The purpose of this study was to determine the validity of previously established ultrasound shear wave elastography (SWE) cut-off values (≥F2 fibrosis) on an independent cohort of patients with chronic liver disease. In this cross-sectional study, approved by the institutional review board and compliant with the Health Insurance Portability and Accountability Act, 338 patients undergoing liver biopsy underwent SWE using an Aixplorer ultrasound machine (SuperSonic Imagine, Aix-en-Provence, France). Median SWE values were calculated from sets of 10 elastograms. A single blinded pathologist evaluated METAVIR fibrosis staging as the gold standard. The study analyzed 277 patients with a mean age of 48 y. On pathologic examination, 212 patients (76.5%) had F0-F1 fibrosis, whereas 65 (23.5%) had ≥F2 fibrosis. Spearman's correlation of fibrosis with SWE was 0.456 (p < 0.001). A cut-off value of 7.29 kPa yielded sensitivity of 95.4% and specificity of 50.5% for the diagnosis of METAVIR stage ≥F2 liver fibrosis in patients with liver disease using the SuperSonic Imagine Aixplorer SWE system.
Objective: To evaluate whether the Aorta-Lesion-Attenuation-Difference on contrast-enhanced CT can aid in the differentiation of malignant and benign oncocytic renal neoplasms.
Materials and methods: Two independent cohorts—an initial (biopsy) dataset and a validation (surgical) dataset—with oncocytomas and chromophobe renal cell carcinomas (chRCC) were included in this IRB-approved retrospective study. A region of interest was placed on the renal mass and abdominal aorta on the same CT image slice to calculate an Aorta-Lesion- Attenuation-Difference (ALAD). ROC curves were plotted for different enhancement phases, and diagnostic performance of ALAD for differentiating chRCC from oncocytomas was calculated.
Results: Seventy-nine renal masses (56 oncocytomas, 23 chRCC) were analyzed in the initial (biopsy) dataset. Thirty-six renal masses (16 oncocytomas, 20 chRCC) were reviewed in the validation (surgical) cohort. ALAD showed a statistically significant difference between oncocytomas and chromophobes during the nephro- graphic phase (p < 0.001), early excretory phase (p < 0.001), and excretory phase (p = 0.029). The area under the ROC curve for the nephrographic phase was 1.00 (95% CI: 1.00–1.00) for the biopsy dataset and showed the narrowest confidence interval. At a threshold value of 25.5 HU, sensitivity was 100 (82.2%–100%) and specificity was 81.5 (61.9%–93.7%). When tested on the validation dataset on measurements made by an inde- pendent reader, the AUROC was 0.93 (95% CI: 0.84–1.00) with a sensitivity of 100 (80.0%–100%) and a specificity of 87.5 (60.4%–97.8%).
Conclusions: Nephrographic phase ALAD has potential to differentiate benign and malignant oncocytic renal neoplasms on contrast-enhanced CT if histologic evaluation on biopsy is indeterminate.
Image-guided biopsy and ablation relies on successful identification and targeting of lesions. Currently, image-guided procedures are routinely performed under ultrasound, fluoroscopy, magnetic resonance imaging, or computed tomography (CT) guidance. However, these modalities have their limitations including inadequate visibility of the lesion, lesion or organ or patient motion, compatibility of instruments in an magnetic resonance imaging field, and, for CT and fluoroscopy cases, radiation exposure. Recent advances in technology have resulted in the development of a new generation of navigational guidance tools that can aid in targeting lesions for biopsy or ablations. These navigational guidance tools have evolved from simple hand-held trajectory guidance tools, to electronic needle visualization, to image fusion, to the development of a body global positioning system, to growth in cone-beam CT, and to ablation volume planning. These navigational systems are promising technologies that not only have the potential to improve lesion targeting (thereby increasing diagnostic yield of a biopsy or increasing success of tumor ablation) but also have the potential to decrease radiation exposure to the patient and staff, decrease procedure time, decrease the sedation requirements, and improve patient safety. The purpose of this article is to describe the challenges in current standard image-guided techniques, provide a definition and overview for these next-generation navigational devices, and describe the current limitations of these, still evolving, next-generation navigational guidance tools.
This study aimed to determine whether active ultrasound surveillance may obviate the need for surgical resection in selected patients with small testicular lesions (STLs). A retrospective 11-year review was conducted of adults who were diagnosed with an STL on scrotal ultrasonography and who either had orchiectomy or sonographic follow-up during a period of at least 3 months. A total of 101 subjects were enrolled. Ultrasound findings, clinical features, histopathology/follow-up imaging were recorded. Logistic regression analysis was performed to select independent risk factors for the diagnosis of malignancy. Seventeen (16.8%) subjects underwent immediate surgery, 8 (7.9%) of 101 underwent surgery after ultrasound follow-up, and 76 (75.3%) of 101 were followed with ultrasound only. The follow-up period ranged from 1 to 7 months in the 8 patients who ultimately underwent surgery after ultrasound follow-up and from 6 to 84 months in the 76 patients followed up with ultrasound only. All 15 malignant cases underwent immediate surgery without follow-up sonography. The frequency of lesions, either benign at surgery or stable on ultrasound, was 85.1% (86 of 101; 95% confidence interval, 77%-91%). Logistic regression analysis showed that lesion size was the only independent risk factor for malignancy in hypoechoic STLs (P < 0.05). Most of the STLs were stable on serial sonograms and likely benign. Active ultrasound surveillance may be an appropriate management strategy in patients with STLs.
The purpose of this study is to determine the reliability of shear-wave elastographic estimates of the Young modulus in thyroid follicular neoplasms.
SUBJECTS AND METHODS:
In this study, 35 adults with follicular nodules diagnosed by fine-needle aspiration (FNA) biopsy were enrolled. A single sonographer examined all nodules in three planes (sagittal, transverse, and transverse center). Two raters independently placed ROIs in each nodule. Intra- and interrater reliability were computed as intraclass correlation coefficients (ICCs) and were reported using the Guidelines for Reporting Reliability and Agreement Studies.
Thirty-five subjects with 35 follicular pattern nodules diagnosed by FNA biopsy were enrolled; 23 (65.7%) patients were female, with a mean age of 55.1 years (range, 23-85 years). For rater 1, intrarater agreement showed ICCs for single measurements of 0.87, 0.87, and 0.90 in the sagittal, transverse, and transverse center plans, respectively; ICCs for the median of multiple measurements were 0.97, 0.94, and 0.96 in the sagittal, transverse, and transverse center planes, respectively. For rater 2, intrarater agreement showed ICCs for single measurements of 0.94, 0.86, and 0.92 in the sagittal, transverse, and transverse center planes, respectively; ICCs for the median of multiple measurements were 0.97, 0.92, and 0.96 in the sagittal, transverse, and transverse center planes, respectively. Interrater agreement between measurements performed for the same subject showed ICCs for single measurements of 0.87, 0.87, and 0.80 in the sagittal, transverse, and transverse center planes, respectively; ICCs for the median of multiple measurements were 0.96, 0.93, and 0.92 in the sagittal, transverse, and transverse center planes, respectively.
ROI placement is a reliable method for estimating the Young modulus of tissue in follicular thyroid nodules.
The purpose of this study is to determine the reliability of shear-wave elastographic estimates of the Young modulus in thyroid follicular neoplasms. In this study, 35 adults with follicular nodules diagnosed by fine-needle aspiration (FNA) biopsy were enrolled. A single sonographer examined all nodules in three planes (sagittal, transverse, and transverse center). Two raters independently placed ROIs in each nodule. Intra- and interrater reliability were computed as intraclass correlation coefficients (ICCs) and were reported using the Guidelines for Reporting Reliability and Agreement Studies. Thirty-five subjects with 35 follicular pattern nodules diagnosed by FNA biopsy were enrolled; 23 (65.7%) patients were female, with a mean age of 55.1 years (range, 23-85 years). For rater 1, intrarater agreement showed ICCs for single measurements of 0.87, 0.87, and 0.90 in the sagittal, transverse, and transverse center plans, respectively; ICCs for the median of multiple measurements were 0.97, 0.94, and 0.96 in the sagittal, transverse, and transverse center planes, respectively. For rater 2, intrarater agreement showed ICCs for single measurements of 0.94, 0.86, and 0.92 in the sagittal, transverse, and transverse center planes, respectively; ICCs for the median of multiple measurements were 0.97, 0.92, and 0.96 in the sagittal, transverse, and transverse center planes, respectively. Interrater agreement between measurements performed for the same subject showed ICCs for single measurements of 0.87, 0.87, and 0.80 in the sagittal, transverse, and transverse center planes, respectively; ICCs for the median of multiple measurements were 0.96, 0.93, and 0.92 in the sagittal, transverse, and transverse center planes, respectively. ROI placement is a reliable method for estimating the Young modulus of tissue in follicular thyroid nodules.
PURPOSE: To demonstrate the clinical translation of optical molecular imaging (OMI) for the localization of focal hepatic lesions during percutaneous hepatic interventions.
MATERIALS AND METHODS: Institutional review board approval was obtained for this prospective, single-center, HIPAA-compliant trial. Patients who were suspected of having hepatocellular carcinoma or liver metastases from colorectal cancer and were scheduled for percutaneous liver biopsy or thermal ablation were eligible for this study. Patients (n = 5) received 0.5 mg per kilogram of body weight of indocyanine green (ICG) intravenously 24 hours prior to their scheduled procedure in this study. Intraprocedurally, a handheld device composed of an endoscope that fits coaxially through a standard 17-gauge introducer needle was advanced into the liver, and real-time measurements of ICG fluorescence were obtained. A point-of-care fluorescence imaging system was used to image ICG fluorescence in biopsy samples. Target-to-background ratios (TBRs) were calculated by dividing the mean fluorescence intensity in the lesion by the mean fluorescence intensity in the adjacent liver parenchyma. The reference standard for determination of proper needle positioning in patients undergoing biopsy was final pathologic analysis of biopsy specimens or follow-up imaging.
RESULTS: Intraprocedural OMI was successfully performed in six lesions (two lesions in patient 3) in five patients. The median size of the targeted lesions was 16 mm (range, 10-21 mm). Four of five biopsies (80%) yielded an accurate pathologic diagnosis, and one biopsy specimen showed benign liver parenchyma; both ablated lesions showed no residual disease 1 month after the procedure. The median overall added procedure time to perform OMI was 2 minutes. ICG was found to localize with TBRs greater than 2.0 (median, 7.9; range, 2.4-13.4) in all target lesions. No trial-related adverse events were reported.
CONCLUSION: The clinical translation of OMI to percutaneous hepatic interventions was demonstrated.
PURPOSE: To evaluate the accuracy of shear-wave elastography (SWE) for staging liver fibrosis in patients with diffuse liver disease (including patients with hepatitis C virus [HCV]) and to determine the relative accuracy of SWE measurements obtained from different hepatic acquisition sites for staging liver fibrosis.
MATERIALS AND METHODS: The institutional review board approved this single-institution prospective study, which was performed between January 2010 and March 2013 in 136 consecutive patients who underwent SWE before their scheduled liver biopsy (age range, 18-76 years; mean age, 49 years; 70 men, 66 women). Informed consent was obtained from all patients. SWE measurements were obtained at four sites in the liver. Biopsy specimens were reviewed in a blinded manner by a pathologist using METAVIR criteria. SWE measurements and biopsy results were compared by using the Spearman correlation and receiver operating characteristic (ROC) curve analysis.
RESULTS: SWE values obtained at the upper right lobe showed the highest correlation with estimation of fibrosis (r = 0.41, P < .001). Inflammation and steatosis did not show any correlation with SWE values except for values from the left lobe, which showed correlation with steatosis (r = 0.24, P = .004). The area under the ROC curve (AUC) in the differentiation of stage F2 fibrosis or greater, stage F3 fibrosis or greater, and stage F4 fibrosis was 0.77 (95% confidence interval [CI]: 0.68, 0.86), 0.82 (95% CI: 0.75, 0.91), and 0.82 (95% CI: 0.70, 0.95), respectively, for all subjects who underwent liver biopsy. The corresponding AUCs for the subset of patients with HCV were 0.80 (95% CI: 0.67, 0.92), 0.82 (95% CI: 0.70, 0.95), and 0.89 (95% CI: 0.73, 1.00). The adjusted AUCs for differentiating stage F2 or greater fibrosis in patients with chronic liver disease and those with HCV were 0.84 and 0.87, respectively.
CONCLUSION: SWE estimates of liver stiffness obtained from the right upper lobe showed the best correlation with liver fibrosis severity and can potentially be used as a noninvasive test to differentiate intermediate degrees of liver fibrosis in patients with liver disease.
Ultrasound elastography, also termed sonoelastography, is being used increasingly in clinical practice to aid the diagnosis and management of diffuse liver disease. Elastography has been shown to be capable of differentiating advanced and early-stage liver fibrosis, and consequently a major application in clinical liver care includes progression to cirrhosis risk stratification through (1) assessment of liver fibrosis stage in HCV and HBV patients, (2) distinguishing non-alcoholic steatohepatitis from simple steatosis in non-alcoholic fatty liver disease patients, and (3) prognostic evaluation of liver disease is autoimmune liver disease. In addition, elastographic characterization of focal liver lesions and evaluation of clinically significant portal hypertension have the potential to be clinically useful and are areas of active clinical research.
Amyloidosis is extremely rare, with an estimated 2225 new US cases reported annually. Signs and symptoms of the disease are subtle and imaging findings are not pathognomonic. Currently, diagnosis requires biopsy to demonstrate the deposition of amyloid. Elastography is a new imaging modality that evaluates tissue elasticity. It has shown to have efficacy in characterizing thyroid nodules, detecting prostate cancer, and staging liver fibrosis. We present a case of hepatic amyloidosis in a 51-year-old male that demonstrates significantly increased stiffness with a median value of 99.1 kPa (range 25.7-188.9 kPa) on shear-wave elastography (SWE) imaging, which is significantly higher than the cut-off range reported for cirrhosis on SWE (10.4-11.5 kPa). This finding raises the possibility that elastographic imaging may be sensitive to tissue mechanical changes induced by amyloid deposition.
This article reviews the clinical applications of current ultrasound elastography methods in non-hepatic conditions including thyroid nodules, prostate cancer, chronic kidney disease, solid renal lesions, pancreatic lesions, and deep vein thrombosis. Pathophysiology alters tissue mechanical properties via ultrastructural changes including fibrosis, increased cellularity, bleeding, and necrosis, creating a target biomarker, which can be imaged qualitatively or quantitatively with US elastography. US elastography methods can add information to conventional US methods and improve the diagnostic performance of conventional US in a range of disease processes.
BACKGROUND: Brown adipose tissue (BAT) consumes glucose when it is activated by cold exposure, allowing its detection in humans by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT). The investigators recently described a novel noninvasive and nonionizing imaging method to assess BAT in mice using contrast-enhanced ultrasound (CEUS). Here, they report the application of this method in healthy humans.
METHODS: Thirteen healthy volunteers were recruited. CEUS was performed before and after cold exposure in all subjects using a continuous intravenous infusion of perflutren gas-filled lipid microbubbles and triggered imaging of the supraclavicular space. The first five subjects received microbubbles at a lower infusion rate than the subsequent eight subjects and were analyzed as a separate group. Blood flow was estimated as the product of the plateau (A) and the slope (β) of microbubble replenishment curves. All underwent (18)F-FDG PET/CT after cold exposure.
RESULTS: An increase in the acoustic signal was noted in the supraclavicular adipose tissue area with increasing triggering intervals in all subjects, demonstrating the presence of blood flow. The area imaged by CEUS colocalized with BAT, as detected by ¹⁸F-FDG PET/CT. In a cohort of eight subjects with an optimized CEUS protocol, CEUS-derived BAT blood flow increased with cold exposure compared with basal BAT blood flow in warm conditions (median Aβ = 3.3 AU/s [interquartile range, 0.5-5.7 AU/s] vs 1.25 AU/s [interquartile range, 0.5-2.6 AU/s]; P = .02). Of these eight subjects, five had greater than twofold increases in blood flow after cold exposure; these responders had higher BAT activity measured by (18)F-FDG PET/CT (median maximal standardized uptake value, 2.25 [interquartile range, 1.53-4.57] vs 0.51 [interquartile range, 0.47-0.73]; P = .02).
CONCLUSIONS: The present study demonstrates the feasibility of using CEUS as a noninvasive, nonionizing imaging modality in estimating BAT blood flow in young, healthy humans. CEUS may be a useful and scalable tool in the assessment of BAT and BAT-targeted therapies.
The sonoelastographic appearances of stones in a phantom were evaluated in this study. Ten stones were embedded into a tissue-mimicking meat phantom. The stone axial (vertical) and transverse (horizontal) dimensions measured by an electronic digital caliper, gray-scale ultrasound, and strain elastography (SE) were compared in 5 groups with stones embedded at different depths. In this study, physically measured axial and transverse stone dimensions were 1.17 to 6.86 and 1.30 to 11.15 mm, respectively. Strain elastography showed a characteristic 3-layer pattern associated with stones, comprising a superficial transition region, a hard region, and a deep transition region. As SE data were available in group 5, only data of groups 1 to 4 were analyzed. Compared with physical measurements, measurement mean errors of SE horizontal and SE vertical dimensions ranged from -0.20 to 0.42 mm and from -1.28 to -0.05 mm, respectively, in the 4 groups. Paired t testing demonstrated a significant horizontal dimension measurement error difference between B mode and SE method in group 4 (0.44 vs -0.20 mm, P < 0.05; F = 1.18, P > 0.05), but not in the other groups. Strain elastography horizontal dimension measurement error was not statistically correlated with stone size in the 4 groups. Strain elastography vertical dimension measurement error significantly correlated with stone size only in group 4 (P < 0.05). Preliminary results indicate that stone horizontal and vertical dimensions can be measured using SE in a soft tissue phantom, including when shadowing precludes measurement of vertical dimension on conventional 2-dimensional ultrasound. These results provide substantial motivation to further investigate SE as a modality to image stones in clinical practice.
OBJECTIVE: The purpose of this article is to investigate whether specific clinical and sonographic characteristics are predictive of a benign Afirma test result.
MATERIALS AND METHODS: We conducted a retrospective study of Afirma gene expression classifier analysis performed in 44 patients with 45 indeterminate thyroid fine-needle aspiration (FNA) cytologic results between March 2013 and April 2014. Of these, 33 of 45 nodules (73.3%) were repeat atypia of undetermined significance (AUS) and follicular lesions of undetermined significance (FLUS), or follicular neoplasm (FN) and suspicious for a follicular neoplasm (SFN) before Afirma testing.
RESULTS: Of the 45 nodules, 21 (46.7%) were cytologically diagnosed as FLUS, 16 (35.6%) were diagnosed as AUS, and eight (17.8%) were diagnosed as FN or SFN. By Afirma testing, 23 of the 45 nodules (51.1%) were benign, 21 (46.7%) were suspicious, and one (2.2%) had nondiagnostic results. The mean (± SD) nodule size was smaller in the Afirma-benign group than in the Afirma-suspicious group (1.8 ± 0.8 cm [95% CI, 1.4-2.1] vs 2.2 ± 0.8 cm [95% CI, 1.8-2.6]; p < 0.035). No sonographic feature was statistically significantly different between the Afirma-benign and -suspicious groups, including nodule solidity (p = 0.225), echogenicity (p = 0.543), calcification (p = 0.542), and hypervascularity (p = 0.976). All nodules were ovoid shaped and had circumscribed margins in both Afirma groups.
CONCLUSION: Smaller nodule size was the only characteristic associated with a benign diagnosis on Afirma testing. Sonographic characteristics are not helpful in cases that had a repeat indeterminate FNA finding before Afirma testing.
BACKGROUND: There currently is a need for a non-invasive measure of renal fibrosis. We aim to explore whether shear wave elastography (SWE)-derived estimates of tissue stiffness may serve as a non-invasive biomarker that can distinguish normal and abnormal renal parenchymal tissue.
METHODS: Participants with CKD (by estimated GFR) and healthy volunteers underwent SWE. Renal elasticity was estimated as Young's modulus (YM) in kilopascals (kPa). Univariate Wilcoxon rank-sum tests were used.
RESULTS: Twenty-five participants with CKD (median GFR 38 mL/min; quartile 1, quartile 3 28, 42) and 20 healthy controls without CKD underwent SWE performed by a single radiologist. CKD was associated with increased median YM (9.40 [5.55, 22.35] vs. 4.40 [3.68, 5.70] kPa; p = 0.002) and higher median intra-subject inter-measurement estimated YM's variability (4.27 [2.89, 9.90] vs. 1.51 [1.21, 2.05] kPa; p < 0.001).
CONCLUSIONS: SWE-derived estimates of renal stiffness and intra-subject estimated stiffness variability are higher in patients with CKD than in healthy controls. Renal fibrosis is a plausible explanation for the observed difference in YM. Further studies are required to determine the relationship between YM, estimated renal stiffness, and renal fibrosis severity.
Diagnostic tests have wide clinical applications, including screening, diagnosis, measuring treatment effect, and determining prognosis. Interpreting diagnostic test results requires an understanding of key statistical concepts used to evaluate test efficacy. This review explains descriptive statistics and discusses probability, including mutually exclusive and independent events and conditional probability. In the inferential statistics section, a statistical perspective on study design is provided, together with an explanation of how to select appropriate statistical tests. Key concepts in recruiting study samples are discussed, including representativeness and random sampling. Variable types are defined, including predictor, outcome, and covariate variables, and the relationship of these variables to one another. In the hypothesis testing section, we explain how to determine if observed differences between groups are likely to be due to chance. We explain type I and II errors, statistical significance, and study power, followed by an explanation of effect sizes and how confidence intervals can be used to generalize observed effect sizes to the larger population. Statistical tests are explained in four categories: t tests and analysis of variance, proportion analysis tests, nonparametric tests, and regression techniques. We discuss sensitivity, specificity, accuracy, receiver operating characteristic analysis, and likelihood ratios. Measures of reliability and agreement, including κ statistics, intraclass correlation coefficients, and Bland-Altman graphs and analysis, are introduced.