Time-intensity Curve Analysis Research Articles

Diffuse Large B-Cell Epstein-Barr Virus-Positive Primary CNS Lymphoma in Non-AIDS Patients: High Diagnostic Accuracy of DSC Perfusion Metrics.

Immunodeficiency-associated CNS lymphoma may occur in different clinical scenarios beyond AIDS. This subtype of CNS lymphoma is diffuse large B-cell and Epstein-Barr virus-positive. Its accurate presurgical diagnosis is often unfeasible because it appears as ring-enhancing lesions mimicking glioblastoma or metastasis. In this article, we describe clinicoradiologic features and test the performance of DSC-PWI metrics for presurgical identification. Patients without AIDS with histologically confirmed diffuse large B-cell Epstein-Barr virus-positive primary CNS lymphoma (December 2010 to January 2022) and diagnostic MR imaging without onco-specific treatment were retrospectively studied. Clinical, demographic, and conventional imaging data were reviewed. Previously published DSC-PWI time-intensity curve analysis methodology, to presurgically identify primary CNS lymphoma, was used in this particular lymphoma subtype and compared with a prior cohort of 33 patients with Epstein-Barr virus-negative CNS lymphoma, 35 with glioblastoma, and 36 with metastasis data. Normalized curves were analyzed and compared on a point-by-point basis, and previously published classifiers were tested. The standard percentage of signal recovery and CBV values were also evaluated. Seven patients with Epstein-Barr virus-positive primary CNS lymphoma were included in the study. DSC-PWI normalized time-intensity curve analysis performed the best for presurgical identification of Epstein-Barr virus-positive CNS lymphoma (area under the receiver operating characteristic curve of 0.984 for glioblastoma and 0.898 for metastasis), followed by the percentage of signal recovery (0.833 and 0.873) and CBV (0.855 and 0.687). When a necrotic tumor is found in a potentially immunocompromised host, neuroradiologists should consider Epstein-Barr virus-positive CNS lymphoma. DSC-PWI could be very useful for presurgical characterization, with especially strong performance of normalized time-intensity curves.

Pharmacokinetic modeling of PSMA-targeted nanobubbles for quantification of extravasation and binding in mice models of prostate cancer.

Contrast-enhanced ultrasound (CEUS) by injection of microbubbles (MBs) has shown promise as a cost-effective imaging modality for prostate cancer (PCa) detection. More recently, nanobubbles (NBs) have been proposed as novel ultrasound contrast agents. Unlike MBs, which are intravascular ultrasound contrast agents, the smaller diameter of NBs allows them to cross the vessel wall and target specific receptors on cancer cells such as the prostate-specific membrane antigen (PSMA). It has been demonstrated that PSMA-targeted NBs can bind to the receptors of PCa cells and show a prolonged retention effect in dual-tumor mice models. However, the analysis of the prolonged retention effect has so far been limited to qualitative or semi-quantitative approaches. This work introduces two pharmacokinetics models for quantitative analysis of time-intensity curves (TICs) obtained from the CEUS loops. The first model is based on describing the vascular input by the modified local density random walk (mLDRW) model and independently interprets TICs from each tumor lesion. Differently, the second model is based on the reference-tissue model, previously proposed in the context of nuclear imaging, and describes the binding kinetics of an indicator in a target tissue by using a reference tissue where binding does not occur. Our results show that four estimated parameters, β, , , for the mLDRW-input model, and γ for the reference-based model, were significantly different (p-value <0.05) between free NBs and PSMA-NBs. These parameters estimated by the two models demonstrate different behaviors between PSMA-targeted and free NBs. These promising results encourage further quantitative analysis of targeted NBs for improved cancer diagnostics and characterization.

Factors influencing the time-intensity curve analysis of contrast-enhanced ultrasound in kidney transplanted patients: Toward a standardized contrast-enhanced ultrasound examination.

BackgroundTime-intensity curve analysis (TIC analysis) based on contrast-enhanced ultrasound (CEUS) provides quantifiable information about the microcirculation of different tissues. TIC analysis of kidney transplantations is still a field of research, and standardized study protocols are missing though being mandatory for the interpretation of TIC parameters in the clinical context. The aim of this study was to evaluate the impact of different sizes and forms of regions of interest (ROIs) on the variance of different TIC parameters and the level of interoperator variance between the different ROI methods in kidney transplantations.MethodsIn 25 renal transplanted patients, 33 CEUS of the transplanted kidney were performed, and TIC analysis with ROIs sized 5 mm2 (ROI5), 10 mm2 (ROI10), and ROIs circumscribing the outlines of anatomical regions (ROIAnat) were analyzed based on CEUS examination. The TIC analysis was repeated by a second independent operator for ROI5 and ROIAnat.ResultsStatistical analysis revealed significant differences between TIC parameters of different ROI methods, and overall, the interoperator variance was low. But a greater ROI surface (ROI10) led to higher values of the intensity parameters A and AUC compared with ROI5 (p < 0.05). The difference in the ROI form led to high variation of certain TIC parameters between ROI5 and ROIAnat in the myelon [intraclass correlation coefficient (A, ICC = 0.578 (0.139–0.793); TIC parameter (TTP); and ICC = 0.679 (0.344–0.842) (p < 0.05)]. A mean variation of 1 cm of the depth of ROI5 in the cortex did not show significant differences in the TIC parameters, though there was an impact of depth of ROIAnat on the values of TIC parameters. The interoperator variance in the cortex was low and equal for ROI5 and ROIAnat, but increased in the myelon, especially for ROIAnat. Furthermore, the analysis revealed a strong correlation between the parameter AUC and the time interval applied for the TIC analysis in the cortex and myelon (r = 0.710, 0.674, p < 0.000).ConclusionOur findings suggest the application of multiple ROIs of 5 mm2 in the cortex and medulla to perform TIC analysis of kidney transplants. For clinical interpretation of AUC, a standardized time interval for TIC analysis should be developed. After the standardization of the TIC analysis, the clinical predictive value could be investigated in further studies.

Quantitative classification of invasive and noninvasive breast cancer using dynamic magnetic resonance imaging of the mammary gland.

ObjectivesBreast cancers are classified as invasive or noninvasive based on histopathological findings. Although time-intensity curve (TIC) analysis using magnetic resonance imaging (MRI) can differentiate benign from malignant disease, its diagnostic ability to quantitatively distinguish between invasive and noninvasive breast cancers has not been determined. In this study, we evaluated the ability of TIC analysis of dynamic MRI data (MRI-TIC) to distinguish between invasive and noninvasive breast cancers.Material and MethodsWe collected and analyzed data for 429 cases of epithelial invasive and noninvasive breast carcinomas. TIC features were extracted in washout areas suggestive of malignancy.ResultsThe graph determining the positive diagnosis rate for invasive and noninvasive cases revealed that the cut-off θi/ni value was 21.6° (invasive: θw > 21.6°, noninvasive: θw ≤ 21.6°). Tissues were classified as invasive or noninvasive using this cut-off value, and each result was compared with the histopathological diagnosis. Using this method, the accuracy of tissue classification by MRI-TIC was 88.6% (380/429), which was higher than that using ultrasound (73.4%, 315/429).ConclusionMRI-TIC is effective for the classification of invasive vs. noninvasive breast cancer.

Multiparametric Ultrasound of Cervical Lymph Node Metastases in Head and Neck Cancer for Planning Non-Surgical Therapy.

Background: We aimed to evaluate multiparametric ultrasound, to achieve a better understanding of the baseline characteristics of suspected cervical lymph node metastases in head and neck cancer before induction chemotherapy or chemoradiation. Methods: From February 2020 to April 2021, our complete ultrasound examination protocol was carried out on clinically evident malignant lymph nodes of histologically proven HNSCC in the pre-therapeutic setting. Results: A total of 13 patients were eligible for analysis. Using elastography, irregular clear hardening in areas in the center of the lymph node could be detected in all cases. Elastographic Q-analysis showed a significantly softer cortex compared to the center and surrounding tissue. The time–intensity curve analysis showed high values for the area under the curve and a short time-to-peak (fast wash-in) in all cases compared to the surrounding tissue. A parametric evaluation of contrast enhanced the ultrasound in the early arterial phase and showed an irregular enhancement from the margin in almost all investigated lymph nodes. These results show that the implementation of comprehensive, multiparametric ultrasound is suitable for classifying suspected lymph node metastasis more precisely than conventional ultrasound alone in the pre-therapeutic setting of HNSCC. Thus, these parameters may be used for improvements in the re-staging after chemoradiation or neoadjuvant therapy monitoring, respectively.

Correlation between quantitative parameters of CEUS and Ki-67 labeling index in soft-tissue sarcoma.

Apart from the immunohistochemical Ki-67 labeling index (LI), clinicians need a non-invasive and convenient way to predict the prognosis of patients with soft-tissue sarcoma (STS). To investigate the correlation between quantitative parameters of contrast-enhanced ultrasound (CEUS) and Ki-67 LI in STS. A total of 25 patients diagnosed with STS who underwent CEUS examination using SonoVue®, between January 2019 to November 2020, were included in the study. They were then divided into a high-proliferation group and low-proliferation group according to 30% Ki-67 positive tumor cells. The quantitative parameters in the semi-automatic time intensity curve analysis software, including arrival time, time to peak, peak intensity, rise time (RT), rise slope, 50% wash-out time, and 50% wash-out intensity, were extracted from the time intensity curve of CEUS by two independent observers. Statistical evaluation of the correlation and difference between CEUS quantitative parameters and Ki-67 LI between the two groups was performed. According to the area under the curve (AUC) analysis, optimal cutoff points of parameters with significant difference were determined. CEUS RT of the high-proliferation group in STS was significantly higher than that of the low-proliferation group (ρ = 0.509, P = 0.01). The most reasonable cutoff to distinguish between low- and high-proliferation groups was 10.84 s. The sensitivity, specificity, and the AUC were 86.7%, 80%, and 0.80, respectively. CEUS RT was correlated with Ki-67 LI of STS, which can be used as a minimally invasive auxiliary tool to predict the prognosis of STS in clinical practice.

Features of cystadenofibroma on magnetic resonance imaging: an update using the O-RADS lexicon and considering diffusion-weighted and perfusion imaging

PurposeCystadenofibroma (CAF) is a rare tumour of the ovary that can be confused with a borderline or malignant lesion due to its morphological characteristics. The study aims to analyse the MRI (magnetic resonance imaging) features of histologically proven ovarian cystadenofibromas according to lexicon-based and O-RADS (Ovarian-Adnexal Reporting and Data System) descriptors, with particular attention to time-intensity curves (TIC) and Diffusion-Weighted sequences (DWI); we also wanted to test the performance of O-RADS MRI risk stratification system in this particular subgroup of patients. MethodsWe have included all patients who performed MR between October 2019 and December 2021 after an inconclusive trans-vaginal ultrasound. All patients underwent surgery with histological results of CAF. According to the O-RADS lexicon, we reported the morphological characteristics of each lesion and their appearance in the perfusion-weighted imaging (PWI) and DWI sequences. We assessed the risk of malignancy for each lesion through O-RADS MRI score. ResultsTwenty-one histologically proven CAF were analysed, of which 20 benign and one borderline with degeneration into adenocarcinoma. We described the typical morphological characteristics of CAF according to lexicon-based and O-RADS descriptors. Analysis of time-intensity curves (TIC) in PWI sequences showed a slow and progressive enhancement of solid tissue (type I curve), configuring an O-RADS score of 2 or 3, except for the only malignant lesion that showed a type II curve and restriction in DWI (O-RADS 4). ConclusionsOur study is the largest comprising PWI and DWI sequences, highlighting their pivotal role. O-RADS score correctly classified the masses as benign or malignant.

Gastric Cancer Angiogenesis Assessment by Dynamic Contrast Harmonic Imaging Endoscopic Ultrasound (CHI-EUS) and Immunohistochemical Analysis-A Feasibility Study.

Tumor vascular perfusion pattern in gastric cancer (GC) may be an important prognostic factor with therapeutic implications. Non-invasive methods such as dynamic contrast harmonic imaging endoscopic ultrasound (CHI-EUS) may provide details about tumor perfusion and could also lay out another perspective for angiogenesis assessment. Methods: We included 34 patients with GC, adenocarcinoma, with CHI-EUS examinations that were performed before any treatment decision. We analyzed eighty video sequences with a dedicated software for quantitative analysis of the vascular patterns of specific regions of interest (ROI). As a result, time-intensity curve (TIC) along with other derived parameters were automatically generated: peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in perfusion index (WiPI), ROI area, and others. We performed CD105 and CD31 immunostaining to calculate the vascular diameter (vd) and the microvascular density (MVD), and the results were compared with CHI-EUS parameters. Results: High statistical correlations (p < 0.05) were observed between TIC analysis parameters MVD and vd CD31. Strong correlations were also found between tumor grade and 7 CHI-EUS parameters, p < 0.005. Conclusions: GC angiogenesis assessment by CHI-EUS is feasible and may be considered for future studies based on TIC analysis.

“DIFFERENTIATING BENIGN FROM MALIGNANT BREAST LESIONS- CLINICAL, HISTOPATHOLOGICAL AND IMAGING CORRELATION”

Introduction: Breast cancer is the second most common cancer in Indian women. Breast cancer is a signicant cause of worldwide morbidity and mortality. Mammography and ultrasound are used as the rst line of investigation for the early detection and localization of breast tumors. Mammography has high sensitivity in case of patients with fatty parenchyma however low sensitivity in case of patients with dense breasts, implants, and post-surgical scar, thus breast MRI with higher sensitivity and specicity due to its ability to depict excellent soft-tissue contrast has become increasingly important in the detection of breast cancer. DCE-MRI has improved specicity in characterizing breast lesions by analysis of time-intensity curves. Diffusion-weighted imaging can improve the sensitivity and specicity of MRI in the evaluation of breast lesions by calculating the ADC values a quantitative measure that is a useful tool for tumor detection and differentiating between benign and malignant breast lesions. To evaluate the role of diffusion-weighted MRI andObjective: dynamic contrast-enhanced MRI in differentiating benign from malignant breast lesions and to compare the ndings of diffusion-weighted MRI and dynamic enhanced MRI with histopathological or FNAC ndings. A totalMaterial And Methods: of 30 patients with palpable breast lumps with either positive or negative ndings on mammography and ultrasound were included in this study. All patients included in this study rst underwent lm-screen mammography. Ultrasonography was done with convex and linear probes. This was followed by MRI. T1W axial, T2W axial, SPAIR/ Fat Saturated T2 weighted axial images were acquired in appropriate imaging planes. Diffusion-weighted images were obtained using b values of 0 and 1000 and ADC values were calculated. Dynamic contrast-enhanced MR was performed using fat-suppressed 3D T1 weighted images after injection of gadolinium and time-intensity curves were generated. A single precontrast scan was followed by 4 post- contrast scans which were obtained for a total duration of 4 min 24 seconds. Findings of the MRI (Diffusion-weighted and dynamic contrast enhancement) were analyzed and correlated with histopathological and FNAC ndings to evaluate their use as a diagnostic modality. A total of 30 female patients presenting with palpable breast lumps were included in theResults: study. Out of 30 patients, 20 cases were malignant (66.67%) and 10 cases were benign (33.3%). Fibroadenoma accounted for a majority of benign lesions (4 out of 10 benign lesions) while IDC accounted for the majority of malignant lesions (15 out of 20 malignant lesions). Dynamic CE-MR is a reliable tool for differentiating between benign and malignant lesions based on kinetic curves. 7 out of 10 benign lesions showed a type I curve while the rest showed a type II curve while the majority (15/20) of malignant lesions showed a type III curve. 8 out of 10 benign breast lesions did not show restricted diffusion on DWI while all malignant lesions showed restricted diffusion on DWI. In our study, the mean ADC value for benign lesions was 1.59 x 10 mm/s while the mean ADC value for malignant lesions was 0.88 x 10 mm/s. Using the ROC curve, the cut-off value of ADC was calculated to be 1.19 x 10 mm/s which gives sensitivity and specicity of 95% and 90% respectively. The individual sensitivity for DCE-MRI and DWI was calculated to be 95% and 95% while the individual specicity for DCE-MRI and DWI was calculated to be 70% and 90% respectively. After a combined analysis of DCE-MRI and DWI using a positive result from any of the two techniques as malignancy, the sensitivity and specicity were 95% and 80% respectively.

Contrast-Enhanced Ultrasound: An Effective Method for Noninvasive Diagnosis of Mummified Thyroid Nodules.

Mummified thyroid nodules are a special type of thyroid nodule, which is benign, but is often diagnosed as malignant by ultrasound. This study investigated the usefulness of contrast-enhanced ultrasound (CEUS) in the diagnosis of mummified nodules. 66 patients with mummified nodules were divided into two groups: a no-enhancement group and a low-enhancement group. 32 patients with papillary thyroid carcinoma (PTC) were recruited in control group. In the no-enhancement group, CEUS showed that there was no contrast agent entering the nodules, with or without a little dot enhancement or regular ring enhancement around the nodules. The low-enhancement group showed low enhancement inside nodules, which was similar to that in the PTC group. In semiquantitative time-intensity curve analyses, intensity maximum of the central area of nodules in the low-enhancement group was lower than that in the PTC group (P < 0.05) and time to peak of the central area of nodules in the low-enhancement group was lower than that in the PTC group (P < 0.05). The results demonstrate that CEUS could be used to effectively diagnose mummified nodules, obviating the need for patients to undergo invasive examination such as biopsy or even surgery.

Comparison of Contrast-Enhanced Ultrasonography to Color Doppler Ultrasound in Evaluation of Carotid Body Tumors.

ObjectiveThe objectives of this study were to prospectively 1) explore the characteristics and enhanced patterns of carotid body tumors (CBTs) at color Doppler ultrasound (CDU) and contrast-enhanced ultrasonography (CEUS) qualitatively and quantitatively and 2) compare CDU and CEUS for their morphology and vascularity signature.MethodsCDU and CEUS with Sonovue® were used to evaluate 25 CBT lesions. The comparison between these ultrasonic modalities included the size, Shamblin type, vascularity, and feeding vessels of the lesion areas. The time–intensity curve (TIC) analysis was used to obtain the dynamics of the contrast-enhancement features of CBTs.ResultsThe TIC analysis presented a fast wash-in [wash-in time: 3.00 ± 1.10 s, mean ± SD] and slow wash-out [wash-out time: 58.79 ± 24.21 s, mean ± SD] pattern in the CBT lesions, with a high area under the curve (AUC) of 669.68 ± 143.46 mm2 (mean ± SD). In comparison with CDU, CEUS was superior in identifying Shamblin type I or III CBT lesions (χ2 = 17.389, p=0.002). It detected a significant difference in the AUC between moderate and marked vascularity groups (563.33 ± 102.63 vs. 707.22 ± 138.81, t=-2.311, p=0.031.), while CDU observed no significant difference between these two groups. Although CDU was more sensitive than CEUS in detecting feeding vessels (100% vs. 88%), CEUS better visualized the origins of feeding vessels (χ2 = 9.162, p=0.010).ConclusionCEUS can better investigate the Shamblin type and vascularity of CBT lesions than CDU. CBTs displayed a fast wash-in, slow wash-out pattern with high AUC in the TIC analysis in the CEUS mode. CDU is more sensitive in detecting feeding vessels than CEUS, while CEUS can better visualize the origins of feeding vessels.

O-RADS MRI Classification of Indeterminate Adnexal Lesions: Time-Intensity Curve Analysis Is Better Than Visual Assessment.

Background The MRI Ovarian-Adnexal Reporting and Data System (O-RADS) enables risk stratification of sonographically indeterminate adnexal lesions, partly based on time-intensity curve (TIC) analysis, which may not be universally available. Purpose To compare the diagnostic accuracy of visual assessment with that of TIC assessment of dynamic contrast-enhanced MRI scans to categorize adnexal lesions as benign or malignant and to evaluate the influence on the O-RADS MRI score. Materials and Methods The European Adnex MR Study Group, or EURAD, database, a prospective multicenter study of women undergoing MRI for indeterminate adnexal lesions between March 2013 and March 2018, was queried retrospectively. Women undergoing surgery for an adnexal lesion with solid tissue were included. Solid tissue enhancement relative to outer myometrium was assessed visually and with TIC. Contrast material washout was recorded. Lesions were categorized according to the O-RADS MRI score with visual and TIC assessment. Per-lesion diagnostic accuracy was calculated. Results A total of 320 lesions (207 malignant, 113 benign) in 244 women (mean age, 55.3 years ± 15.8 [standard deviation]) were analyzed. Sensitivity for malignancy was 96% (198 of 207) and 76% (157 of 207) for TIC and visual assessment, respectively. TIC was more accurate than visual assessment (86% [95% CI: 81, 90] vs 78% [95% CI: 73, 82]; P < .001) for benign lesions, predominantly because of higher specificity (95% [95% CI: 92, 98] vs 76% [95% CI: 68, 81]). A total of 21% (38 of 177) of invasive lesions were rated as low risk visually. Contrast material washout and high-risk enhancement (defined as earlier enhancement than in the myometrium) were highly specific for malignancy for both TIC (97% [95% CI: 91, 99] and 94% [95% CI: 90, 97], respectively) and visual assessment (97% [95% CI: 92, 99] and 93% [95% CI: 88, 97], respectively). O-RADS MRI score was more accurate with TIC than with visual assessment (area under the receiver operating characteristic curve, 0.87 [95% CI: 0.83, 0.90] vs 0.73 [95% CI: 0.68, 0.78]; P < .001). Conclusion Time-intensity curve analysis was more accurate than visual assessment for achieving optimal diagnostic accuracy with the Ovarian-Adnexal Reporting and Data System MRI score. Clinical trial registration no. NCT01738789 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Vargas and Woo in this issue. An earlier incorrect version appeared online. This article was corrected on March 7, 2022.

Multiparametric Ultrasound Approach Using a Tree-Based Decision Classifier for Inconclusive Focal Liver Lesions Evaluated by Contrast Enhanced Ultrasound.

Background: Multiparametric ultrasound (MPUS) is a concept whereby the examiner is encouraged to use the latest features of an ultrasound machine. The aim of this study was to reanalyze inconclusive focal liver lesions (FLLs) that had been analyzed via contrast enhanced ultrasound (CEUS) using the MPUS approach with the help of a tree-based decision classifier. Materials and methods: We retrospectively analyzed FLLs that were inconclusive upon CEUS examination in our department, focusing our attention on samples taken over a period of two years (2017−2018). MPUS reanalysis followed a three-step algorithm, taking into account the liver stiffness measurement (LSM), time–intensity curve analysis (TIC), and parametric imaging (PI). After processing all steps of the algorithm, a binary decision tree classifier (BDTC) was used to achieve a software-assisted decision. Results: Area was the only TIC-CEUS parameter that showed a significant difference between malign and benign lesions with a cutoff of >−19.3 dB for washout phenomena (AUROC = 0.58, Se = 74.0%, Sp = 45.7%). Using the binary decision tree classifier (BDTC) algorithm, we correctly classified 71 out of 91 lesions according to their malignant or benignant status, with an accuracy of 78.0% (sensitivity = 62%, specificity = 45%, and precision = 80%). Conclusions: By reevaluating inconclusive FLLs that had been analyzed via CEUS using MPUS, we managed to determine that 78% of the lesions were malignant and, in 28% of them, we established the lesion type.

The value of real-time contrast-enhanced ultrasound combined with CT enhancement in the differentiation of subtypes of renal cell carcinoma.

This study aimed to evaluate the value of real-time contrast-enhanced ultrasound (CEUS) combined with contrast-enhanced computed tomography (CECT) in the differential diagnosis of clear cell renal cell carcinoma (CCRCC), papillary renal cell carcinoma (PRCC), and chromophobe renal cell carcinoma (CRCC). In the present study, 82 patients with CCRCC, 24 patients with PRCC, and 19 patients with CRCC were confirmed by pathology of the resected tumor. All patients were evaluated by CEUS and CECT before the operation. In addition, the contrast enhancement mode of CEUS and CECT and the contrast parameters of the region of interest (ROI) time-intensity curve between the lesions and the surrounding normal renal parenchyma by CEUS were compared and analyzed. Compared with the pathological results, the diagnostic accuracy of ultrasound in the 3 groups was 87.8% (72/82), 83.3% (20/24) and 73.7% (14/19). There was no significant difference between CEUS and CECT in the diagnostic accuracy of all groups (P>0.05). Meanwhile, compared with the surrounding renal parenchyma by CEUS, 82.5% (66/80) of CCRCC lesions showed "fast-forward and fast/slow-retrograde," while 83.3% (20/24) of PRCC, and 84.2% (16/19) showed "slow-forward and fast/slow-retrograde." Significant differences in the enhancement modes of CEUS were found among the CCRCC, PRCC, and CRCC lesions (P < 0.05). And the enhancement modes could be quantitatively analyzed by the ROI time-intensity curve of the lesion. Moreover, lesions enhanced by CECT and 74.4% (61/82) of CCRCC lesions showed "fast-forward and fast/slow-retrograde," while 66.7% (16/24) of PRCC and 84.2% (16/19) of CRCC showed "slow-forward and fast/slow-retrograde." The contrast modes and enhancement uniformity of CEUS and CECT showed no significant differences among the CCRCC, PRCC, and CRCC lesions (P > 0.05). CEUS and quantitative analysis of ROI time-intensity curve can be used for differential diagnosis of the 3 RCC subtypes. The combination of CEUS and CECT can help us differentiate RCC subtypes and is of great significance for clinical treatment strategies and prognostication.

Intracranial Pressure and Cerebral Hemodynamic Monitoring After Cardiac Arrest in Pediatric Pigs Using Contrast Ultrasound-Derived Parameters.

We explore the correlation of contrast-enhanced ultrasound (CEUS) parameters to intracranial pressure (ICP) in a porcine experimental model of pediatric cardiac arrest. Eleven pediatric pigs underwent electrically induced cardiac arrest followed by cardiopulmonary resuscitation. ICP was measured using intracranial bolt monitor and CEUS was monitored through a cranial window. Various CEUS parameters were monitored at baseline, immediately post return of spontaneous circulation (ROSC), 1 hour-post ROSC, and 3 hours post-ROSC. There was significant ICP correlation with wash-out slope assessed by CEUS time intensity curve analysis at immediate post-ROSC. At 3 hours post-ROSC there was also significant negative correlation between ICP and peak enhancement which may be due to the evolution of anoxic injury. The use of CEUS in assessing disruption of cerebral hemodynamics and ICP post cardiac arrest will need future validation and comparison to other imaging modalities. The correlation between CEUS parameters and ICP may be due to the alterations in cerebral autoregulation that result from anoxic brain injury.

Quantification of dynamic contrast-enhanced ultrasound (CEUS) in non-cystic breast lesions using external perfusion software

The aim of this present clinical pilot study is the display of typical perfusion results in patients with solid, non-cystic breast lesions. The lesions were characterized using contrast enhanced ultrasound (CEUS) with (i) time intensity curve analyses (TIC) and (ii) parametric color maps. The 24 asymptomatic patients included were genetically tested for having an elevated risk for breast cancer. At a center of early detection of familial ovary and breast cancer, those patients received annual MRI and grey-scale ultrasound. If lesions remained unclear or appeared even suspicious, those patients also received CEUS. CEUS was performed after intravenous application of sulfur hexafluoride microbubbles. Digital DICOM cine loops were continuously stored for one minute in PACS (picture archiving and communication system). Perfusion images and TIC analyses were calculated off-line with external perfusion software (VueBox). The lesion diameter ranged between 7 and 15 mm (mean 11 ± 3 mm). Five hypoechoic irregular lesions were scars, 6 lesions were benign and 12 lesions were highly suspicious for breast cancer with irregular enhancement at the margins and a partial wash out. In those 12 cases, histopathology confirmed breast cancer. All the suspicious lesions were correctly identified visually. For the perfusion analysis only Peak Enhancement (PE) and Area Under the Curve (AUC) added more information for correctly identifying the lesions. Typical for benign lesions is a prolonged contrast agent enhancement with lower PE and prolonged wash out, while scars are characterized typically by a reduced enhancement in the center. No differences (p = 0.428) were found in PE in the center of benign lesions (64.2 ± 28.9 dB), malignant lesions (88.1 ± 93.6 dB) and a scar (40.0 ± 17.0 dB). No significant differences (p = 0.174) were found for PE values at the margin of benign lesions (96.4 ± 144.9 dB), malignant lesions (54.3 ± 86.2 dB) or scar tissue (203.8 ± 218.9 dB). Significant differences (p < 0.001) were found in PE of the surrounding tissue when comparing benign lesions (33.6 ± 25.2 dB) to malignant lesions (15.7 ± 36.3 dB) and scars (277.2 ± 199.9 dB). No differences (p = 0.821) were found in AUC in the center of benign lesions (391.3 ± 213.7), malignant lesions (314.7 ± 643.9) and a scar (213.1 ± 124.5). No differences (p = 0.601) were found in AUC values of the margin of benign lesions (313.3 ± 372.8), malignant lesions (272.6 ± 566.4) or scar tissue (695.0 ± 360.6). Significant differences (p < 0.01) were found in AUC of the surrounding tissue for benign lesions (151.7 ± 127.8), malignant lesions (177.9 ± 1345.6) and scars (1091 ± 693.3). There were no differences in perfusion evaluation for mean transit time (mTT), rise time (RT) and time to peak (TTP) when comparing the center to the margins and the surrounding tissue. The CEUS perfusion parameters PE and AUC allow a very good assessment of the risk of malignant breast lesions and thus a downgrading of BI-RADS 4 lesions. The use of the external perfusion software (VueBox, Bracco, Milan, Italy) did not lead to any further improvement in the diagnosis of suspicious breast lesions and does appears not to have any additional diagnostic value in breast lesions.

Impact of region-of-interest size and location on quantitative contrast-enhanced ultrasound of canine splenic perfusion

BackgroundDuring contrast enhanced ultrasound (CEUS), the features of the regions of interest (ROI) can affect the value of the perfusion-related parameters obtained from a time intensity curve (TIC). In veterinary medicine, conflicting have been reported on the influence of ROI size and location on renal CEUS. There are some disagreeing evidences regarding the optimal method for selecting ROI in quantitative analysis of renal perfusion using CEUS.The aim of this study was to evaluate the effect of the size and location of ROIs in the spleen of conscious dogs on perfusion variables determined using sulphur hexafluoride contrast-enhanced ultrasounds.ResultsA prospective observational study on 15 client-owned mixed-breed adult dogs was performed using a system equipped with contrast-tuned imaging technology. Qualitative and quantitative assessments of the spleen enhancement pattern were carried out. Three square ROIs (0.05 cm2) were manually drawn in a row and spaced 1 mm apart, placing adjacent ROIs at three different depths. Three medium rectangular ROIs (0.3 cm2) include the 3 smallest ROIs in each row, indicated by the letters A, B and C, and a single large square ROI (1 cm2) was drawn containing all previous ROIs. Software analysis of time-intensity curves generated within each ROI allowed us to calculate the perfusion-related parameters: peak enhancement, time to peak, regional blood flow, mean transit time and regional blood volume.The coefficient of variation for all blood-related parameters was always lower in the larger ROI than in the other smaller ROIs. ROI A and B, positioned proximally and medially, levels respectively, showed similar coefficients of variation to the largest ROI. The analysis of variance model exhibited a significant effect of location and size of the ROIs in the quantitative analysis of canine spleen perfusion, with a reduction of perfusion-related parameters in the distal ROI.ConclusionsThe recommendation for a quantitative CEUS examination of a dog’s spleen is to analyze splenic perfusion by drawing a sufficiently large ROI proximal to the ultrasound beam on the splenic parenchyma. This may be of clinical relevance in the diagnosis of splenic diseases.

Evaluating the therapeutic effect of lenvatinib against advanced hepatocellular carcinoma by measuring blood flow changes using contrast-enhanced ultrasound.

BackgroundThe antitumor effect of a drug is considered to be associated with a decrease in tumor blood flow.AimsWe investigated whether the efficacy of lenvatinib (LEN) could be accurately assessed by measuring blood flow in hepatocellular carcinoma (HCC) during early treatment stages.Methods and resultsBlood flow changes and treatment results of 19 patients who underwent contrast‐enhanced ultrasound (CEUS), before and after LEN administration, in Kurume University Hospital from July 2018 to June 2020 were examined. Blood flow was evaluated after the intravenous administration of perflubutane (0.015 ml/kg). The vascular phase was photographed and used as RAW data, and time‐intensity curve analysis was used to obtain the region of interest (ROI) on the entire tumor nodule and quantify tumor blood flow. The evaluation was performed before and 1 and 4 weeks after LEN administration. Mean ± standard deviation (SD) values of the brightness of blood flow in the background liver before and 1 and 4 weeks after LEN administration were 2.84 × 10−4 ± 2.94 × 10−4, 3.07 × 10−4 ± 3.79 × 10−4, and 10.0 × 10−4 ± 20.8 × 10−4 dB, respectively. Blood flow in the background liver did not significantly decrease at 1 and 4 weeks compared with that before treatment. Mean ± SD values of the brightness of blood flow in HCC before and 1 and 4 weeks after administration were 3.49 × 10−3 ± 4.58 × 10−3, 1.16 × 10−3 ± 1.57 × 10−3, and 6.39 × 10−3 ± 22.8 × 10−3 dB, respectively. Blood flow in HCC after 1 week was significantly lower than that before administration (p = .0192). The therapeutic effects were significantly higher in the group with ≥50% blood flow reduction in HCC at 1 week after administration (p = .0038) and the group with reduced blood flow in HCC at 4 weeks after administration (p = .0051) than those before administration.ConclusionEarly blood flow evaluation by CEUS may be useful in predicting the therapeutic effect of LEN for unresectable advanced HCC.

Establishment of a Diagnostic Method for Pelvic Sentinel Lymph Node Metastasis by Contrast-Enhanced Ultrasound in Uterine Cancer

This study investigated the usefulness of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in distinguishing metastasis of pelvic sentinel lymph nodes (SLNs) in patients with gynecological cancer. We examined 74 SLNs of patients with endometrial cancer (n = 26) and cervical cancer (n = 11). Patients underwent US and CEUS followed by SLN biopsy; US and CEUS results were evaluated visually and quantitatively and compared between pathological metastasis-negative and -positive groups. To support CEUS results, the microvessel density of SLNs was evaluated immunohistochemically. Seventeen positive and 40 negative SLNs were evaluable. Margin and enhancement patterns by visual assessment revealed significant differences (p = 0.046 and 0.022, respectively). In quantitative time–intensity curve analyses, the weakest peak intensities (PImin), PI ratio and PI difference indicated significant differences (p = 0.045, p < 0.001 and p < 0.001, respectively). The areas under the receiver operating characteristic curves (AUCs) were 0.64, 0.82 and 0.83, respectively. The most effective PI ratio from the AUC was 1.3 (sensitivity = 82%, specificity = 70%), and the PI difference from the AUC was 20 (sensitivity = 88%, specificity = 70%). Microvessel density was significantly lower in metastatic lesions than in other areas. The quantitative analysis of CEUS seemed to be a reasonable method for distinguishing lymph node metastasis in patients with gynecological cancer.

Efficacy of Contrast-Enhanced Harmonic Endoscopic Ultrasound for Pancreatic Solid Tumors with a Combination of Qualitative and Quantitative Analyses: A Prospective Pilot Study

Image evaluation of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) and additional time-intensity curve (TIC) analysis enable qualitative and quantitative analyses of pancreatic tumor based on real-time perfusion imaging. To evaluate the efficacy of CEH-EUS with a combination of qualitative and quantitative analyses of pancreatic solid tumors. Patients were scheduled to undergo EUS-guided fine needle aspiration (FNA) for pancreatic solid tumors were prospectively enrolled between 11/2016 and 12/2018 and underwent CEH-EUS. The vascular and enhancement patterns were qualitatively evaluated and heterogeneous enhancement was defined to be indicative of malignancy. The echo intensity change during 60s in the tumor was quantitatively evaluated by time intensity curve analysis. In total, 100 patients were enrolled in this study. The final diagnoses were malignant lesions in 87 patients and benign legions in 13 patients. There were four categories of enhancement and patterns: hypovascular with heterogeneous, hypovascular with homogeneous, hypervascular heterogeneous, and hypervascular homogeneous enhancement. The diagnostic capability of qualitative analysis was the sensitivity, specificity, and accuracy of 89%, 62%, and 85%, respectively. With respect to time intensity curve analysis, the time to peak of malignant lesions was significantly shorter than those of benign lesions (P = 0.0009) with an optimal cutoff value of 12.81s on the receiver operating characteristic curve analysis. With the combination of qualitative and quantitative analyses, the sensitivity, specificity, and accuracy were improved to 100%, 54%, and 94%, respectively. CEH-EUS with combined qualitative and quantitative analyses for pancreatic tumors might be useful as a complement for EUS-FNA. The UMIN Clinical Trials Registry (UMIN000025192).