Fetoplacental oxygenation in an intrauterine growth restriction rat model by using blood oxygen level-dependent MR imaging at 4.7 T.

PURPOSE: 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 oxygenation MATERIALS AND METHODS: All 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. RESULTS: 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). CONCLUSION: 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.

Diffusion-weighted imaging for evaluation of uterine arterial embolization of fibroids.

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/mm(2) ) 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) mm(2) /s, P = 0.13). On 6-months, ADC continued to decrease compared with baseline (1.27 × 10(-3) mm(2) /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.

Use of intravoxel incoherent motion MR imaging to assess placental perfusion in a murine model of placental insufficiency.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Macromolecular capillary leakage is involved in the onset of anaphylactic hypotension.

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.

Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: analysis of response and progression-free survival in the RECORD-1 study.

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.

Pulmonary embolism during pregnancy: diagnosis with lung scintigraphy or CT angiography?

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Metastatic renal carcinoma: evaluation of antiangiogenic therapy with dynamic contrast-enhanced CT.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.