Intraoperative Contrast-enhanced Ultrasound Research Articles

Application of contrast-enhanced ultrasonography during radiofrequency ablation for renal tumors

Objective To assess the intraoperative efficacy of contrast-enhanced ultrasonography (CEUS) in the radiofrequency ablation (RFA) of renal tumors.Methods RFA was performed on 110 renal tumors (size range:1.5-8.6 cm,49 located in the left,55 right and 3 bilateral) in 107 selected patients.Conventional tumor biopsy was conducted for pathological diagnosis using 18G biopsy needle after RFA.CEUS was performed in all patients before,during and after RFA to assess the necrotic area.Once suspicious residual lession was discovered by CEUS,another round of RFA was taken immediately.Initial follow-up enhanced CT and CEUS was performed seven days after the procedure,with subsequent CEUS and enhanced CT after one month,three months,and six months to assess the necrotic area.Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor.Results With CEUS performed during RFA,110 tumors (100％) were successfully ablated during one operation.Of these,five tumors was subjected to additional RFA treatment for the suspicious residual lesion detected by CEUS right after initial RFA.Elimination of areas covered the entire tumor after the second RFA.No residual or recurrence tumors was confirmed by both enhanced CT and CEUS during follow-up.All patients survived in the follow-up phase which ranged from 3 to 18 months(mean 11 months).Conclusions With the application of intraoperative CEUS,there were less residual tumors after RFA. Key words: Ultrasonography; Microbubbles; Kidney neoplasms; Catheter ablation

PD-0003 Comparison of GD-EOB-DTPA Enhanced Mri and Contrast-Enhanced Intraoperative Ultrasound using Sonazoid in Patients Undergoing Liver Resection for Colorectal Liver Metastasis

ABSTRACT Introduction Two imaging modalities dedicated for liver specific phase, namely Gd-EOB-DTPA enhanced MRI (EOB-MRI) and contrast-enhanced intraoperative ultrasound (CE-IOUS) using Sonazoid have been recently developed. Both are reportedly useful for diagnosis and staging in patients undergoing surgery for colorectal liver metastasis. The aim of this study is to compare diagnostic ability of these modalities. Methods A prospective clinical trial has been undertaken (UMIN-CTR ID: 000005537). Consecutive 84 patients with colorectal liver metastasis were scheduled for liver resection between January 2011 and November 2011. Of these, 66 patients underwent contrast-enhanced CT, EOB-MRI, preoperative contrast-enhanced ultrasound, fundamental intraoperative ultrasound, CE-IOUS, and liver resection of curative intent. Eighteen patients were excluded from this trial because they underwent laparoscopic liver resection (n = 7), did not undergo contrast-enhanced CT due to a history of allergy (n = 1), underwent probe laparotomy due to peritoneal metastasis (n = 1), had more than ten liver metastases (n = 9). Hepatobiliary phase was referred for diagnosis of liver metastasis in EOB-MRI. After laparotomy and exploration including fundamental IOUS, 0.5 ml of Sonazoid was injected through peripheral vein. Thorough liver screening on CE-IOUS was performed 10 to 15 minutes later under harmonic mode, where hypoechoic liver lesions were regarded as liver metastases. A nodule which was temporary diagnosed as metastasis in any imaging modality was resected. Radiofrequency ablation was not performed. All possible liver metastases were resected as long as it was identified by IOUS. Intraoperative needle biopsy was allowed alternative to resection for indeterminate nodules. Results A total of 190 nodules were temporary diagnosed as liver metastases in at least one imaging modality in the 66 patients. Of 190, 177 were diagnosed as adenocarcinoma in histological examination, 8 were adversely diagnosed as benign lesion in histological examination, and the other 5 could not be identified during operation and were finally diagnosed benign through postoperative follow-up. Fifteen were newly found during IOUS and 11 of them were finally diagnosed as adenocarcinoma. Thirteen were newly found during CE-IOUS and 11 of them were finally diagnosed as adenocarcinoma. Sensitivity and positive-predictive value were 83 and 97% for contrast-enhanced CT, 83 and 97% for EOB-MRI, 76 and 96% for preoperative contrast-enhanced ultrasound, 89 and 96% for fundamental IOUS, and 98 and 97% for CE-IOUS. Conclusion EOB-MRI and contrast-enhanced CT are complementary to each other. CE-IOUS scored high diagnostic value for diagnosis of colorectal liver metastasis.

Fate of disappeared hepatic metastasis after mFOLFOX6 plus bevacizumab therapy.

e14127 Background: Neoadjuvant and conversion chemotherapy for liver limited metastasis from colorectal cancer (CRC) is a current topic. Minute liver metastasis sometimes disappears on preoperative imaging and intraoperative examination (including contrast enhanced intraoperative ultrasonography (CEIOUS)) after chemotherapy using highly effective regimen, such as FOLFOX or FOLFIRI with molecular targeted agent. We reported a high pathological complete response (CR) rate of resected liver metastasis from CRC after preoperative mFOLFOX6 plus bevacizumab (Bmab) therapy (AACR 2011, abstract #3218), but It is still unclear whether disappeared lesions after chemotherapy need to be removed. Methods: Out of 17 patients with liver limited metastasis from CRC treated with mFOLFOX6 plus Bmab therapy, 9 patients (52%) underwent liver resection after chemotherapy. In 6 of the 9 patients, one or more disappeared lesion(s) after the chemotherapy was not resected and followed up by enhanced CT once every 3 months. Follow up period was 9 to 33 months (22 months in median). Results: Before chemotherapy, 53 liver metastases were detected in the 6 patients. After chemotherapy, 29 (55%) lesions were not detected by preoperative CT or CEIOUS. All the 24 lesion, which were pointed out at the operation, were resected. By histological examination, no viable tumor cell was observed in 12 lesions (50%) among resected lesions. In follow up period, in situ recurrence occurred in 5 lesions (17%) in 4 patients. Three of the 4 patients underwent curative resection of re-detected liver metastases. Conclusions: It was reported that cancer cells remain over 80% of clinically disappeared lesion after conventional chemotherapy. In the present study, only 17% of disappeared lesion after mFOLFOX6 plus Bmab therapy caused in situ recurrence. With this result and a high pathological CR rate of the resected liver metastases after mFOLFOX6 plus Bmab therapy, it is speculated that complete resection for disappeared lesions after this chemotherapy is not always necessary.

Fate of metastatic foci after chemotherapy and usefulness of contrast‐enhanced intraoperative ultrasonography to detect minute hepatic lesions

Along with advances in the chemotherapy for colorectal cancer, the strategy for hepatic metastasis has been changed. One of the most striking issues is that initially unresectable hepatic metastases can be resectable after chemotherapy with considerably high frequency. In addition, advanced chemotherapy leads to the downsizing of the metastatic foci in the liver, which is sometimes difficult to detect with conventional intraoperative ultrasonography (IOUS). To discover the undetectable hepatic lesions with IOUS, we have introduced contrast-enhanced intraoperative ultrasonography (CEIOUS). In the present study, we present evidence that viable cancer cells exist in even the shrunken tumors with high frequency and that CEIOUS contributes to detecting the minute foci. This study was composed of eight patients; four of them had initially unresectable metastasis, and the remaining four had either H2 or H3 status of hepatic metastases. All of them underwent hepatic resection after chemotherapy. A total of 57 metastatic lesions were detected before chemotherapy. Thirty lesions were demonstrated by CEIOUS with perflubutane and resected. In the pathological examination, tumor cells were not found in 12 of the 30 resected lesions. The degree of pathological liver damage was grade 1 or less in all patients, and no serious complication occurred after surgery in any of the patients. The present study showed that viable cancer cells remained with high frequency, even in the minute hepatic metastasis which was reduced in size after chemotherapy, and CEIOUS was a useful examination for detecting the minute hepatic foci.

815 Usefulness of Contrast-Enhanced Intraoperative Ultrasonography in Colorectal Liver Metastases After Preoperative Chemotherapy

815 Usefulness of Contrast-Enhanced Intraoperative Ultrasonography in Colorectal Liver Metastases After Preoperative Chemotherapy

Contrast‐enhanced intraoperative ultrasound for hepatocellular carcinoma: high sensitivity of diagnosis and therapeutic impact

Postoperative early recurrence is a crucial issue in the treatment of hepatocellular carcinoma (HCC) patients. Some early recurrences seem to occur from minute tumors which were overlooked during both preoperative and intraoperative investigations. Therefore, it is urgently necessary to increase detectability of minute HCCs during operation. If they could be detected and resected during surgery, the prognosis should be improved. The purpose of this study is to investigate the usefulness of contrast-enhanced intraoperative ultrasound (CEIOUS) for the diagnosis and treatment of HCC. Institutional ethics committee approval and informed consent were obtained. Fifty-two patients (mean age 65 years; 38 males and 14 females) who underwent liver resection with either preoperative computed tomography during angiography (CTA) or CEIOUS with Sonazoid (perflubutane microbubble contrast agent) were studied. We determined the presence of HCC on the basis of the histopathological findings of resected specimens. The sensitivity of CEIOUS [97.6% (95% CI 91.8-99.4)] was higher than that of CTA [89.4% (95% CI 81.1-94.3)]. The positive predictive values of CEIOUS [91.2% (95% CI 83.6-95.5) and CTA [91.6% (95% CI 83.6-95.9)] were similar. Eight new HCCs from 7 patients, which accounted for 9.4% (8/85) of the total HCCs, were correctly detected and diagnosed by CEIOUS, and we performed an additional partial hepatectomy in 3 of these 7 patients. CEIOUS with Sonazoid provided increased sensitivity of detection of small HCCs compared with preoperative CTA, thereby leading to a more appropriate surgical procedure and contributing to complete tumor removal.

Intraoperative high resolution linear contrast enhanced ultrasound (IOUS) for detection of microvascularization of malignant liver lesions before surgery or radiofrequeny ablation

The aim of this study was to evaluate the value of linear contrast enhanced intraoperative ultrasound (CE-IOUS) to improve detection of malign liver tumors lesions before surgery or radiofrequency ablation (RFA). 50 patients were included for surgery of malignant liver tumors (mean age 61 years (19-80); male n = 35, female n = 15), suffering from HCC (n = 15), colorectal liver-metastasis (n = 28), CCC (n = 2) or other malign liver lesions (n = 5). Preoperative CE-CT (n = 38), CE-MRI (n = 23) or PET-CT (n = 8) confirmed hepatic tumor manifestation. Before undergoing surgery, intraoperative conventional (IOUS) as well as CE-IOUS were performed by one experienced examiner in all cases using multifrequency linear probes (6-9 MHz, 6-15 MHz; LOGIQ E9; GE Healthcare, Milwaukee, WI, USA). CE-IOUS was performed after bolus injection of 5 ml up to 15 ml SonoVue(®) (Bracco Imaging SpA, Milan, Italy). Digitally stored images of CE-IOUS were compared with fundamental B-Scan and preoperative imaging (CE-CT, CE-MRI and PET-CET). In 28 of 50 patients (56%), additional lesions were found using CE-IOUS (mean tumor size 8 mm, range 4-12 mm). This resulted in a change of surgical strategy or the intraoperative application of RFA in 27 patients (54%). Modification of therapy due to additionally found liver lesions was statistically significant (p < 0.05). Comparing conventional IOUS and CE-IOUS, 14 additional lesions in 10 patients were seen by CE-IOUS. All lesions seen in B-scan could also be detected with CE-IOUS. This is the first study using contrast-enhanced ultrasound with high resolution linear probes for intraoperative detection of malignant liver lesions. Compared to preoperative imaging and also conventional IOUS more than 50% additional lesions were found leading to therapeutic consequences of patients. A recently started prospective study has to show whether these changes in the surgical or interventional therapy will influence morbidity, mortality and especially the recurrence rate.

Usefulness of Contrast-Enhanced Intraoperative Ultrasound Using Sonazoid in Patients With Hepatocellular Carcinoma

To assess the usefulness of contrast-enhanced intraoperative ultrasound (CE-IOUS) using Sonazoid (gaseous perflubutane) in patients with hepatocellular carcinoma (HCC). Contrast-enhanced intraoperative ultrasound using Sonazoid, a novel ultrasonic contrast agent enabling Kupffer imaging, may enable differentiation of HCC among new focal liver lesions found during fundamental intraoperative ultrasound (fundamental-NFLLs). Between February 2007 and February 2009, a total of 192 consecutive patients were enrolled. Fundamental intraoperative ultrasound and CE-IOUS were performed successively after laparotomy. The vascularity of 1 representative lesion was examined in harmonic mode for approximately 1 minute after the intravenous injection of Sonazoid (vascular phase). Approximately 15 minutes after the vascular phase, total liver scanning in the harmonic mode was commenced (Kupffer phase). One additional injection of Sonazoid was allowed to examine the vascularity of another lesion, if necessary. A tentative diagnosis of HCC was made when a lesion was either hypervascular during the vascular phase or hypoechoic during the Kupffer phase. A final diagnosis of HCC was made on the basis of the results of a histological examination or dynamic computed tomography findings obtained during the 12-month postoperative period. Seventy-nine fundamental-NFLLs were found in 50 patients (26%), 17 (22%) of which were finally diagnosed as HCC. The sensitivity, specificity, and accuracy of CE-IOUS for differentiating HCC among fundamental-NFLLs were 65%, 94%, and 87%, respectively. Contrast-enhanced intraoperative ultrasound identified 21 additional new hypoechoic lesions in 16 patients, of which 14 lesions (67%) in 11 patients were finally diagnosed as HCC. This prospective study protocol was approved by the institutional review board of the Tokyo University Hospital. An English-language summary of the protocol was submitted (registration ID: UMIN000003046) to the Clinical Trials Registry managed by the University Hospital Medical Information Network in Japan (http://www.umin.ac.jp/ctr/index.htm). With help of CE-IOUS using Sonazoid, more accurate intraoperative staging for HCC can be performed.

Improved outcome of percutaneous radiofrequency ablation in renal cell carcinoma: a retrospective study of intraoperative contrast-enhanced ultrasonography in 73 patients

To evaluate the impact of contrast-enhanced ultrasonography (CEUS) during percutaneous radiofrequency ablation (PRFA) procedure in renal cell carcinoma (RCC). From January 2008 to July 2010, 73 patients with sporadic unilateral RCC were enrolled to our study (57 men and 16 women, age range: 37-78 years, mean age 57.9 years). The diameter of the tumor was 1.7-5.8, 3.4 cm on average. The patients were divided into two groups depending on the intraoperative ultrasonography type: CEUS group and conventional ultrasound group. Patients in CEUS group received CEUS before insertion of the electrode, and the second CEUS was performed right after the initial ablation to dynamically evaluate the images. If there was highly suspicious residue, additional ablation and repeated CEUS were applied. Patients in the conventional ultrasound group received PRFA guided by gray-scale ultrasound. All of these patients received contrast-enhanced computed tomography (CT) examination 7 days after the procedure (patients in CEUS group received CEUS conducted with each CT scan), with subsequent CT and CEUS assessment at 3, 6, and every 6 months thereafter. The mean follow-up period was 22 months (range: 12-42 months). All tumors were biopsied before RFA. The local tumor control rate was 94.6% (35/37) in the CEUS group and 86.1% (31/36) in the conventional ultrasound group (P < 0.05); the cancer-specific survival rate and the overall survival rate were 100%. The post-RFA (12 months) mean GFR levels were 84.7 ± 27.5 mL/min/1.73 m(2) (P > 0.05, compared with pre-GFR: 86.4 ± 26.2 mL/min/1.73 m(2)) in the CEUS group and 81.9 ± 22.8 mL/min/1.73 m(2) (P > 0.05, compared with pre-GFR: 83.5 ± 23.7 mL/min/1.73 m(2)) in the conventional ultrasound group. Intraoperative CEUS can "real-time" monitor the ablated area during PRFA procedure. This technique can help to achieve a higher success rate compared with conventional ultrasound. No impact of intraoperative CEUS has been found on GFR level.

Intraoperative Ultrasound with Contrast Medium in Resective Pancreatic Surgery: A Pilot Study

The introduction of contrast-enhanced ultrasound has been a major innovation in liver and pancreatic imaging. Previous studies have validated its intraoperative use during liver surgery, while there is a lack of data regarding its use during pancreatic surgery. The purpose of the present study was to prospectively evaluate the possible role of contrast-enhanced intraoperative ultrasound (CEIOUS) during resective pancreatic surgery for primary lesion characterization and intraoperative staging. Thirty-four patients (70% males, mean age 67.9years) were selected for pancreatic surgery between October 2006 and July 2009. All patients underwent intraoperative ultrasound with intravenous injection of 4.8mL sulfur-hexafluoride microbubbles. Location of the primary tumor, relation to the main vessels, contrast medium uptake modalities, presence of liver metastases, and multifocal pancreatic involvement were evaluated. The majority of operations were pancreatoduodenectomies (70.6%) performed for pancreatic ductal adenocarcinoma (64.7%). Additional lesions were detected by ultrasound in six patients (17.6%: liver metastases in four patients, a hemangioma in one patient, and a further pancreatic lesion in one patient). In five of these patients (5/34, 14.7%) surgical management was modified by these findings. All these new findings were diagnosed before injection of contrast medium, except for a metastasis from a neuroendocrine tumor; the characterization of the hemangioma was possible only after contrast injection. Intraoperative findings regarding location of primary tumor, relation to the main vessels, and lesion characterization did not differ from those obtained with preoperative imaging. In our experience intraoperative ultrasound is a valid technique for intraoperative staging prior to pancreatic resection; it is unclear whether, in pancreatic surgery, the addition of contrast enhancement adds any benefit to traditional intraoperative ultrasound.

Abstract 3218: High pathological CR rate and low recurrence rate was observed in liver metastasis of colorectal cancer after preoperative bevacizumab plus FOLFOX therapy

Abstract [Background] We reported the effectiveness of intraoperative contrast-enhanced ultrasonography using perflubutane (SONAZOIDTM) for complete resection of liver metastasis from colorectal cancer (CRC) after Bevacizumab (Bmab)+FOLFOX therapy (Annual meeting of AACR, 2010). In this study, we report pathological CR (pCR) rate of resected liver tumors and recurrence rate of disappeared lesions that were not resected. [Material and methods] Sixteen patients of advanced CRC with liver metastasis only (no extrahepatic lesion) were treated with Bmab+FOLFOX therapy. Response rate of chemotherapy was 81%. Among the 16 patients, 8 (50%) were underwent liver resection after chemotherapy. We study 6 of the 8 patients, who were followed up longer than a year (20-33 months). [Result] By CT angiography, 47 liver metastases were detected before chemotherapy. By intraoperative contrast-enhanced ultrasonography, 26 liver tumors were detected and resected. In histological examination, 11 (42%) were without viable cancer cell (pCR). Among 21 lesions that were not detected by intraoperative ultrasound and not resected, only 2 lesions were re-detected in follow up period and both lesion were resected. [Conclusion] High pCR rate and low recurrence rate was observed in liver metastasis of colorectal cancer after preoperative Bmab + FOLFOX therapy. Contrast-enhanced ultrasonography was effective for complete resection of liver metastases, as well as low recurrence rate of disappeared lesion after chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3218. doi:10.1158/1538-7445.AM2011-3218

Portal blood flow via the peribiliary vascular plexus demonstrated by contrast‐enhanced ultrasonography with Sonazoid

We report two cases in which portal blood flow via the peribiliary vascular plexus (PBP) was clearly demonstrated using contrast-enhanced intra-operative ultrasonography (CE-IOUS). Two patients who underwent hemihepatectomies were investigated using CE-IOUS. Before injection of the contrast medium, both the hepatic arterial and portal venous flows of the hemiliver to be resected were interrupted by ligating those corresponding vessels at the hepatic hilum. Subsequently, the perfluorobutane microbubbles were injected intravenously. In the early vascular phase, a remarkable intermittent flow was visualized in the lumen of the portal branches whose inflows were interrupted. The flow of the portal vein then disappeared as a result of ligating the hepatic duct concomitantly with the surrounding connective tissue. We considered that the portal venous flow appearing under the condition of total disruption of original inflow was supplied from the hepatic artery through the PBP. This is the first report of blood flow via the PBP in human liver visualized by dynamic image study.

Combined Use of Contrast‐Enhanced Intraoperative Ultrasonography and a Fluorescence Navigation System for Identifying Hepatic Metastases

The purpose of this study was to assess the concomitant use of contrast-enhanced intraoperative ultrasound (CE-IOUS) using the new microbubble agent Sonazoid, and to assess the fluorescence navigation system (Photo Dynamic Eye, or PDE) using indocyanine green (ICG) as a novel tool for identifying colorectal metastatic lesions compared with preoperative contrast-enhanced multiple row-detected computed tomography (MDCT) and gadoxetic acid-enhanced MRI. Thirty-two patients who underwent a liver resection for colorectal metastatic carcinoma from 2008 to 2009 were included in the present study. ICG was intravenously injected within 2weeks of the operation. The liver was inspected with CE-IOUS using Sonazoid and PDE for visualizing small metastatic lesions. A lesion analysis was performed with the postoperative histopathological examination of the resected tissues. The clinical values of CE-IOUS and PDE to confirm the malignant lesion diagnoses were statistically evaluated. A total of 56 lesions were identified based on the histopathological findings of the biopsies and resected tissues; of these, 52 were confirmed to be metastases, whereas 4 were benign tumors. The numbers of identified metastases by MDCT/MRI and CE-IOUS/PDE were 46 and 51, respectively. The use of CE-IOUS and PDE improved the diagnostic sensitivity compared with the use of MDCT and EOB-MRI (98.1 vs. 88.5%, respectively; P=0.050). The present results suggested that the concomitant use of CE-IOUS with the Sonazoid and PDE system may be a useful and safe method, in addition to CT or MRI.

Surgical Strategies for Hepatocellular Carcinoma with Special Reference to Anatomical Hepatic Resection and Intraoperative Contrast-Enhanced Ultrasonography

Here we described our strategies to attain a better prognosis for hepatocellular carcinoma (HCC) patients by surgery. Among a variety of attempts conducted to date, we focused on anatomical resection and intraoperative contrast-enhanced ultrasonography. There are still controversies with respect to the significance of anatomical resection. We analyzed the significance of this surgical procedure in 207 patients without macrovascular invasion. These patients underwent either anatomical resection or non-anatomical resection. We found that the patients with anatomical resection had higher recurrence-free survival rate than those with non-anatomical resection. Univariable analysis showed that liver damage, the serum level of α-fetoprotein, tumor number, surgical margin, and type of surgery (anatomical or non-anatomical resection) were significant predictive factors for intrahepatic recurrence. Multivariable analysis revealed that multiple tumors, α-fetoprotein, and non-anatomical resection were independent risk factors for recurrence. We conclude that anatomical resection is a recommendable surgical procedure in patients without macrovascular invasion. A recent innovation is the development of contrast-enhanced ultrasonography. Then we have applied this to liver surgery intraoperatively. We confirm that vascular images contribute to a precise diagnosis and the detection of small portal tumor thrombi, and that Kupffer images are useful to discover the minute tumors. In addition, by clarifying the relationship between tumors and the vascular architecture, real-time 3-dimensional images using Kupffer imaging are a promising guide during the surgical procedures, although further development is needed.

First experience using intraoperative contrast-enhanced ultrasound during endovascular aneurysm repair for infrarenal aortic aneurysms

Endovascular aortic repair (EVAR) has become an additional treatment option for patients with infrarenal aortic aneurysms and suitable aortic morphology. However, endoleaks are commonly encountered and represent a relevant risk for secondary treatment failure. In addition, impaired renal function or allergic reactions to intravascular iodine application might represent exclusion criteria for conventional infrarenal endovascular aortic repair using intraoperative angiography with iodine contrast media. Real-time contrast-enhanced ultrasound (CEUS) with a low mechanical index (MI) is a promising method recently introduced for follow up after endovascular infrarenal aortic repair. In this study, intraoperative CEUS using SonoVue as ultrasound contrast agent was evaluated in 17 patients for localization of the proximal infrarenal landing zone, the distal iliac fixation area, and identification of endoleaks in patients suitable for endovascular aortic repair with an infrarenal aortic neck > or =10 mm and non-aneurysmal common iliac arteries. For comparison, 20 patients were treated by conventional EVAR using intraoperative fluoroscopy and iodine contrast media. Intraoperative application of contrast-enhanced ultrasound (iCEUS) for identification of the infrarenal landing zone and proximal stent graft release was achieved in 14 out of 17 patients (82.4%), as verified by intraoperative angiography or postinterventional imaging. Intraoperative CEUS-assisted visualization of the distal fixation area proximal to the level of the iliac bifurcation was achieved in 89.3% (25 out of 28 iliac arteries examined) in comparison to intraoperative angiography or postinterventional CEUS, computed tomography (CT), or magnetic resonance (MR) angiography. Three selected patients having contraindications for iodine-based contrast media were treated by iCEUS-assisted EVAR without the use of any iodine contrast during fluoroscopy. Time for exposure to intraoperative radiation, volume of contrast medium used, and the number of intraoperative angiographies and postinterventional CT or MR angiographies were significantly reduced in the iCEUS-assisted EVAR group in comparison to conventional endovascular aortic treatment (P < .002 or less for all parameters). Intraoperative application of CEUS detected more endoleaks than conventional EVAR (8/17 vs 4/20; P = .08) treated by proximal stent graft extension in one symptomatic patient with a type Ia endoleak. Intraoperative CEUS-assisted EVAR in patients with infrarenal aortic aneurysms represents a new option for intraoperative visualization of aortoiliac segments required as proximal or distal fixation zones and identification of endoleaks, especially in those patients with contraindications for usage of iodine-containing contrast agents, in association with a reduction of iodine contrast media used and radiation exposure during fluoroscopy.

The current status of contrast-enhanced ultrasound in China.

This review article provides an overview of the use of contrast-enhanced ultrasound (CEUS) in China. Currently, the only licensed contrast agent is SonoVue, a sulfur hexafluoride-filled microbubble contrast agent. In combination with a low mechanical index contrast-specific imaging mode, SonoVue-enhanced CEUS can be used to visualize the micro and macro-vasculature continuously. Since 2004, CEUS has been widely used in China in various clinical scenarios. The authors compared CEUS with baseline ultrasound or contrast-enhanced computed tomography with regard to characterization of focal liver lesions (FLLs). On CEUS, heterogeneous or homogeneous hyperenhancement during the arterial phase and washout in the portal/late phase are typical findings for hepatocellular carcinoma. The enhancement features of intrahepatic cholangiocarcinoma, infected FLLs, focal fatty infiltration, focal fatty sparing, complex cystic FLLs, and uncommon benign FLLs were carefully depicted. CEUS was also used for patient selection in ablation therapy and evaluation of response to ablation for liver cancer. The utility of three-dimensional CEUS of the liver was also explored. In non-liver use, CEUS in hilar cholangiocarcinoma, gallbladder, breast, and prostate was initially investigated. In addition, CEUS was used in interventional procedures such as CEUS-guided hemostatic injection, intraoperative CEUS in neurosurgery, and evaluation of response to high-intensity focused ultrasound ablation of uterine fibroids. The Chinese experience has resulted in increased use of CEUS.

Abstract 1457: Intraoperative contrast-enhanced ultrasonography using perflubutane for liver resection

Abstract [Background] Bevacizumab (Bmab) is now widely used for metastatic colorectal cancer (CRC) treatment in the world. Through the high response of metastatic CRC to Bmab combination therapy, neoadjuvant chemotherapy using Bmab plus FOLFOX is a new strategy for the treatment of liver metastasis. As liver metastases shows high shrinkage by Bmab plus FOLFOX therapy, intraoperative contrast-enhanced ultrasonography using perflubutane (SONAZOIDTM) is supposed to be effective for complete detection and resection of small metastatic lesion after chemotherapy. [Material and methods] Forty-five patients with metastatic CRC were underwent Bmab combination chemotherapy in our institute (response rate and disease control rate was 72% and 94%, respectively). Among them, 8 patient (18%) were underwent liver resection after Bmab+mFOLFOX6 treatment. Median cycle of preoperative chemotherapy was 6.5 (5-17). [Result] By CT angiography, 52 liver metastases were detected before chemotherapy and 27 after chemotherapy. By intraoperative contrast-enhanced ultrasonography using SONAZOIDTM, 31 liver tumors were detected and resected. In histological examination, 13 of the resected 31 lesion (41%) were without viable cancer cell (pCR). [Conclusion] Intraoperative contrast-enhanced ultrasonography was effective for complete resection of liver metastasis after Bmab plus FOLFOX therapy. High pCR rate for liver metastasis was observed by Bmab plus FOLFOX therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1457.

Contrast-enhanced intraoperative ultrasound improves detection of liver metastases during surgery for primary colorectal cancer

BackgroundComputed tomography (CT) is the most common staging investigation in colorectal cancer (CRC). Up to 25% of patients are found to have previously undetected hepatic lesions when intraoperative ultrasound (IOUS) of the liver is used during CRC resection. We aimed to assess the ability of IOUS to detect additional liver lesions/metastases at primary colorectal resection, and to evaluate whether contrast-enhanced IOUS (CE-IOUS) improves the detection and characterization of hepatic lesions. MethodsWe performed a single-centre, prospective pilot study. At CRC resection, patients underwent IOUS of the liver. Contrast-enhanced IOUS of the liver was undertaken using i.v. sulphur hexafluoride micro-bubbles (SonoVue®, 4.8ml). Findings of CT, non-enhanced IOUS and CE-IOUS were compared. Changes in staging or management were noted. Additional lesions were corroborated with iron oxide magnetic resonance imaging (MRI). ResultsAmong 21 patients, IOUS demonstrated additional lesions in seven (33%). Contrast altered the diagnosis of non-enhanced IOUS in four (20%) and changed the management strategy in three (14%) patients. Thus, IOUS in combination with the contrast agent altered the intraoperative or postoperative management plan in four patients. ConclusionsIn the first study of its kind, early results suggest that the ability of IOUS to detect additional metastases is improved by CE-IOUS, and that this may impact on surgical staging and management.

Application of contrast-enhanced intraoperative ultrasonography in the decision-making about hepatocellular carcinoma operation

To evaluate the detection and differentiation ability of contrast-enhanced intraoperative ultrasonography (CE-IOUS) in hepatocellular carcinoma (HCC) operations. Clinical data of 50 HCC patients were retrospective analyzed. The sensitivity, specificity, false negative and false positive rates of contrast enhanced magnetic resonance imaging (CE-MRI), IOUS and CE-IOUS were calculated and compared. Surgical strategy changes due to CE-IOUS were analyzed. Lesions detected by CE-MRI, IOUS and CE-IOUS were 60, 97 and 85 respectively. The sensitivity, specificity, false negative rate, false positive rate of CE-MRI were 98.2%, 98.6%, 98.6%, 60.0%, respectively; for IOUS were 50.0%, 90.9%, 1.8%, 1.4%, respectively; and for CE-IOUS were 1.4%, 40.0%, 50.0%, 9.1%, respectively. The operation strategy of 9 (9/50, 18.0%) cases was changed according to the results of CE-IOUS. Compared with CE-MRI, CE-IOUS performs better in detection and differentiation of small metastasis and regenerative nodules. It plays an important role in the decision-making of HCC operation.

Characterization of microvascularization of liver tumor lesions with high resolution linear ultrasound and contrast enhanced ultrasound (CEUS) during surgery: First results

Evaluation of high resolution linear ultrasound and intra-operative linear contrast enhanced ultrasound (CEUS) and its benefit for the detection and characterization of tumor lesions. Twenty patients were investigated preoperatively regarding tumor detection using CT (n = 8) or MRI (n = 12) and image fusion (VNav) (n = 3). All patients had surgery for their hepatic tumor (hepatocellular carcinoma (HCC), cholangiocellular carcinoma (CCC), metastasis, and adenoma). Ultrasound was performed intra-operatively first with B-scan using a convex probe. Than multifrequency linear transmitters (6-9 MHz, 6-15 MHz, LOGIQ E9, GE) were applied for B-scan, coulor coded Doppler sonography (CCDS) and Power Doppler followed by dynamic CEUS with Contrast Harmonic Imaging (CHI) after bolus injection of a maximum of 15 mL SonoVue®. In 9 cases with the use of intra-operative CEUS additional tumor lesions (diameter 4-15 mm) could be detected and were histologically confirmed after surgical resection (7 cases) or intra-operative biopsy (2 cases). Using intraoperative CEUS 64 tumor lesions could be detected compared to 51 tumor lesions detected by preoperative CT or MRI (p < 0.05). Using the 6-15 MHz multifrequency linear transducer with CHI, arterial perfusion of adenomas, neuroendocrine metastases and HCC lesions was detectable. In 3 cases a resection was not achievable. Two of these cases were treated with radio frequency ablation (RFA). The other case had no curable option due to multifocal tumor manifestation. The intra-operative use of high-resolution linear transducer techniques with CEUS offers new diagnostic perspectives for an effective liver surgery.