Olivier Lucidarme

Enhancement of liver parenchyma after injection of hepatocyte-specific MRI contrast media: a comparison of gadoxetic acid and gadobenate dimeglumine

To compare enhancement of liver parenchyma in MR imaging after injection of hepatocyte‐specific contrast media.

Noninvasive Contrast-enhanced US Quantitative Assessment of Tumor Microcirculation in a Murine Model: Effect of Discontinuing Anti-VEGF Therapy

PURPOSE To determine, by using contrast material-enhanced ultrasonography (US), how quickly renal tumors grafted in mice begin to revascularize after stopping bevacizumab treatment. MATERIALS AND METHODS All experiments were approved by the regional ethics committee. A human tumor cell line SK-NEP-1 was grafted at day 0 in the left kidney of 50 nude mice. Forty-two mice developed tumors and longitudinal follow-up was performed on 32 surviving mice. From day 13, 14 controls received biweekly saline; 11 mice received biweekly bevacizumab until day 35 (continuous); and seven received biweekly bevacizumab until day 22, then biweekly placebo until day 35 (discontinued). Contrast-enhanced US was performed on days 13, 14, 22, 27, and 35. Once the injected contrast material distribution reached an equilibrium phase, high-acoustic pressure pulses were applied to destroy microbubbles in the capillary bed in the imaged plane. Reperfusion was monitored, and time-signal intensity (SI) curves were obtained from the linear average of SIs in intratumoral and matched-depth renal cortex regions of interest. A kinetic parameter calculated from reperfusion curves reflects local perfusion, normalized with respect to adjacent renal cortex perfusion. Normalized perfusion obtained from each group was compared with that from the other groups and with necrosis percentages and microvascular density assessed histologically at day 35. Comparisons were made by using analyses of variance and Tukey-Kramer tests. RESULTS The lowest excised mean tumor weights (+/- standard deviation) corresponded to the longest bevacizumab-treatment duration: 1.4 g +/- 1.1 (continuous-treatment) compared with 2.3 g +/- 2.1 (discontinued) and 3.7 g +/- 1.9 (control) (P = .01). On day 35, the respective control and continuously treated groups had comparable and significantly larger necrotic areas: 37% +/- 14 and 32% +/- 17 larger than the discontinued-treatment group (15% +/- 9; P < .05). Normalized perfusion increased significantly with time (P = .02) in the discontinued-treatment group after therapy ceased (day 22). CONCLUSION Noninvasively measured contrast-enhanced US parameters demonstrated tumor revascularization after stopping antiangiogenic therapy in this murine tumor model.

Validation of ultrasound contrast destruction imaging for flow quantification

Abstract Our purpose was to validate in vitro a kinetic flow model based on microbubble signal decay curve. Using a 3.5 MHz transducer and phase-inversion (1.8 MHz central transmit frequency), a renal dialysis cartridge oriented vertically was imaged in the transverse plane as 1:1000 dilution of AF0150 was infused at 50, 100, 200, 300 and 400 mL/min. Ten gray-scale images were acquired at each infusion rate using 2.5, 5 and 10 frames/s at 100%, 40%, 15% or 1% of maximum transmit power. Video-intensity measured on each 10 images was fit to a kinetic model using Sigma Plot that yielded microbubble concentration, velocity and destruction per frame. These were correlated with the experimental conditions. At 100% power, video-intensity on the first frame (microbubble concentration at equilibrium) was similar for all flow and frame rates. The model fit the experimental data for all flows at 10 frames/s and for flows lower than 400 and 100 mL/min at 5 frames/s and 2.5 frames/s, respectively. The calculated flow was similar to the experimental flow rates, regardless of technique (r 2 = 0.98). Microbubble fraction destroyed per frame was similar for all flow and frame rates and increased linearly with transmit power (r 2 > 0.98). These results suggest that using appropriate power and frame rate for a given flow rate, estimates of fractional blood volume, flow and destruction fraction can be calculated from the decay curve using 10 frames that can be acquired in 1 to 4 s. (E-mail: rmattrey@ucsd.edu)

Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials

AbstractImaging 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.

Angiogenesis model for ultrasound contrast research

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.

CT hepatic venography: 3D vascular segmentation for preoperative evaluation

Preventing complications during hepatic surgery in living-donor transplantation or in oncologic resections requires a careful preoperative analysis of the hepatic venous anatomy. Such an analysis relies on CT hepatic venography data, which enhances the vascular structure due to contrast medium injection. However, a 3D investigation of the enhanced vascular anatomy based on typical computer vision tools is ineffective because of the large amount of occlusive opacities to be removed. This paper proposes an automated 3D approach for the segmentation of the vascular structure in CT hepatic venography, providing the appropriate tools for such an investigation. The developed methodology relies on advanced topological and morphological operators applied in mono- and multiresolution filtering schemes. It allows to discriminate the opacified vessels from the bone structures and liver parenchyma regardless of noise presence or inter-patient variability in contrast medium dispersion. The proposed approach was demonstrated at different phases of hepatic perfusion and is currently under extensive validation in clinical routine.

Dual-mode registration of dynamic contrast-enhanced ultrasound combining tissue and contrast sequences

This study proposes a new method for automatic, iterative image registration in the context of dynamic contrast-enhanced ultrasound (DCE-US) imaging. By constructing a cost function of image registration using a combination of the tissue and contrast-microbubble responses, this new method, referred to as dual-mode registration, performs alignment based on both tissue and vascular structures. Data from five focal liver lesions (FLLs) were used for the evaluation. Automatic registration based on the dual-mode registration technique and tissue-mode registration obtained using the linear response image sequence alone were compared to manual alignment of the sequence by an expert. Comparison of the maximum distance between the transformations applied by the automatic registration techniques and those from expert manual registration reference showed that the dual-mode registration provided better precision than the tissue-mode registration for all cases. The reduction of maximum distance ranged from 0.25 to 9.3mm. Dual-mode registration is also significantly better than tissue-mode registration for the five sequences with p-values lower than 0.03. The improved sequence alignment is also demonstrated visually by comparison of images from the sequences and the video playbacks of the motion-corrected sequences. This new registration technique better maintains a selected region of interest (ROI) within a fixed position of the image plane throughout the DCE-US sequence. This should reduce motion-related variability of the echo-power estimations and, thus, contribute to more robust perfusion quantification with DCE-US.

Abstract 4106: Modified RECIST for monitoring hepatocellular carcinoma with computed tomography: Inter-reader variability of the response

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. In clinical trials, computer tomography (CT) is a widely used imaging technique for the monitoring of HCC patients, and modified RECIST (mRECIST) have been suggested as appropriate criteria in part because they distinguish the viable part from the necrotic part of the tumor. Based on longitudinal changes of tumor burden, this study investigates the causes of inter-reader variability in evaluating the therapeutic response of HCC when relying on mRECIST. 24 patients with advanced (unresectable and/or metastatic) HCC enrolled in a phase I/II multicentre international study were retrospectively reviewed. From the originally selected target lesions, 41 were randomly selected. Original mRECIST expert evaluations were aggregated to the retrospective readings of three radiologists having different expertise (non mRECIST experts). All the 150 readings performed by each readers were made in using an electronic calliper. Precision of measurements between couple of readers was analysed by assessing standard deviation (SD) and reproducibility coefficient (RDC). The agreement of readers responses were compared by using Kappa coefficient statistic. The variability between non-experts and the variability between mRECIST expert and non-experts were analysed. Reader9s disagreement at declaring progressive (PD) and responding (PR) patient, were visually classified between variability of the measure, difference in the perception of tumour boundaries and differences in using either RECIST or mRECIST criteria for a given lesion. SD of measurements between non-experts ranged [24.9%; 36.3%] and RDC was 16.6 [13.85; 23.95]. Kappa coefficients was 0.41 [0.28; 0.55]. SD of expert against non-experts ranged [33.2%; 41.1%] and RDC was 18.8 [16.02; 24.53]. Kappa coefficients was 0.20 [0.06; 0.35]. Pooling the four readers together, rate of discrepancy at declaring respectively PD or PR by patients was 47.8% (11/23) and 34.8% (8/23). 90.9% (10/11) of discrepancies at declaring PD were due to different perceptions of tumour boundaries. Discrepancy at declaring PR was, in 62.5% of the cases, correlated to the application of mRECIST, 25% was correlated to different perception of tumours boundaries. Inter-reader variability of HCC measurements was large which leads to poor agreement in the response. The main cause of discrepancy at declaring PD originated from the complexity of HCC patterns and the poor definition of tumours boundaries while discrepancies at detecting PR come from the variability of readers at selecting the viable part of the tumours. In the context of HCC clinical trials, reliability of endpoints depend on the criteria involved. Present study must be completed with an inter-reader analysis of the variability between mRECIST experts. Citation Format: hubert Beaumont, Sophie Egels, Antoine Iannessi, Eric Bonnard, Christopher Foley, Olivier Lucidarme. Modified RECIST for monitoring hepatocellular carcinoma with computed tomography: Inter-reader variability of the response. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4106.

On-line scalable image access for medical remote collaborative meetings

The increasing need of remote medical investigation services in the framework of collaborative multidisciplinary meetings (e.g. cancer follow-up) raises the challenge of on-line remote access of (large amount of) radiologic data in a limited period of time. This paper proposes a scalable compression framework of DICOM images providing low-latency display through low speed networks. The developed approach relies on useless information removal from images (i.e. not related with the patient body) and the exploitation of the JPEG2000 standard to achieve progressive quality encoding and access of the data. This mechanism also allows the efficient exploitation of any idle times (corresponding to on-line visual image analysis) to download the remaining data at lossless quality in a way transparent to the user, thus minimizing the perceived latency. The experiments performed in comparison with exchanging uncompressed or JPEGlossless compressed DICOM data, showed the benefit of the proposed approach for collaborative on-line remote diagnosis and follow-up services.