Alain Luciani

Liver Cirrhosis: Intravoxel Incoherent Motion MR Imaging—Pilot Study

PURPOSE To retrospectively evaluate a respiratory-triggered diffusion-weighted (DW) magnetic resonance (MR) imaging sequence combined with parallel acquisition to allow the calculation of pure molecular-based (D) and perfusion-related (D*, f) diffusion parameters, on the basis of the intravoxel incoherent motion (IVIM) theory, to determine if these parameters differ between patients with cirrhosis and patients without liver fibrosis. MATERIALS AND METHODS The institutional review board approved this retrospective study; informed consent was waived. IVIM DW imaging was tested on three alkane phantoms, on which the signal-intensity decay curves according to b factors were logarithmically plotted. Ten b factors (0, 10, 20, 30, 50, 80, 100, 200, 400, 800 sec/mm(2)) were used in patients. Patients with documented liver cirrhosis (cirrhotic liver group, n = 12) and patients without chronic liver disease (healthy liver group, n = 25) were included. The mean liver D, D*, and f values were measured and compared with the apparent diffusion coefficient (ADC) computed by using four b values (0, 200, 400, 800 sec/mm(2)). Liver ADC and D, f, and D* parameters were compared between the cirrhotic liver group and healthy liver group. Means were compared by using the Student t test. RESULTS Signal-intensity decay curves were monoexponential on phantoms and biexponential in patients. In vivo, mean ADC values were significantly higher than D in the healthy liver group (ADC = 1.39 x 10(-3) mm(2)/sec +/- 0.2 [standard deviation] vs D = 1.10 x 10(-3) mm(2)/sec +/- 0.7) and in the cirrhotic liver group (ADC = 1.23 x 10(-3) mm(2)/sec +/- 0.4 vs D = 1.19 x 10(-3) mm(2)/sec +/- 0.5) (P = .03). ADC and D* were significantly reduced in the cirrhotic liver group compared with those in the healthy liver group (respective P values of .03 and .008). CONCLUSION Restricted diffusion observed in patients with cirrhosis may be related to D* variations, which reflect decreased perfusion, as well as alterations in pure molecular water diffusion in cirrhotic livers.

Early 18F-FDG PET for Prediction of Prognosis in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment Versus Visual Analysis

The purpose of this study was to assess the prognostic value of early 18F-FDG PET using standardized uptake value (SUV) compared with visual analysis in patients with diffuse large B-cell lymphoma (DLBCL). Methods: Ninety-two patients with newly diagnosed DLBCL underwent 18F-FDG PET prospectively before and after 2 cycles of chemotherapy (at midtherapy). Maximum SUV (SUVmax) and mean SUV (SUVmean) normalized to body weight and body surface area, as well as tumor-to-normal ratios, were computed on the most intense uptake areas. The SUVs, tumor-to-normal ratios, and their changes over time were compared with visual analysis for predicting event-free survival (EFS) and overall survival, using receiver-operating-characteristic (ROC) analysis. Survival curves were estimated with Kaplan–Meier analysis and compared using the log-rank test. Results: With visual analysis, the accuracy of early PET to predict EFS was 65.2%. The 2-y estimate for EFS was 51% (95% confidence interval [CI], 34%–68%) in the PET-positive group compared with 79% (95% CI, 68%–90%) in the PET-negative group (P = 0.009). An optimal cutoff value of 65.7% SUVmax reduction from baseline to midtherapy obtained from ROC analysis yielded an accuracy of 76.1% to predict EFS. The 2-y estimate for EFS was 21% (95% CI, 0%–42%) in patients with SUVmax reduction ≤ 65.7% compared with 79% (95% CI, 69%–88%) in those with reduction > 65.7% (P < 0.0001). Fourteen patients considered as positive on visual analysis could have been reclassified as good responders. Conclusion: SUV-based assessment of therapeutic response during first-line chemotherapy improves the prognostic value of early 18F-FDG PET compared with visual analysis in DLBCL.

Potential of fecal microbiota for early-stage detection of colorectal cancer

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC‐associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor‐free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early‐ and late‐stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC‐associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor‐related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.

Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation.

Background/Purpose:Liver transplantation (LT) is the best theoretical treatment of hepatocellular carcinoma (HCC) fulfilling the Milan criteria (TNM stages 1–2). However, LT is limited by organ availability and tumor progression on the waiting list. Liver resection (LR) may represent an alternative in these patients. The aim of this study is to report the results of LR in transplantable patients. Patients:From 1990 to 2007, 274 patients underwent liver resection for HCC. Sixty-seven (24%) met the Milan criteria on pathologic study of the specimen. Ten were TNM stage 1 and 57 stage 2 and all had chronic liver disease. There were 56 men and 11 women with a mean age of 63. LR included 12 major hepatectomies, 14 bisegmentectomies, 14 segmentectomies, and 27 nonanatomic resections. Thirty-seven resections were performed through a laparoscopic approach and there were only 8 open resections since 1998. Results:Three patients died postoperatively (4.5%), none after laparoscopic resection. Morbidity rate was 34%. After a mean follow-up of 4.8 years, 36 patients (54%) developed intrahepatic tumor recurrence. Twenty-eight (77%) were again transplantable of which 16 (44%) were transplanted. Two additional patients underwent pre-emptive LT (ie before recurrence). When considering 44 patients <65 years at the time of resection (ie upper age limit for LT), the rates of recurrence, transplantable recurrence, and intention to treat salvage transplantation (patients with transplantable recurrence actually transplanted) were 59%, 80%, and 61%, respectively. Overall and disease free 5-year survival rates were 72% and 44%, respectively. Survival was not influenced by TNM stage 1 or 2, AFP level, tumor differentiation, or the presence microscopic vascular invasion. Survival after salvage LT was 70% and 87% when calculated from the date of LT and LR, respectively. Conclusion:LR for small solitary HCC in compensated cirrhosis yields an overall survival rate comparable to upfront LT. Despite a significant recurrence rate, close imaging monitoring after resection allows salvage LT in 61% of patients with recurrence on intention to treat analysis.

Long term in vivo biotransformation of iron oxide nanoparticles.

The long term outcome of nanoparticles in the organism is one of the most important concerns raised by the development of nanotechnology and nanomedicine. Little is known on the way taken by cells to process and degrade nanoparticles over time. In this context, iron oxide superparamagnetic nanoparticles benefit from a privileged status, because they show a very good tolerance profile, allowing their clinical use for MRI diagnosis. It is generally assumed that the specialized metabolism which regulates iron in the organism can also handle iron oxide nanoparticles. However the biotransformation of iron oxide nanoparticles is still not elucidated. Here we propose a multiscale approach to study the fate of nanomagnets in the organism. Ferromagnetic resonance and SQUID magnetization measurements are used to quantify iron oxide nanoparticles and follow the evolution of their magnetic properties. A nanoscale structural analysis by electron microscopy complements the magnetic follow-up of nanoparticles injected to mice. We evidence the biotransformation of superparamagnetic maghemite nanoparticles into poorly-magnetic iron species probably stored into ferritin proteins over a period of three months. A putative mechanism is proposed for the biotransformation of iron-oxide nanoparticles.

Sarcopenia Impacts on Short- and Long-term Results of Hepatectomy for Hepatocellular Carcinoma.

OBJECTIVE To evaluate the prevalence of sarcopenia among European patients with resectable hepatocellular carcinoma (HCC) and to assess its prognostic impact on overall and disease-free survival. BACKGROUND Identification of preoperative prognostic factors in liver surgery for HCC is required to better select patients and improve survival. Recent studies have shown that preoperative discrimination of patients with low skeletal muscle mass (sarcopenic patients) using computed tomography was associated with morbidity and mortality after liver and colorectal surgery. Assessment of sarcopenia could be used to evaluate patients before hepatectomy for HCC. METHODS All consecutive patients who underwent hepatectomy for HCC in our institution, between February 2006 and September 2012, were included. Univariate and multivariate analyses evaluating prognostic factors of postoperative mortality and cancer recurrence were performed, including preoperative, surgical, and histopathological factors. RESULTS Among 198 patients who underwent hepatectomy for HCC, 109 patients had an available computed tomographic scan and represent the study cohort. After a median follow-up of 21.23 months, 27 patients (24.8%) died. There were 20 deaths among the 59 patients who had sarcopenia and only 7 deaths in the nonsarcopenic group. Sarcopenic patients had significantly shorter median overall survival than nonsarcopenic patients (52.3 months vs 70.3 months; P = 0.015). On multivariate analysis, sarcopenia was found to be an independent predictor of poor overall survival (hazard ratio = 3.19; P = 0.013) and disease-free survival (hazard ratio = 2.60; P = 0.001). CONCLUSIONS Sarcopenia was found to be a strong and independent prognostic factor for mortality after hepatectomy for HCC in European patients and could be used to evaluate eligibility of patients with HCC before surgery.

Image Guidance for Endovascular Repair of Complex Aortic Aneurysms: Comparison of Two-dimensional and Three-dimensional Angiography and Image Fusion

PURPOSE To evaluate the feasibility of image fusion (IF) of preprocedural arterial-phase computed tomography with intraprocedural fluoroscopy for roadmapping in endovascular repair of complex aortic aneurysms, and to compare this approach versus current roadmapping methods (ie, two-dimensional [2D] and three-dimensional [3D] angiography). MATERIALS AND METHODS Thirty-seven consecutive patients with complex aortic aneurysms treated with endovascular techniques were retrospectively reviewed; these included aneurysms of digestive and/or renal arteries and pararenal and juxtarenal aortic aneurysms. All interventions were performed with the same angiographic system. According to the availability of different roadmapping software, patients were successively placed into three intraprocedural image guidance groups: (i) 2D angiography (n = 9), (ii) 3D rotational angiography (n = 14), and (iii) IF (n = 14). X-ray exposure (dose-area product [DAP]), injected contrast medium volume, and procedure time were recorded. RESULTS Patient characteristics were similar among groups, with no statistically significant differences (P ≥ .05). There was no statistical difference in endograft deployment success between groups (2D angiography, eight of nine patients [89%]; 3D angiography and IF, 14 of 14 patients each [100%]). The IF group showed significant reduction (P < .0001) in injected contrast medium volume versus other groups (2D, 235 mL ± 145; 3D, 225 mL ± 119; IF, 65 mL ± 28). Mean DAP values showed no significant difference between groups (2D, 1,188 Gy · cm(2) ± 1,067; 3D, 984 Gy · cm(2) ± 581; IF, 655 Gy · cm(2) ± 457; P = .18); nor did procedure times (2D, 233 min ± 123; 3D, 181 min ± 53; IF, 189 min ± 60; P = .59). CONCLUSIONS The use of IF-based roadmapping is a feasible technique for endovascular complex aneurysm repair associated with significant reduction of injected contrast agent volume and similar x-ray exposure and procedure time.

Assessment of Critical Limb Ischemia in Patients with Diabetes: Comparison of MR Angiography and Digital Subtraction Angiography

OBJECTIVE The purpose of our study was to evaluate the diagnostic accuracy of hybrid MR angiography by comparison with digital subtraction angiography (DSA) in diabetic patients with critical limb ischemia. SUBJECTS AND METHODS Thirty-one patients prospectively underwent both hybrid MR angiography and DSA. The hybrid MR angiography study consisted of high-resolution MR angiography of a single calf and foot using a contrast-enhanced 3D gradient-echo volumetric interpolated breath-hold examination with surface coils, followed by three-station bolus chase MR angiography with a dedicated peripheral vascular coil. Two blinded reviewers separately analyzed maximum-intensity-projection hybrid MR angiograms and DSA images. The peripheral vessels were divided into 10 anatomic segments for review. The status of each segment was graded as normal, stenosis less than 50% in diameter, stenosis greater than 50%, or occluded. The sensitivity and specificity of hybrid MR angiography were determined using DSA as the gold standard. Treatment options were considered separately from the results of each examination. RESULTS Among 310 analyzed segments, the sensitivities of hybrid MR angiography for stenosis and occlusion were, respectively, 95% and 95% for reviewer 1 and 96% and 90% for reviewer 2. The specificities of hybrid MR angiography for stenosis and occlusion were, respectively, 98% and 98% for reviewer 1 and 98% and 99% for reviewer 2. In 25 patients (81%), the quality of bolus chase MR angiography images was insufficient to assess runoff arteries. All treatments proposed on the basis of DSA findings were endorsed by hybrid MR angiography findings. Eleven more treatments were formulated on the basis of hybrid MR angiography findings. Of these, four were due to overestimation of stenosis on MR angiography and seven were due to the detection of patent infrageniculate arteries on hybrid MR angiography that were not detected on DSA. CONCLUSION Hybrid MR angiography depicts runoff arteries not seen on DSA. Hybrid MR angiography may be useful for treatment planning in selected diabetic patients with critical limb ischemia.

Imaging the lymphatic system: possibilities and clinical applications

The lymphatic system is anatomically complex and difficult to image. Lymph ducts are responsible for the drainage of part of the body’s interstitial fluid. Lymph nodes account for the enrichment of lymph fluid, and can be involved in a large variety of diseases, especially cancer. For a long time, lymphatic imaging was limited to the sole use of conventional lymphography involving invasive procedures and patient discomfort. New contrast agents and techniques in ultrasound, nuclear medicine, and MR imaging are now available for imaging of both the lymphatic vessels and the lymph nodes. The objective of this review is to discuss the different imaging modalities of the lymphatic system, with a special focus on the new possibilities of lymphatic imaging including enhanced MR lymphography, sentinel node and positron emission tomography imaging, and contrast-enhanced ultrasound.

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

ObjectivesDynamic 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 MethodsThis 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. ResultsA 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