Static and dynamic responses to hyperoxia of normal placenta across gestation with T2*-weighted sequences.

OBJECTIVES: T2*-weighted sequences have been identified as non-invasive tools to study the placental oxygenation in-vivo. This study aims to investigate both static and dynamic responses to hyperoxia of the normal placenta across gestation. METHODS: We conducted a single-center prospective study including 52 uncomplicated pregnancies. Two T2*-weighted sequences were performed: T2*-relaxometry was performed before and after maternal hyperoxia. The histogram distribution of T2* values was assessed by fitting a gamma distribution as T2*~Γ(αß). A dynamic acquisition (BOLD protocol) was also performed before and during oxygen supply, until placental oxygen saturation. The signal change over time was modeled using a sigmoid function, used to determine the intensity of enhancement (∆BOLD,%), a temporal variation coefficient (λ,min-1 , controlling the slope of the curve), and the maximal steepness (Vmax, ∆BOLD.min-1 ) of placental enhancement. RESULTS: The histogram analysis of the T2* values in normoxia showed a whole-placenta variation, with a decreasing linear trend in the mean T2* value (R= -0.83, 95% CI [-0.9, -0.71], p<0.001) along with a more peaked and narrower distribution of T2* values across gestation. After maternal hyperoxia, the mean T2* ratios (mean T2*hyperoxia / mean T2*baseline ) were positively correlated with gestational age, while the other histogram parameters remained stable, suggesting a translation of the histogram towards higher values with a similar aspect. The ∆BOLD showed a non-linear increase across gestation. Conversely, the λ(min-1 ) parameter, showed an inverted trend across gestation, with a significantly weaker correlation (R = -0.33, 95% CI [-0.58, -0.02], p=0.04, R2 = 0.1). As a combination of ∆BOLD and λ, the changes in Vmax throughout gestation were mainly influenced by the changes in ∆BOLD and resulted in a positive non-linear correlation with gestational age. CONCLUSION: Our results suggest that the decrease in the T2* placental signal over gestation does not reflect a dysfunction. The BOLD effect, representative of a free-diffusion model of oxygenation, highlights the growing differences in oxygen saturation between mother and fetus across gestation (∆BOLD), and placental permeability to oxygen (λ). This article is protected by copyright. All rights reserved.

Placental T2* and BOLD effect in response to hyperoxia in normal and growth-restricted pregnancies: multicenter cohort study.

OBJECTIVES: Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) facilitates the non-invasive in-vivo evaluation of placental oxygenation. The aims of this study were to identify and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between pregnancies with and those without fetal growth restriction (FGR). METHODS: This was a prospective multicenter study (NCT02238301) of 19 pregnancies with FGR (estimated fetal weight (EFW) on ultrasound < 5th centile) and 75 non-FGR pregnancies (controls) recruited at two centers in Paris, France. Using a 1.5-Tesla MRI system, the same multi-echo gradient-recalled echo (GRE) sequences were performed at both centers to obtain placental T2* values at baseline and in hyperoxic conditions. The relative BOLD effect was calculated according to the equation 100 × (hyperoxic T2* - baseline T2*)/baseline T2*. Baseline T2* values and relative BOLD effect were compared according to EFW (FGR vs non-FGR), presence/absence of Doppler anomalies and birth weight (small-for-gestational age (SGA) vs non-SGA). RESULTS: We observed a relative BOLD effect in response to hyperoxia in the human placenta (median, 33.8% (interquartile range (IQR), 22.5-48.0%)). The relative BOLD effect did not differ significantly between pregnancies with and those without FGR (median, 34.4% (IQR, 24.1-48.5%) vs 33.7% (22.7-47.4%); P = 0.95). Baseline T2* Z-score adjusted for gestational age at MRI was significantly lower in FGR pregnancies compared with non-FGR pregnancies (median, -1.27 (IQR, -4.87 to -0.10) vs 0.33 (IQR, -0.81 to 1.02); P = 0.001). Baseline T2* Z-score was also significantly lower in those pregnancies that subsequently delivered a SGA neonate (n = 23) compared with those that delivered a non-SGA neonate (n = 62) (median, -0.75 (IQR, -3.48 to 0.29) vs 0.35 (IQR, -0.79 to 1.05); P = 0.01). CONCLUSIONS: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in pregnancies with FGR. Further studies are needed to evaluate whether such parameters may detect placental insufficiency before it has a clinical impact on fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

How and why should the radiologist look at the placenta?

This editorial comment refers to the article "Identification of suspicious invasive placentation based on clinical MRI data using textural features and automated machine learning" by Sun et al. in European Radiology. KEY POINTS: • Understanding how the placenta works is one of the major challenges facing radiologists. • New perspectives are opening up for MRI studies of the placenta. • The authors propose a new approach to placental MRI based on texture analysis and machine learning.

Dynamic contrast enhanced MRI of the placenta: A tool for prenatal diagnosis of placenta accreta?

BACKGROUND: Ultrasound (US) is the primary imaging modality for the diagnosis of placenta accreta, but it is not sufficiently accurate. MRI morphologic criteria have recently emerged as a useful tool in this setting, but their analysis is too subjective. Recent studies suggest that gadolinium enhancement may help to distinguish between the stretched myometrium and placenta within a scar area. However, objective MRI criteria are still required for prenatal diagnosis of placenta accreta. The purpose of this study was to assess the diagnostic value of dynamic contrast gadolinium enhancement (DCE) MRI patterns for placenta accreta. MATERIALS AND METHODS: MR images were acquired with a 1.5-T unit at 30-35 weeks of gestation in women with a history of Caesarian section, a low-lying anterior placenta, and US features compatible with placenta accreta. Sagittal, axial and coronal SSFP (Steady State Free Precession) sequences were acquired before injection. Then, contrast-enhanced dynamic T1-weighted images were acquired through the entire cross-sectional area of the placenta. Images were obtained sequentially at 10- to 14-s intervals for 2 min, beginning simultaneously with the bolus injection. Functional analysis was performed retrospectively, and tissular relative enhancement parameters were extracted from the recorded images. The suspected area of accreta (SAA) was placed in the region of the previous scar, and a control area (CA) of similar size was placed on the same image plane, as far as possible from the SAA. Semi-quantitative analysis of DCE-MR images was based on the kinetic enhancement curves in these two regions of interest (ROI). Three tissular relative enhancement parameters were compared according to the pregnancy outcomes, namely time to peak, maximal signal intensity, and area under the enhancement curve. RESULTS: We studied 9 women (43%) with accreta and 12 women (57%) with a normal placenta. All three tissular relative enhancement parameters differed significantly between the two groups (p < 10-3). CONCLUSION: The use of dynamic contrast-enhanced MRI at 30-35 weeks of gestation in women with a high risk of placenta accreta allows the extraction of tissular enhancement parameters that differ significantly between placenta accreta and normal placenta. It therefore provides objective parameters on which to base the diagnosis and patient management.

Warthin's tumor of parotid gland: Surgery or follow-up? Diagnostic value of a decisional algorithm with functional MRI.

PURPOSE: Warthin's tumor is the second most frequent benign tumor of the parotid gland, with no risk of malignant evolution. That is why surgery should be avoided if the preoperative diagnosis is certain. The aim of the study was to assess the added value of a decisional algorithm for the preoperative diagnosis of Warthin's tumor. MATERIALS AND METHODS: This retrospective IRB-approved study included 75 patients who underwent standardised MRI with conventional sequences (T1- and T2-weighted images, and T1 post-contrast sequences with fat saturation) and functional sequences: diffusion (b0, b1000) and perfusion MR. Two independent readers reviewed the images using the decisional algorithm. The conclusion of each reader was: the lesion is or is not a Warthin's tumor. The MRI conclusion was compared with histology or with cytology and follow-up. We calculated the Cohen's kappa coefficient between the two observers and the sensitivity and specificity of the algorithm-helped-reading for the diagnosis of Warthin's tumor. RESULTS: Seventy-five patients; histology (n=61) or cytology and follow-up (n=14) results revealed 20 Warthin's tumors and 55 other tumors. Using the algorithm, sensitivity and specificity were 80-96%, and 85-100%, respectively for readers 1 and 2. The Cohen's kappa coefficient between the two observers was 0.79 (P<0.05) for the diagnosis of Warthin's tumor. CONCLUSION: Our decisional algorithm helps the preoperative diagnosis of Warthin's tumor. The specificity of the technique is sufficient to avoid surgery if a parotid gland tumor presents all the MRI characteristics of a Warthin's tumor.

Placental elastography in a murine intrauterine growth restriction model.

OBJECTIVE: To compare placental elasticity in normal versus intrauterine growth restriction (IUGR) murine pregnancies using shear wave elastography (SWE). METHODS: Intrauterine growth restriction was created by ligation of the left uterine artery of Sprague-Dawley rats on E17. Ultrasonography (US) and elastography were performed 2 days later on exteriorized horns after laparotomy. Biparietal diameter (BPD) and abdominal diameter (AD) were measured and compared in each horn. Placental elasticity of each placenta was compared in the right and left horns, respectively, using the Young's modulus, which increases with increasing stiffness of the tissue. RESULTS: Two hundred seventeen feto-placental units from 18 rats were included. Fetuses in the left ligated horn had smaller biometric measurements than those in the right horn (6.7 vs 7.2 mm, p < 0.001, and 9.2 vs 11.2 mm, p < 0.001 for BPD and AD, respectively). Mean fetal weight was lower in the pups from the left than the right horn (1.65 vs 2.11 g; p < 0.001). Mean (SD) Young's modulus was higher for placentas from the left than the right horn (11.7 ± 1.5 kPa vs 8.01 ± 3.8 kPa, respectively; p < 0.001), indicating increased stiffness in placentas from the left than the right horn. There was an inverse relationship between fetal weight and placental elasticity (r = 0.42; p < 0.001). CONCLUSION: Shear wave elastography may be used to provide quantitative elasticity measurements of the placenta. In our model, placentas from IUGR fetuses demonstrated greater stiffness, which correlated with the degree of fetal growth restriction.

Radiological evaluation of response to treatment: application to metastatic renal cancers receiving anti-angiogenic treatment.

Targeted therapies have considerably improved the prognosis of patients with metastatic renal cancer (mRCC) but there are no reliable response assessment criteria reflecting the clinical benefits, because there is no regression in size, or it is delayed. Such criteria would help early identification of non-responders, who would then benefit from a change of treatment, and would avoid their being subjected to unnecessary side effects related to the treatment. We will review the imaging techniques currently available for evaluating tumour response in mRCC patients, including the response evaluation criteria in solid tumours (RECIST), the Choi criteria, the modified Choi criteria, and the CT size and attenuation criteria (SACT). We will also discuss functional imaging techniques, which are based on the physiological characteristics of the tumours, such as perfusion CT, magnetic resonance imaging or ultrasound (DCE-CT, DCE-MRI, DCE-US), diffusion MRI, BOLD MRI and new positron emission tomography (PET) tracers. It is not possible at present to propose a unanimously acknowledged criterion for evaluating tumour response to targeted therapy. However, there is a real need for this according to oncologists and the pharmaceutical industry, and radiologists need to be involved in reflecting on the subject.

Perfusion in ENT imaging.

UNLABELLED: Perfusion MRI is an essential part of characterizing salivary gland tumors. The shape of the curves can provide a guide as to the type of lesion: benign (ascending plateau) or malignant (descending plateau), and can also occasionally strongly suggest a histological type such as a Warthin tumor (intense, rapid contrast enhancement with washout>30%). Perfusion imaging (CT or MRI) for other head and neck tumors is currently being developed and is being assessed. It should be a tool to assist in choosing the most appropriate initial treatment (chemotherapy, radiotherapy or surgery) and should also allow poor responders to conservative treatment to be identified and recurrences to be detected in post-treatment damaged tissues. AIMS: (a) to determine when to perform perfusion MRI; (b) to determine the type of perfusion to carry out: CT, T1-weighted MRI; (c) to determine how to position the region of interest to plot the perfusion curve; (d) to know how to interpret MRI curves for salivary gland tumors; (e) to know how to interpret the information obtained from perfusion CT or MRI for the upper aerodigestive tract.

In vivo MRI assessment of placental and foetal oxygenation changes in a rat model of growth restriction using blood oxygen level-dependent (BOLD) magnetic resonance imaging.

OBJECTIVES: To evaluate whether changes in BOLD signal intensities following hyperoxygenation are related to intrauterine growth restriction (IUGR) in a rat model. METHODS: IUGR was induced in pregnant rats by ligating the left vascular uterine pedicle at day 16 of gestation. BOLD MR imaging using a balanced steady-state free-precession (balanced-SSFP) sequence on a 1.5-T system was performed on day 19. Signal intensities (SI) before and after maternal hyperoxygenation were compared in the maternal liver and in control and growth-restricted foetoplacental units (FPUs). RESULTS: Maternal hyperoxygenation resulted in a significant increase in SI in all regions of interest (P < 0.05) in the 18 rats. In the control group, the SI (mean ± SD) increased by 21 % ± 15 in placentas (n = 74) and 13 % ± 8.5 in foetuses (n = 53). In the IUGR group, the increase was significantly lower: 6.5 % ± 4 in placentas (n = 36) and 7 %± 5.5 in foetuses (n = 34) (P < 0.05). CONCLUSION: BOLD MRI allows non-invasive assessment of the foetoplacental response to maternal hyperoxygenation in the rat and demonstrates its alteration in an IUGR model. This imaging method may provide a useful adjunct for the early diagnosis, evaluation, and management of human IUGR. KEY POINTS: • Intra-uterine growth restriction is an important cause of perinatal morbidity and mortality. • Blood oxygen level-dependent MRI non-invasively assesses foetoplacental response to maternal hyperoxygenation. • In the rat, foetoplacental response to maternal hyperoxygenation is altered in IUGR. • Functional MRI may help to assess human IUGR.

SPIO-enhanced magnetic resonance imaging study of placental perfusion in a rat model of intrauterine growth restriction.

OBJECTIVE: To assess placental perfusion with magnetic resonance imaging (MRI) and superparamagnetic iron oxide (SPIO) in a rat model of intrauterine growth restriction (IUGR). DESIGN: Experimental animal study. SETTING: The study complied with US National Institutes of Health recommendations for animal care. POPULATION: Thirty-two rats at day 16 of gestation underwent surgical ligation of the left uterine vessel to induce IUGR. METHODS: Eighteen rats were examined by MRI 3 days later, after bolus injection of ferucarbotran. MAIN OUTCOME MEASURE: Signal intensities were measured in the maternal left ventricle and in the placentas of the two horns. Quantitative microcirculation parameters were calculated and compared between the placentas of the two horns. RESULTS: Fifty-four kinetic curves of placental perfusion were obtained in 11 rats. The mean placental blood flow was significantly lower in the ligated horns than in the normal horns (108.1 versus 159.4 ml/minute/100 ml, p = 0.0004). The mean fractional volume of the maternal vascular placental compartment did not differ significantly between the pathological (42.8%) and normal placentas (39.2%). CONCLUSIONS: Placental perfusion, including changes during experimental IUGR, can be measured in rats by using MRI with SPIO. These findings could have implications for human studies of placental microcirculation and for the management of disorders related to placental dysfunction.

[Kidney and iodinated and gadolinium-based contrast agents]. / Rein et produits de contraste iodés et gadolinés.

UNLABELLED: In patients with renal failure, iodinated contrast agents may cause acute deterioration of the renal function and gadolinium-based contrast agents (GBCAs) may cause nephrogenic systemic fibrosis (NSF). The administration of a contrast agent must thus be reviewed for each patient and evaluation of renal function is paramount even though its estimation using formulas derived from the creatinine level may fluctuate. For iodinated contrast agents, contrast induced nephropathy is reduced by hydratation, preferably intravenous, when the GFR is less than 60 ml/min. The risk for intravenous injections is less than the risk for arterial injections, and the GFR threshold may be reduced to 45 ml/min. For gadolinium-based contrast agents, patients at risk for NSF are those with end-stage renal disease and patients undergoing dialysis. In such cases, the injection of a gadolinium-based contrast agent is only considered after a risk-benefit analysis has been completed, an alternate linear or macrocyclic agent issued and the dose limited to 0,1 mmol Gd/kg. Recently, recommendations from US and European agencies have converged. LEARNING OBJECTIVES: to be familiar with the risk factors of CIN with iodinated contrast agents; to be familiar with hydration procedures for patients at risk of CIN; to be familiar with the diagnostic criteria of NSF; to be familiar with the classification of GBCA with regards to the risk of NSF; to be familiar with the contraindications of the different groups of GBCA.

Dynamic contrast enhanced optical imaging of capillary leakage.

We studied in vivo the vascular permeability of two fluorescent contrast agents in three types of capillary, using a fibered confocal fluorescence microscopy system. Mice were imaged after injection of a macromolecular (albumin FITC 68,000 daltons) or low-molecular-weight contrast agent (FITC 389 daltons). We studied continuous capillaries in muscles (FITC n = 4, albumin FITC n = 6), fenestrated capillaries in mesenteries (FITC n = 8, albumin FITC n = 10), and discontinuous capillaries in xenografted tumors (FITC n = 2, albumin FITC n = 4). Signal intensity (SI) was measured in capillary and interstitial regions, and time-enhancement curves were drawn. Two-compartment models were constructed to determine quantitative microcirculation parameters. The arrival of the bolus of the two different contrast agents was observed in mesentery and muscle capillaries but not in tumor capillaries. Interstitial leakage of the low-molecular-weight contrast agent was observed almost instantaneously, whereas the macromolecular agent remained within the vessels. Signal intensity declined over the observation period, specifically in the tumor. No quantitative microcirculation parameters could be obtained with either of two bi compartmental models, owing to model instability. This study shows that the microcirculation can be reproducibly observed in different types of capillary in vivo with this fibered fluorescence imaging device. Further work is required to quantify microvascular parameters.

Dynamic contrast-enhanced magnetic resonance imaging: definitive imaging of placental function?

The placenta constitutes a complex circulatory interface between the mother and fetus, but the relationship between the maternal and fetal circulation is still very difficult to study in vivo. There is growing evidence that magnetic resonance imaging (MRI) is useful and safe during pregnancy, and MRI is increasingly used for fetal and placental anatomical imaging. MRI functional imaging is now a modern obstetric tool and has the potential to provide new insights into the physiology of the human placenta. Placental perfusion has been studied during the first pass of an MR contrast agent, by arterial spin labeling, diffusion imaging, T1 and T2 relaxation time measurement using echo-planar imaging, and by a combination of magnetization transfer with established stereological methods. The BOLD (blood oxygen level-dependent) effect offers new perspectives for functional MRI evaluation of the placenta.

[Imaging of response to treatment in oncology]. / Imagerie de la réponse aux traitements en cancérologie.

Imaging plays a crucial role in oncology to assist in the management of patients and selection of drug regimen. Recent advances in imaging techniques allowing to predict and evaluate response to treatments in oncology will be reviewed. The standard in the evaluation of response to treatment is based on the measurement of lesion size. Functional imaging assesses physiological or molecular processes that may be earlier indicators of early response to treatment. Dynamic imaging of tumor vascularization assesses the biodistribution of a contrast agent within tumoral tissues. Diffusion-weighted MR imaging can differentiate free water from water restricted by tissues, providing an assessment of tumor cellularity. MR spectroscopy assesses the relative quantity of specific chemical components within normal and tumoral tissues. 18 FDG PET imaging provides an assessment of the metabolic activity of tissues. FDG uptake is proportional to cellular proliferation and number of viable cells within a tumor. Results from studies assessing the role of these emerging imaging techniques remain preliminary and the medical community must determine their respective role in the routine evaluation of response to treatment in oncological patients.

In vivo dynamic MRI measurement of the noradrenaline-induced reduction in placental blood flow in mice.

PURPOSE: We developed a new model for in vivo placental perfusion measurements based on dynamic MRI in mice. As noradrenaline has been implicated in the pathogenesis of preeclampsia, we examined whether it reduced placental perfusion in mice, and whether such a reduction could be detected with our MRI model. MATERIALS AND METHODS: Mice at 16 days of gestation were injected intramuscularly with saline or noradrenaline solution. A conventional gadolinium chelate was then injected IV, and a single-slice T1-weighed 2D Fast SPGR sequence was acquired for 200 s. Signal intensity was measured on all the images and converted into contrast agent tissue concentrations in the maternal left ventricle (input function) and placentas. A one-compartment model was developed using compartmental and numerical modeling software. Mean blood flow (F) was calculated from a transfer constant. RESULTS: Twenty-six mice were studied, yielding a total of 55 MRI measurements of placental perfusion (29 in the control group and 26 in the noradrenaline group). Mean placental blood flow (F) was significantly lower in the noradrenaline group (0.72+/-0.84 ml/min/g of placenta) than in the control group (1.26+/-0.54 ml/min/g of placenta). CONCLUSION: Noradrenaline reduces placental perfusion in mice. Our MRI dynamic model might be useful for detecting and investigating abnormal placental blood flow, thereby avoiding the need for invasive procedures and animal sacrifice.

[Placental functional assessment using MRI: mice today, humans tomorrow?]. / L'IRM fonctionnelle pour l'étude de la fonction placentaire: aujourd'hui chez la souris, demain chez l'homme?

Placental insufficiency, a process due to either poor placental perfusion or permeability, may lead to progressive deterioration in placental function and materno-fetal morbidity. Advances in MR contrast media pharmacokinetic studies of transit through tissues and dynamic MRI allow to characterize organs microcirculation in vivo. Placental function assessment might be achieved using analysis of dynamic contrast enhanced MRI of tracers. A murine model of placental assessment has been constructed. Herein, principles, results and limitations of such techniques are discussed as well as their potential interest and weaknesses in humans.

Evaluation of tumoral enhancement by superparamagnetic iron oxide particles: comparative studies with ferumoxtran and anionic iron oxide nanoparticles.

This study was designed to compare tumor enhancement by superparamagnetic iron oxide particles, using anionic iron oxide nanoparticles (AP) and ferumoxtran. In vitro, relaxometry and media with increasing complexity were used to assess the changes in r2 relaxivity due to cellular internalization. In vivo, 26 mice with subcutaneously implanted tumors were imaged for 24 h after injection of particles to describe kinetics of enhancement using T1 spin echo, T2 spin echo, and T2 fast spin echo sequences. In vitro, the r2 relaxivity decreased over time (0-4 h) when AP were uptaken by cells. The loss of r2 relaxivity was less pronounced with long (Hahn Echo) than short (Carr-Purcell-Meiboom-Gill) echo time sequences. In vivo, our results with ferumoxtran showed an early T2 peak (1 h), suggesting intravascular particles and a second peak in T1 (12 h), suggesting intrainterstitial accumulation of particles. With AP, the late peak (24 h) suggested an intracellular accumulation of particles. In vitro, anionic iron oxide nanoparticles are suitable for cellular labeling due to a high cellular uptake. Conversely, in vivo, ferumoxtran is suitable for passive targeting of tumors due to a favorable biodistribution.

Optimization of the sources in local hyperthermia using a combined finite element-genetic algorithm method.

This article describes an optimization process specially designed for local and regional hyperthermia in order to achieve the desired specific absorption rate in the patient. It is based on a genetic algorithm coupled to a finite element formulation. The optimization method is applied to real human organs meshes assembled from computerized tomography scans. A 3D finite element formulation is used to calculate the electromagnetic field in the patient, achieved by radiofrequency or microwave sources. Space discretization is performed using incomplete first order edge elements. The sparse complex symmetric matrix equation is solved using a conjugate gradient solver with potential projection pre-conditionning. The formulation is validated by comparison of calculated specific absorption rate distributions in a phantom to temperature measurements. A genetic algorithm is used to optimize the specific absorption rate distribution to predict the phases and amplitudes of the sources leading to the best focalization. The objective function is defined as the specific absorption rate ratio in the tumour and healthy tissues. Several constraints, regarding the specific absorption rate in tumour and the total power in the patient, may be prescribed. Results obtained with two types of applicators (waveguides and annular phased array) are presented and show the faculties of the developed optimization process.

Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media.

We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI) to study hemodynamic parameters in human prostate tumor xenografts, following treatment with the vascular endothelial growth factor-A (VEGF) receptor tyrosine kinase inhibitor, ZD4190. Using a macromolecular contrast agent (P792), a fast MR imaging protocol and a compartmental data analysis, we were able to demonstrate a significant simultaneous reduction in tumor vascular permeability, tumor vascular volume and tumor blood flow (43%, 30% and 42%, respectively) following ZD4190 treatment (100 mg/kg orally, 24 h and 2 h prior to imaging). This study indicates that MR imaging can be used to measure multiple hemodynamic parameters in tumors, and that tumor vascular permeability, volume and flow, can change in response to acute treatment with a VEGF signaling inhibitor.