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Background: Association of drugs acting against different antiangiogenic mechanisms may increase therapeutic effect and reduce resistance. Noninvasive monitoring of changes in the antiangiogenic response of individual tumors could guide selection and administration of drug combinations. Noninvasive detection of early therapeutic response during dual, vertical targeting of the vascular endothelial growth factor pathway was investigated in an ectopic subcutaneous xenograft model for human pancreatic tumor., Methods: Dynamic contrast-enhanced ultrasound 12 MHz was used to monitor tumor-bearing Naval Medical Research Institute mice beginning 15 days after tumor implantation. Mice received therapy from 15 to 29 days with sorafenib (N = 9), ziv-aflibercept (N = 11), combined antiangiogenic agents (N = 11), and placebo control (N = 14). Sorafenib (BAY 43-9006; Nexavar), a multikinase inhibitor acting on Raf kinase and receptor tyrosine kinases-including vascular endothelial growth factor receptors 2 and 3-was administered daily (60 mg/kg, per os). Ziv-aflibercept (ZALTRAP), a high-affinity ligand trap blocking the activity of vascular endothelial growth factor A, vascular endothelial growth factor B, and placental growth factor was administered twice per week (40 mg/kg, intraperitoneally)., Results: Functional evaluation with dynamic contrast-enhanced ultrasound indicated stable tumor vascularization for the control group while revealing significant and sustained reduction after 1 day of therapy in the combined group ( P = .007). There was no survival benefit or penalty due to drug combination. The functional progression-free survival assessed with dynamic contrast-enhanced ultrasound was significantly higher for the 3 treated groups; whereas, the progression-free survival based on tumor size did not discriminate therapeutic effect., Conclusions: Dynamic contrast-enhanced ultrasound, therefore, presents strong potential to monitor microvascular modifications during antiangiogenic therapy, a key role to monitoring antiangiogenic combining therapy to adapt dose range drug.

Purpose: To assess the added value of the dynamic contrast-enhanced sequence (DCE) to combination T2-weighted imaging (T2w) + diffusion-weighted imaging (DWI) in detecting prostate cancer (PCa) recurrence after HIFU (high-intensity focused ultrasound)., Methods: Forty-five males with clinical and biological suspected PCa recurrence were retrospectively selected. All underwent multi-parametric MRI (mpMRI) before biopsies. Two readers independently assigned a Likert score of cancer likelihood on T2w + DWI + DCE and T2w + DWI images. Prostatic biopsies were taken as the gold standard., Results: Recurrent PCa was identified at biopsy for 37 patients (82%). Areas under the receiver-operating curve of T2w + DWI and T2w + DWI + DCE imaging were not significantly different for both readers. Using a Likert score ≥ 3 for the PCa diagnosis threshold, sensitivity at the lobe level for the (1) senior and (2) junior reader for T2w +DWI +DCE sensitivity was (1) 0.97 and (2) 0.94 vs. (1) 0.94 and (2) 0.97 for T2w + DWI., Conclusion: Accuracy of mpMRI was not significantly improved by adding DCE to T2w + DWI. Sensitivity was high for T2w + DWI + DCE and T2w + DWI with no significant difference for either the junior or senior reader., Key Points: • MpMRI has the capability to detect PCa recurrence in post-HIFU monitoring. • The sensitivity of T2w and DWI for detecting PCa recurrence was not improved by DCE. • Readers with different degrees of experience did not improve their performance with DCE.

The aim of this study was to evaluate the capacity of BR55, an ultrasound contrast agent specifically targeting vascular endothelial growth factor receptor 2 (VEGFR2), to distinguish the specific anti-VEGFR2 therapy effect of sunitinib from other anti-angiogenic effects of a therapy (imatinib) that does not directly inhibit VEGFR2. Sunitinib, imatinib and placebo were administered daily for 11 d (264 h) to 45 BalbC mice bearing ectopic CT26 murine colorectal carcinomas. During the course of therapy, B-mode ultrasound, contrast-enhanced ultrasound and VEGFR2-targeted contrast-enhanced ultrasound were performed to assess tumor morphology, vascularization and VEGFR2 expression, respectively. The angiogenic effects on these three aspects were characterized using tumor volume, contrast-enhanced area and differential targeted enhancement. Necrosis, microvasculature and expression of VEGFR2 were also determined by histology and immunostaining. B-Mode imaging revealed that tumor growth was significantly decreased in sunitinib-treated mice at day 11 (p < 0.05), whereas imatinib did not affect growth. Functional evaluation revealed that the contrast-enhanced area decreased significantly (p < 0.02) and by similar amounts under both anti-angiogenic treatments by day 8 (192 h): -23% for imatinib and -21% for sunitinib. No significant decrease was observed in the placebo group. Targeted contrast-enhanced imaging revealed lower differential targeted enhancement, that is, lower levels of VEGFR2 expression, in sunitinib-treated mice relative to placebo-treated mice from 24 h (p < 0.05) and relative to both placebo- and imatinib-treated mice from 48 h (p < 0.05). Histologic assessment of tumors after the final imaging indicated that necrotic area was significantly higher for the sunitinib group (21%) than for the placebo (8%, p < 0.001) and imatinib (11%, p < 0.05) groups. VEGFR2-targeted ultrasound was able to sensitively differentiate the anti-VEGFR2 effect from the reduced area of tumor with functional flow produced by both anti-angiogenic agents. BR55 molecular imaging was, thus, able both to detect early therapeutic response to sunitinib in CT26 tumors as soon as 24 h after the beginning of the treatment and to provide early discrimination (48 h) between tumor response during anti-angiogenic therapy targeting VEGFR2 expression and response during anti-angiogenic therapy not directly acting on this receptor., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Dynamic contrast-enhanced ultrasound (DCE-US) sequences are subject to motion which can disturb functional flow quantification. This can make estimated parameters more variable or unreliable. Methods that compensate for motion are therefore desirable. The most commonly used motion correction techniques in DCE-US register the images in the sequence with respect to a user-selected reference image. However, this image may not include all features that are representative of the whole sequence. Moreover, image-based registration neglects pertinent, functional-flow information contained in the DCE-US sequence. An operator-free method is proposed that combines the motion estimation and flow-parameter quantification (M/Q method) in a single mathematical framework. This method is based on a realistic multiplicative model of the DCE-US noise. By computing likelihood in this model, motion and flow parameters are both estimated iteratively. First, the maximization is accomplished by estimating functional and motion parameters. Then, a final registration based on a non-parametric temporal smoothing of the sequence is performed. This method is compared to a conventional (mutual information) registration method where all the images of the sequence are registered with respect to a reference image chosen by an expert. The two methods are evaluated on simulated sequences and DCE-US sequences acquired in patients (N = 15). The M/Q method demonstrates significantly (p < 0.05) lower Dice coefficients and Hausdorff distance than the conventional method on the simulated data sets. On the in vivo sequences analysed, the M/Q methods outperformed the conventional method in terms of mean Dice and Hausdorff distance on 80% of the sequences, and in terms of standard deviation of Dice and Hausdorff distance on 87% of the sequences.

Objectives: Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure., Materials and Methods: This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point., Results: A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate., Conclusions: Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Ultrasound (US) scanners typically apply lossy, non-linear modifications to the US data for visualization purposes. The resulting images are then stored as compressed video data. Some system manufacturers provide dedicated software for quantification purposes to eliminate such processing distortions, at least partially. This is currently the recommended approach for quantitatively assessing changes in contrast-agent concentration from clinical data. However, the machine-specific access to US data and the limited set of analysis functionalities offered by each dedicated-software package make it difficult to perform comparable analyses with different US systems. The objective of this work was to establish if linearization of compressed video images obtained with an arbitrary US system can provide an alternative to dedicated-software analysis of machine-specific files for the estimation of echo-power. For this purpose, an Aplio 50 system (Toshiba Medical Systems, Tochigi, Japan), coupled with dedicated CHI-Q (Contrast Harmonic Imaging Quantification) software by Toshiba Medical Systems, was used. Results were compared with two approaches that apply algorithms to estimate relative echo-power from compressed video images: commercially available VueBox software by Bracco Suisse SA (Geneva, Switzerland) and in-laboratory software called PixPower. The echo-power estimated by CHI-Q analysis indicated a strong linear relationship versus agent concentration in vitro (R(2) ≥ 0.9996) for dynamic range (DR) settings of DR60 and DR80, with slopes between 9.22 and 9.57 dB/decade (p = 0.05). These values approach the theoretically predicted dependence of 10.0 dB/decade (equivalent to 3 dB for each concentration doubling). Echo-power estimations obtained from compressed video images with VueBox and PixPower also exhibited strong linear proportionality with concentration (R(2) ≥ 0.9996), with slopes between 9.30 and 9.68 dB/decade (p = 0.05). On an independent in vivo data set (N = 24), the difference in echo-power estimation between CHI-Q and each of the other two approaches was calculated after excluding regions that contain pixels affected by saturated or thresholded pixel values. The mean difference in estimates (expressed in decibels) was -0.25 dB between VueBox and CHI-Q (95% confidence interval: -0.75 to 0.26 dB) and -0.17 dB between PixPower and CHI-Q (95% confidence interval: -0.67 to 0.13 dB). To achieve linearization of data, one of the approaches (VueBox) requires calibration files provided by the software manufacturer for each machine type and setting. The other (PixPower) requires empirical correction of the imaging dynamic range based on ground truth data. These requirements could potentially be removed if US system manufacturers were willing to make relevant information on the applied processing publically available. Reliable echo-power estimation from linearized data would facilitate inclusion of different US systems in multicentric studies and more widespread implementation of emerging techniques for quantitative analysis of contrast ultrasound., (2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved)

Imaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points • DCE ultrasound can quantify and extract specific blood flow parameters, such as flow velocity, relative vascular volume and relative blood flow rate. • DCE ultrasound can be performed repeatedly and is therefore ideally suited for pharmacokinetic and pharmacodynamic studies evaluating vascular-targeted drugs. • DCE ultrasound provides a reproducible method of assessing the vascular effects of therapy in pre-clinical and early clinical trials, which is easily translatable into routine clinical practice.

Contrast-enhanced ultrasound (CEUS), with the recent development of both contrast-specific imaging modalities and microbubble-based contrast agents, allows noninvasive quantification of microcirculation in vivo. Nevertheless, functional parameters obtained by modeling contrast uptake kinetics could be impaired by respiratory motion. Accordingly, we developed an automatic respiratory gating method and tested it on 35 CEUS hepatic datasets with focal lesions. Each dataset included fundamental mode and cadence contrast pulse sequencing (CPS) mode sequences acquired simultaneously. The developed method consisted in (1) the estimation of the respiratory kinetics as a linear combination of the first components provided by a principal components analysis constrained by a prior knowledge on the respiratory rate in the frequency domain, (2) the automated generation of two respiratory-gated subsequences from the CPS mode sequence by detecting end-of-inspiration and end-of-expiration phases from the respiratory kinetics. The fundamental mode enabled a more reliable estimation of the respiratory kinetics than the CPS mode. The k-means algorithm was applied on both the original CPS mode sequences and the respiratory-gated subsequences resulting in clustering maps and associated mean kinetics. Our respiratory gating process allowed better superimposition of manually drawn lesion contours on k-means clustering maps as well as substantial improvement of the quality of contrast uptake kinetics. While the quality of maps and kinetics was satisfactory in only 11/35 datasets before gating, it was satisfactory in 34/35 datasets after gating. Moreover, noise amplitude estimated within the delineated lesions was reduced from 62 ± 21 to 40 ± 10 (p < 0.01) after gating. These findings were supported by the low residual horizontal (0.44 ± 0.29 mm) and vertical (0.15 ± 0.16 mm) shifts found during manual motion correction of each respiratory-gated subsequence. The developed technique could be used as a basis for accurate quantification of perfusion parameters for the evaluation and follow-up of patients under antiangiogenic therapies.

Angiogenesis regulation is one of the newest fronts in the fight against cancer. Anti-angiogenic therapy is based on inhibiting factors required to solicit vessel formation thus cutting-off the tumor's supply of nutriments and oxygen. Initial vascular response is followed by formation of necrosis. Volumetric regression occurs more tardively. Effective monitoring of this new therapeutic approach thus requires imaging techniques that can detect early microvascular changes. A number of clinical studies provide evidence that contrast-enhanced ultrasound (CEUS) can provide early indication of tumor response to anti-angiogenic therapy. More sophisticated imaging and analysis techniques for CEUS and contrast agents targeted for adhesion to anti-angiogenic markers have also demonstrated promise in animal model studies. This review underlines the relevance of CEUS for anti-angiogenic therapy monitoring by summarizing the current clinical results, emerging CEUS techniques and preclinical data., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

The recent introduction of high-end ultrasound equipment combined with recent contrast agents provides marked improvements in the characterization of focal liver lesions as previously reported by monocentric studies. The aim of the present study was to evaluate the diagnostic performance of Contrast-Enhanced Ultrasonography (CEUS) using SonoVue as well as its medico-economic value for characterization of focal liver lesions. These nodules were not characterized on previous CT or conventional sonography. This prospective multicentric study conducted in 15 French centres found diagnostic performances similar to those reported for CT and MRI, with a concordance rate of 84.5%, sensitivity greater than 80% and specificity greater than 90% for all types of lesions. Higher acceptance was found for CEUS compared to other imaging modalities. Economical assessment based on examination reimbursment and contrast agent cost showed a lower cost for contrast ultrasound versus CT and MRI. This French multicentric study confirmed the high diagnostic value of CEUS for focal liver lesion characterization and demonstrated a lower economical impact compared to other imaging modalities such as CT and MRI.

Quantitative analysis of tissue perfusion using contrast-enhanced ultrasound is still limited by shadowing, which is caused by inadequate compensation for microbubble contrast agent attenuation. Many previous methods have been developed for attenuation correction in soft tissues. However, no method has been proposed to correct for microbubble attenuation in vivo. In this article, a model to estimate microbubble attenuation is presented, using the time-intensity variation in a highly echogenic distal area without contrast uptake. This model is based on the assumption that a linear relationship holds between local microbubble attenuation and local backscatter. The model was applied to 12 murine renal perfusion studies. Parametric images of microbubble attenuation were generated, corresponding to dynamic contrast agent-specific sequences without shadowing. Contrast uptake kinetics consistent with the physiology were retrieved in all perfused areas. This method therefore proved to be of potential interest in the quantification of tissue perfusion in small animal studies.

Despite recent advances in contrast-enhanced ultrasound imaging, evaluation of tissue perfusion with contrast-enhanced ultrasound is still impaired by shadowing effects. These effects are particularly relevant in small animal studies due to high frequency imaging. Current methods of tissue attenuation correction are not suited for contrast-enhanced ultrasound examinations, because microbubble acoustic response to ultrasound waves is far more complex than that of tissues. A method allowing in vivo tissue attenuation correction in the presence of contrast agents is presented.

The aim of this paper was to validate the combination of two original methods for assessing perfusion in small animal studies using Contrast-Enhanced Ultrasound. Respiratory motion was first removed using a frame selection method. This method, based on a Principal Component Analysis, enabled the definition of two subsequences, corresponding to the end-of-inspiration plane and to the end-of-expiration plane. Attenuation caused by contrast agent microbubbles was then estimated. The developed method, based on the assumption that a linear relationship holds between local attenuation and backscatter, used the time-intensity variation in a highly echogenic distal area without contrast uptake to estimate local attenuation coefficients. Ten murine renal perfusion studies were investigated after a bolus injection of SonoVue. Replenishment kinetics were acquired too and were finally modeled with an exponential function. Preliminary results were promising. Indeed, the SonoVue concentration was more faithfully represented than on native images, which allowed a better assessment of perfusion parameters in the whole field of view.

Objective: Our goal was to develop a reliable technique that has minimal operator dependence for quantifying lymph node enhancement to test and optimize new sonography contrast formulations., Materials and Methods: Twenty healthy rabbits were studied using five agents, labeled A-G. Agents D and E were the same agent and agents F and G were Imagent, studied blindly to test reproducibility. One milliliter of contrast agent was injected into each hind footpad. A 13-MHz transducer was fixed over the popliteal node, which was imaged at a 4.8-MHz central transmit frequency using phase-inversion technology at 100% power and one frame per second. Immediately after each injection, the footpad was massaged 12 times for 30 sec each time and then imaged after each massage to assess the number of times the node could be refilled from each injection. Lymph node video intensity was measured, and the degree of enhancement was evaluated using analysis of variance with the massage number and the agent used as independent variables., Results: Lymph node enhancement was observed after the first massage with all agents. Degree of enhancement was least with agents A and B, intermediate with agents D and F, and greatest with agent C. Agent A was effective after the first two massages, agent B after the first four, agent C after all 12, agent D after the first eight, and agent F after the first nine. Performance of agents D and F was similar to that of their duplicates, E and G., Conclusion: We established a reproducible technique to quantify lymph node enhancement that can distinguish between different agents. The differences in performance suggest that it is possible to optimize agent formulation for indirect sonographic lymphography.

Rationale and Objectives: To optimize an angiogenesis model for imaging research that is stable and can be imaged several times over the angiogenic time course., Materials and Methods: Mice and rats received two injections of 0.4 mL of extract of basement membrane matrix (Matrigel; Becton Dickinson Labware, Bedford, MA) in the subcutaneous spaces on either side of the spine. One of the two Matrigel plugs in each animal had either 0.1 microg/mL of basic fibroblast growth factor (bFGF) (11 mice), 1.0 microg/mL of bFGF (12 mice, 5 rats), or 1.0 microg/mL of bFGF and 60 U/mL of heparin (11 mice). Three to 12 days after implantation, animals were imaged before and after the administration of up to four injections of 0.1 mL AF0150. Phase inversion imaging was used on a Siemens Elegra (Siemens ultrasound, Issaquah, WA) equipped with a 13 MHz VFX transducer. Three observers subjectively assessed the pattern of enhancement using a four-point scale. The Matrigel plugs were then removed and two observers graded the angiogenic response on a four-point scale. Ten Matrigel plugs, five with 1.0 microg/mL bFGF and five without, were evaluated histologically following immunohistochemical staining with anti-CD31., Results: The angiogenic response was greater in Matrigel plugs with 1.0 than with 0.1 microg/mL of bFGF. Heparin did not increase the angiogenic response. Vessels were predominantly at the periphery of the plugs with variable central penetration. Plugs appeared anechoic and homogeneous on ultrasound. Contrast enhancement within the plug occurred in 44% of mice with an angiogenic response at or after day 6 and the enhancement increased with the angiogenic response. In the others, peripheral enhancement could not be distinguished from the enhancement of surrounding tissues that were also hyperemic. The thicker rat skin interfered with plug assessment., Conclusion: A stable angiogenesis model without the complexity of tumors is described. This model offers the opportunity to image the development and/or inhibition of angiogenesis. Neovasculature in Matrigel was detectable using ultrasound contrast. Quantitative studies correlating the degree of enhancement to microvascular density will be determined in subsequent studies.

Purpose: To investigate changes in destruction-replenishment curves (in vitro and in vivo) that result from microbubble destruction in feeding vessels that pass through the imaging plane before microbubbles enter the region of interest (ROI)., Materials and Methods: During continuous injections of an ultrasonographic contrast agent, nonlinear gray-scale images were obtained in vitro in the longitudinal plane of a renal dialysis cartridge flow phantom (flow rates of 100, 200, and 400 mL/min) and in vivo in the coronal plane of the left kidneys of two rabbits (two kidneys). Destruction-replenishment curves were obtained for the dialysis cartridge in ROIs located immediately after the entrance of the microbubbles into the image plane and further from the entrance, after microbubbles had traveled across the complete length of the imaging plane. Replenishment curves were also obtained from ROIs in the rabbit kidneys at the level of segmental arteries, distal interlobar arteries, and the cortex., Results: The ROIs immediately after the entrance of the microbubbles in the image plane of the dialysis cartridge and in the segmental artery of the kidney followed a typical exponential function, A(1 - e-alphat). Early portions of curves obtained in ROIs filled with microbubbles that had already passed through the image plane of the dialysis cartridge or in the renal cortex were not well described by such a function. The shape of the curve and the variations as a function of flow rate can be explained by means of a mathematical model based on indicator-dilution theory., Conclusion: When the feeding vessels of an ROI travel across the ultrasound field before they reach the measurement region, the typical shape of the replenishment curve is modified (reduced velocity parameter and plateau)., (Copyright RSNA, 2003.)

Our goal was to compare two quantification methods of ultrasound contrast agents available in clinical practice [continuous wave Doppler intensity (CWDI) and power Doppler intensity (PWDI)] to the reference technique (radio-frequency analysis) with a simple recirculating flow phantom using a renal dialysis cartridge. Measurements were made at different doses of perflenapent emulsion and BR1. Cineloops of power Doppler images were recorded using a clinically available ultrasound unit (HDI 3000). Simultaneously, integrated backscatter (IBS) was measured by analysis of radiofrequency signals, whereas Doppler signal intensity was measured with a continuous wave Doppler device. A linear relationship was found between CWDI and IBS and between PWDI and IBS when R(2) was calculated for each pair of parameters injection-by-injection. Results are summarized by the average R(2) for all injections between CWDI and IBS (BR1: R(2) = 0.93 +/- 0.05, perflenapent emulsion: R(2) = 0.94 +/- 0.03) and between PWDI and IBS (BR1: R(2) = 0.88 +/- 0.07, perflenapent emulsion: R(2) = 0.79 +/- 0.09). However, for all data obtained from all different injected doses and for both contrast agents, there was considerable variation of CWDI and PWDI values measured for a given value of IBS. In conclusion, for a fixed microbubble population, CWDI and PWDI can be proposed for quantification of USCA. However, their important variations observed at each dose make it difficult to link a single value of PWDI or CWDI or IBS to a single microbubble distribution composition.

Objective: The objective of this study was to evaluate inter- and intraobserver agreement in the diagnosis of central pulmonary embolism using contrast-enhanced helical CT among observers with variable experience in the interpretation of pulmonary CT angiograms., Materials and Methods: Helical CT angiograms of 60 patients clinically suspected of having pulmonary embolism were analyzed retrospectively and independently by two chest radiologists, one cardiovascular radiologist, and three general radiologists. The films were rated a second time by the chest radiologists to assess intraobserver variability. Findings for pulmonary embolism were categorized as positive, negative, or indeterminate at the main, lobar, and segmental pulmonary artery levels., Results: The observers interpreted 19-21 CT angiograms as positive for pulmonary embolism (mean, 19.7) and one to six as indeterminate (mean, 3.2). Agreement occurred among all observers in 50 patients (83.3%), among five observers in six patients (10.0%), among four observers in three patients (5.0%), and among three observers in one patient (1.7%). Interobserver agreement was very good (kappa, .85) for the diagnosis of pulmonary embolism on a per-patient basis. Agreement on a per-artery basis for all arteries was moderate (66%; kappa, .56); for lobar arteries was good (83%; kappa, .75); and for segmental arteries was moderate (57%; kappa, .47). Mean intraobserver agreement on a per-patient basis was very good (93%; kappa, .87)., Conclusion: Inter- and intraobserver agreement in the diagnosis of pulmonary embolism with helical CT is very good despite a wide variety of experience among radiologists.

Objective: Our goal was to evaluate dynamic contrast-enhanced subtraction MRI in the diagnosis of isolated clustered calcifications of the breast., Materials and Methods: One hundred seventy-two patients underwent surgical biopsy for isolated clustered breast calcifications. Their mammograms showed round (n = 88) or linear/irregular (n = 84) microcalcifications. All patients had a preoperative Gd-DOTA-enhanced subtraction dynamic study. Any early contrast enhancement in the breast parenchyma concomitant with early enhancement of normal vessels was considered positive., Results: Fifty-eight in situ carcinomas, 22 invasive carcinomas, and 92 benign lesions were found at histological analysis. Dynamic MR sequences showed early contrast enhancement in 76 of 80 malignant lesions (sensitivity 95%) and in 45 of 92 benign lesions (specificity 51%). Two invasive and two intraductal carcinomas did not show early contrast enhancement. Three independent observers agreed in rating early contrast enhancement in 143 of 172 lesions., Conclusion: Poor specificity limits the diagnostic accuracy of dynamic contrast-enhanced subtraction MRI in distinguishing benign from malignant microcalcifications on mammography.

Purpose: To determine the accuracy of contrast material-enhanced subtraction dynamic magnetic resonance (MR) imaging in the diagnosis of nonpalpable breast tumors., Materials and Methods: One hundred forty-three patients underwent surgical biopsy of a nonpalpable breast lesion. Their mammograms showed microcalcifications (n = 80), opacity (n = 52), architectural distortion (n = 10), or asymmetric density (n = 1). All patients underwent a preoperative gadolinium tetraazacyclododecanetetraacetic acid-enhanced subtraction dynamic study. Any early contrast enhancement in the breast parenchyma was considered pathologic., Results: At histologic analysis, 27 intraductal carcinomas, 37 invasive carcinomas, and 79 benign lesions were found. Dynamic MR studies showed early contrast enhancement in 61 of 64 breast cancers (sensitivity, 95%) and in 37 of 79 benign lesions (specificity, 53%). Two invasive lobular carcinomas and one tubular carcinoma showed no early contrast enhancement., Conclusion: Subtraction dynamic MR imaging may be helpful to rule out malignancy in nonpalpable breast tumors.