Two types of “harmonic imaging” techniques are widely used in ultrasound diagnosis. One type is tissue harmonic imaging, which uses higher harmonics generated on propagation of ultrasound through tissue and improves lateral resolution and clarity in B-mode images. The other is contrast harmonic imaging with gas microbubble contrast agents, which can detect tumor vessels and tissue perfusions. The basic physics of both types is explained here.

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Although transabdominal ultrasound (US) of the pancreas has some limitations, such as obesity and overlying bowel gas, which often interfere with visualization of the pancreas, imaging of the pancreas with US is the best initial imaging modality in the diagnosis and evaluation of patients with acute pancreatitis and chronic pancreatitis. Advances in US equipment and echo-enhancement techniques have improved the evaluation of vascularity in the pancreas. In a recent study, contrast-enhanced ultrasound was reported to be comparable to CT in its capacity to provide precise information about the severity of acute pancreatitis. In chronic pancreatitis, contrast-enhanced ultrasound was reported to be useful in differentiating chronic pancreatitis and pancreatic cancer. US has some advantages over CT in being free from ionizing radiation, having a superior cost-benefit ratio, and having a lower toxicity associated with the microbubbles used intravenously as a contrast medium. US will play a more important role in both patients with acute pancreatitis and those with chronic pancreatitis.

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Pancreatic neoplasms are derived from epithelial and nonepithelial elements and classified into two categories: solid and cystic tumors. The solid epithelial tumor includes ductal cell carcinomas, acinar cell carcinomas, and islet cell tumors. On the other hand, cystic epithelial tumors include serous cystic neoplasms (SCN), mucinous cystic neoplasms (MCN), and intraductal papillary mucinous tumors (IPMT). Ultrasonography is one of the most noninvasive and less-expensive modalities for detecting a pancreatic mass and characterizing the tumor tissue. Additionally, color Doppler imaging is very sensitive to arterial blood flow, making it valuable for differentiating islet cell tumors from ductal carcinomas. Contrast-enhanced ultrasonography (CEUS) is also useful for estimating a small amount of blood flow into hypovascular tumors; therefore, differential diagnosis of islet tumors or inflammatory pseudotumors from ductal cancer is possible. Moreover, CEUS is efficient for assessing the volume of mural nodule or tumor projection in a cystic lesion, which is thought to be important for us to choose therapeutic strategies. Endoscopic ultrasonography (EUS) is the most efficacious tool for establishing definite diagnosis of a solid mass as well as prediction of tumor expansion of a carcinoma. IDUS is also useful for evaluating minimal invasion of intraductal papillary-mucinous adenocarcinomas (IPMC). Recently, endoscopic ultrasound-guided fine needle aspiration biopsy (FNA) is recommended to obtain pathological proof of an uncertain nodule.

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The aim of this chapter is to discuss the topography of the pancreas with an emphasis on the relationship between the gland and the surrounding vessels, then to review the traditional scanning techniques used in pancreatic sonography. Finally, we recommend some additional scanning techniques to increase diagnostic confidence. In the case of traditional scanning techniques, there is no single scanning method for observing the whole gland. Four principal sectional views should be recognized: a) The transverse view demonstrates the gland as well as vascular landmarks. The examination usually begins with the patient supine. The probe is located just below the xiphoid process. The splenic vein is the most important vascular landmark in this plane. It runs from right to left across the upper abdomen. The pancreatic body and tail are anterior to it. b) The sagittal view demonstrates the pancreas as an oval structure between the celiac axis and the superior mesenteric artery. The anteroposterior diameter and shape as well as the location vary considerably according to the respiratory condition. c) The oblique view in the right upper abdomen shows the superior mesenteric vein joining the splenic vein to form the main portal trunk. This vascular landmark is seen sandwiched between the pancreatic head anteriorly and the uncinate process posteriorly. d) The oblique view in the left intercostal space shows the spleen. The pancreatic tail appears as a homogenous band-like structure in the splenic hilus. The probe is usually placed near the left midaxillary line between ribs. Alternative scanning (our recommended) techniques are as follows a) It is especially important to rotate the probe to minimize the amount of gas in the stomach and duodenum as well as to widen appropriate acoustic windows. The pancreas can be clearly observed by rotating the probe, which allows a rapid and clear assessment of the gland. b) In difficult cases, the probe is located above the pancreatic head are obliquely radiate the beam toward the pancreatic tail, and then slide the probe above the pancreatic tail and obliquely radiate the beam toward the pancreatic head. This so-called “cross-line” method with/without probe rotation is suitable for easy visualization of the whole gland and the neighboring vessels. Conclusion: Some authors have advocated the uptake of 200 CC of water to use the water-filled stomach as an acoustic window. Others have recommended changing the patient's position to an oblique or erect position, for example. Other maneuvers include applying probe pressure on the area of interest on the abdomen. However, these techniques have had very little success. When traditional approaches have failed or provided limited results, the above alternative scanning techniques, although requiring additional effort to learn them,, will minimize the diagnostic problems currently inherent to traditional scanning methods.

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Contrast-enhanced ultrasound is performed with injections of microbubble contrast agents such as Levovist^® and Sonazoied^®. Contrast-enhanced diagnostic imaging rapidly developed in the 1980s by the introduction of intra-arterial CO₂ injection¹⁾. In September 1999, Levovist^®, a microbubble contrast agent, became available commercially in Japan. Contrast-enhanced imaging using Levovist^® is based on the fact that microbubbles are readily disrupted by exposure to ultrasound. This causes the microbubbles to produce a nonlinear ultrasound signal as they disappear. Specialized imaging modalities such as harmonic imaging are used to visualize nonlinear signal properties of microbubbles effectively. Contrast-enhanced diagnostic imaging techniques have become highly influential in the diagnosis and treatment of liver, pancreas and gallbladder tumors. This report outlines the usefulness of Levovist^® imaging and its effectiveness in the diagnostic differentiation of tumors in the liver, pancreas and gallbladder. A next-generation contrast agent, Sonazoid^®, also became available in January 2007 with insurance reimbursement. Currently, insurance reimbursement applies only when Sonazoid^® is used for diagnosis of tumorous diseases of the liver. Imaging data using Sonazoid^® obtained from pancreatic tumor cases are also described in this report.

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The utility of endoscopic ultrasonography (EUS) in the diagnosis of pancreatic diseases has been established already, and EUS is now thought to be an essential technique. Because electronic scanning EUS produces the same or better B-mode images, it will replace mechanical scanning EUS in the near future. Furthermore, electronic scanning EUS will make full use of many software programs such as color Doppler flow imaging, power Doppler flow imaging, three-dimensional imaging, and real-time tissue elastography. In this report, we will outline the various kinds of diagnostic imaging that are possible with electronic scanning EUS.

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Intraductal ultrasonography (IDUS) was developed as a technique for visualizing arterial structures. We have employed IDUS during endoscopy to visualize the bile duct and pancreatic duct both in vitro and in vivo. We previously reported the clinical usefulness of IDUS in various pancreatic diseases, especially intraductal papillary mucinous neoplasm (IPMN) and pancreatic cancer. The IDUS probe usually used in recent years has a diameter of 6 French with a 20-MHz or 30-MHz radial scan transducer made by Aloka or Olympus. We inserted it into the biopsy channel of a duodenoscope and via the duodenal major papilla into the main pancreatic duct after endoscopic pancreatography without endoscopic sphincterotomy. In branch duct IPMN cases, over 90% of cases with mural nodules depicted by IDUS were carcinoma or adenoma. IDUS is useful for deciding whether surgical resection is indicated and determining the surgical resection line. In pancreatic cancer cases, IDUS can demonstrate a tumor as a hypoechoic lesion with irregular margins if the IDUS probe is led to the desired site. IDUS images of chronic pancreatitis cases show a rough pattern of pancreatic parenchyma with a hypoechoic band surrounding the main pancreatic duct corresponding to the periductal fibrosis occasionally. Furthermore, they do not have irregular margins like pancreatic cancer cases have. It is suggested that IDUS is useful for differential diagnosis between benign and malignant stricture of the main pancreatic duct. We encountered some cases in which only IDUS could demonstrate the tumor, which was not detected by any other modalities. IDUS, which makes it possible to evaluate pancreatic diseases, should be actively performed following endoscopic pancreatography.

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Several studies indicated that there were gender differences in left ventricular (LV) systolic function. Gender differences in left ventricular diastolic function were also reported. However, there has been no study about gender differences in left ventricular diastolic function in Japanese. The purpose of this study is to assess gender differences in left ventricular function including diastolic function in patients with normal left ventricular ejection fraction and normal echocardiographic findings. Subjects were 163 patients under 60 years of age, including 108 men and 55 women, with LV ejection fraction (EF) over 65%. LVEF, both mitral E and A wave velocities, mitral E/A ratio, deceleration time of E wave (DcT), Tei index, ejection time (ET), isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT) and left ventricular mass index (LVMI) were measured using Doppler echocardiography. Patients with hypertension and diabetes mellitus were then excluded from the 163 patients, which left 134 patients including 85 men and 49 women to be analyzed. There was no difference in LVEF between genders. E wave velocity (79±19 vs 69±15 cm/s, p<0.005) was higher in women than in men, but A wave velocity, DcT and E/A ratio were not different between genders. ET (311±23 vs 292±31 ms, p<0.005) was longer in women than in men, but ICT and IRT were not different between genders. Tei index (0.38±0.11 vs 0.44±0.12, p<0.005) was smaller in women than in men, probably because of a gender difference in ET. LVMI (102±29 vs 119±25g/m², p<0.005) was smaller in women than in men. We conclude that it is necessary to pay attention to these gender differences when evaluating left ventricular function.

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We report a 29-year-old woman who presented with clinical features of acute pulmonary embolism. She was obese and took oral contraceptives, which she had obtained by personal import over the Internet. Transthoracic echocardiography revealed right ventricular pressure overload on the first day. On the second day, transthoracic echocardiography showed a serpentine thrombus trapped across the patent foramen ovale (PFO) protruding into the right and left atria. After the appearance of sudden hypoxemia on the third day, transesophageal echocardiography demonstrated right atrial enlargement, and a small right-to-left shunt through a PFO without any intracardiac thrombus. Computed tomography suggested massive thrombi in both the superior and inferior venae cavae. We chose anticoagulation and thrombolytic therapy rather than surgical thrombectomy. We thought elevated right-chamber pressure due to pulmonary hypertension favored the establishment of a right-to-left shunt, and that a long thrombus was temporarily trapped across the foramen ovale and finally caused recurrent pulmonary embolism. Although PFO has been reported to be an important predictor of adverse outcome in patients with pulmonary embolism, the patient recovered rapidly and was discharged from the hospital. It was suggested that serial transthoracic echocardiography is useful for assessing the rapidly changeable pathophysiology in patients with acute pulmonary embolism.

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Background: The ratio of early transmitral velocity to early diastolic velocity of the mitral annulus (E/E′) has been shown to be an excellent predictor of left ventricular filling pressure. However, the clinical significance of mildly elevated E/E′ (8≤E/E′≤15) remains to be clarified. Left atrial (LA) volume would reflect the duration and severity of left ventricular diastolic dysfunction. There is a graded relation between LA volume index (LAVI) and severity of diastolic dysfunction. Purpose: We hypothesized that LAVI could be useful for predicting increased PAWP in coronary heart disease patients with mildly elevated E/E′. Subjects and Methods: Patients admitted to the coronary care unit at our hospital who had indwelling pulmonary artery catheters were eligible. Fifty-eight patients without atrial fibrillation or severe mitral regurgitation underwent echocardiography (Sonos 5500 or 7500; S3 probe; Philips). Tissue Doppler imaging of the mitral annulus was also obtained. Early diastolic E′ velocity was measured from the septal mitral annulus velocity profile in the apical 4-chamber view. LA volume was assessed by the biplane Simpson′s method from apical 4- and 2-chamber views in end systole. LAVI was obtained by correcting for body surface area. PAWP was measured simultaneously in all the patients. Results: In 23 patients with mildly elevated E/E′ (8≤E/E′≤15) , there was no correlation between PAWP and E/E′ (p=0.40). However, LAVI positively correlated with PAWP in those patients (r=0.64, p⟨0.001). LAVI≥32ml/m² was the optimal cutoff to predict PAWP≥15mmHg (sensitivity 72%, specificity 80%). Conclusion: LAVI could be a useful adjunct measure for predicting increased PAWP in coronary heart disease patients with mildly elevated E/E′.

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