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American Institute of Ultrasound in Medicine <strong>Proceedings</strong> J Ultrasound Med 32(suppl):S1–S134, 2013tive value using the stiffness criterion were 90% (19/21), 93% (95/102),73% (19/26), and 98% (95/97); and 88% (15/17), 91% (60/66), 71%(15/21), and 97% (60/62) using the size criterion. We had 2 false-negatives,both papillary cancer with cystic content giving the soft appearance, and7 false-positives (3 lymphocytic thyroiditis and 4 colloid goiter). Of 150,27 (18%) nodules were classified as inconclusive by the stiffness criterionand 62 (42%) by the size criterion.Conclusions—Shear wave E of suspicious thyroid nodulesusing the stiffness criterion is precise and helpful to differentiate betweenbenign and malignant thyroid nodules, and we recommend it to be incorporatedin clinical practice. The size criterion is less helpful due to manyinconclusive cases, despite having good specificity and a good negativepredictive value.1506963 Ultrasound- and Ultrasound Elastography-Based ClinicalScore for Screening of Thyroid NodulesNami Azar, Edwin Vargas Velandia,* Ronald Novak, DeanNakamoto Radiology, University Hospitals Case MedicalCenter, Case Western Reserve University, Cleveland, Ohio USAObjectives—In current clinical practice, most centers performbiopsies on all thyroid nodules with a size >1 cm independent of the sonographicfindings. Our aim was to develop an imaging-based clinical scorefor better characterization of thyroid nodules with the aim of reducingnonindicated thyroid biopsies.Methods—In a retrospective review, data of patients who presentedwith suspicious thyroid nodules and underwent conventional(Doppler) ultrasound (US), US quantification elastography, and USguidedfine-needle aspiration (FNA) were analyzed. The nodules wereinitially classified as benign or malignant according to the FNA result. Thefollowing imaging parameters (internal flow, irregular margins, hypoechogenicity,calcifications, size [volume and diameter], and quantificationelastography) were analyzed under a direct logistic regression as accuratepredictors of malignancy. Four clinical scores were designed based onthese parameters and compared as diagnostic methods.Results—A convenience sample of 130 subjects was chosenfor analysis. In this sample, thyroids of 24 subjects (18%) were proven bypathology to be malignant, and 106 (82%) were benign. Direct logistic regressionwas used to calculate areas under the curve (AUCs) for 4 clinicalscoring indices (S1–S4), and regression parameters were used tocompare the AUCs using the method of DeLong et al. Overall, 1 scoringindex (S1), including irregular margins, hypoechogenicity, size, internalflow, and quantification elastography, was determined to be the best predictorof malignancy due to its larger AUC of 0.938. Choosing an indexscore of 5.0 maximized both sensitivity (95.8%) and specificity (87.7%)for predicting malignancy and would theoretically curtail the number ofbiopsies by 72.3%.Conclusions—Our clinical score based on imaging parametersevaluated during a conventional US examination exhibits high sensitivityand specificity for identifying malignant thyroid nodules. Application ofthis tool in daily clinical practice may reduce the number of nonindicatedthyroid biopsies. Our study was limited by a small population size, and furtheranalyses with larger patient samples are warranted.1540472 Linear and Nonlinear Elastosonographic Data May AidDifferentiation of Thyroid NodulesRafal Slapa, 1 * Bartosz Migda, 1 Wieslaw S Jakubowski, 1Jacek Bierca, 2 Jadwiga Slowinska-Srzednicka 3 1 DiagnosticImaging, Medical University of Warsaw, Warsaw, Poland;2Surgery, Hospital at Solec, Warsaw, Poland; 3 Endocrinology,Center for Postgraduate Medical Education, Warsaw, PolandObjectives—Although elastography can assist in the differentialdiagnosis of thyroid nodules, its diagnostic performance is not ideal atpresent. Further improvements in the technique and the diagnostic criteriaare necessary for this examination to provide a useful contribution todiagnosis. The aim of the study was to evaluate a new linear/nonlinear approachfor strain elastosonography of thyroid nodules, based on the analysisof time-strain curves, and to compare it with classic elasticity scoreand thyroid strain ratio methods.Methods—During 2009 to 2011, 67 patients scheduled for thyroidectomy(62 with myasthenia gravis) were evaluated with B-mode andpower Doppler ultrasound of the whole thyroid. During ultrasound examination,96 dominant nodules were examined with strain elastosonographywith Aplio XG (Toshiba, Japan) with a linear 5–17-MHz transducer.The stiffness of each thyroid nodule was evaluated with classic features ofstrain elastosonography qualitatively (with elasticity scores) and semiquantitativelywith thyroid tissue strain/nodule strain ratios with applicationof Elasto Q (Toshiba). Moreover, a novel original approach toelasticity data based on evaluation of time-strain curves was applied. Statisticalanalysis was performed with Statistica 10 (StatSoft, Inc).Results—There were 7 papillary carcinomas and 89 benignnodules. Classic elastosonographic analysis with the elasticity score andelasticity ratio on statistical analysis did not show a significant differencebetween cancer and benign nodules (P = .431 and .156). On linear/nonlinearanalysis of time-strain curves, excellent differentiation (P = 5.6 × 10 –9 )was possible with a new parameter: the relative length of nonlinear relaxation.With a threshold of 0.5, sensitivity was 100% and specificity 85.4%(area under the receiver operating characteristic curve = 0.975).Conclusions—The analysis of linear and nonlinear elastosonographicdata may greatly improve differential diagnosis of thyroidnodules. Further multicenter large-scale studies evaluating the usefulnessof linear/nonlinear elastosonographic phenomena (involving evaluationof vioscoelasticity, eg, shear wave spectroscopy) in differential diagnosisof thyroid cancer are warranted. (Supported by Ministry of Science ofPoland grant N402 476437.)1540131 Noninvasive Determination of Corneal Elasticity UsingAcoustic Radiation Force After Corneal Cross-LinkingRaksha Urs, 1 * Harriet Lloyd, 1 Ronald Silverman 1,21Ophthalmology, Columbia University Medical Center, NewYork, New York USA; 2 Frederic L. Lizzi Center for BiomedicalEngineering, Riverside Research Institute, New York, New YorkUSAObjectives—There is immense interest in corneal cross-linkingtherapy (CXL) to strengthen the cornea for treatment of keratoconus. Currently,biomechanical tests to assess efficacy of CXL in vivo are limited.The objective of this project is to demonstrate the use of acoustic radiationforce (ARF) to determine the stiffness of the rabbit cornea in vivo beforeand after CXL.Methods—The corneas of 2 live rabbits were exposed to ARFusing a single-element transducer (25-MHz central frequency, 6-mm aperture,18-mm focal length; Panametrics V324-SU). The beam sequenceconsisted of 20 pushing tone bursts of 400 microseconds duration (80%duty cycle), with imaging impulses interleaved in the dead time to allowradiofrequency (RF) data acquisition during the push mode. M-mode datawere collected for another 200 milliseconds after the push sequence. Theright eyes of the rabbits were then cross-linked with ultraviolet light andriboflavin. ARF measurements were performed once a week for 4 weeksfollowing CXL. A spline-based algorithm was used to determine continuousdisplacement of the front and back surfaces of the cornea, using RFdata sampled at 400 MHz (12 bits/sample), to determine the change incorneal thickness and strain. The acoustic output was characterized witha 40-µm-diameter needle hydrophone calibrated up to 60 MHz and measuredto be 2.5 MPa. An absorption coefficient of 0.93 dB/cm-MHz wasused to estimate the force in the cornea. ARF-induced strain was fit to theVoigt model to determine the elastic modulus.Results—The mean elastic modulus values during the 4 weeksof follow-up were 36 ± 8 and 32 ± 1 kPa for the untreated eyes and 49 ±S15
American Institute of Ultrasound in Medicine <strong>Proceedings</strong> J Ultrasound Med 32(suppl):S1–S134, 20135 and 45 ± 12 kPa for the cross-linked eyes. A paired t test revealed a statisticallysignificant difference between untreated and cross-linked eyesin 1 rabbit (P = .04). While corneal stiffness increased with cross-linkingin the other treated rabbit, the change was not statistically significant.Conclusions—Results show that changes in corneal stiffnessafter CXL can be measured in vivo using ARF. Future studies will be performedto evaluate the use of this method for detection of keratoconus,where the cornea’s biomechanical properties are believed to be altered.Contrast-Enhanced UltrasoundModerators: Yuko Kono, MD, PhD, Theresa Tuthill, PhD1541199 Volumetric Contrast-Enhanced Ultrasound Imaging ofRenal PerfusionMarshall Mahoney, Anna Sorace, Kenneth Hoyt* Universityof Alabama at Birmingham, Birmingham, Alabama USAObjectives—The goal of this project was to evaluate wholeorganultrasound (US) imaging and microbubble (MB) contrast agents forcharacterizing perfusion in a phantom and an animal model and also to assessthe impact of US scanning parameters on volumetric image quality.Methods—Real-time volumetric contrast-enhanced US(VCEUS) imaging was performed using the BioSONIC VIEW system(Bioscan Inc) equipped with a broadband 4DL14-5/38 probe. An MBsensitiveharmonic imaging mode (transducer transmits at 5 MHz and receivesat 10 MHz) was used to acquire VCEUS data. Followingmicrobubble infusion, custom programs implemented in MATLAB(MathWorks) processed volumetric data sets and time-intensity curves toestimate perfusion parameters, namely, peak intensity, time to peak intensity,wash-in rate, and area under the curve. The VCEUS system was testedin vitro using a tissue-mimicking flow phantom at volume flow rates of 10,20, 30, and 40 mL/min and MB concentrations of 0.005, 0.01, and 0.02mL/L. The system was also tested using healthy Sprague Dawley rats tofurther analyze renal perfusion imaging results. All experiments used theDefinity (Lantheus Medical Imaging) MB contrast agent.Results—All 3D reconstructions allowed visualization of invitro and in vivo perfusion parameters. Volume summarizing statisticsfrom in vitro experiments demonstrated that wash-in rate and time-to-peakmeasurements were proportional to volume flow rates, while the peak intensityand area under the curve measurements were proportional to theMB dose concentration. Results acquired in rat kidney demonstrated thatparametric measurements were consistent for each animal. Importantly, rotationof the imaging transducer (up to 90°) did not impact renal perfusionmeasurements at high-volume frame rates. Collectively, results indicatethat MB destruction-replenishment and time-intensity curve parametricanalysis with real-time volumetric ultrasound imaging is a promisingmodality for characterizing renal perfusion properties.Conclusions—VCEUS imaging was shown to be a promisingmodality for evaluating renal perfusion. Preliminary results are encouraging,and this imaging modality may prove feasible for evaluating acuteand chronic kidney disease.1540209 Parametric Contrast-Enhanced Ultrasound With Evaluationof Arrival Time Maps May Aid Differentiation BetweenAdrenal Nodular Hyperplasia and Adenomas: Initial ResultsRafal Slapa, 1 * Anna Kasperlik-Zaluska, 2 Bartosz Migda, 1Wieslaw S Jakubowski 1 1 Diagnostic Imaging, Medical Universityof Warsaw, Warsaw, Poland; 2 Endocrinology, Center forPostgraduate Medical Education, Warsaw, PolandObjectives—Only some nonmalignant adrenal masses as somemyelolipomas and cysts present pathognomonic features on computed tomography,the examination of choice for evaluation of adrenal glandpathology. Proper diagnosis in the cohort of nonmalignant adrenal massesmay be important for further management. The aim of the study has beento evaluate possibilities of differentiation of nonmalignant masses of adrenalswith application of a new technique for evaluation of enhancement afteradministration of an ultrasound contrast agent: parametric imaging.Methods—Seventeen nonmalignant adrenal masses in 14 patientswere evaluated by dynamic examination after administration of 2.4mL of the ultrasound contrast agent SonoVue with an Aplio XG convex1–6-MHz transducer and parametric imaging. Patterns of parametric imagingof the arrival time and time to peak were evaluated. The final diagnosiswas based on computed tomography, magnetic resonance imaging,biochemical studies, follow-up, and/or surgery.Results—There were 5 myelolipomas, 5 hyperplastic nodules, 4adenomas, 2 hemangiomas with hemorrhage, and 1 cyst. Arrival time patternsof hyperplastic nodules (5/5) presented characteristic differential featuresof peripheral laminar inflow of SonoVue. Patterns for adenomas varied:nonenhancement (1/4), central enhancement (2/4), and peripheral/centralinhomogeneous enhancement (1/4). Patterns for myelolipoma and hemangiomawere different from those for adrenal hyperplastic nodules.Conclusions—Parametric imaging may differentiate adrenaladenomas from hyperplastic nodules and could be complementary to computedtomography. This could potentially influence the choice of treatmentin patients with Conn syndrome and warrants further multicenterlarge-scale studies. (Supported by Ministry of Science of Poland grantN402 481239.)1541233 Volumetric Molecular Ultrasound Imaging of TumorVascularity in a Preclinical Model of Prostate CancerAnna Sorace, Marshall Mahoney, Kurt Zinn, Kenneth Hoyt*University of Alabama at Birmingham, Birmingham, AlabamaUSAObjectives—The goal of this project was to evaluate volumetricmolecular ultrasound (US) imaging of tumor vascularity in a preclinicalmodel or prostate cancer.Methods—Real-time volumetric molecular US imaging wasperformed using the BioSONIC VIEW system (Bioscan Inc) equippedwith a broadband 4DL14-5/38 probe. An MB-sensitive harmonic imagingmode (transducer transmits at 5 MHz and receives at 10 MHz) was usedto acquire molecular US images. Nude athymic mice (n = 10) were implantedwith 2 million prostate cancer cells (PC3), and tumors were allowedto grow to approximately 1 cm in diameter. Microbubbles(Targestar-SA; Targeson) were conjugated with multiple antibodies targetingtumor vascularity (α vβ 3, p-selectin, and vascular endothelial growthfactor receptor 2) or with an immunoglobulin G isotype control antibody.Following tail vein injection of the MB contrast agent, a 5-minute delayallowed systemic circulation and target receptor binding. Molecular USimages were captured to determine the amount of MBs bound and flowing.Then a high-intensity pulse via an external US transducer was administeredto destroy all MBs, followed by an additional US scan todetermine residual circulating MBs. Custom MATLAB software (Math-Works) was developed to determine overall intratumoral image intensity.Subtraction of US image data from before and after MB bursting yieldeda measure of MBs bound to the targeted tumor receptors. All animals receivedboth MB types following a 2-hour delay between injections.Results—Molecular US imaging of targeted MBs yielded aconsiderable increase in intratumoral image enhancement over that obtainedusing control MBs, as evident from volume reconstruction of segmentedtumor data. More specifically, molecular US image enhancementusing targeted MBs ranged from 30% to 160% when compared to controldata from the same population of animals. Targeted MB image enhancementwas consistent with fraction tumor vascularity measures.Conclusions—Whole-tumor molecular US imaging is a promisingstrategy for assessing biomarkers of prostate cancer vascularity, andfurther research is warranted.S16
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Page 7 and 8: 2013 AIUM Award WinnersJoseph H. Ho
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