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Resume Les therapies ciblees ont considerablement ameliore le pronostic des patients atteints d’un cancer du rein metastatique (CCRm) mais on ne dispose pas de criteres d’evaluation de reponse fiables refletant les benefices cliniques car la regression en taille est absente ou retardee. Ces criteres permettraient l’identification precoce des non-repondeurs qui beneficieraient alors d’un changement therapeutique et leur eviteraient d’inutiles effets secondaires lies au traitement. Nous passerons en revue les techniques d’imagerie actuellement disponibles pour l’evaluation de la reponse tumorale chez les patients CCRm, dont les criteres de reponse des tumeurs solides (RECIST), les criteres Choi, les criteres Choi modifies, et les criteres de densite et de taille en CT (SACT). Nous aborderons aussi les techniques d’imagerie fonctionnelle qui se basent sur les caracteristiques physiologiques des tumeurs telles que le scanner, l’imagerie par resonance magnetique ou l’echographie de perfusion (DCE-CT, DCE-MRI, DCE-US), l’IRM de diffusion, l’IRM par effet BOLD et les nouveaux traceurs en tomographie par emission de positons (TEP). Il n’est pas possible actuellement de proposer un critere unanimement reconnu pour l’evaluation de la reponse tumorale aux therapies dites ciblees. Cependant, il s’agit d’un besoin reel exprime par les oncologues et les industriels, et les radiologues doivent s’impliquer dans cette reflexion.

To investigate blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging in an intrauterine growth restriction (IUGR) rat model as a noninvasive in vivo tool to evaluate the response of the fetoplacental units (FPUs) to oxygenationAll procedures were approved by the animal care committee. The study was performed between February and July 2010. The IUGR model based on the ligation of the left uterine vascular pedicle at embryonic day 17 of gestation was validated by weighing placentas and fetuses after MR imaging. FPUs in the left and right uterine horns were IUGR cases and controls, respectively. A small-animal 4.7-T MR imager was used. Multiple gradient-echo sequence (repetition time msec/echo time msec, 800/1.8-49.8) was performed at embryonic day 19. T2* relaxation time was measured before and after maternal hyperoxygenation for live FPUs in placenta, fetal liver, and brain. The effect of hyperoxygenation on BOLD MR imaging was analyzed with change in T2* between hyperoxygenation and ambient air. After dissection, live fetuses from both horns were identified and weighed. Changes in T2* were compared based on Student t tests. A mixed model was used to compare BOLD effect among horns and organs.Sixteen rats were studied. There was a significant fetal weight decrease in the IUGR FPUs (-21.9%; P.001). Change in T2* differed significantly between IUGR cases and controls for placenta (5.25 msec vs 11.25 msec; P.001) and fetal brain (3.7 msec vs 7.17 msec; P = .02), whereas there was no significant difference in the fetal liver (2.72 msec vs 3.18 msec; P = .47).BOLD MR imaging at 4.7 T can be used to evaluate the response to oxygenation in normal and IUGR FPUs. This technique has a potential role in the assessment of human pregnancy.

Purpose To determine whether diffusion-weighted imaging (DWI) characteristics could predict the effectiveness of uterine arterial embolization in treatment of fibroids. Methods This retrospective study included 17 women (27 fibroids) who underwent uterine arterial embolization for fibroids. MR imaging (1.5 T) was performed before, 1 week and 6 months after uterine arterial embolization. The volume, T2 signal, T1 signal, enhancement after contrast media injection, DWI signal (b = 500 s/mm2) and apparent diffusion coefficient (ADC) were assessed for fibroids. Results DWI signal or ADC, whether before or 1 week after the procedure, did not show a statistical relationship to success of uterine arterial embolization. On the 1-week follow-up, 22% of fibroids enhanced vs. 85% on baseline, P < 0.0001 and DW signal intensity increased. ADC values in fibroids decreased between baseline and 1-week (1.61 vs. 1.53 × 10−3 mm2/s, P = 0.13). On 6-months, ADC continued to decrease compared with baseline (1.27 × 10−3 mm2/s, P = 0.002), but with a lower signal on DWI. No changes were observed in myometrium ADC at any time point. Conclusion Our study demonstrated that DWI and ADC reflected early and delayed changes in fibroids after embolization; however, we were not able to demonstrate a statistically significant relationship with outcome. Magn Reson Med 70:1739–1747, 2013. © 2013 Wiley Periodicals, Inc.

The objectives of this study were to evaluate the potential of intravoxel incoherent motion (IVIM) magnetic resonance imaging at 4.7 T to distinguish decreased placental perfusion from normal perfusion in a controlled murine model and to determine the effect of transient maternal hyperoxygenation on placental microvascularization.The study was approved by our animal care committee. Ten pregnant rats underwent ligation of the left uterine vascular pedicle on the 17th embryonic day (E17). A multishot diffusion-weighted spin-echo echo-planar imaging sequence, using 14 b values (b10 to b800), was performed on the 19th embryonic day (E19) under room air and during maternal hyperoxygenation. For each placenta and its 2 layers, the signal intensity decay curve according to the b values was obtained. The following IVIM parameters were calculated using biexponential fitting: the diffusion coefficient (D), the pseudodiffusion coefficient (D*), and the perfusion fraction (f). Mixed regression modeling was used to analyze the effect of ligation status, oxygenation, and the placental layer on IVIM parameters.Seventy-three placentas were examined: 23 in the ligated horn and 50 in the nonligated control horn. The IVIM parameters were obtained for 67% of the placentas. In the control horn, the mean (SD) values on room air were 28% (13%), 9.6 (9) ×10(-3) mm(2)/s, and 0.88 (0.36) ×10(-3) mm(2)/s for the perfusion fraction, the pseudodiffusion coefficient, and the diffusion coefficient, respectively. The perfusion fraction was significantly decreased in the ligated horn (-6.7% [1.9%]; P = 0.001) and during maternal hyperoxygenation (-3.3 [1.64%]; P = 0.047). The diffusion coefficient increased significantly during the hyperoxygenation (0.26 [0.04] × 10(-3) mm(2)/s; P = 0.0001) and in the inner placental layer (0.21 [0.05] ×10(-3) mm(2)/s; P = 0.0001).The perfusion fraction is a sensitive marker of decreased placental perfusion. The perfusion fraction and the diffusion coefficient are modified during the hyperoxygenation. Our IVIM-based approach may help in the investigation and early diagnosis of vascular diseases during pregnancy.

Background The role of the hypovolemic component secondary to the microcirculatory changes in the onset of inaugural anaphylactic hypotension remains debated. We investigated the microcirculatory permeability in a model of anaphylactic shock using a fluorescence confocal microscopy imaging system. Methods Ovalbumin-sensitized anesthetized Brown Norway rats were randomly allocated into two groups (n = 6/group): control and anaphylaxis, respectively induced by intravenous saline or ovalbumin at time 0 (T0). The mesentery was surgically exposed. Macromolecular fluorescein isothiocyanate-dextran was intravenously injected (T0-5min) allowing in vivo visualization of the mesenteric microvascular network by fluorescence microscopy. After a period of stabilization of the contrast agent concentration, a 5-s movie was recorded to obtain baseline signal intensity. Following T0, 5-s movies were recorded every 30 s for 30 min. Capillary leakage of fluorescein isothiocyanate-dextran was assessed in interstitium and compared between groups. Data are expressed as mean ± SD. Results Following anaphylactic shock onset, an early, progressive, and global signal intensity increase over time was detected in the interstitium. Mean index leakage differed between control and anaphylaxis (respectively 20 ± 11 vs. 170 ± 127%; P < 0.0001), starting at 2 min after shock onset and progressively increasing. Index leakage correlated with the drop in arterial blood pressure until T0 + 10 min (r = -0.75, P = 0.0001). Conclusions During anaphylaxis, interstitial capillary leakage occurs within minutes after shock onset. Compared with controls, the mesenteric microcirculation showed at least 8-fold-increased macromolecular capillary leakage. The inflammation-induced microcirculatory changes with subsequent intravascular fluid transfer might be involved in the onset of the inaugural hypotension during anaphylactic shock.

To evaluate the rate of positive, negative, and indeterminate results and the agreement between initial and expert readings for lung scintigraphy and computed tomographic (CT) angiography performed in patients suspected of having pulmonary embolism (PE) during pregnancy.Institutional review board approval was obtained. The authors retrospectively analyzed the images from lung scintigraphy and CT angiography performed in pregnant patients during the past 9 years. Images from 46 CT angiographic examinations performed in 43 patients and 91 of 94 lung scintigraphic examinations were reviewed by experts, whose readings were then compared with the initial reports. For CT angiography, the quality of opacification was graded as good, suboptimal, or poor and intraarterial attenuation was measured.The rates of positive findings (seven of 43 patients [16%] with CT angiography and 10 of 91 patients [11%] with scintigraphy, P = .36), negative findings (28 of 43 patients [65%] with CT angiography and 64 of 91 patients [70%] with scintigraphy, P = .54), and indeterminate findings (eight of 43 patients [19%] with CT angiography and 17 of 91 patients [19%] with scintigraphy, P = .99) were similar for CT angiography and lung scintigraphy. There were four discrepancies between initial and expert readings for CT angiography (κ = 0.84; confidence interval: 0.68, 0.99) and 14 for lung scintigraphy (κ = 0.75; 95% confidence interval: 0.63, 0.87). Opacification was classified as good for only 23 of the 46 CT angiographic examinations (50%). Attenuation values were significantly different among the groups with good, suboptimal, or poor opacification. Alternative diagnoses unsuspected at chest radiography were demonstrated at CT angiography in five of the 43 patients (12%). The mean maternal radiation dose was 0.9 mSv for lung scintigraphy and 7.3 mSv for CT angiography.Lung scintigraphy and CT angiography have comparable performances for PE diagnosis during pregnancy. Interobserver agreement is better for CT angiography, which also enables alternative diagnosis of unsuspected disease but delivers higher maternal radiation dose.

L’evaluation des traitements est un enjeu de plus en plus important en cancerologie, qu’il s’agisse de l’evaluation des nouveaux traitements ou du monitoring individuel d’un patient. Les criteres utilises actuellement sont morphologiques, bases sur l’evolution de la tailledeslesions, telsque les criteres RECIST. Mais les variations de tailles sont retardees, et avec les nouveaux traitements cibles tels que les antiangiogeniques, elles sont faibles. Cela implique l’utilisation de larges cohortes pour mettre en evidence l’efficacite d’un traitement et rend difficile le monitoring individuel. L’utilisation des techniques d’imagerie fonctionnelle, en scanner, en IRM, en echographie ou en tomographie par emission de positrons (TEP), apporte de nouveaux espoirs. Les parametres obtenus grâce a ces techniques(perfusion, permeabilite, diffusion, metabolisme, composition, elasticite) sont modifies precocement par les traitements. Ces parametres fonctionnels pourraient devenir des biomarqueurs pour l’evaluation et le suivi des traitements. Les etudes ayant demontre leur utilite sont preliminaires, il reste a standardiser les techniques d’acquisition et a evaluer a plus large echelle, en fonction des situations cliniques, quels sont les parametres fonctionnels les plus adaptes.

Most methods define a limited number of “target” lesions to be measured and other “non-target” lesions to be evaluated qualitatively. RECIST criteria are the most widely used although other criteria have been proposed that are derived from them based on size alone, or size and attenuation. Modified RECIST (mRECIST) criteria only concern hepatocellular carcinoma and only take into account the viable portion (enhanced after injection during the arterial phase). Cheson criteria are more complex as target lesions are defined differently depending on the organ (lymph nodes, liver or spleen, other organs), and involve both CT and PET scans, as well as the clinical examination and bone marrow biopsy.

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.

To evaluate whether changes in BOLD signal intensities following hyperoxygenation are related to intrauterine growth restriction (IUGR) in a rat model. 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). Maternal hyperoxygenation resulted in a significant increase in SI in all regions of interest (P

Background and objectives Objective response as determined by Response Evaluation Criteria in Solid Tumors (RECIST) is low among patients with metastatic renal cell carcinoma (mRCC) treated with targeted agents, despite significantly improved progression-free survival (PFS). A modified response threshold may be more clinically meaningful than RECIST for identifying patients who may derive a PFS benefit from targeted therapy. Patients and methods We performed a retrospective analysis of data from the phase III RECORD-1 trial of everolimus versus placebo in patients with mRCC who had failed sunitinib or sorafenib (ClinicalTrials.gov identifier: NCT00410124 ). A series of tumour response thresholds, defined by the best change in the sum of the longest tumour diameters (ΔSLD) of target lesions, was evaluated to distinguish ‘responders’ from ‘non-responders’ with respect to significant improvement in PFS. Results The optimal threshold for determining a response to everolimus was −5% ΔSLD. At this threshold, median PFS was 8.4 months in responders and 5.0 months in non-responders (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.6–3.7). Conclusion In patients who have failed vascular endothelial growth factor receptor–tyrosine kinase inhibitor (VEGFr-TKI) therapy, everolimus affords superior PFS to placebo, regardless of change in tumour burden. However, a ⩾5% reduction in SLD is a better predictor of PFS benefit than the classical ⩾30% reduction used with RECIST.

To determine whether tumor perfusion parameters assessed by using dynamic contrast material-enhanced computed tomography (CT) could help predict and detect response in patients receiving antiangiogenic therapy for metastatic renal cell carcinoma.Institutional ethics committee approval and informed consent were obtained. In two phase-III trials involving 51 patients with metastatic renal cell carcinoma (38 men, 13 women; age range, 30-80 years) receiving antiangiogenic drugs (sorafenib [n = 10], sunitinib [n = 22]), a placebo (n = 12), or interferon alfa (n = 7), serial dynamic contrast-enhanced CT was performed, during 90 seconds before and after injection of 80 mL of iobitridol. Perfusion parameters of a target metastatic tumor (tumor blood flow [TBF], tumor blood volume [TBV], mean transit time, and vascular permeability-surface area product) were calculated. Values before and after treatment were compared by using a Wilcoxon signed rank test, and relative changes in groups were compared by using the Wilcoxon rank sum test. Results were compared with Response Evaluation Criteria in Solid Tumors response and with progression-free and overall survival by using Kaplan-Meier curves.Among patients receiving antiangiogenic drugs, baseline perfusion parameters were higher in responders than in stable patients (TBF = 245.3 vs 119.5 mL/min/100 mL, P = .04; TBV = 15.5 vs 8.2 mL/100 mL, P = .02) but were not significantly predictive of survival. After the first cycle of treatment, there was a significant decrease in TBF (162.5 vs 76.7 mL/min/100 mL, P = .0002) and TBV (9.1 vs 3.9 mL/100 mL, P.0001) in patients receiving antiangiogenic treatment.Renal carcinoma perfusion parameters determined with dynamic contrast-enhanced CT can help predict biologic response to antiangiogenic drugs before beginning therapy and help detect an effect after a single cycle of treatment.