Dynamic contrast-enhanced ultrasound with carbon dioxide microbubbles as adjunct to arteriography of liver tumors

Purpose The goal of the study is to evaluate utility of contrast enhanced ultrasound (US) with carbon dioxide microbubbles in evaluation of hepatic lesions.Methods Twenty eight patients with single or multiple t hepatic lesions (11 hepatocellular carcinoma, 8 hemangiomas, 5 metastases, 1 adenoma, 1 focal nodular hyperplasia, 2 regenerative nodules) were examined. US exam was performed during intraarterial injection of 10 ml of CO₂ through the same catheter employed for liver arteriography. The US exam was videotaped in its salient phases. Characteristics of enhancement were evaluated and correlated with histological findings or patient follow up.Results Sonographic angiography clearly demonstrated vascularization of the lesions. Hepatocellular carcinoma, hemangioma, metastases, focal nodular hyperplasia, and regenerative nodules had very characteristic patterns. The injection of CO₂ allowed detection of small additional nodules.Conclusion Sonographic angiography can improve characterization and staging of hepatic tumors. Low cost and the simplicity of the technique should encourage further experimentation.     

Multimodality diagnosis of liver tumors: feature analysis with CT, liver-specific and contrast-enhanced MR, and a computer model

RATIONALE AND OBJECTIVES: The purpose of this study was to measure and to clarify the diagnostic contributions of image-based features in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. MATERIALS AND METHODS: Six experienced abdominal radiologists each read images from 146 cases (including a contrast material-enhanced computed tomographic [CT] scan and contrast-enhanced and unenhanced magnetic resonance [MR] images) following a checklist-questionnaire requiring them to rate quantitatively each of as many as 131 image features and then reported on each of the two differentiations. The diagnostic value of each feature was assessed, and linear discriminant analysis was used to develop statistical prediction rules (SPRs) for merging feature data into computerized "second opinions." For the two differentiations, accuracy (area under the receiver operating characteristic curve [Az]) was then determined for the radiologists' readings by themselves and for each of three SPRs. RESULTS: Thirty-seven candidate features had diagnostic value for each of the two differentiations (a slightly different feature set for each). Radiologists' performance at both differentiations was excellent (Az = 0.929 [benign vs malignant] and 0.926 [hepatocyte-containing vs non-hepatocyte-containing]). Performance of the SPR that operated on the features from all modalities together was better than that of radiologists (Az = 0.936 [benign vs malignant] and 0.951 [hepatocyte-containing vs non-hepatocyte-containing]), but this difference was of marginal statistical significance (P = .11). Contrast-enhanced MR imaging and contrast-enhanced CT each made significant adjunctive contributions to accuracy compared with unenhanced MR imaging alone. CONCLUSION: Many CT- and MR imaging-based features have diagnostic value in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. Radiologists could also benefit from the fully informed SPR's "second opinions."     

US characterization of focal hepatic lesions with intermittent high-acoustic-power mode and contrast material

RATIONALE AND OBJECTIVES: This study was performed to determine whether ultrasound (US) performed with SonoVue, a contrast agent that contains microbubbles filled with sulfur hexafluoride vapor, depicts differential patterns of contrast enhancement in focal hepatic lesions. MATERIALS AND METHODS: Forty focal hepatic lesions (15 hepatocellular carcinomas [HCCs], 10 metastases, 11 hemangiomas, and four focal nodular hyperplasias) in 39 patients were evaluated by means of US, color Doppler US, and contrast-enhanced US performed by using intermittent high-acoustic-power mode. Contrast-enhanced helical computed tomography (11 patients) and US-guided fine needle aspiration (28 patients) were used as reference procedures. Contrast enhancement patterns were defined by means of both subjective and objective analysis, and baseline and contrast-enhanced US scans were reviewed offline. RESULTS: Thirteen of 15 HCCs, eight of 10 metastases, and all four hemangiomas with an atypical pattern at baseline US were correctly characterized after SonoVue injection. Two of 15 HCCs and two of 10 metastases remained indeterminate, with no characteristic baseline or contrast-enhanced patterns identified. Baseline US was essential in characterizing all hemangiomas with a typical pattern (n = 7), and color Doppler US with spectral analysis of tumoral vessels was essential in characterizing focal nodular hyperplasia. The percentage of diagnostic agreement with reference procedures was significantly increased (P < .001) for contrast-enhanced US compared with baseline US. CONCLUSION: Characteristic patterns of US contrast enhancement with SonoVue help in characterizing and differentiating focal hepatic lesions.     

动态增强MRI在肺肿瘤中应用的研究进展

动态增强MRI作为一种无创、快速的功能性检查技术,对肿瘤组织内部微血管情况和生物学活性的良好的反映能力。所以,在肿瘤的早期诊断与判断预后方面显示出了独特的优势,该技术已经逐渐的应用于临床,并显示出良好的效果。本文主要对动态增强MRI技术在肺肿瘤的早期诊断、鉴别诊断、判断预后等方面的应用进行综述。     

Focal Hepatic Lesions: Contrast-Enhancement Patterns at Pulse-Inversion Harmonic US using a Microbubble Contrast Agent

Objective

To analyze the contrast-enhancement patterns obtained at pulse-inversion harmonic imaging (PIHI) of focal hepatic lesions, and to thus determine tumor vascularity and the acoustic emission effect.

Materials and Methods

We reviewed pulse-inversion images in 90 consecutive patients with focal hepatic lesions, namely hepatocellular carcinoma (HCC) (n=43), metastases (n=30), and hemangioma (n=17). Vascular and delayed phase images were obtained immediately and five minutes following the injection of a microbubble contrast agent. Tumoral vascularity at vascular phase imaging and the acoustic emission effect at delayed phase imaging were each classified as one of four patterns.

Results

Vascular phase images depicted internal vessels in 93% of HCCs, marginal vessels in 83% of metastases, and peripheral nodular enhancement in 71% of hemangiomas. Delayed phase images showed inhomogeneous enhancement in 86% of HCCs; hypoechoic, decreased enhancement in 93% of metastases; and hypoechoic and reversed echogenicity in 65% of hemangiomas. Vascular and delayed phase enhancement patterns were associated with a specificity of 91% or greater, and 92% or greater, respectively, and with positive predictive values of 71% or greater, and 85% or greater, respectively.

Conclusion

Contrast-enhancement patterns depicting tumoral vascularity and the acoustic emission effect at PIHI can help differentiate focal hepatic lesions.     

Comparison of fundamental sonography, tissue-harmonic sonography, fundamental compound sonography, and tissue-harmonic compound sonography for focal hepatic lesions

Image qualities of fundamental, tissue-harmonic, fundamental compound, and tissue-harmonic compound sonography for evaluating focal hepatic lesions were compared. Two radiologists, blinded to the type of techniques and to the final diagnosis, independently evaluated 384 images of 96 hepatic lesions: hemangiomas (n=35), hepatic cystic lesions (n=28), cirrhosis-related nodules (n=22), focal nodular hyperplasia (n=1), and metastases (n=10). All images were graded in terms of lesion conspicuity, margin sharpness, and overall image quality using a 4- or 5-point scale. In the cases of cystic lesions, posterior acoustic enhancement and internal artifacts were also analyzed. A Friedman test was used for multiple statistical comparisons of the four techniques for all parameters. Compound imaging was significantly superior to fundamental imaging regarding lesion conspicuity, margin sharpness, and overall quality (P<0.05). For posterior enhancement and internal artifacts within the cyst, harmonic ultrasonography (US) was significantly better than fundamental US (P<0.05). For evaluating focal hepatic lesions on US, compound imaging provided better lesion conspicuity, better margin sharpness, and better overall image quality than fundamental imaging did. Tissue harmonic imaging also provided better posterior enhancement and fewer internal artifacts of the cyst than fundamental imaging.     

Focal Hepatic Lesions: Evaluation with Contrast-Enhanced Gray-Scale Harmonic US

Objective

To determine the findings of various focal hepatic lesions at contrast-enhanced gray-scale ultrasound (US) using a coded harmonic angio (CHA) technique and emphasizing lesion characterization.

Materials and Methods

The study involved 95 patients with 105 focal hepatic lesions, namely 51 hepatocellular carcinomas (HCCs), 22 metastases, 22 hemangiomas, four cases of focal nodular hyperplasia (FNH), and six nontumorous nodules. After the injection of a microbubble contrast agent (SH U 508A), gray-scale harmonic US studies using a CHA technique were performed with a combination of continuous scanning to assess the intratumoral vasculature (vascular imaging) and interval-delay scanning to determine the sequential enhancement pattern (acoustic emission imaging). Each imaging pattern was categorized and analyzed.

Results

At vascular imaging, 69% of HCCs (35/51) showed irregular branching vessels, while in 91% of metastases (20/22) a peripherally stippled pattern was observed. Intratumoral vessels were absent in 95% of hemangiomas (21/22) and all nontumorous lesions (6/6), while in 75% of FNHs (3/4) a spoke-wheel pattern was evident. At acoustic emission imaging, 71% of HCCs (36/51) showed heterogeneous enhancement and 86% (19/22) of metastases showed rim- or flame-like peripheral enhancement during the early phase, with washout occurring in all HCCs and metastases (100%, 73/73) during the late phase. In hemangiomas, enhancement was either peripheral and nodular (19/22, 86%) or persistent and homogeneous (3/22, 14%), and 75% of FNHs (3/4) became isoechoic during the late phase.

Conclusion

At contrast-enhanced gray-scale US using a CHA technique, a period of continuous scanning depicted the intratumoral vasculature, and interval-delay scanning demonstrated the sequential enhancement pattern. The characteristic findings of various focal hepatic lesions were thus determined.     

超声造影在海岛地区恶性淋巴瘤化疗中的应用

目的探讨恶性淋巴瘤化疗后采用超声造影观察其淋巴结动态灌注的变化。方法10例恶性淋巴瘤患者经不同化疗周期后，对20个（颈部、髂血管旁）病变淋巴结病灶进行超声造影观察，分析其造影增强的图像特点。结果恶性淋巴瘤化疗后造影特点表现为坏死区造影期间不增强，内部无强化。结论可采用超声造影技术对恶性淋巴瘤进行治疗后随访并指导后续治疗。     

The added diagnostic value of 64-row multidetector CT combined with contrast-enhanced US in the evaluation of hepatocellular nodule vascularity: implications in the diagnosis of malignancy in patients with liver cirrhosis

The aim of this study was to assess the added diagnostic value of contrast-enhanced US (CEUS) combined with 64-row multidetector CT (CT) in the assessment of hepatocellular nodule vascularity in patients with liver cirrhosis. One hundred and six cirrhotic patients (68 male, 38 female; mean age ± SD, 70 ± 7 years) with 121 biopsy-proven hepatocellular nodules (72 hepatocellular carcinomas, 10 dysplastic and 15 regenerative nodules, 12 hemangiomas, and 12 other benignancies) detected during US surveillance were prospectively recruited. Each nodule was scanned by CEUS during the arterial (10–40 s), portal venous (45–90 s), and delayed sinusoidal phase (from 100 s after microbubble injection to microbubble disappearance). Nodule vascularity at CEUS, CT, and combined CEUS/CT was evaluated side-by-side by two independent blinded readers who classified nodules as benign or malignant according to reference diagnostic criteria. The combined assessment of CEUS/CT provided higher sensitivity (97%, both readers) than did separate assessment of CEUS (88% reader 1; 87% reader 2) and CT (74% reader 1; 71% reader 2; P < 0.05), while no change in specificity was provided by combined analysis. The combined assessment of hepatocellular nodule vascularity at CT and CEUS improved sensitivity in the diagnosis of malignancy in patients with liver cirrhosis.     

实验兔钝性肝损伤的CT动态增强表现

目的 探讨CT动态增强扫描在兔钝性肝损伤(rabbit hepatic injury,BHI)模型中的诊断价值.方法 新西兰大白兔40只,采用钢球自由落体对剑突直接撞击,建立兔BHI模型.采用美国通用(GE)公司Hispeed双螺旋CT机行肝脏平扫及增强,注射对比剂开始后8～10 s、35～40 s、120～150 s分别为肝动脉期、门脉期及平衡期.观察增强前后损伤的位置、范围、边界、肝包膜撕裂、有无活动性出血、主要肝静脉有无受累及腹腔积血的CT特征,并与大体解剖情况对比.结果 动态增强扫描显示率明显高于平扫,单一撕裂13只,多发性撕裂伤18只,肝包膜下血肿7处,肝实质内血肿9处,肝包膜裂口17只25处,活动性出血9处,主要肝静脉损伤5处;与大体解剖符合情况分别为13/13(只),18/18(只),7/9(处),9/9(处),25/30(处),9/5(处),5/4(处).按Moore分级,CT/剖腹探查结果分别为:Ⅰ级5/4只,Ⅱ级15/13只,Ⅲ级9/11只,Ⅳ级6/6只,Ⅴ级1/2只,Ⅵ级0只.结论 动态CT增强扫描尤其静脉期和平衡期对明确有无肝脏损伤及判断损伤程度具有重要的价值.     

Detection of Hepatic VX2 Tumors in Rabbits: Comparison of Conventional US and Phase-Inversion Harmonic US During the Liver-Specific Late Phase of Contrast Enhancement

Objective

To compare phase-inversion sonography during the liver-specific phase of contrast enhancement using a microbubble contrast agent with conventional B-mode sonography for the detection of VX2 liver tumors.

Materials and Methods

Twenty-three rabbits, 18 of which had VX2 liver tumor implants, received a bolus injection of 0.6 g of Levovist (200 mg/ml). During the liver-specific phase of this agent, they were evaluated using both conventional sonography and contrast-enhanced phase-inversion harmonic imaging (CE-PIHI). Following sacrifice of the animals, pathologic analysis was performed and the reference standard thus obtained. The conspicuity, size and number of the tumors before and after contrast administration, as determined by a sonographer, were compared between the two modes and with the pathologic findings.

Results

CE-PIHI demonstrated marked hepatic parenchymal enhancement in all rabbits. For VX2 tumors detected at both conventional US and CE- PIHI, conspicuity was improved by contrast-enhanced PIHI. On examination of gross specimens, 52 VX2 tumors were identified. Conventional US correctly detected 18 of the 52 (34.6%), while PIHI detected 35 (67.3%) (p < 0.05). In particular, conventional US detected only three (8.3%) of the 36 tumors less than 10 mm in diameter, but CE-PIHI detected 19 such tumors (52.8%) (p < 0.05).

Conclusion

Compared to conventional sonography, PIHI performed during the liver-specific phase after intravenous injection of Levovist is markedly better at detecting VX2 liver tumors.     

Characterization of hypoechoic focal hepatic lesions in patients with fatty liver: diagnostic performance and confidence of contrast-enhanced ultrasound

The objective of this study was to assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) to characterize hypoechoic focal hepatic lesions (HFHL) in fatty liver (FL). A study group of 105 patients with FL and 105 HFHLs (52 malignant and 53 benign) underwent CEUS after SonoVue administration. Two blinded readers independently reviewed baseline ultrasound (US) and CEUS scans and classified each lesion as malignant or benign on a five-point scale of confidence, and recorded whether further imaging work-up was needed. Sensitivity, specificity, areas under the receiver operating characteristic (ROC) curve (A (z)), and interobserver agreement were calculated. We observed that the diagnostic confidence improved after reviewing CEUS scans for both readers (A (z)=0.706 and 0.999 and A (z)=0.665 and 0.990 at baseline US and CEUS, respectively; p<0.0001). Inter-reader agreement increased (weighted k=0.748 at baseline US vs. 0.882 at CEUS). For both readers, after CEUS, the occurrence of correctly characterized lesions increased (from 27/105 [27.5%] to 94/105 [89.5%], and from 19/105 [18.1%] to 93/105 [88.6%], respectively; p<0.0001) and the need for further imaging decreased (from 93/105 [88.6%] to 26/105 [24.8%], and from 96/105 [91.4%] to 40/105 [38.1%], respectively; p<0.0001). We conclude that CEUS improves the diagnostic performance of radiologists in the characterization of HFHLs in FL and reduces the need for further imaging work-up.     

Transient increased segmental hepatic enhancement distal to portal vein obstruction on dynamic gadolinium-enhanced gradient echo MR images

The purpose of the present study was to demonstrate the frequency of occurrence of transient increased segmental hepatic enhancement distal to portal veto obstruction in patients with a lobar (main branch) portal vein obstruction. MR images of all patients with main and lobar branch portal vein obstruction examined by dynamic gadolinium enhanced gradient echo MR images between December 1990 and July 1994 were reviewed retrospectively. All studies included T2-weighted imaging, Tl-weighted spoiled gradient echo‘fast low angle shot ([FLASH])’ and postgadolinium enhanced PLASH imaging at 1, 45, and 90 sec and 10 min. Fourteen patients were identified with portal vein obstruction which Included: six with main portal and right and left branch occlusion, six with right lobar, and two with left lobar. In the six patients with main portal vein obstruction, enhancement on 1-sec postgadolinium FLASH images was homogenous (three patients), diffusely heterogeneous (two patients), or peripherally hyperintense (one patient). In eight of eight patients with isolated obstruction of the right or left lobar portal vein, transient-increased segmental enhancement distal to portal vein occlusion was observed on immediate postcontrast images. Relatively high signal intensity of the involved segments was present on 1-sec images and liver parenchymal enhancement became more homogeneous by 45 to 90 sec in all cases. In conclusion, transient-increased segmental enhancement occurred in eight of eight patients with isolated right or left portal vein occlusion. We postulate that this effect occurs due to increased hepatic arterial blood flow in the presence of portal vein obstruction.     

Small nodules (1-2 cm) in liver cirrhosis: characterization with contrast-enhanced ultrasound

Objective

To determine the diagnostic efficacy of arterial phase contrast-enhanced ultrasound (CEUS) for characterizing small hepatic nodules (1-2 cm) in patients with high-risk for hepatocellular carcinoma (HCC).

Materials and methods

Over 12 months, CEUS was performed in 59 patients at high-risk for HCC with small hepatic nodules (1-2 cm; mean, 1.5 cm). Based only on arterial phase (<45 s) vascular intensity and pattern, lesions were prospectively diagnosed as HCC if there was hypervascularity without known features of hemangioma. The diagnosis of HCC was made regardless of the presence or absence of washout. Verification of diagnosis was made by liver transplantation (n = 13), biopsy (n = 12), resection (n = 3) or clinical and imaging follow-up for at least 12 months (n = 31).

Results

At of the time of CEUS, the 59 nodules were diagnosed as HCC in 26 and benign lesions in 33, including 20 regenerative/dysplastic nodules (RN/DN), 11 hemangiomas, and 2 focal fat sparing. All 26 nodules with arterial phase hypervascularity without hemangioma-like features were HCC. However, CEUS misdiagnosed HCC as RN/DN in 4 cases with arterial iso- (n = 3) or hypovascularity (n = 1). CEUS correctly diagnosed all 11 hemangiomas. The sensitivity, specificity, and accuracy of CEUS for diagnosing HCC were 86.7, 100, and 93.2%.

Conclusions

Arterial phase vascular intensity and pattern of CEUS are highly accurate for the diagnosis of small (1-2 cm) HCC and hemangioma in liver cirrhosis. On CEUS, arterial phase hypervascularity without a hemangioma-pattern alone may be sufficient for diagnosis of small HCC. Infrequent iso/hypovascular HCC may erroneously suggest RN/DN necessitating biopsy or close follow-up.     

MRI during fast infusion of Gd-DTPA: results in hepatic and pancreatic enhancement

The authors describe the results obtained with dynamic MRI of the parenchymal organs during the infusion of contrast agents. Thirteen patients with hepatic and pancreatic lesions were studied. RASE sequences were characterized by TR of 260 ms, TE of 16 ms, NEX 1, matrix 128 × 256. Infusion of the contrast agent started 15 s prior to the beginning of the pulse sequence and continued throughout the pulse sequence (25 s). In this way, a continuous inflow of contrast agent in abdominal organs was expected during the acquisition time. The conventional dose of Gd-DTPA was employed (0.1 mmol/kg).The results demonstrate a highly relevant pancreatic enhancement in the early arterial phase of perfusion, with values of SE/N of 18.1 versus 8.5 in the subsequent sequence. However, in the liver the perfusion study did not improve the parenchymal enhancement, with values of 9.3 versus 15.3 in the late phase. There was no improvement of hypontense lesion detections in the liver, while the hypervascular lesions were visualized with a high signal intensity in the early perfusion study, disappearing in the later sequences. Correspondence to: P. Pavone     

Hepatic artery embolization of experimental hepatic tumors with absolute ethanol

Hepatic artery embolization with absolute ethanol (HAEE) was done in rats and rabbits with experimentally induced liver tumors, and its effects on liver parenchyma and tumors were analyzed microscopically in comparison with those of controls. HAEE with 0.1 ml in rats brought massive tumor necrosis and minimal damage to liver parenchyma. But HAEE with 0.15 ml in rabbits induced moderate to massive necrosis of liver parenchyma with minimal to moderate tumor necrosis. Damage to the intrahepatic bile ductules was also seen in both animals. Many problems should be resolved before clinical use.     

Indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography: Assessment of the additional diagnostic value of contrast-enhanced ultrasound in the non-cirrhotic liver

Objective

To assess the additional diagnostic value of contrast-enhanced ultrasound (CEUS) in the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography (CT).

Methods

Fifty-five solid hepatic lesions (1–4 cm in diameter) in 46 non-cirrhotic patients (26 female, 20 male; age ± SD, 55 ± 10 years) underwent CEUS after being detected on contrast-enhanced CT which was considered as non-diagnostic after on-site analysis. Two blinded independent readers assessed CT and CEUS scans and were asked to classify retrospectively each lesion as a malignant or benign based on reference diagnostic criteria for the different hepatic lesion histotypes. Diagnostic accuracy and confidence (area – A_z – under ROC curve) were assessed by using gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging (n = 30 lesions), histology (n = 7 lesions), or US follow-up (n = 18 lesions) as the reference standards.

Results

Final diagnoses included 29 hemangiomas, 3 focal nodular hyperplasias, 1 hepatocellular adenoma, and 22 metastases. The additional review of CEUS after CT images improved significantly (P < .05) the diagnostic accuracy (before vs after CEUS review = 49% [20/55] vs 89% [49/55] – reader 1 and 43% [24/55] vs 92% [51/55] – reader 2) and confidence (A_z, 95% Confidence Intervals before vs after CEUS review = .773 [.652–.895] vs .997 [.987–1] – reader 1 and .831 [.724–.938] vs .998 [.992–1] – reader 2).

Conclusions

CEUS improved the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced CT by identifying some specific contrast enhancement patterns.