Laurent Milot

Dynamic Microbubble Contrast-enhanced US to Measure Tumor Response to Targeted Therapy: A Proposed Clinical Protocol with Results from Renal Cell Carcinoma Patients Receiving Antiangiogenic Therapy

PURPOSE To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US). MATERIALS AND METHODS The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected. RESULTS In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P < .002), with repeated-measure reproducibility of 9%-15%. Significant decreases were also seen with the bolus method, but with poor correlation of changes in bolus peak (r = 0.46, P = .066) and area under the curve (r = 0.47, P = .058), compared with infusion measurements. Changes in DCE US parameters over 2 weeks did not correlate with PFS and could not be used to predict long-term assessment of best response by using RECIST. Follow-up times ranged 28-501 days; the median was 164 days. CONCLUSION DCE US provides reproducible and sensitive assessment of vascular changes in response to antiangiogenic therapy. The disruption-replenishment infusion protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome.

Transient MR elastography (t-MRE) using ultrasound radiation force: Theory, safety, and initial experiments in vitro

The purpose of our study was to assess the feasibility of using ultrasound radiation force as a safe vibration source for transient MR elastography (t‐MRE). We present a theoretical framework to predict the phase shift of the complex MRE signal, the temperature elevation due to ultrasound, and safety indicators (ISPPA, ISPTA, MI). Next, we report wave images acquired in porcine liver samples in vitro. MR thermometry was used to estimate the temperature elevation induced by ultrasound. Finally, we discuss the implications of our results with regard to the feasibility of using radiation force for t‐MRE in a clinical setting, and a specific echo‐planar imaging (EPI) MRE sequence is proposed. Magn Reson Med 60:871–881, 2008.

Liver steatosis quantification using magnetic resonance imaging: a prospective comparative study with liver biopsy.

Background and Aims: To prospectively determine the accuracy of liver fat quantification with magnetic resonance imaging (MRI). Patients and Methods: The population consisted of 40 patients (mean age, 52.5 years; range, 23-78 years). The same day, all patients underwent MRI and ultrasonography-guided liver biopsy. The histological evaluation of steatosis was performed by an experienced liver pathologist blinded to the MRI results. On T1-weighted in- and opposed-phase images, one radiologist, experienced in abdominal imaging, blinded to the clinical and pathological results, recorded signal intensity (SI) by mean regions of interest placed at same locations in both phases. Fat-water ratio was obtained by dividing SI of liver in opposed-phase sequence by SI of liver in in-phase sequence. The fat-water ratio and the histological grade of steatosis were compared by linear regression. Receiver operating characteristic curve was used to define the sensitivity and specificity of fat-water ratio as a diagnostic tool for evaluation of steatosis. Results: Diagnoses were nonalcoholic fatty liver disease (n = 25), alcoholic liver disease (n = 10), cholangiopathy (n = 2), and autoimmune hepatitis (n = 3). Fatty liver infiltration was present in 80% of patients. The mean (SD) percentage of fatty hepatocytes was 38.7% (29.2). Fat-water ratio and steatosis grade were highly correlated (r = 0.852, P < 0.0001). Sensitivity and specificity of fat-water ratio to detect fatty infiltration greater than 20% were 96% and 93%, respectively. Conclusions: This prospective study demonstrates that MRI can be proposed as a noninvasive method to screen and quantify liver steatosis.

Intérêt de la double lecture du scanner corps entier dans la prise en charge des polytraumatisés

PURPOSE: To assess the value of standard double reading of whole body CT in the management of polytrauma patients. MATERIALS AND METHODS: Prospective study between January and July 2005. Two senior radiologists with expertise in trauma imaging, blinded to clinical findings, reviewed 105 initial CT examinations of polytrauma patients. These examinations had initially been interpreted by the on-call radiologist. The second interpretations were performed within 12 hours of admission, and were considered the gold standard. RESULTS: A total of 105 patients were included with 82 males (78%) and 23 females (22%), aged between 2 and 83 years. The level of admission was graded III (n=64), II (n=30) and I (n=11). The second reading identified 3 lesions that were not initially described, each requiring a change in management, including splenic rupture (n=1), thoracic spine fracture (n=1) and epidural hematoma (n=1), with no unfavorable impact on mortality. Additional errors in the initial interpretation were identified: peripheral fractures (n=38), chest (n=36), brain (n=31), abdominal (n=28), spine (n=19) and maxillofacial (17) lesions and contrast extravasation (n=6). CONCLUSION: Based on the large number and severity of some lesions missed at initial interpretation of whole body CT of polytrauma patients, we recommend standard double reading of these examinations.

Long-term Outcome of Percutaneous Transhepatic Therapy for Benign Bilioenteric Anastomotic Strictures

PURPOSE To evaluate the long-term outcomes of a percutaneous transhepatic approach in benign bilioenteric anastomoses with calibration of the stenosis to 15 F and extended internal/external drainage. MATERIALS AND METHODS Between February 2000 and May 2007, the efficacy of this percutaneous transhepatic procedure was retrospectively studied in 39 patients with benign postoperative bilioenteric anastomotic strictures. The main purpose of the protocol was to repair the anastomosis by calibration of the stenosis to 15 F with a silicone drain and perform internal/external drainage for at least 1 year. The follow-up period ranged from 12 to 65 months (mean, 34.4 months), and outcomes were classified according to the patients clinical symptoms and laboratory parameters and the need for further interventions. RESULTS The procedure was successful in 38 of 39 patients. Four patients were lost to follow-up during or after drainage. The duration of drainage (41 internal catheters in 34 patients) ranged from 126 days to 488 days (mean, 346 d). Twenty-seven patients had positive outcomes during the mean follow-up of 34 months, and six patients had negative outcomes. The bile duct patency probability according to the Kaplan-Meier method was and 70.6% at 34 months after drain removal. CONCLUSIONS Percutaneous treatment of benign biliary strictures with calibrated stent implantation and extended drainage has good long-term results and may be an effective alternative to surgery. Advantages over surgery are its minimal invasiveness and reduced risk of complications.

Water enema computed tomography : diagnostic tool in suspicion of colorectal tumor

OBJECTIVES The aim of this study was to assess the accuracy of water enema multi-row computed tomography for detecting clinically suspected colorectal tumor. PATIENTS AND METHODS A water enema multi-row computed tomography (WE-MR-CT) was performed in 128 consecutive patients (71 women, mean age 67.7 years) referred for suspicion of colorectal cancer. We defined at least one centimeter size of the lesion as the threshold of detection. The results of WE-MR-CT were compared with the diagnosis obtained by colonoscopy, pathology or clinical follow-up. RESULTS The overall sensitivity and specificity of water enema multi-row CT in identifying patients with colorectal lesions were 95.5% and 93.5%, respectively. The negative predictive value was 98.8% for a 10-mm threshold lesion size. WE-MR-CT allowed identifying synchronous lesions in three cases. CONCLUSIONS WE-MR-CT can accurately detect supracentimetric colorectal tumors. The performance of this technique should be further evaluated in prospective studies.

Imagerie par résonance magnétique en opposition de phase et ses applications hépatiques

Resume L’elargissement des indications de l’IRM en pathologie digestive, en particulier pour l’exploration des tumeurs hepatiques, a conduit a developper des sequences visant a approcher les caracteristiques histologiques de ces dernieres. L’opposition de phase est une technique d’imagerie par resonance magnetique visant a supprimer le signal de la graisse et de l’eau a un niveau cellulaire. Disponible sur toute machine, cette sequence est la plus sensible pour la detection de petite quantite de graisse intra-lesionnelle. Ses meilleures indications sont l’exploration de la steatose hepatique, la caracterisation des tumeurs en fonction de leur contenu en graisse (adenome, carcinome hepatocellulaire…) ainsi que la detection des tumeurs, surtout sur foie remanie. Ne necessitant aucune injection de produit de contraste et faisant appel aux techniques d’imagerie rapide, elle s’impose comme un temps incontournable de l’imagerie par resonance magnetique du foie.

Quantifying vascular heterogeneity using microbubble disruption-replenishment kinetics in patients with renal cell cancer.

PurposeThe purposes of this study were to establish the physiological interpretation of the shape parameter of the dynamic contrast-enhanced ultrasound (DCE-US) lognormal perfusion model and to evaluate the clinical significance of the parameter in a sample of patients undergoing antiangiogenic therapy for metastatic renal cell carcinoma (mRCC). Materials and MethodsThe physiological interpretation of the lognormal shape parameter was explored using computer simulations of disruption-replenishment in fractal models of the microcirculation generated by a piecewise iterative algorithm in MATLAB. Architectural variety was accomplished by introducing random perturbations to the diameter, length, and branching angles to the growing vascular tree. The shape parameter was extracted from the time-intensity curves and compared with the transit time distributions calculated directly from the simulations. Dynamic contrast-enhanced ultrasound data were obtained from 31 consenting patients with mRCC being treated with antiangiogenic therapy. Lognormal parameters related to the blood volume, mean flow speed, and vascular morphology/heterogeneity extracted before, during, and after therapy were correlated with progression-free survival (PFS). Cox proportional hazard ratios were calculated alongside receiver operator characteristics for different combinations of the vascular parameters to determine their ability to distinguish patients who would progress early (less than the median PFS) versus late (greater than the median PFS). ResultsThe lognormal shape parameter correlated strongly to the width of the transit time distribution calculated directly from the simulations, and by extension, to the morphology/heterogeneity of the microvascular network (Spearman r = 0.80, P < 0.001, n = 28). Shorter time to progression was predicted by higher baseline heterogeneity (P = 0.003) and a reduction in tumor blood volume less than 43% (P = 0.002) after 2 weeks of treatment. Combining baseline parameters with changes that occur shortly after starting treatment increased the sensitivity and specificity of DCE-US to identify which patients would progress/resist therapy early versus late compared with when the vascular parameters were considered in isolation. ConclusionsThe DCE-US shape parameter from the lognormal perfusion model is representative of microvascular morphology/heterogeneity and may be used to noninvasively characterize the vascular architecture of cancer lesions. A more abnormal flow distribution at baseline predicts for poorer outcome for patients treated with antiangiogenic therapy for metastatic renal cell cancer. Combining pretreatment and on-treatment measurements of vascularity can improve the performance of DCE-US to predict which patients will progress earlier versus later when on antiangiogenic therapy for mRCC.

Hereditary hemorrhagic telangiectases: magnetic resonance imaging features in liver involvement.

Abstract: In hereditary hemorrhagic telangiectasia (HHT), the liver demonstrates a large pattern of findings, including telangiectases, arteriovenous shuntings, focal liver lesions, and ischemic cholangitis, and provides severe complications such as portal hypertension and cardiac failure. Magnetic resonance imaging allows obtaining complete information (parenchyma, biliary tract, and vessels) of the liver in a 1-step examination. Acknowledgment of typical magnetic resonance imaging features of liver involvement in hereditary hemorrhagic telangiectasia case will result in more accurate diagnosis and can guide therapeutic options.

Prostate Imaging: Evaluation of a Reusable Two-Channel Endorectal Receiver Coil for MR Imaging at 1.5 T

PURPOSE To prospectively compare image quality with use of a two-channel solid reusable phased-array endorectal receiver coil (SPAC) with that of the single-channel inflatable endorectal balloon coil currently in widespread use for 1.5-T magnetic resonance (MR) imaging of the prostate. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Multiparametric prostate MR imaging at 1.5 T was performed in patients who were suspected of having cancer. Thirty consecutive patients were included (mean age, 66.1 years; range, 49-76 years). The first 15 patients were imaged by using a balloon coil and an eight-channel external array, and the remaining 15 were imaged with a SPAC alone. One patient was imaged with both techniques. Axial T2-weighted images acquired at both standard and high spatial resolution were used to compare image quality between coils. Qualitative assessments of image quality were made separately by three radiologists. Signal-to-noise ratio (SNR) profiles were determined on a pixel-by-pixel basis in a 1-cm central band in the prostate by using T1-weighted axial images at the apex, midgland, and base. Interrater reliability was determined by using a two-way intraclass correlation coefficient, qualitative scores were compared by using the Student t test for independent samples, and SNR profiles were plotted by using a Biot-Savart curve approximation. RESULTS SNR of the SPAC was significantly better compared with that of the balloon coil at distances up to 3.0 cm at the apex and 3.5 cm at the base and midgland (P < .001). There was a 7% improvement in SNR at the mean maximal anteroposterior prostate dimension in this cohort and a 96% improvement at half this distance. At both standard and high spatial resolution, significant improvements in overall image quality (P = .015 and P < .001, respectively), visibility of the anterior gland (P = .009 and P < .001, respectively), and noise (P < .001 and P < .001, respectively) were seen when the SPAC was used. Interrater reliability was 0.536 (95% confidence interval: 0.461, 0.603). CONCLUSION Both SNR and image quality were significantly improved with use of the SPAC at 1.5 T compared with use of the single-channel inflatable endorectal balloon coil.