Normal value of virtual touch imaging quantification elastography in measurements of pancreas.

OBJECTIVE: To evaluate pancreatic tissue stiffness and provide a normal reference shear wave velocity (SWV) value of pancreas from healthy adults by Virtual Touch Imaging Quantification (VTIQ) measurements. METHODS: Healthy adult volunteers without known history of hepatobiliary or pancreatic diseases were included. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used. SWV values were measured at the cephalic, corpus and tail of pancreas and replicated different operators' obtained data. Subgroups were classified according to the volunteers' gender, age, body mass index (BMI), depth of measurements and the echogenicity of the pancreas. RESULTS: From February 2023 to July 2023, 33 healthy adult volunteers were included. The success rate of VTIQ measurements in cephalic, corpus and tail regions was 90.90 % (30/33), 96.97 % (32/33) and 90.90 % (30/33) respectively. The color elastograms of healthy adult pancreas showed uniform blue or simultaneously blue and green. The average SWV values were 0.97±0.26 m/s for cephalic, 0.91±0.24 m/s for corpus and 0.97±0.25 m/s for pancreatic tail respectively (P = 0.198). The mean SWV values of pancreas did not show significant difference with age, gender or depth (P >  0.05). BMI was an influence factor in the measurements of SWV values of cephalic and tail of pancreas (P <  0.05). Pancreas with hyperechoic parenchyma showed higher mean SWV values (P <  0.05). The intra-observer (ICC = 0.938 [95% CI: 0.869-0.971]) and the inter-observer (ICC = 0.887 [95% CI: 0.760-0.947]) agreements of VTIQ measurements were excellent. CONCLUSIONS: The mean SWV value of the pancreas in healthy adults was 0.96±0.20 m/s (range: 0.52-1.74 m/s). VTIQ technique can be used in pancreatic stiffness measurements with good reliability.

Contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features for characterizing serous microcystic adenomas (SMAs): In comparison to pancreatic neuroendocrine tumors (pNETs).

Objectives: Serous microcystic adenoma (SMA), a primary benign pancreatic tumor which can be clinically followed-up instead of undergoing surgery, are sometimes mis-distinguished as pancreatic neuroendocrine tumor (pNET) in regular preoperative imaging examinations. This study aimed to analyze preoperative contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features of SMAs in comparison to pNETs. Material and methods: In this retrospective study, patients with imaging-diagnosed pancreatic lesions were screened between October 2020 to October 2022 (ethical approval No. B2020-309R). Performing by a Siemens Sequoia (Siemens Medical Solutions, Mountain View, CA, USA) equipped with a 5C-1 curved array transducer (3.0-4.5 MHz), CEUS examination was conducted to observe the microvascular perfusion patterns of pancreatic lesions in arterial phase, venous/late phases (VLP) using SonoVue® (Bracco Imaging Spa, Milan, Italy) as the contrast agent. Virtual touch tissue imaging and quantification (VTIQ) - SWE was used to measure the shear wave velocity (SWV, m/s) value to represent the quantitative stiffness of pancreatic lesions. Multivariate logistic regression was performed to analyze potential ultrasound and clinical features in discriminating SMAs and pNETs. Results: Finally, 30 SMA and 40 pNET patients were included. All pancreatic lesions were pathologically proven via biopsy or surgery. During the arterial phase of CEUS, most SMAs and pNETs showed iso- or hyperenhancement (29/30, 97 % and 31/40, 78 %), with a specific early honeycomb enhancement pattern appeared in 14/30 (47 %) SMA lesions. During the VLP, while most of the SMA lesions remained iso- or hyperenhancement (25/30, 83 %), nearly half of the pNET lesions revealed an attenuated hypoenhancement (17/40, 43 %). The proportion of hypoenhancement pattern during the VLP of CEUS differed significantly between SMAs and pNETs (P = 0.021). The measured SWV value of SMAs was significantly higher than pNETs (2.04 ± 0.70 m/s versus 1.42 ± 0.44 m/s, P = 0.002). Taking a SWV value > 1.83 m/s as a cutoff in differentiating SMAs and pNETs, the area under the receiver operating characteristic curve (AUROC) was 0.825, with sensitivity, specificity and likelihood ratio (+) of 85.71 %, 72.73 % and 3.143, respectively. Multivariate logistic regression revealed that SWV value (m/s) of the pancreatic lesion was an independent variable in discriminating SMA and pNET. Conclusion: By comprehensively evaluating CEUS patterns and SWE features, SMA and pNET may be well differentiated before the operation. While SMA typically presents as harder lesion in VTIQ-SWE, exhibiting a specific honeycomb hyperenhancement pattern during the arterial phase of CEUS, pNET is characterized by relative softness, occasionally displaying a wash-out pattern during the VLP of CEUS.

Preoperative ultrasound radiomics for predicting clinically relevant postoperative pancreatic fistula after pancreatectomy.

OBJECTIVES: To evaluate the efficacy of the radiomics model based on preoperative B-mode ultrasound (BMUS) and shear wave elastography (SWE) for predicting the occurrence of clinically relevant-postoperative pancreatic fistula (CR-POPF). METHODS: Patients who were scheduled to undergo pancreatectomy were prospectively enrolled and received ultrasound assessment within one week before surgery. The risk factors of POPF (grades B and grades C) were analyzed. Preoperative BMUS images, SWE values of pancreatic lesions and surrounding parenchyma were used to build preoperative prediction radiomics models. Radiomic signatures were extracted and constructed using a minimal Redundancy Maximal Relevance (mRMR) algorithm and an L1 penalized logistic regression. A combined model was built using multivariate regression which incorporated radiomics signatures and clinical data. RESULTS: From January 2020 to November 2021, a total of 147 patients (85 distal pancreatectomies and 62 pancreaticoduodenectomies) were enrolled. During the three-week follow-up after pancreatectomy, the incidence rates of grade B/C POPF were 28.6% (42/147). Radiomic signatures constructed from BMUS of pancreas parenchymal regions (panRS) achieved an area under the receiver operating characteristic curve (AUC) of 0.75, accuracy of 68.7%, sensitivity of 85.7 %, and specificity of 61.9 % in preoperative noninvasive prediction of CR-POPF. The AUC of the radiomics model increased to 0.81 when panRS was used for the prediction of CR-POPF after pancreaticoduodenectomy. CONCLUSIONS: Radiomics model based on ultrasound images was potentially useful for predicting CR-POPF. Patients with high-risk factors should be closely monitored when postoperation.

Pancreatic neuroendocrine tumor: prediction of tumor grades by radiomics models based on ultrasound images.

OBJECTIVE: We aimed to investigate whether the radiomics analysis based on B-mode ultrasound (BMUS) images could predict histopathological tumor grades in pancreatic neuroendocrine tumors (pNETs). METHODS: A total of 64 patients with surgery and histopathologically confirmed pNETs were retrospectively included (34 male and 30 female, mean age 52.4 ± 12.2 years). Patients were divided into training cohort (n = 44) and validation cohort (n = 20). All pNETs were classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity according to WHO 2017 criteria. Maximum relevance minimum redundancy, least absolute shrinkage and selection operator were used for feature selection. Receiver operating characteristic curve analysis was used to evaluate the model performance. RESULTS: Finally, 18 G1 pNETs, 35 G2 pNETs, and 11 G3 pNETs patients were included. The radiomic score derived from BMUS images to predict G2/G3 from G1 displayed a good performance with an area under the receiver operating characteristic curve of 0.844 in the training cohort, and 0.833 in the testing cohort. The radiomic score achieved an accuracy of 81.8% in the training cohort and 80.0% in the testing cohort, a sensitivity of 0.750 and 0.786, a specificity of 0.833 and 0.833 in the training/testing cohorts. Clinical benefit of the score also exhibited superior usefulness of the radiomic score, as shown by the decision curve analysis. CONCLUSIONS: Radiomic data constructed from BMUS images have the potential for predicting histopathological tumor grades in patients with pNETs. ADVANCES IN KNOWLEDGE: The radiomic model constructed from BMUS images has the potential for predicting histopathological tumor grades and Ki-67 proliferation indexes in patients with pNETs.

Application of ultrasound shear wave elastography in pre-operative and quantitative prediction of clinically relevant post-operative pancreatic fistula after pancreatectomy: a prospective study for the investigation of risk evaluation model.

OBJECTIVES: The aim of this study was to modify recognized clinically relevant post-operative pancreatic fistula (CR-POPF) risk evaluation models with quantitative ultrasound shear wave elastography (SWE) values and identified clinical parameters to improve the objectivity and reliability of the prediction. METHODS: Two prospective, successive cohorts were initially designed for the establishment of CR-POPF risk evaluation model and the internal validation. Patients who scheduled to receive pancreatectomy were enrolled. Virtual touch tissue imaging and quantification (VTIQ)-SWE was used to quantify pancreatic stiffness. CR-POPF was diagnosed according to 2016 International Study Group of Pancreatic Fistula standard. Recognized peri-operative risk factors of CR-POPF were analyzed, and the independent variables selected from multivariate logistic regression were used to build the prediction model. RESULTS: Finally, the CR-POPF risk evaluation model was built in a group of 143 patients (cohort 1). CR-POPF occurred in 52/143 (36%) patients. Constructed from SWE values and other identified clinical parameters, the model achieved an area under the receiver operating characteristic curve of 0.866, with sensitivity, specificity, and likelihood ratio of 71.2%, 80.2%, and 3.597 in predicting CR-POPF. Decision curve of modified model revealed a better clinical benefit compared to the previous clinical prediction models. The models were then examined via internal validation in a separate collection of 72 patients (cohort 2). CONCLUSIONS: Risk evaluation model based on SWE and clinical parameters is a potential non-invasive way to pre-operatively, objectively predict CR-POPF after pancreatectomy. CLINICAL RELEVANCE STATEMENT: Our modified model based on ultrasound shear wave elastography may provide an easy access in pre-operative and quantitative evaluating the risk of CR-POPF following pancreatectomy and improve the objectivity and reliability of the prediction compared to previous clinical models. KEY POINTS: • Modified prediction model based on ultrasound shear wave elastography (SWE) provides an easy access for clinicians to pre-operatively, objectively evaluate the risk of clinically relevant post-operative pancreatic fistula (CR-POPF) following pancreatectomy. • Prospective study with validation showed that the modified model provides better diagnostic efficacy and clinical benefits compared to previous clinical models in predicting CR-POPF. • Peri-operative management of CR-POPF high-risk patients becomes more possible.

Non-invasive evaluation of vascular architecture of focal liver lesions by micro vascular imaging.

OBJECTIVE: To explore the value of vascular architecture detected by micro vascular imaging (MVI) in preoperative diagnosis of focal liver lesions (FLLs). METHODS: In this retrospective study, patients with surgery and histopathologically proved or radiologically confirmed FLLs were included. Vascular architecture of FLLs were acquired by color Doppler flow imaging (CDFI) and MVI on LOGIQ™ E20 ultrasound machine (C1-6 convex array probes). Alder semiquantitative analysis (grade 0-3) and morphologic features of blood vessels (pattern a-f) were used to assess the blood flow within the FLLs. Interobserver agreement for evaluating blood flow of FLLs was analyzed. Using Adler's grading or morphologic patterns as diagnostic criteria for malignant FLLs, the diagnostic efficiency was analyzed and compared. RESULTS: From October 2021 and February 2022, 50 patients diagnosed with 40 malignant FLLs and 10 benign FLLs were finally included. The Kappa value within two observers for evaluating the blood flow of FLLs was 0.78 for MVI and 0.55 for CDFI. According to Alder semiquantitative analysis, more high-level blood flow signals (grade 2-3) were detected by MVI than CDFI (P < 0.05). Based on high-level blood flow signals (grade 2-3) and hypervascular supply patterns (pattern e and f), the diagnostic accuracy for malignant FLLs were 76% and 68% for MVI, 56% and 38% for CDFI, respectively. CONCLUSION: MVI is superior to CDFI in evaluating vascular architecture of FLLs. The high-level flow signals and hypervascular pattern detected by MVI have a useful and complementary value in preoperative non-invasive identification of malignant FLLs.

Prediction of Pathological Grades of Pancreatic Neuroendocrine Tumors Based on Dynamic Contrast-Enhanced Ultrasound Quantitative Analysis.

Objective: To investigate whether the dynamic contrast-enhanced ultrasound (DCE-US) analysis and quantitative parameters could be helpful for predicting histopathologic grades of pancreatic neuroendocrine tumors (pNETs). Methods: This retrospective study conducted a comprehensive review of the CEUS database between March 2017 and November 2021 in Zhongshan Hospital, Fudan University. Ultrasound examinations were performed by an ACUSON Sequioa unit equipped with a 3.5 MHz 6C−1 convex array transducer, and an ACUSON OXANA2 unit equipped with a 3.5 MHz 5C−1 convex array transducer. SonoVue® (Bracco Inc., Milan, Italy) was used for all CEUS examinations. Time intensity curves (TICs) and quantitative parameters of DCE-US were created by Vuebox® software (Bracco, Italy). Inclusion criteria were: patients with histopathologically proved pNETs, patients who underwent pancreatic B-mode ultrasounds (BMUS) and CEUS scans one week before surgery or biopsy and had DCE-US imaging documented for more than 2 min, patients with solid or predominantly solid lesions and patients with definite diagnosis of histopathological grades of pNETs. Based on their prognosis, patients were categorized into two groups: pNETs G1/G2 group and pNETs G3/pNECs group. Results: A total of 42 patients who underwent surgery (n = 38) or biopsy (n = 4) and had histopathologically confirmed pNETs were included. According to the WHO 2019 criteria, all pNETs were classified into grade 1 (G1, n = 10), grade 2 (G2, n = 21), or grade 3 (G3)/pancreatic neuroendocrine carcinomas (pNECs) (n = 11), based on the Ki−67 proliferation index and the mitotic activity. The majority of the TICs (27/31) of pNETs G1/G2 were above or equal to those of pancreatic parenchyma in the arterial phase, but most (7/11) pNETs G3/pNECs had TICs below those of pancreatic parenchyma from arterial phase to late phase (p < 0.05). Among all the CEUS quantitative parameters of DCE-US, values of relative rise time (rPE), relative mean transit time (rmTT) and relative area under the curve (rAUC) were significantly higher in pNETs G1/G2 group than those in pNETs G3/pNECs group (p < 0.05). Taking an rPE below 1.09 as the optimal cut-off value, the sensitivity, specificity and accuracy for prediction of pNETs G3/pNECs from G1/G2 were 90.91% [58.70% to 99.80%], 67.64% [48.61% to 83.32%] and 85.78% [74.14% to 97.42%], respectively. Taking rAUC below 0.855 as the optimal cut-off value, the sensitivity, specificity and accuracy for prediction of pNETs G3/pNECs from G1/G2 were 90.91% [66.26% to 99.53%], 83.87% [67.37% to 92.91%] and 94.72% [88.30% to 100.00%], respectively. Conclusions: Dynamic contrast-enhanced ultrasound analysis might be helpful for predicting the pathological grades of pNETs. Among all quantitative parameters, rPE, rmTT and rAUC are potentially useful parameters for predicting G3/pNECs with aggressive behavior.

Early Assessment of Chemoradiotherapy Response for Locally Advanced Pancreatic Ductal Adenocarcinoma by Dynamic Contrast-Enhanced Ultrasound.

Objective: To evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) and quantitative parameters in early prediction of tumor response to chemoradiotherapy (CRT) in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). Patients and Methods: In this prospective study, patients with biopsy-proved and histopathologically proved LAPC who underwent regular CRT were recruited. DCE-US evaluations were performed before and four months after CRT. SonoVue-enhanced contrast-enhanced ultrasound (CEUS) was performed by an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, USA) equipped with a 5C1 MHz convex array transducer. Time−intensity curves were created by VueBox software (Bracco, Italy), and various DCE-US quantitative parameters were obtained. Taking Response Evaluation Criteria in Solid Tumors (RECIST) based on computed tomography (CT) or magnetic resonance imaging (MRI) as the gold standard, DCE-US parameters were compared between the treatment responder group (RG) and non-responder group (NRG). The correlation between the DCE-US parameters and the serum carbohydrate antigen 19-9 (CA 19-9) level was also analyzed. Results: Finally, 21 LAPC patients (mean age 59.3 ± 7.2 years) were included. In comparing the RG (n = 18) and NRG (n = 3), no significant change could be found among the mean size of the lesions (31.2 ± 8.1 mm vs. 27.2 ± 8.3 mm, p = 0.135). In comparing the TICs between the two groups, the LAPC lesions in the RG took a longer time to reach peak enhancement and to wash out. Among all the DCE-US parameters, RT (rise time), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiWoAUC (wash-in and wash-out area under the curve) decreased significantly after CRT in the RG (p < 0.05). The RT ratio, WiAUC ratio, WoAUC ratio and WiWoAUC ratio were closely correlated with the change in serum CA 19-9 level in the RG (p < 0.05). Conclusion: DCE-US might be a potential imaging method for non-invasive follow-up for early response in LAPC patients treated by CRT.

Prediction of pancreatic fistula after pancreatectomy by virtual touch tissue imaging and quantification (VTIQ) technology.

OBJECTIVES: The aim of this study was to quantitatively evaluate the stiffness of pancreatic parenchyma and solid focal pancreatic lesions (FPLs) by virtual touch tissue imaging and quantification (VTIQ) technique and to investigate the potential usefulness of VTIQ method in the prediction of post-operative pancreatic fistula (POPF) after pancreatectomy. METHODS: In this prospective study, patients who scheduled to undergo pancreatectomy were initially enrolled and received VTIQ assessment within one week before surgery. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used to measure the shear wave velocity (SWV) value of FPLs and the body part pancreatic parenchyma. The palpation stiffness of pancreas was qualitatively evaluated during operation by surgeons. POPF was finally diagnosed and graded through a three-weeks post-operative follow-up according to international study group of pancreatic fistula (ISGPF). SWV values were compared between POPF positive and negative group. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy of SWV value in predicting POPF. RESULTS: From December 2020 to June 2021, 44 patients were finally enrolled in this study, among which, 26 patients were identified to develop POPF after pancreatectomy. The SWV value of pancreatic parenchyma in POPF positive group was significantly lower than that in POPF negative group (P = 0.001). However, there was no significant difference in palpation stiffness between the two groups (P = 0.124). Besides, neither the SWV value of FPL nor the SWV ratio between FPL to surrounding pancreatic parenchyma differ significantly between POPF positive and negative group (P > 0.05). Taking SWV value of pancreatic parenchyma >1.10 m/s as a cut-off value for predicting POPF, area under the receiver operating characteristic curve (AUROC) was 0.864 with 72.2% sensitivity, 92.3% specificity, 86.7% positive predictive value (PPV) and 82.8% negative predictive value (NPV), respectively. CONCLUSIONS: VTIQ technique might be a potential non-invasive imaging method to predict POPF before pancreatectomy in future clinical practice.

The value of dynamic contrast enhanced ultrasound (DCE-US) in monitoring treatment effect of high-intensity focused ultrasound (HIFU) in locally advanced pancreatic cancer (LAPC).

PURPOSE: To evaluate the feasibility of dynamic contrast enhanced ultrasound (DCE-US) in predicting treatment response of high-intensity focused ultrasound (HIFU) in patients with locally advanced pancreatic cancer (LAPC) lesions. PATIENTS AND METHODS: In this prospective study, 10 patients with pathologically confirmed LAPC lesions (7 men, 3 women; average age, 61.13±5.80 years) were prospectively enrolled. All patients received HIFU treatment with peak intensity at 12000 W/cm2. Contrast enhanced ultrasound (CEUS) was performed with an ACUSON Oxana 2 ultrasound equipment and a 6 C-1 transducer (1-6 Hz). A dose of 2.4 ml SonoVue was injected for each examination. Time intensity curves (TICs) were generated and quantitative analyses were performed by SonoLiver software. B mode ultrasound (BMUS) features, CEUS enhancement patterns, TICs, CEUS quantitative parameters and serum carcinoma antigen 19-9 (CA19-9) levels were compared before and 4 weeks after HIFU treatment. Statistical analyses were performed with SPSS Version 20.0 and GraphPad Prism 5. RESULTS: While comparing before and after HIFU, no significant difference was obtained on mean size of lesion, BMUS or CEUS features. After HIFU treatment, TICs showed decreased and delayed enhancement. Among all CEUS quantitative parameters, significant decrease could be found in maximum intensity (MI) (60.66±23.95% vs 41.31±26.74%) and mean transit time (mTT) (76.66±47.61 s vs 38.42±28.35 s). CA19-9 level decreased significantly after HIFU (2747.92±4237.41 U/ml vs 715.08±1773.90 U/ml) (P = 0.05). CONCLUSION: DCE-US combining with quantitative analysis might be a useful imaging method for early treatment response evaluation of HIFU in LAPC lesions.