA. RESULTS: Image contrast derived from the planar phase shift image of an acrylic plate of uniform thickness exceeded the contrast of the traditional attenuation image by an approximate factor of two. Comparison of the planar phase shift images from a single, uniform thickness polystyrene plate with two polystyrene plates demonstrated an approximate linearity of the estimated phase shift with plate thickness (-1600 rad vs -2970 rad). Tomographic phase shift images of the habanero pepper exhibited acceptable spatial resolution and contrast comparable to the corresponding attenuation image. CONCLUSIONS: This work demonstrated the feasibility of laboratory-based phase shift tomosynthesis and suggests that phase shift imaging could potentially provide a new imaging biomarker. Further investigation will be needed to determine if phase shift contrast will be able to provide new tissue contrast information or improved clinical performance.

Detecting peritoneal dissemination of ovarian cancer in mice by DWIBS.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) is a relatively new diffusion-based pulse sequence that produces positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18)F-FDG)-like images. We tested the feasibility of DWIBS in detecting peritoneal ovarian cancer in a syngeneic mouse model. Female C57BL/6 mice were injected intraperitoneally with ID8 murine ovarian carcinoma cells. After 11 weeks, the abdomen was imaged by DWIBS. A respiratory gating diffusion-weighted spin-echo echo-planar imaging in abdomen was used (imaging parameters of field of view of 47×47 mm(2), matrix size of 64×64 zero-filled to 256×256 and b-value of 1500 s/mm(2)). We also performed FDG microPET as the reference standard. For comparison of the correlating surface areas of tumor foci on both DWIBS and FDG microPET imaging, two-dimensional region-of-interest (ROI) analysis was performed, and correlation between the two modalities was determined. Mice were also subjected to macroscopic examination for tumor location and pathology after imaging. DWIBS in all mice depicted the tumors as abnormal high signal intensity. The results show that the ROI analysis of correlating lesions reveals relatively high correlation (r²=0.7296) and significant difference (P=.021) between DWIBS and FDG microPET. These results demonstrate that DWIBS has the potential for detecting peritoneal dissemination of ovarian cancer. Nonetheless, due to low ratios of image signal-to-noise and motion artifacts, DWIBS can be limited for lesions near the liver.

Phase-contrast digital tomosynthesis.

PURPOSE: Phase-contrast (PC) edge enhancement occurs at the boundary between different tissues and is an interference effect that results from the differential phase-shifts that the x-rays acquire while traversing the two tissues. While observable in planar phase-contrast radiographs, the impact of digital tomosynthesis on this edge enhancement effect has not been previously reported. The purpose of this work is to demonstrate: (1) that phase-contrast digital tomosynthesis (PC-DTS) is possible with a conventional x-ray source, (2) that the reconstructed tomosynthesis images demonstrate and retain edge enhancement as compared to planar phase-contrast radiographs and (3) tomosynthesis improves object contrast by reducing the effects of superimposed structures. METHODS: An unmodified, commercially available cabinet x-ray system (Faxitron LX-60) was used. The system contains a tungsten anode x-ray tube that was operated at 24 kVp and 3 mAs for each PC radiographic image taken, with a nominal focal spot size of 0.010 mm. The digital detector uses CsI/CMOS with a pixel size of 0.054 mm x 0.054 mm. Objects to be imaged were attached to a computer-controlled rotating motor and are rotated +/- 25 degrees about a central position in one degree increments. At each increment, three phase-contrast radiographs are taken and then averaged to reduce the effect of noise. These planar images are then used to reconstruct a series of 56 longitudinal tomographic images with an image offset increment of about 0.7 mm. RESULTS: Tomographic z-plane resolution was measured to be approximately 4 mm. When compared to planar PC images, the tomosynthesis images were shown to retain the PC boundary edge enhancement in addition to an improvement in object contrast. CONCLUSIONS: Our work demonstrates that PC digital tomosynthesis retains the edge-enhancement observed in planar PC radiograph and further improves soft-tissue conspicuity by reducing the effects of superimposed tissue structure.

Evaluation of an intraperitoneal ovarian cancer syngeneic mouse model using 18F-FDG MicroPET imaging.

OBJECTIVES: The objective of this study was to evaluate the syngeneic immunocompetent mouse model by using the micro-positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (F-FDG microPET) imaging of ovarian tumor growth. METHODS: ID8 ovarian carcinoma cells derived from C57BL/6 mice were intraperitoneally injected into female C57BL/6 mice. Mice were injected with F-FDG (7.4 MBq, intravenous injection), and microPET images were obtained 40 minutes later. Micro-computed tomographic images were also obtained immediately after microPET images for anatomical reference. F-FDG microPET images were acquired at baseline and at 4, 8, 10, and 11 weeks after tumor cell injection. The maximum standardized uptake value (SUVmax) in each time point was obtained from the images and compared to follow the tumor growth. RESULTS: Physiological uptake of F-FDG was intensely found in the bladder and heart and frequently in the gastrointestinal tract. Diffused uptake of F-FDG was observed in the peritoneal cavity of all tumor-bearing mice at 4 weeks, and high focal uptakes were developed in the peritoneal cavity at 8 to 11 weeks. High focal uptakes increased over time, correlating with a progressive increase in the SUVmax of F-FDG. At 11 weeks, the SUVmax value was significantly increased (1.49 ± 0.10 at 11 weeks vs 0.29 ± 0.03 at baseline, P < 0.01). Tumors in the gut and peritoneum were confirmed by anatomical and histopathological examination. CONCLUSIONS: Our results demonstrate that the peritoneal tumor growth in the syngeneic ovarian cancer model can be detected by the F-FDG microPET imaging.

A novel in vitro assay to assess phosphorylation of 3'-[(18)F]fluoro-3'-deoxythymidine.

PURPOSE: 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) is phosphorylated by thymidine kinase 1 (TK-1), a cell cycle regulated enzyme. Appropriate use of [(18)F]FLT tracer requires validation of the TK-1 activity. Here, we report development of a novel phosphoryl-transfer assay to assess phosphorylation of [(18)F]FLT both in tumor cell lysates and tumor cells. PROCEDURES: The intrinsic F-18 radioactivity was used to quantify both substrate and phosphorylated products using a rapid thin layer chromatography method. Phosphorylation kinetics of [(18)F]FLT in SW480 and DiFi tumor cell lysates and cellular uptake were measured. RESULTS: The apparent Michaelis-Menten kinetic parameters for [(18)F]FLT are K(m) = 4.8 ± 0.3 µM and V(max) = 7.4 pmol min(-1) per 1 × 10(6) cells with ~2-fold higher TK-1 activity in DiFi versus SW480 lysates. CONCLUSIONS: The apparent K (m) of [(18)F]FLT was comparable to the value reported with purified recombinant TK-1. The uptake of [(18)F]FLT by SW480 cells is inhibited by nitrobenzylthioinosine or dipyridamole indicating that uptake is mediated predominantly by the equilibrative nucleoside transporters in these tumor cells.

T2 detection of tumor invasion within segmented components of glioblastoma multiforme.

PURPOSE: To use T2-weighted images to detect tumor invasion when comparing normal individuals to groups of gliomablastoma multiforme (GBM) patients with varying levels of CXCR4, a chemokine receptor that promotes tumor migration. MATERIALS AND METHODS: T2-weighted images were acquired preoperatively in 22 treatment-naïve GBM patients. Two groups were formed based on the expression levels of CXCR4. A third group of normal volunteers was used for comparison. Each image was segmented to obtain four different clusters for tissue types identified as white matter, basal ganglia, gray matter/edema and cerebrospinal fluid (CSF)/tumor. Signal intensity histograms were formed for each cluster and compared between groups. RESULTS: In every cluster the GBM groups displayed significantly higher standard deviations of intensity distributions when compared to normal subjects. Significant differences in skewness were found between normal subjects and GBM patients in the white matter, basal ganglia, and CSF/tumor. Further, when the two groups of GBM patients were compared the CXCR4-high group was found to have a significant shift in the median intensity values in the cluster containing gray matter and peritumoral edema. CONCLUSION: T2 signal intensity histograms in normal subjects differ significantly from those obtained from GBM groups, suggesting widespread dissemination of disease.

Organized shells on clay nanotubes for controlled release of macromolecules.

The use of tubular halloysite clay as a nanotemplate for layer-by-layer (LbL) shell assembly and its utilization for controlled release of drug macromolecules are studied. The LbL nanoshell allowed additional control for the sustained release of drug loaded halloysite tubes. The number of polymeric layers in the shell and molecular weight of the assembled polymers influences the drug release rate. Three bilayer shells of chitosan and gelatin of 15 nm thicknesses gave the best encapsulation and retardation in the release rate of dexamethasone. An encapsulation of the macromolecules inside the lumen of the biocompatible clay nanotubes coupled with the polyelectrolyte shell formation provides a novel formulation for the controlled release of bioactive agents.

CXCR4 expression is elevated in glioblastoma multiforme and correlates with an increase in intensity and extent of peritumoral T2-weighted magnetic resonance imaging signal abnormalities.

OBJECTIVE: With the objective of investigating the utility of CXCR4, a chemokine receptor known to mediate glioma cell invasiveness, as a molecular marker for peritumoral disease extent in high-grade gliomas, we sought to characterize the expression profile of CXCR4 in a large panel of tumor samples and determine whether CXCR4 expression levels within glioblastoma multiforme might correlate with radiological evidence of a more extensive disease process. METHODS: Freshly resected tumor tissue samples were processed for immunohistochemical and quantitative polymerase chain reaction analyses to identify and quantify expression levels of CXCR4 and its corresponding ligand CXCL12. T1 postcontrast and T2-weighted magnetic resonance imaging brain scans were used to generate voxel signal intensity histograms that were quantitatively analyzed to determine the extent and intensity of peritumoral signal abnormality as a marker of disseminated disease in the brain. RESULTS: CXCR4 expression was markedly elevated in Grade III and IV tumors compared with Grade II gliomas. Significantly, when patients with glioblastoma multiforme were segregated into two groups based on CXCR4 expression level, we observed a statistically significant increase in the intensity and extent of peritumoral magnetic resonance imaging signal abnormalities associated with CXCR4 high-expressing gliomas. CONCLUSION: Our data confirm that high-grade gliomas robustly express CXCR4 and demonstrate a correlative relationship between expression levels of the CXCR4 receptor and the magnetic resonance imaging-based finding of a diffuse and more extensive disease process in the brain. CXCR4 expression status may, therefore, prove useful as a marker of disseminated disease in patients with glioblastoma multiforme.

Functional colonography of Min mice using dark lumen dynamic contrast-enhanced MRI.

Dark lumen MRI colonography detects colonic polyps by minimization of the intestinal lumen signal intensity. Here we validate the use of perfluorinated oil as an intestinal-filling agent for dark lumen MRI studies in mice, enabling the physiological characterization of colonic polyps by dynamic contrast-enhanced MRI. In control and Min (multiple intestinal neoplasia) mice with and without pretreatment with oral dextran sodium sulfate (DSS), polyps as small as 0.94 mm diameter were consistently identified using standard 2D gradient echo imaging (voxel size, 0.23 x 0.16 x 0.5 mm). In serial studies, polyp growth rates were heterogeneous with an average approximately 5% increase in polyp volume per day. In DSS-treated control mice the colon wall contrast agent extravasation rate constant, K(trans), and extravascular extracellular space volume fraction, v(e), values were measured for the first time and found to be 0.10 +/- 0.03 min(-1) and 0.23 +/- 0.09, respectively. In DSS-treated Min mice, polyp K(trans) values (0.09 +/- 0.04 min(-1)) were similar to those in the colon wall but the v(e) values were substantially lower (0.16 +/- 0.03), suggesting increased cellular density. The functional dark-lumen colonography approach described herein provides new opportunities for the noninvasive assessment of gastrointestinal disease pathology and treatment response in mouse models.

Quantifying cerebral changes in adolescence with MRI and deformation based morphometry.

PURPOSE: To identify and quantify structural changes in the maturing brain between childhood and adolescence. MATERIALS AND METHODS: Two three-dimensional T1-weighted MR volumes of the brain were acquired from eight subjects, 6 to 7 years apart. The subjects were 9 to 12 years old on the first scan and 15 to 19 years old on the second scan. The MR scans were converted to one millimeter isotropic volumes, globally aligned with a rigid transform, inhomogeneity corrected, and nonrigid deformation fields between the aligned volumes were calculated. Masks for brain regions were automatically warped with the deformation fields and volumes of brain regions calculated. Color overlays based on the nonrigid deformation fields were generated to identify local volume changes. RESULTS: Gray matter decreased as much as 60% and white matter increased as much as 250%. The biggest gray matter changes were in the head of the caudates, areas of the putamens, and areas of the thalamus. Some of the biggest white matter changes were in the forceps minor, forceps major, and internal capsule. CONCLUSION: Deformation based morphometry with serial scans provides a method to study regional structural changes with brain growth and maturation.

Microwave-induced nucleophilic [18F]fluorination on aromatic rings: synthesis and effect of halogen on [18F]fluoride substitution of meta-halo (F, Cl, Br, I)-benzonitrile derivatives.

The meta-halo-3-methylbenzonitrile derivatives (-F, -Cl, -Br, -I) were synthesized as model compounds to study reactivity towards aromatic nucleophilic substitution. A single-mode microwave system was incorporated into a commercial radiochemical synthetic module for (18)F labeling. Labeling yields of 64% for fluoro-, 13% for bromo- and 9% for chloro-precursors were achieved in DMSO in <3 min. The observed order of reactivity of the leaving groups toward aromatic nucleophilic substitution was F>>Br>Cl>>>I.

Halloysite clay nanotubes for controlled release of protective agents.

Halloysite aluminosilicate nanotubes with a 15 nm lumen, 50 nm external diameter, and length of 800 +/- 300 nm have been developed as an entrapment system for loading, storage, and controlled release of anticorrosion agents and biocides. Fundamental research to enable the control of release rates from hours to months is being undertaken. By variation of internal fluidic properties, the formation of nanoshells over the nanotubes and by creation of smart caps at the tube ends it is possible to develop further means of controlling the rate of release. Anticorrosive halloysite coatings are in development and a self-healing approach has been developed for repair mechanisms through response activation to external impacts. In this Perspective, applications of halloysite as nanometer-scale containers are discussed, including the use of halloysite tubes as drug releasing agents, as biomimetic reaction vessels, and as additives in biocide and protective coatings. Halloysite nanotubes are available in thousands of tons, and remain sophisticated and novel natural nanomaterials which can be used for the loading of agents for metal and plastic anticorrosion and biocide protection.

Diffusion-weighted imaging of inflammatory myopathies: polymyositis and dermatomyositis.

Muscles of myositis patients examined with MRI demonstrate heterogeneous pathology ranging from unaffected muscle groups to severe inflammation, fat infiltration, and eventually, more serious fat replacement. The purpose of this investigation was to characterize myositic thigh muscles using diffusion-weighted imaging (DWI) and to examine fluid motion at various disease stages. We chose to characterize total fluid motion within the muscle using the model proposed by Le Bihan et al (6,7) in which the apparent diffusion coefficient (ADC), diffusion in the extra- and intracellular muscle compartments (D), perfusion in capillaries (pseudodiffusion) (D*), and volume fraction of capillary perfusion (f) are determined. Unaffected patient muscles have DWI coefficients equivalent to those of normal muscles. Inflamed muscles show elevated ADC and D values compared to normal muscles (P < 0.0005), and fat-infiltrated muscles have lower values than control muscles (P < 0.001). Inflamed muscles have lower f values than unaffected muscles (P < 0.009), suggesting decreased fractional volume of capillary perfusion. DWI provides quantitative data on molecular fluid motion in diseased muscles and affords the potential for longitudinal monitoring of myositic patients.

Polychromatic phase-contrast computed tomography.

Polychromatic phase-contrast radiography differs from traditional (absorption-only) radiography in that the method requires at least a partially coherent x-ray source and the resulting images contain information about the phase shifts of x-rays in addition to the traditional absorption information. In a typical embodiment, this effect results in a measurable enhancement in image contrast at the edges of objects. In this study, a phase-contrast imaging system was adapted to allow an object to be imaged at multiple projections, and these projections were used to generate phase-contrast computed tomography images. The images obtained with this technique show edge enhancements surrounding the objects within the image.

Ovarian volume measurements in mice with high-resolution ultrasonography.

OBJECTIVE: The aim of our study was to evaluate the intraobserver and interobserver variability of ovarian volume measurements in mice with high-resolution 2-dimensional ultrasonography (2DUS) and 3-dimensional ultrasonography (3DUS). METHODS: Ovaries of 10 nude mice were visualized with a small-animal ultrasound scanner and a 40-MHz probe. For each ovary, volume was measured 3 times by 2 independent readers using both 2DUS and 3DUS methods. The 2DUS method used a biplane ellipsoid model. The 3DUS method estimated the volume by integrating 10 to 12 parallel image planes of the ovary after semiautomated outlining of the boundaries. For each type of measurement, intraobserver and interobserver standard error of measurement (SEM) values and minimal detectable volume changes were calculated by analysis of variance. RESULTS: Two-dimensional ultrasonography showed much poorer reproducibility, with higher absolute intraobserver and interobserver SEM values (0.50 and 0.61 mm3, respectively) than 3DUS (0.20 and 0.35 mm3; P < .01). Relative intraobserver and interobserver SEM values were also much higher for 2DUS (12.20% and 14.88%) than for 3DUS (5.12% and 8.97%; P < .01). The minimal volume changes that could be detected with a 95% confidence level in successive measurements by the same (or different) observers were 33.90% (41.22%) for 2DUS and 14.10% (24.87%) for 3DUS. CONCLUSIONS: High-resolution 3DUS can provide a reliable tool for noninvasive, longitudinal ovarian volume measurements in mice.

An objective method for combining multi-parametric MRI datasets to characterize malignant tumors.

Medical imaging has made significant contributions to the characterization of malignant tumors. In many cases, however, maps from multiple modalities may be required for more complete tumor mapping. In this manuscript we propose an objective method for combining multiple imaging datasets with the goal of characterizing malignant tumors. We refer to the proposed technique as the percent overlap method (POM). To demonstrate the power and flexibility of the POM analysis, we present four patients with recurrent glioblastoma multiforme. Each patient had multiple magnetic resonance imaging procedures resulting in seven different parameter maps. Chemical shift imaging was used to provide three metabolite ratio maps (Cho:NAA, Cho:Cre, Lac:Cre). A perfusion scan provided regional cerebral blood volume and permeability maps. Diffusion and carbogen-based hypoxia mapping data were also acquired. Composite maps were formed for each patient using POM, then were compared to results from the ISODATA clustering technique. The POM maps of likely recurrent tumor regions were found to be consistent with the ISODATA clustering method. This manuscript presents an objective method for combining parameters from multiple physiologic imaging techniques into a single composite map. The accuracy of the map depends strongly on the sensitivity of the chosen imaging parameters to the disease process at the time of image acquisition. Further validation of this method may be achieved by correlation with histological data.

Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results.

PURPOSE: The objective of this study was to assess changes in the water apparent diffusion coefficient (ADC) and in pharmacokinetic parameters obtained from the fast-exchange regime (FXR) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during neoadjuvant chemotherapy in breast cancer. MATERIALS AND METHODS: Eleven patients with locally advanced breast cancer underwent MRI examination prior to and after chemotherapy but prior to surgery. A 1.5-T scanner was used to obtain T1, ADC and DCE-MRI data. DCE-MRI data were analyzed by the FXR model returning estimates of K(trans) (volume transfer constant), v(e) (extravascular extracellular volume fraction) and tau(i) (average intracellular water lifetime). Histogram and correlation analyses assessed parameter changes post-treatment. RESULTS: Significant (P < .05) changes or trends towards significance (P < .10) were seen in all parameters except tau(i), although there was qualitative reduction in tau(i) values post-treatment. In particular, there was reduction (P < .035) in voxels with K(trans) values in the range 0.2-0.5 min(-1) and a decrease (P < .05) in voxels with ADC values in the range 0.99 x 10(-3) to 1.35 x 10(-3) mm2/s. ADC and v(e) were negatively correlated (r = -.60, P < .02). Parameters sensitive to water distribution and geometry (T(1), v(e), tau(i) and ADC) correlated with a multivariable linear regression model. CONCLUSION: The analysis presented here is sensitive to longitudinal changes in breast tumor status; K(trans) and ADC are most sensitive to these changes. Relationships between parameters provide information on water distribution and geometry in the tumor environment.

Repeatability of a reference region model for analysis of murine DCE-MRI data at 7T.

PURPOSE: To test the repeatability of a reference region (RR) model for the analysis of dynamic contrast-enhanced MRI (DCE-MRI) in a mouse model of cancer at high field. MATERIALS AND METHODS: Seven mice were injected with 10(6) 4T1 mammary carcinoma cells and imaged eight to 10 days later on a Varian 7.0T scanner. Two DCE-MRI studies were performed for each mouse (separated by 2.5 hours). The RR model was used to analyze the data, and returned estimates on the perfusion-permeability index (Ktrans) for the RR and the tissue of interest (TOI), as well as the extravascular extracellular volume fraction (ve) for the TOI. RESULTS: When the first injection was compared with the second injection, all parameters tested were highly correlated (r2=0.90, 0.62, 0.82 for the RR Ktrans, TOI Ktrans, and TOI ve, respectively, with P<0.001 for all). To observe a statistically significant change (at the 5% level) in a treatment study with seven animals in each group, log10 changes of 0.084 and 0.077 in the tumor Ktrans and ve, respectively, are required. CONCLUSION: If a reliable arterial input function (AIF) is unavailable, the RR model is a reasonable alternative to measuring MRI contrast-agent (CA) kinetics in mouse models of cancer at high field.