Assessment of hepatocellular carcinoma by contrast-enhanced ultrasound with perfluorobutane microbubbles: comparison with dynamic CT

Objective

The aim of this study was to evaluate tumour vascularity and Kupffer cell imaging in hepatocellular carcinoma (HCC) using contrast-enhanced ultrasonography (CEUS) with Sonazoid (perfluorobutane) and to compare performance with dynamic CT.

Methods

We studied 118 nodules in 88 patients with HCC. HCC was diagnosed as a hyperenhancement lesion in the arterial phase with washout in the portal phase on dynamic CT or by percutaneous biopsy. We observed tumour vascularity at the early vascular phase (10–30 s after contrast injection) and Kupffer imaging at the post-vascular phase (after 10 min).

Results

Detection of vascularity at the early vascular phase was 88% in nodules that were found to be hypervascular on dynamic CT and 28% in hypo-/isovascular nodules; the detection of local recurrence nodules was 92%. The detection of vascularity was significantly lower in nodules >9 cm deep than in those ≤9 cm deep, but was not affected by tumour size. The detection of tumours at the post-vascular phase on CEUS was 83% in nodules with low density in the portal phase on dynamic CT and 82% in nodules with isodensity. The rate did not depend on the severity of underlying liver disease; rates decreased in nodules deeper than 9 cm, those smaller than 2 cm in diameter and in iso-enhancing nodules at the early vascular phase of CEUS.

Conclusion

CEUS with Sonazoid is a useful tool for assessing the vascularity of HCC and is equal to that of dynamic CT; however, the detectability of HCC vascularity is affected by location.The development of imaging modalities has facilitated the detection and accurate diagnosis of hepatocellular carcinoma (HCC). Assessment of tumour vascularity and for the presence of Kupffer cells are important in differential diagnosis, the choice of treatment and for assessment of the therapeutic response. HCC tumour vascularity has been evaluated extensively using various imaging modalities, including colour or power Doppler ultrasonography [1,2], angiography, dynamic CT [3], CT during angiography [4,5] and MRI [3]. Dynamic helical CT is minimally invasive and provides information regarding arterial or portal supplies by scanning at different time intervals following an injection of contrast agent. Therefore, dynamic CT is the standard modality used in clinical assessment of tumour vascularity. Assessment of Kupffer cells is possible using superparamagnetic iron oxide (SPIO)-enhanced MRI [6,7]. The presence of Kupffer cells indicates normal or benign liver tissue, whereas the absence of Kupffer cells indicates non-liver tissue such as malignant neoplasms. Thus, evaluation of the presence of Kupffer cells is useful in the differential diagnosis of focal liver lesions.Microbubble contrast agents are available for clinical use with ultrasound. Levovist (Schering AG, Berlin, Germany) is a first-generation contrast agent widely used to characterise focal liver lesions [8-12]. The advent of Sonazoid, a second-generation contrast agent (perfluorobutane; Diichi Sankyo, Tokyo, Japan), enables low mechanical index continuous real-time imaging and Kupffer imaging [13-15]. Therefore, contrast-enhanced ultrasound (CEUS) using Sonazoid could potentially offer high-quality, detailed vascular information and clearer Kupffer imaging. The aim of the present study was to compare CEUS using Sonazoid with dynamic CT in the assessment and characterisation of HCC.     

Accuracy of contrast-enhanced ultrasound in the detection of bladder cancer

Objective

To assess the accuracy contrast-enhanced ultrasound (CEUS) in bladder cancer detection using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound.

Methods

43 patients with suspected bladder cancer underwent conventional cystoscopy with transurethral biopsy of the suspicious lesions. 64 bladder cancers were confirmed in 33 out of 43 patients. Baseline ultrasound and CEUS were performed the day before surgery and the accuracy of both techniques for bladder cancer detection and number of detected tumours were analysed and compared with the final diagnosis.

Results

CEUS was significantly more accurate than ultrasound in determining presence or absence of bladder cancer: 88.37% vs 72.09%. Seven of eight uncertain baseline ultrasound results were correctly diagnosed using CEUS. CEUS sensitivity was also better than that of baseline ultrasound per number of tumours: 65.62% vs 60.93%. CEUS sensitivity for bladder cancer detection was very high for tumours larger than 5 mm (94.7%) but very low for tumours <5 mm (20%) and also had a very low negative predictive value (28.57%) in tumours <5 mm.

Conclusion

CEUS provided higher accuracy than baseline ultrasound for bladder cancer detection, being especially useful in non-conclusive baseline ultrasound studies.Carcinoma of the urinary bladder is the most common malignancy of the urinary tract that must be ruled out in patients with haematuria with negative upper urinary tract findings [1]. Cystoscopy remains the most sensitive method of detecting bladder cancer, but has several limitations: it is an invasive procedure; it is uncomfortable in some patients and it requires sedation or anaesthesia. Conventional ultrasound (US) is one of the imaging techniques used to screen for bladder cancer, but with variable accuracy. The best results are obtained using the latest equipment and new imaging tools such as three-dimensional (3D) ultrasound [2-5]. Angiogenesis is essential to allow growth of malignancies, and the detection of tumoural neovascularisation is one of the keys of imaging modalities to achieve a definite diagnosis. CT and MRI are accurate techniques for bladder cancer detection when they are performed with the injection of intravascular contrast agents. Detection relies on the identification of bladder cancer neovascularisation and recent studies have shown high accuracy with both techniques [6,7]. The introduction of microbubble contrast agents and the development of contrast-specific software have increased the value of ultrasound in the field of oncology [8,9]. Ultrasound contrast agents are strictly intravascular and are very sensitive in revealing tumour microvascularisation, helping in the detection and characterisation of malignancies [10-13]. Recently, the behaviour of bladder cancer has been described after the administration of ultrasound contrast agent, and its diagnosis relies on the detection of hypervascular wall bladder thickening [14].The aim of our study was to retrospectively assess the value of contrast-enhanced ultrasound (CEUS) in bladder cancer detection in a selected high-risk group of patients using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound.     

Contrast-enhanced ultrasonography of hepatocellular carcinoma: correlation between quantitative parameters and histological grading

Objective

The quantitative parameters in the contrast-enhanced ultrasonography time–intensity curve of hepatocellular carcinoma (HCC) were studied to explore their possible implication for histological grading of HCC.

Methods

A total of 130 HCC patients (115 males and 15 females; age: 48.13±11.00 years) were studied using contrast-enhanced ultrasonography time–intensity curve and histological pathology. The quantification software Sonoliver® (TomTec Imaging Systems, Unterschleissheim, Germany) was applied to derive time–intensity curves of regions of interest in the interior of HCCs and in reference. Quantitative parameters of 115 patients were successfully obtained, including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), rise slope (RS) and washout time (WT). Histological grading of HCC was performed using haematoxylin–eosin staining, and monoclonal antibodies specific for smooth muscle actin were used to observe unpaired arteries (UAs).

Results

There were significant differences among WTs in the three differentiated HCC groups (p<0.05). However, there were no significant differences among RT, TTP, RS and IMAX in the differentiated HCC groups. Moreover, the number of UAs in the differentiated HCC groups showed no statistical significance.

Conclusion

WT plays an important role in predicting well, moderately and poorly differentiated HCC.The majority of hepatocellular carcinomas (HCCs) develop through multistep hepatocarcinogenesis [1]. Various types of hepatocellular nodules are seen in cirrhotic livers. The International Working Party of the World Congress of Gastroenterology classifies hepatocellular nodules into six types: regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, well-differentiated HCC, moderately differentiated HCC and poorly differentiated HCC. The histopathological grades and types constitute well-established prognostic factors [2]. Thus, early diagnosis and confirmation of the type of hepatocellular nodules present and cellular differentiation before treatment are important.Although definite differentiation among HCC by imaging is usually impossible, the relationship between tumour cellular differentiation and image findings has been studied using contrast-enhanced (CE) CT, CEMRI and CE ultrasonography (CEUS). Tumour pathological differentiation correlates well with image findings [,3−8].Dynamic CEUS during the past decade has noticeably improved the detection and characterisation of focal liver lesions [9]. A previous study showed that CEUS and spiral CT provided a similar diagnostic accuracy in the characterisation of focal liver lesion [10]. The appearance of HCC on CEUS has also been described well. Current low-mechanical-index techniques for CEUS using second-generation microbubble agents have advantages in characterising HCC, including real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules. Some studies postulated that variations of enhancement patterns may be related to the pathological function of HCC [,5−8]. Moderately differentiated HCCs generally show classic enhancement features, with presence of hypervascularity in the arterial phase and washout during the portal phase, whereas well and poorly differentiated tumours account for most atypical variations in the arterial phase and portal venous phase [7].Reports assessing hepatocellular nodules have been based on visual analysis, despite the disadvantages of interobserver variability and low reproducibility of results. Although quantitative analysis CEUS perfusion provides more objective, reliable and reproducible results [11], the time–intensity curve (TIC) of CEUS has been obtained by quantification software for offline analysis [,12−14], from which a series of semi-quantitative perfusion parameters is extracted and analysed. An analysis of the parameters of TIC in HCC has proven the correlation of CEUS with unpaired arteries (UAs) in HCC [14]. In the present study, we compare the quantitative parameters in CEUS and UAs in different pathological gradings of HCCs to explore their possible implication for histological grading of HCC.     

Imaging features of hepatic angiomyolipomas on real-time contrast-enhanced ultrasound

The aim of this study was to evaluate the imaging features of hepatic angiomyolipoma (AML) on contrast-enhanced ultrasound (CEUS). The imaging features of 12 pathologically proven hepatic AML lesions in 10 patients who had undergone baseline ultrasound (BUS) and CEUS examinations were evaluated retrospectively. The enhancement extent, pattern and dynamic change, along with the enhancement process, on CEUS were analysed. The diagnostic results of BUS and CEUS before pathological examination were also recorded. The results showed that 75% (9/12) of the AML lesions exhibited mixed echogenicity on BUS and most showed remarkable hyperechogenicity in combination with a hypoechoic or anechoic portion. Arterial flow signals were detected in 75% (9/12) of the lesions on colour Doppler imaging. On CEUS, 66.7% (n = 8) of the 12 lesions exhibited hyperenhancement in the arterial phase, slight hyperenhancement (n = 2) or isoenhancement (n = 6) in the portal phase, and slight hyperenhancement (n = 1) or isoenhancement (n = 7) in the late phase. Three (25%) lesions exhibited hyperenhancement in the arterial phase and hypoenhancement in both portal and late phases. One (8.3%) lesion exhibited hypoenhancement throughout the CEUS process. Before pathological examination with BUS, only 3 (25%) lesions were correctly diagnosed as hepatic AML. Conversely, on CEUS, correct diagnoses were made for 66.8% (8/12) of hepatic AMLs. Therefore, arterial hyperenhancement and subsequent sustained enhancement on CEUS were found in the majority of hepatic AMLs. The combination of BUS and CEUS leads to the correct diagnosis in the majority of hepatic AMLs, and is higher than the success rate achieved by BUS alone.Hepatic angiomyolipoma (AML) is generally considered a rare benign mesenchymal tumour of the liver [1]. With the increasing clinical application of imaging, more and more hepatic AMLs are being detected [2, 3]. Baseline ultrasound (BUS) is the first-line imaging modality for liver use owing to its relatively low cost, non-invasiveness, easy manipulation and ready availability; however, its ability to characterise focal liver lesions (FLLs) cannot meet the requirement in the clinical setting [4]. The advent of the second-generation ultrasound contrast agents and contrast-specific ultrasound techniques allows depiction of the micro- and macro-circulation of FLLs, which has facilitated a great improvement in the characterisation of FLLs [5, 6]. However, until now, few reports in the literature have described the use of contrast-enhanced ultrasound (CEUS) in hepatic AML [7–11]. Herein we analyse retrospectively the imaging features of 12 hepatic AMLs on CEUS; the diagnostic results of BUS and CEUS before pathological examination are also recorded.     

Characterisation of breast papillary neoplasm on automated breast ultrasound

Intraductal papillary neoplasms of the breast form a wide spectrum of pathological changes with benign intraductal papilloma and papillary carcinoma. They can occur anywhere within the breast ductal system. This review illustrates some characteristic appearances of breast papillary neoplasms on coronal planes reconstructed by automatic breast volume scan. Such manifestations are not uncommon in papillary neoplasms, and familiarity will enable confident diagnosis.Papillary lesions of the breast are a heterogeneous group of breast lesions, including intraductal papilloma, atypical papilloma and intraductal papillary carcinoma [1,2]. Although the management of intraductal papillomas is varied, surgical excision is generally recommended as a precaution against the risk of a subsequent carcinoma [3,4]. Recently, some studies have suggested that patients with a tumour measuring <1.5 cm and an ultrasound Breast Imaging—Reporting and Data System (BI-RADS) category of 3 or 4a can be potentially selected for vacuum-assisted biopsy, but only if the tumour does not extend into the branching ducts [5,6]. Ueng et al [2] recommended that localised papillary lesions should be excised completely with a small rim of uninvolved breast tissue without any prior needle instrumentation if and when the papillary nature can be determined by imaging. Therefore, a careful imaging evaluation is necessary because it could help to identify the papillary neoplasm nature and select the high-risk lesions for proper treatment.Ultrasound has a greater sensitivity for detecting all papillary lesions than mammography [7]. Recently, automated breast ultrasound scanners have been developed, and the ultrasound volume data set of the whole breast can be acquired in a standard manner [8]. They have already shown potential for characterisation of breast tumours [9,10]. However, these studies did not detail the ultrasound features of intraductal papillary neoplasms on automated breast ultrasound. The reconstructed coronal views are also expected to provide more information and thus help to differentiate these lesions from other focal breast abnormalities.     

Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma

Objective:

To explore the potential of quantitative analysis of contrast-enhanced ultrasonography (CEUS) in differentiating focal nodular hyperplasia (FNH) from hepatocellular carcinoma (HCC).

Methods:

34 cases of FNH and 66 cases of HCC (all lesions <5 cm) were studied using CEUS to evaluate enhancement patterns and using analytic software Sonoliver® (Image-Arena™ v.4.0, TomTec Imaging Systems, Munich, Germany) to obtain quantitative features of CEUS in the region of interest. The quantitative features of maximum of intensity (IMAX), rise slope (RS), rise time (RT) and time to peak (TTP) were compared between the two groups and applied to further characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS.

Results:

The sensitivity and specificity of CEUS for diagnosis of FNH were 67.6% and 93.9%, respectively. For quantitative analysis, IMAX and RS in FNHs were significantly higher than those in HCCs (p<0.05), while RT and TTP in FNHs were significantly shorter (p<0.05). Both the 11 FNHs and 62 HCCs with hypo-enhancing patterns in the late phase were further characterised with their quantitative features, and the sensitivity and specificity of IMAX for diagnosis of FNH were 90.9% and 43.5%, RS 81.8% and 80.6%, RT 90.9% and 71.0%, and TTP 90.9% and 71.0%, respectively.

Conclusion:

The quantitative features of CEUS in FNH and HCC were significantly different, and they could further differentiate FNH from HCC following conventional CEUS.

Advances in knowledge:

Our findings suggest that quantitative analysis of CEUS can improve the accuracy of differentiating FNH from HCC.Dynamic contrast-enhanced ultrasonography (CEUS) has noticeably improved the detection and characterisation of focal liver lesions during the past decade [1]. The enhancement patterns of the lesion are evaluated in three vascular phases (the hepatic arterial, portal venous and late phases), where the hepatic arterial phase provides information on the degree and pattern of vascularity and the portal venous and late phases provide important information on the differention between benign and malignant liver lesions [1]. A previous study has shown that CEUS using SonoVue® (Bracco, Milan, Italy) and spiral-CT provides similar diagnostic accuracy in the characterisation of focal liver lesions [2].The typical enhancement of focal nodular hyperplasia (FNH) on CEUS showed hyperenhancement in the three vascular phases with a stellate vascular and centrifugal enhancement in the arterial phase or a hypoenhancing central scar in the late phase [1, 3–5]. However, these features have not been observed in all cases of FNH, particularly in small lesions. A study on FNH showed that 3 out of 13 lesions (23.1%) were hypoenhancing in the late phase [6] and 3 out of 10 lesions <3 cm had spoke-wheel patterns and 2 had central scars [4]. There is also a broad variation of stellate vascular enhancement in FNHs with a range from 27.3% to 73.3% and of central scar with a range from 36.4% to 63.3% [3–5]. Thus, it can be difficult to differentiate atypical FNHs from other hypervascular malignant tumours, such as hepatocellular carcinoma (HCC), and hypervascular metastases [3]. Furthermore, a hypoenhancing central scar has been described in fibrolamellar HCC and sclerosing or scirrhous HCC [7, 8], and a central feeding artery with spoke-wheel sign has also been described in two scirrhous HCCs [8]. Hence, a comprehensive approache rather than simply estimating the haemodynamics could be beneficial for differential diagnosis.The current low-mechanical-index techniques for CEUS are capable of real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules, from which time–intensity curves can be obtained by means of analytic software and then a series of semi-quantitative perfusion measurements extracted and analysed [9–11]. This method has shown a possible benefit in diagnosing FNH by enabling analysis of the quantitative parametric curves of the five types of hypervascular liver lesions [9]. In the present study, CEUS was applied to evaluate enhancing patterns of FNH and HCC; quantitative features of CEUS in the two groups were generated with the analytic software Sonoliver® (TomTec Imaging Systems, Germany) and compared to explore their potential in the differential diagnosis. Furthermore, the quantitative analysis of CEUS was used to characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS.     

Contrast-enhanced ultrasound of intrahepatic cholangiocarcinoma: correlation with pathological examination

Objective

To investigate the correlation between enhancement patterns of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and pathological findings.

Methods

The CEUS enhancement patterns of 40 pathologically proven ICC lesions were retrospectively analysed. Pathologically, the degree of tumour cell and fibrosis distribution in the lesion was semi-quantitatively evaluated.

Results

4 enhancement patterns were observed in the arterial phase for 32 mass-forming ICCs: peripheral rim-like hyperenhancement (n=19); heterogeneous hyperenhancement (n=6); homogeneous hyperenhancement (n=3); and heterogeneous hypo-enhancement (n=4). Among the four enhancement patterns, the differences in tumour cell distribution were statistically significant (p<0.05). The hyperenhancing area on CEUS corresponded to more tumour cells for mass-forming ICCs. Heterogeneous hyperenhancement (n=2) and heterogeneous hypo-enhancement (n=2) were observed in the arterial phase for four periductal infiltrating ICCs. In this subtype, fibrosis was more commonly found in the lesions. Heterogeneous hyperenhancement (n=1) and homogeneous hyperenhancement (n=3) were observed in the arterial phase for four intraductal growing ICCs. This subtype tended to have abundant tumour cells.

Conclusion

The CEUS findings of ICC relate to the degree of carcinoma cell proliferation at pathological examination. Hyperenhancing areas in the tumour always indicated increased density of cancer cells.Intrahepatic cholangiocarcinoma (ICC) originates in the small bile duct and is grouped according to the International Classification of Diseases code, with hepatocellular carcinoma (HCC) being the primary liver tumour. It is the second most common primary liver tumour and is highly malignant. Although ICC is a relatively rare tumour, interest in this disease is rising because incidence and mortality rates for ICC are increasing steadily worldwide [1-5].ICC is notoriously difficult to diagnose and is usually fatal, owing to its late clinical presentation and the lack of effective non-surgical therapeutic modalities. It tends to present with non-specific symptoms such as malaise, weight loss and abdominal pain. Most patients have unresectable disease at presentation and die within 12 months from the effects of cancer cachexia and a subsequent rapid decline in performance status.According to growth characteristics, ICC is subcategorised into mass-forming, periductal infiltrating or intraductal-growing types by the Liver Cancer Study Group of Japan [6]. These subtypes show different biological behaviours and have different clinical outcomes. Mass-forming ICC spreads between hepatocyte plates and expands via the hepatic sinusoidal spaces. It often invades the adjacent peripheral branches of the portal vein. Periductal-infiltrating ICC tends to spread along the bile duct wall via the nerve and perineural tissue of Glisson''s capsule towards the porta hepatis. Intraductal-growing ICCs are usually small or polypoid and do not invade deeply into the submucosal layer, often spreading superficially along the mucosa surface. Characterisation of the tumours in terms of their growth pattern is necessary for optimal treatment planning and prognosis assessing. The prognosis for mass-forming and periductal-infiltrating cholangiocarcinoma is generally unfavourable, but is much better for the intraductal-growing type after surgical resection, and long-term patient survival can be expected [7,8].Contrast-enhanced ultrasound (CEUS) has been increasingly applied in liver imaging. By administration of ultrasound contrast agents, CEUS can display dynamic blood flow perfusion and microcirculation of liver lesions [9], similar to CT and MRI. In previous studies, CEUS had a similar diagnostic accuracy for ICC to CT and was suggested as an alternative diagnostic option when CT examination was not available for patients with iodine allergy or impaired renal function [10]. It was confirmed that CT and/or MRI findings of ICC were correlated with pathological findings; that is, the hyperenhancing areas always indicated a large number of tumour cells and the areas of delayed enhancement corresponded to fibrotic stroma at pathological examination. In addition, different morphological subtypes tended to exhibit distinct enhancement characteristics on CT [7,8,11-13]. On CEUS, besides the specific feature of peripheral rim-like hyperenhancement, diverse imaging findings of ICC were reported [9,10,14-17]. These different CEUS appearances may reflect the differences in pathological subtypes or components of ICC. The aim of this study was to investigate the correlation between the enhancement pattern of ICC on CEUS and pathological findings. This information may be useful for diagnosis, treatment planning and prognostic evaluation of ICC.     

Sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach in the lumbar region

Objectives

The use of ultrasound to guide peripheral nerve blocks is now a well-established technique in regional anaesthesia. However, despite reports of ultrasound guided epidural access via the paramedian approach, there are limited data on the use of ultrasound for central neuraxial blocks, which may be due to a poor understanding of spinal sonoanatomy. The aim of this study was to define the sonoanatomy of the lumbar spine relevant for central neuraxial blocks via the paramedian approach.

Methods

The sonoanatomy of the lumbar spine relevant for central neuraxial blocks via the paramedian approach was defined using a “water-based spine phantom”, young volunteers and anatomical slices rendered from the Visible Human Project data set.

Results

The water-based spine phantom was a simple model to study the sonoanatomy of the osseous elements of the lumbar spine. Each osseous element of the lumbar spine, in the spine phantom, produced a “signature pattern” on the paramedian sagittal scans, which was comparable to its sonographic appearance in vivo. In the volunteers, despite the narrow acoustic window, the ultrasound visibility of the neuraxial structures at the L3/L4 and L4/L5 lumbar intervertebral spaces was good, and we were able to delineate the sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach.

Conclusion

Using a simple water-based spine phantom, volunteer scans and anatomical slices from the Visible Human Project (cadaver) we have described the sonoanatomy relevant for ultrasound-guided central neuraxial blocks via the paramedian approach in the lumbar region.Ultrasound is frequently used to guide central venous cannulation [1] and peripheral nerve blocks [2,3]. However, published data suggest that it is rarely used for imaging the spine or for central neuraxial blocks (CNBs; epidural and spinal injections) [4], which is surprising considering that there are data suggesting that an ultrasound examination prior to epidural access (pre-puncture scan, preview scan or scout scan) improves technical [5-7] and clinical [7,8] outcomes and also the learning curve of obstetric epidural anaesthesia [9]. Despite these encouraging results, we believe that there are very few anaesthetists who currently perform a preview scan prior to epidural catheterisation [5,7] or real-time ultrasound-guided (USG) CNBs [6,10]. This is quite interesting considering that emergency physicians are able to interpret ultrasound images of the spine [11] and are performing lumbar puncture using ultrasound in the accident and emergency department [11,12]. Reasons for this paucity of data or a lack of interest in USG CNBs in regional anaesthesia are not clear, but the authors believe it may be due to a lack of understanding of spinal sonoanatomy. The aim of this study was to describe the sonoanatomy relevant for USG CNBs via the paramedian approach in the lumbar region.     

Impact of biplane versus single-plane imaging on radiation dose,contrast load and procedural time in coronary angioplasty

Coronary angioplasties can be performed with either single-plane or biplane imaging techniques. The aim of this study was to determine whether biplane imaging, in comparison to single-plane imaging, reduces radiation dose and contrast load and shortens procedural time during (i) primary and elective coronary angioplasty procedures, (ii) angioplasty to the main vascular territories and (iii) procedures performed by operators with various levels of experience. This prospective observational study included a total of 504 primary and elective single-vessel coronary angioplasty procedures utilising either biplane or single-plane imaging. Radiographic and clinical parameters were collected from clinical reports and examination protocols. Radiation dose was measured by a dose–area–product (DAP) meter intrinsic to the angiography system. Our results showed that biplane imaging delivered a significantly greater radiation dose (181.4±121.0 Gycm²) than single-plane imaging (133.6±92.8 Gycm², p<0.0001). The difference was independent of case type (primary or elective) (p = 0.862), vascular territory (p = 0.519) and operator experience (p = 0.903). No significant difference was found in contrast load between biplane (166.8±62.9 ml) and single-plane imaging (176.8±66.0 ml) (p = 0.302). This non-significant difference was independent of case type (p = 0.551), vascular territory (p = 0.308) and operator experience (p = 0.304). Procedures performed with biplane imaging were significantly longer (55.3±27.8 min) than those with single-plane (48.9±24.2 min, p = 0.010) and, similarly, were not dependent on case type (p = 0.226), vascular territory (p = 0.642) or operator experience (p = 0.094). Biplane imaging resulted in a greater radiation dose and a longer procedural time and delivered a non-significant reduction in contrast load than single-plane imaging. These findings did not support the commonly perceived advantages of using biplane imaging in single-vessel coronary interventional procedures.The use of biplane imaging during diagnostic coronary angiography and coronary interventions has been reported to reduce the total contrast load to the patient compared with single-plane imaging [1–8]. Additionally, acquiring two simultaneous images from two orthogonal planes has been reported to be more efficient than single-plane imaging [2, 8–11]. However, there are conflicting reports as to whether the radiation dose to the patient differs between biplane and single-plane imaging during coronary studies [3, 10, 11].Biplane imaging allows two cineangiography runs to be recorded simultaneously with a single injection of contrast. With single-plane imaging, however, the same information can be acquired only by carrying out the two cineangiography runs serially with two separate injections of contrast [1, 2, 8, 10]. Biplane imaging enables the operator to visualise the target lesion in orthogonal planes simultaneously and was presumed to be more efficient than single-plane imaging, particularly in difficult procedures [1, 4, 9, 12]. Accordingly, examinations would become faster, use of fluoroscopy would be reduced, fewer cineangiography runs would be required and the average radiation dose to the patient would be comparatively lower than in the case of procedures performed with single-plane imaging. The contrast load with biplane imaging was also expected to be significantly reduced [3, 4, 11].These perceived advantages of biplane imaging have led to recommendations for its use in paediatric and adult cardiac catheter laboratories [1, 4, 5, 10, 12, 13]. A previous study comparing biplane and single-plane imaging in 1156 diagnostic coronary angiography procedures found a small, but notable, reduction in contrast load accompanied by significantly longer table times and screening times with biplane imaging, although radiation dose was not examined [14].Contrast-induced nephropathy (CIN) is a complication associated with prolonged hospitalisation and development of end-stage renal failure [15]. Patients with pre-existing renal disease, diabetes, congestive heart failure or older age are at the greatest risk in developing CIN [16–18]. These high-risk patients have a calculated incidence of CIN ranging from 10% to 30% [4, 18–20]. Pre-hydration is the primary intervention for preventing contrast nephropathy [18], but is not possible in the setting of emergency (primary) angioplasty procedures. The total contrast load during interventional procedures has been established as an independent predictor of CIN and could be effectively controlled by the operator during primary angioplasty cases [18, 21, 22]. Biplane imaging is commonly employed to minimise the contrast load, especially in patients with renal impairment and those who require primary coronary angioplasty procedures [1, 6, 7, 18, 23].Numerous studies have found that the radiation dose varies significantly according to tube angulations, particularly in the combination of steep left anterior oblique (LAO) with cranial or caudal angulations [24–27]. However, there are no published data on whether the radiation dose with biplane or single-plane imaging during coronary angioplasty differs between the three vascular territories: right coronary artery (RCA), left anterior descending (LAD) and left circumflex/intermediate (LCX). Furthermore, interventional cardiac procedures are operator dependent [28–30]. Hence, it was postulated that senior cardiologists would be more familiar with biplane equipment and thereby more able to reduce radiation dose, contrast load and procedural time than less experienced operators. To our knowledge, no studies have been published that compare the impact of biplane and single-plane imaging in coronary angioplasty procedures.The aims of this study were to determine whether biplane imaging reduces both contrast load and radiation dosage and shortens procedural time in patients undergoing primary or elective coronary angioplasty compared with single-plane imaging. We also investigated if there was a significant difference in radiation dose, contrast load and procedural time between biplane and single-plane imaging during coronary angioplasty in the three main vascular territories (RCA, LAD and LCX) and in procedures performed by operators with various levels of experience.     

Contrast-enhanced ultrasound for characterisation of hepatic lesions appearing non-hypervascular on CT in chronic liver diseases

Objectives

The purpose of this prospective study was to elucidate the efficacy of using contrast-enhanced ultrasound to characterise focal hepatic lesions appearing non-hypervascular on contrast-enhanced CT in chronic liver diseases.

Methods

The study population included 22 patients with cirrhosis or chronic hepatitis, who between them had 27 focal hepatic lesions smaller than 20 mm (mean 13.9±3.4) that appeared non-hypervascular on contrast-enhanced CT. Contrast-enhanced ultrasound with perflubutane microbubble agent (Sonazoid, 0.0075 ml kg^–1) was performed prior to ultrasound-guided needle biopsy, and intensity analysis was done for hepatic lesions in the early phase (−60 s) and late phase (600 s post injection).

Results

All seven early-phase hyperenhanced lesions were hepatocellular carcinoma (HCC). 20 lesions iso- or hypoenhanced during the early phase consisted of 11 regenerative nodules (RNs) and 9 HCCs. HCC was more frequent in early-phase hyperenhanced lesions than in iso- or hypoenhanced lesions (p=0.0108). Both late-phase hypoenhanced lesions were HCCs, whereas 25 late-phase isoenhanced lesions consisted of 11 RNs and 14 HCCs. The enhancement patterns of the 11 RNs included isoenhanced appearance in both the early and late phases in 8 lesions, and early-phase hypoenhancement combined with late-phase isoenhancement in the remaining 3. Both of these enhancement patterns (i.e. either iso–iso or hypo–iso) were found in 9 malignant lesions, 9 (75%) of the 12 well-differentiated HCCs.

Conclusion

Hypervascularity on contrast-enhanced ultrasound with Sonazoid strongly suggested HCC regardless of non-hypervascularity on CT, and late-phase hypoenhancement was another possible finding of HCC. However, characterisation of hepatic lesions with other enhancement patterns was difficult using our technique.The development of hepatocellular carcinoma (HCC) has a profound influence on the prognosis of patients with chronic liver disease (CLD), and there is nearly universal consensus on the importance of adequate HCC surveillance for these patients [1,2]. However, because reliable surveillance of HCC cannot be achieved solely by assessing tumour markers such as α-fetoprotein, it is necessary to utilise currently available imaging modalities effectively and efficiently in patients at risk for developing this neoplasm [3,4]. Differential diagnosis of focal hepatic lesions is a major challenge that must be overcome in order to provide appropriate clinical management of these patients.Based on diagnostic imaging, a hypervascular appearance of focal hepatic lesions in patients with CLD strongly suggests HCC, and a hypervascular lesion larger than 20 mm can be diagnosed as HCC without performing a biopsy [1,5]. On the other hand, non-hypervascular hepatic lesions include non-malignant lesions such as regenerative nodules (RNs) and both low- and high-grade dysplastic nodules; some well-differentiated HCCs also appear as non-hypervascular lesions prior to tumour vascularisation during the multistep process of carcinogenesis [5-9]. Characterisation of non-hypervascular hepatic lesions may prove challenging in patients with CLD. For example, the invasive nature of a needle biopsy is a drawback in cirrhotic patients with impaired coagulation, so diagnostic imaging tools merit serious consideration in this clinical situation.Technical improvements in ultrasound have been outstanding in the past two decades, with the resulting advantages of real-time observation, simple technique and non-invasiveness [10]. Moreover, the use of a microbubble contrast agent allows detailed observation of tumour haemodynamics, which can prove helpful in the detection and characterisation of focal hepatic lesions [11,12]. Stable and sufficient contrast enhancement, including improved signal-to-noise ratio, is achieved in the liver using harmonic imaging in combination with a second-generation contrast agent [13].Sonazoid (GE Healthcare, Little Chalfont, UK) is a novel perflubutane microbubble contrast agent whose clinical efficacy has been demonstrated for the diagnosis of focal hepatic lesions and diffuse liver diseases [14-16]. The microbubbles of this agent are captured in the liver parenchyma during the agent''s circulation in the blood; therefore, contrast-enhanced sonography can generate both haemodynamic-phase and accumulated-phase images [17,18]. These dual-phase images may offer improved diagnostic performance for non-hypervascular hepatic lesions. The purpose of the current study was to examine the clinical significance of using contrast-enhanced ultrasound with Sonazoid to characterise focal hepatic lesions that show a non-hypervascular appearance on contrast-enhanced CT in patients with CLD.     

Ultrasound elastography for musculoskeletal applications

Ultrasound elastography (EUS) is a method to assess the mechanical properties of tissue, by applying stress and detecting tissue displacement using ultrasound. There are several EUS techniques used in clinical practice; strain (compression) EUS is the most common technique that allows real-time visualisation of the elastographic map on the screen. There is increasing evidence that EUS can be used to measure the mechanical properties of musculoskeletal tissue in clinical practice, with the future potential for early diagnosis to both guide and monitor therapy. This review describes the various EUS techniques available for clinical use, presents the published evidence on musculoskeletal applications of EUS and discusses the technical issues, limitations and future perspectives of this method in the assessment of the musculoskeletal system.Ultrasound elastography (EUS) is a recently developed ultrasound-based method, which allows the qualitative visual or quantitative measurements of the mechanical properties of tissue [1-3]. The technique was first introduced in vitro in the early 1990s, and subsequently evolved into a real-time tool for in vivo imaging of the distribution of tissue strain and elastic modulus [4,5]. EUS provides information on tissue stiffness, which complements and is independent from the acoustic impedance and vascular flow information provided by B-mode and Doppler imaging, thus opening a new dimension in diagnostic imaging [1-5].EUS is based upon the general principle that stress applied to tissue causes changes within it, which depend on the elastic properties of tissue [1-5]. Over the years of research on elasticity, there have been several approaches of EUS, resulting in different methods, depending on the way of tissue stress application and the used method to detect and construct an image of tissue displacement [1-3]. Strain (compression) EUS is the commonest technique that allows real-time visualisation of the image on the screen, and it has been successfully employed to detect and characterise lesions in a variety of tissues and organs [6-12].Disease in the musculoskeletal system results in alterations to its biomechanical properties. Although EUS techniques have been extensively employed for in vitro research of muscle and tendon biomechanics since the early 1990s [13], the recent introduction of EUS into commercially available ultrasound systems has driven research activity towards potential clinical applications of this novel method in the musculoskeletal system [14-34].This review aims to describe the various EUS techniques available for clinical use, present the available published evidence on musculoskeletal applications of EUS, and finally discuss the limitations and future perspectives of this technique for assessing the musculoskeletal system.     

Towards clinical assessment of velopharyngeal closure using MRI: evaluation of real-time MRI sequences at 1.5 and 3 T

Objective

The objective of this study was to demonstrate soft palate MRI at 1.5 and 3 T with high temporal resolution on clinical scanners.

Methods

Six volunteers were imaged while speaking, using both four real-time steady-state free-precession (SSFP) sequences at 3 T and four balanced SSFP (bSSFP) at 1.5 T. Temporal resolution was 9–20 frames s⁻¹ (fps), spatial resolution 1.6×1.6×10.0–2.7×2.7×10.0 mm³. Simultaneous audio was recorded. Signal-to-noise ratio (SNR), palate thickness and image quality score (1–4, non-diagnostic–excellent) were evaluated.

Results

SNR was higher at 3 T than 1.5 T in the relaxed palate (nasal breathing position) and reduced in the elevated palate at 3 T, but not 1.5 T. Image quality was not significantly different between field strengths or sequences (p=NS). At 3 T, 40% acquisitions scored 2 and 56% scored 3. Most 1.5 T acquisitions scored 1 (19%) or 4 (46%). Image quality was more dependent on subject or field than sequence. SNR in static images was highest with 1.9×1.9×10.0 mm³ resolution (10 fps) and measured palate thickness was similar (p=NS) to that at the highest resolution (1.6×1.6×10.0 mm³). SNR in intensity–time plots through the soft palate was highest with 2.7×2.7×10.0 mm³ resolution (20 fps).

Conclusions

At 3 T, SSFP images are of a reliable quality, but 1.5 T bSSFP images are often better. For geometric measurements, temporal should be traded for spatial resolution (1.9×1.9×10.0 mm³, 10 fps). For assessment of motion, temporal should be prioritised over spatial resolution (2.7×2.7×10.0 mm³, 20 fps).

Advances in knowledge

Diagnostic quality real-time soft palate MRI is possible using clinical scanners and optimised protocols have been developed. 3 T SSFP imaging is reliable, but 1.5 T bSSFP often produces better images.Approximately 450 babies born in the UK every year have an orofacial cleft [1], the majority of which include the palate [2]. While a cleft palate is commonly repaired surgically at around 6 months [3], residual velopharyngeal insufficiencies require follow-up surgery in 15–50% of cases [4]. This residual defect results in an incomplete closure of the velopharyngeal port, which in turns leads to hypernasal speech. Assessment of velopharyngeal closure in speech therapy is commonly performed using X-ray videofluoroscopy or nasendoscopy [5,6]. While nasendoscopy is only minimally invasive, it may be uncomfortable and provides only an en face view of the velopharyngeal port. In contrast, X-ray videofluoroscopy is non-invasive and produces an image which is a projection of the target anatomy. Additional information may be obtained from projections at multiple angles [5,7], but anatomical structures may overlie each other. Furthermore, soft tissue contrast, such as that from the soft palate, is poor, although it may be improved using a barium contrast agent coating [8] at the expense of making the procedure more invasive and unpleasant. Arguably the greatest drawback of X-ray videofluoroscopy is the associated ionising radiation dose, which carries increased risk in paediatric patients [9].An increasing number of research studies have used MRI to image the soft palate [10-13] and upper vocal tract [14-17]. In contrast to X-ray videofluoroscopy and nasendoscopy, MRI provides tomographic images in any plane with flexible tissue contrast. As a result, MRI has been used to obtain images of the musculature of the palate at rest and during sustained phonation [10,18,19]. It has also been used to image the whole vocal tract at rest or during sustained phonation [20-27] and with a single mid-sagittal image dynamically during speech [13,15-17,28-35].For assessment of velopharyngeal closure, dynamic imaging with sufficient temporal resolution and simultaneous audio recording is required. Audio recording during imaging is complicated by the loud noise of the MRI scanner, and both the safety risk and image degradation caused by using an electronic microphone within the magnet. As a result, optical fibre-based equipment with noise cancellation algorithms must be used [36].In order to fully resolve soft palate motion, Narayanan et al [30] suggested that a minimum temporal resolution of 20 frames s⁻¹ (fps) is required. A similar conclusion was reached by Bae et al [13], based on measurements of soft palate motion extracted from X-ray videofluoroscopy. Using segmented MRI, Inoue et al [35] demonstrated that changes in the velar position that were evident at acquired frame rates of 33 fps were not observed at 8 fps. However, MRI is traditionally seen as a slow imaging modality and achieving sufficient temporal resolution at an acceptable spatial resolution is challenging. Furthermore, as the soft palate is bordered on both sides by air, the associated changes in magnetic susceptibility at the interfaces make images prone to related artefacts.Dynamic MRI of the vocal tract has been performed using both segmented [17,33,37] and real-time acquisitions [13,15,16,28,31,38]. Segmented acquisitions [39] acquire only a fraction of the k-space data required for each image during one repetition of the test phrase and, hence, require multiple identical repetitions. While these segmented techniques permit high temporal and spatial resolutions [35], they require reproducible production of the same phrase up to 256 times [34], leading to subject fatigue. Differences between repeats of up to 95 ms in the onset of speech following a trigger have also been demonstrated [36].In contrast to segmented techniques, real-time dynamic methods permit imaging of natural speech, but require extremely rapid acquisition and often advanced reconstruction methods. The turbo spin echo (TSE) zoom technique [40] has been used to perform real-time MRI of the vocal tract [29,31] and is available as a clinical tool. The zoom technique excites a reduced field of view in the phase encode direction, hence allowing a smaller acquisition matrix and shorter scan for a constant spatial resolution. While such spin echo-based techniques are less susceptible to magnetic field inhomogeneity related signal dropout artefacts than other sequences, the frame rates achieved with these sequences are limited to 6 fps [31]. Gradient echo-based techniques have also been used to achieve similar temporal resolution [12,41,42] in the upper vocal tract, but are often used at much higher frame rates in other MRI applications such as cardiac imaging [43,44]. A number of gradient echo sequence variants exist. Fast low-angle shot (FLASH) type sequences [45] spoil any remaining transverse magnetisation at the end of every sequence repetition (TR). In contrast, steady-state free-precession (SSFP) sequences are not spoiled [46] and the remaining transverse magnetisation is used in the next TR to improve the signal-to-noise ratio (SNR), but renders the images sensitive to signal loss in the presence of motion. Balanced SSFP (bSSFP) sequences include additional gradients to bring the transverse magnetisation completely back into phase at the end of every TR [47,48]. The result is that bSSFP sequences have high SNR and are less sensitive to motion than SSFP sequences, but are more sensitive to field inhomogeneities, which cause bands of signal dropout.Both TSE and the gradient echo techniques discussed here sample in a rectilinear or Cartesian fashion, where one line of k-space is sampled in each echo. However, for real-time speech imaging, the highest acquired frame rates have been achieved by sampling k-space along a spiral trajectory [15,16,30,49]. While spiral imaging is an efficient way to sample k-space and is motion-resilient, it is prone to artefacts, particularly blurring caused by magnetic field inhomogeneities and off-resonance protons (i.e. fat) [50]. Recently, one group successfully used spiral imaging with multiple saturation bands and an alternating echo time (TE) to achieve an acquired real-time frame rate of 22 fps [13,16]. The saturation bands were used to allow a small field of view to be imaged without aliasing artefacts. The alternating TE was used to generate dynamic field maps which were incorporated into the reconstruction to compensate for magnetic field inhomogeneities. However, such advanced acquisition and reconstruction techniques are only available in a small number of research centres.The aim of this work is to optimise and demonstrate high-temporal-resolution real-time sequences available on routine clinical MRI scanners for assessment of soft palate motion and velopharyngeal closure. Consequently, radial and spiral acquisitions were excluded and the work focuses on Cartesian gradient echo sequences with parallel imaging techniques. As more clinical MRI departments now have 3 T scanners, imaging was performed at both 1.5 and 3 T to enable comparisons. At each field strength, we optimised sequences and implemented four combinations of spatial and temporal resolution in six subjects with simultaneous audio recordings.     

Pulmonary tuberculosis associated with the reversed halo sign on high-resolution CT

We describe the case of a 32-year-old woman with pulmonary tuberculosis in whom a high-resolution CT scan demonstrated the reversed halo sign. The diagnosis of tuberculosis was made by lung biopsy and the detection of acid-fast bacilli in the sputum smear and culture. Follow-up assessment revealed a significant improvement in the lesions.The reversed halo sign is observed on high-resolution CT (HRCT) as a focal round area of ground-glass attenuation surrounded by a crescent or ring of consolidation [1, 2]. It was first described as being relatively specific for cryptogenic organising pneumonia [1], but was later observed in several other infectious [3–5] and non-infectious [6, 7] diseases.We report a case of a 32-year-old patient with tuberculosis who exhibited the reversed halo sign on chest CT. To our knowledge, this sign has not been previously described in an adult with pulmonary tuberculosis.     

Factors influencing the degree of enhancement of prostate cancer on contrast-enhanced transrectal ultrasonography: correlation with biopsy and radical prostatectomy specimens

Objectives

This study was designed to identify factors that influenced the degree of enhancement of prostate cancer on contrast-enhanced transrectal ultrasonography (CETRUS).

Methods

139 patients suspected of prostate cancer were evaluated with CETRUS followed by systematic and targeted transrectal ultrasound-guided biopsies. The degree of enhancement of the lesions was objectively measured using peak intensity with time–intensity curve analysis software. Ultrasound findings were correlated with clinical characteristics as well as biopsy and radical prostatectomy findings.

Results

Prostate cancers were detected in 230 biopsy sites from 91 patients. The mean peak intensity value of prostate cancer was significantly higher than that of the benign lesions (9.82±3.73 vs 7.51±2.97; p<0.001), and the peak intensity value of the cancer foci varied across the prostate. The mixed model analysis revealed that the location and Gleason score of tumour foci were the influencing factors of the peak intensity value, and the former had a stronger influence upon peak intensity than the latter (p=0.000 and 0.040, respectively). However, age, prostate volume or serum prostate-specific antigen of the patient had no significant influence on the peak intensity value (p>0.05). Furthermore, the peak intensity value of tumours larger than 5 mm diameter was significantly higher than tumours of 5 mm or smaller diameter (9.28±2.46 vs 6.69±2.65; p<0.001).

Conclusions

The prostate cancer lesions with a higher Gleason score and larger tumour size which were located in the lateral peripheral zone (PZ) were more likely to show a marked enhancement. Lesions with lower peak intensity that are located in the medial PZ should also be treated as suspicious.Prostate cancer is the most commonly diagnosed cancer in males, accounting for 28% of new cancer diagnoses in males and 11% of cancer-related deaths, with an expected 32 050 prostate cancer-specific mortalities in 2010 [1]. The imaging of prostate cancer is central to early detection and staging. However, it is generally acknowledged that detection and localisation of prostate tumours using greyscale ultrasound is poor, because suspicious hypoechoic areas represent cancer in only 9–53% of cases [2-3]. Furthermore, up to 30% of prostate cancers are isoechoic [4-5]. Conventional prostate ultrasound has little advantage over digital rectal examination for detecting malignant areas. Consequently, new strategies for prostate cancer detection are required. Contrast-enhanced ultrasound (CEUS) is a real-time imaging technique with the capability of visualising perfusion patterns [6-8]. This imaging technology has revealed promising perspectives in the diagnosis of prostate cancer owing to its ability to improve the visualisation of tumour vascularity. Several studies have reported that CEUS-targeted biopsy detected more cancer than systematic biopsy by identifying the area with greatest enhancement of the prostate [9-12]. In a recent study reported by Tang et al [13], the haemodynamic parameters such as time to enhancement (AT), time to peak intensity (TTP) and peak intensity (PI) were compared between 44 prostate cancer lesions and 47 benign ones. However, the peak enhancement intensity was found to be the optimal discriminatory parameter. Based on these previous findings, the degree of enhancement of the tumour foci plays a significant role in cancer detection on CEUS imaging.Although CEUS detected more cases of cancer than baseline imaging, the cancer detection rate still remains far from satisfactory [14-15]. Halpern et al [14] compared areas of increased enhancement in the prostate at CEUS with pathological examination and found that only 8 of 31 cancer foci were detected at baseline greyscale imaging, and contrast-enhanced imaging allowed identification of 13 of the 31 cancers (42% sensitivity). In their research, more than half of all cancers failed to show an abnormal enhancement, which indicated that the prostate cancer foci were not always shown as marked enhancement. Mitterberger et al [11] stated that the cancer with increased enhancement found by means of targeted biopsy had a higher mean Gleason score than the ones found by random biopsies, which suggested that the Gleason score of the prostate cancer could influence the degree of enhancement of the tumour to a certain extent. However, to our knowledge, factors influencing the degree of enhancement of the tumour have not yet been systematically investigated. In the present study, we evaluated the peak intensity of prostate cancers during the administration of the ultrasound contrast agent, and aimed to identify factors that influenced the degree of enhancement of prostate cancer on CEUS imaging. We hypothesised that identifying factors influencing the tumour peak intensity value could be useful for differential diagnosis of benign and malignant lesions in the CEUS examination, which would allow for a more accurate determination of the target sites during the subsequent biopsy procedure.     

Focal nodular hyperplasia: characterisation at gadoxetic acid-enhanced MRI and diffusion-weighted MRI

Purpose:

The aim of this study was to assess the enhancement patterns of hepatic focal nodular hyperplasia (FNH) on gadoxetic acid-enhanced MRI and diffusion-weighted (DW) MRI.

Methods:

This retrospective study had institutional review board approval. Gadoxetic acid-enhanced and DW MR images were evaluated in 23 patients with 30 FNHs (26 histologically proven and 4 radiologically diagnosed). The lesion enhancement patterns of the hepatobiliary phase images were classified as heterogeneous or homogeneous signal intensity (SI), and as dominantly high/iso or low SI compared with those of adjacent liver parenchyma. Heterogeneous (any) SI lesions and homogeneous low SI lesions were categorised into the fibrosis group, whereas homogeneous high/iso SI lesions were categorised into the non-fibrosis group. Additionally, lesion SI on T₂ weighted images, DW images and apparent diffusion coefficient (ADC) values were compared between the two groups.

Results:

The lesions showed heterogeneous high/iso SI (n=16), heterogeneous low SI (n=5), homogeneous high/iso SI (n=7) or homogeneous low SI (n=2) at the hepatobiliary phase MR images. The fibrosis group lesions were more likely to show high SI on DW images and T₂ weighted images compared with those in the non-fibrosis group (p<0.05). ADC values tended to be lower in the fibrosis group than those in the non-fibrosis group without significance.

Conclusion:

FNH showed variable enhancement patterns on hepatobiliary phase images during gadoxetic acid-enhanced MRI. SI on DW and T₂ weighted images differed according to the fibrosis component contained in the lesion.

Advances in knowledge:

FNH shows a wide spectrum of imaging findings on gadoxetic acid-enhanced MRI and DW MRI.Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumour after haemangioma, and most frequently occurs in females of childbearing and middle age [1]. It is considered to result from a congenital vascular disorder leading to a hyperplastic response of the surrounding liver parenchyma and is histologically characterised by normal hepatocytes with malformed bile ducts [2,3]. It is generally accepted that FNH can be managed conservatively and most cases do not require surgery because of the lack of malignancy potential and low risk of complications such as rupture or haemorrhage [4,5]. Therefore, the goal of imaging is to make a confident diagnosis and to avoid a biopsy or even surgical resection.MRI is a well-established and widely used diagnostic modality for detecting and characterising focal hepatic lesions and generally allows a confident diagnosis of typical FNH [6–8]. Findings of typical FNH on conventional gadolinium-enhanced MRI are brisk arterial enhancement, iso or slightly low signal intensity (SI) on the portal and equilibrium phase, iso or slightly low SI on T₁ weighted images, iso or slightly high SI on T₂ weighted images, a central scar showing high SI on T₂ weighted images and delayed dynamic enhancement [6–9]. However, when atypical imaging features are present, such as atypical findings of a central scar, high SI on T₁ weighted images or washout during the portal or equilibrium phase, it is not easy to distinguish FNH from other hypervascular tumours, such as hepatocellular adenomas, hypervascular metastasis or fibrolamellar hepatocellular carcinomas [6,9]. Indeed, according to a study by Bieze et al [6], characterisation of FNH and hepatocellular adenoma on standard MRI is inconclusive in 40% of lesions.Gadoxetic acid (Primovist®; Bayer-Schering Pharma, Berlin, Germany) is a new recently approved hepatobiliary gadolinium-based contrast agent. It has dual pharmacokinetic actions that combine extracellular properties for dynamic phase imaging with high hepatocyte-specific uptake and biliary excretion for delayed hepatobiliary phase imaging [10,11]. Many reports have concluded that FNHs show liver-specific enhancement and appear as iso or high SI on hepatobiliary phase imaging, and this enhancement pattern is a new additional criterion for diagnosing FNH, particularly in comparison with hepatocellular adenoma [6,10–15]. However, even though the major enhancement features of FNH are iso or high SI on hepatobiliary phase imaging, the portion of the central stellate scar or radiating fibrous septa of FNH demonstrates low SI owing to a lack of functioning hepatocytes. We postulate that the overall SI of FNH lesions during hepatobiliary phase imaging is dependent on their proportions of cellular and fibrous components.Diffusion-weighted (DW) imaging is useful for the detection and characterisation of hepatic focal lesions [16–18]. In theory, DW imaging measures the random motion of water molecules in biological tissues and reflects tissue properties, such as the size of the extracellular space, viscosity and cellularity [18–20]. According to prior hepatic fibrosis evaluations using DW imaging, lower apparent diffusion coefficient (ADC) values are observed in cirrhotic liver compared with normal liver tissue, which may be owing to restricted diffusion from extracellular fibrosis [21–25]. Despite the fact that FNH is benign, some lesions show diffusion restrictions, probably owing to their high cellularity [26–28], and fibrosis components contained in FNH lesions should influence the degree of diffusion restriction.The purpose of this study was to classify FNH lesions according to their enhancement pattern on hepatobiliary phase imaging and to assess the findings on DW and T₂ weighted imaging of the lesions with regard to those on hepatobiliary phase imaging.     

Primary vaginal cancer: role of MRI in diagnosis,staging and treatment

Primary carcinoma of the vagina is rare, accounting for 1–3% of all gynaecological malignancies. MRI has an increasing role in diagnosis, staging, treatment and assessment of complications in gynaecologic malignancy. In this review, we illustrate the utility of MRI in patients with primary vaginal cancer and highlight key aspects of staging, treatment, recurrence and complications.The incidence of primary vaginal cancer increases with age, with approximately 50% of patients presenting at age greater than 70 years and 20% greater than 80 years.¹ Around 2890 patients are currently diagnosed with vaginal carcinoma in the USA each year, and almost 30% die of the disease.² The precursor for vaginal cancer, vaginal intraepithelial neoplasia (VAIN) and invasive vaginal cancer is strongly associated with human papillomavirus (HPV) infection (93%).^3,4 In situ and invasive vaginal cancer share many of the same risk factors as cervical cancer, such as tobacco use, younger age at coitarche, HPV and multiple sexual partners.^5–7 In fact, higher rates of vaginal cancer are observed in patients with a previous diagnosis of cervical cancer or cervical intraepithelial neoplasia.^7,8As is true for other gynaecologic malignancies, vaginal cancer diagnosis and staging rely primarily on clinical evaluation by the International Federation of Gynecology and Obstetrics (FIGO).⁹ Pelvic examination continues to be the most important tool for evaluating local extent of disease, but this method alone is limited in its ability to detect lymphadenopathy and the extent of tumour infiltration. Hence, FIGO encourages the use of imaging. Fluorine-18 fludeoxyglucose-positron emission tomography (¹⁸F-FDG-PET), a standard imaging tool for staging and follow-up in cervical cancer, can also be used for vaginal tumours, with improved sensitivity for nodal involvement compared to CT alone.¹⁰ In addition to staging for nodal and distant disease, CT [simulation with three dimensional (3D) conformations] is particularly useful for treatment planning and delivery of external beam radiation. MRI, with its excellent soft tissue resolution, is commonly used in gynaecologic malignancies and has been shown to be accurate in diagnosis, local staging and spread of disease in vaginal cancer.^11,12 While no formal studies are available for vaginal cancer, in cervical cancer MRI actually alters the stage in almost 30% of patients.^13–15Treatment planning in primary vaginal cancer is complex and requires a detailed understanding of the extent of disease. Because vaginal cancer is rare, treatment plans remain less well defined, often individualized and extrapolated from institutional experience and outcomes in cervical cancer.^1,16–19 There is an increasing trend towards organ preservation and treatment strategies based on combined external beam radiation and brachytherapy, often with concurrent chemotherapy,^14,20,21 surgery being reserved for those with in situ or very early-stage disease.²² Increasing utilization of MR may provide superior delineation of tumour volume, both for initial staging and follow-up, to allow for better treatment planning.²³     

Prognostic factors associated with a subchondral insufficiency fracture of the femoral head

Objective

The aim of this study was to identify the risk factors associated with the prognosis of a subchondral insufficiency fracture of the femoral head (SIF).

Methods

Between June 2002 and July 2009, 25 patients diagnosed with SIF were included in this study. Sequential radiographs were evaluated for the progression of collapse. Clinical profiles, including age, body mass index, follow-up period and Singh’s index, were documented. The morphological characteristics of the low-intensity band on T₁ weighted MRI were also examined with regards to four factors: band length, band thickness, the length of the weight-bearing portion and the band length ratio (defined as the proportion of the band length to the weight-bearing portion of the femoral head in the slice through the femoral head centre).

Results

Radiographically, a progression of collapse was observed in 15 of 25 (60.0%) patients. The band length in patients with progression of collapse [22.5 mm; 95% confidence interval (CI) 17.7, 27.3] was significantly larger than in patients without a progression of collapse (13.4 mm; 95% CI 7.6, 19.3; p<0.05). The band length ratio in patients with progression of collapse (59.8%; 95% CI 50.8, 68.9) was also significantly higher than in patients without a progression of collapse (40.9%; 95% CI 29.8, 52.0; p<0.05). No significant differences were present in the other values.

Conclusion

These results indicate that the band length and the band length ratio might be predictive for the progression of collapse in SIF.Subchondral insufficiency fractures of the femoral head (SIF) often occur in osteoporotic elderly patients [1-9]. Patients usually suffer from acute hip pain without any obvious antecedent trauma. Radiologically, a subchondral fracture is seen primarily in the superolateral portion of the femoral head [4,5,10]. T₁ weighted MRI reveal a very low-intensity band in the subchondral area of the femoral head, which tends to be irregular, disconnected and convex to the articular surface [2,4,5,7,9,11]. This low-intensity band in SIF was histologically proven to correspond with the fracture line and associated repair tissue [5,9]. Some cases of SIF resolve after conservative treatment [5,11-14]; other cases progress until collapse, thereby requiring surgical treatment [4-10,15]. The prognosis of SIF patients remains unclear.The current study investigated the risk factors that influence the prognosis of SIF based on the progression to collapse.     

MRI features of serous oligocystic adenoma of the pancreas: differentiation from mucinous cystic neoplasm of the pancreas

Objectives

The purpose of this study was to describe the MRI features of the benign pancreatic neoplasm serous oligocystic adenoma (SOA) that differ from those of mucinous cystic neoplasm (MCN), a neoplasm with the potential for malignant degeneration.

Methods

Seven patients with SOA (seven women; mean age 36.6 years) and eight patients with MCN (eight women: mean age 39.9 years) were included. Several imaging features were reviewed: mass size, location, shape, wall thickness, cyst configuration (Type I, unilocular; Type II, multiple clustered cyst; Type III, cyst with internal septation) and signal intensity of the lesion with heterogeneity.

Results

SOA lesions were smaller (3.4 cm) than those of MCN (9.3 cm) (p=0.023). The commonest lesion shape was lobulated (85.7%) for SOA, but oval (50.0%) or lobulated (37.5%) for MCN (p=0.015). The most common cyst configuration was Type II (85.7%) for SOA and Type III (75.0%) for MCN (p=0.008). Heterogeneity of each locule in T₁ weighted images was visible in all cases of MCN, but in no case for SOA (p=0.004).

Conclusion

SOA could be differentiated from MCN by identifying the imaging features of lobulated contour with multiple clustered cyst configurations and homogeneity of each locule in T₁ weighted MR images.Serous oligocystic adenoma (SOA) is a recently described rare, benign pancreatic neoplasm and a morphological variant of serous microcystic adenoma, because it contains six or fewer cysts and the cysts are large (>2 cm) [1,2]. Pathologically, SOA is a benign pancreatic neoplasm composed of a few relatively large cysts uniformly lined with glycogen-rich cuboidal epithelial cells [3]. According to the World Health Organization classification, SOA is a subgroup of pancreatic serous cystic tumours and the term SOA is a synonym for macrocystic serous cystadenoma [3,4].The CT and MRI features of SOA of the pancreas are documented [2]. On CT and MRI, SOA typically appears as a small unilocular or bilocular cyst (<5 cm) with a thin wall (<2 mm) that lacks mural nodules or calcifications [2]. Because the cystic spaces are >2 cm, SOA images can be mistaken for mucinous cystic neoplasm (MCN), pseudocyst or intraductal papillary mucinous tumour [2,5-7]. It is very difficult to differentiate SOA from MCN by clinical and radiological features [2,6,8,9]. SOA does not require resection unless it causes symptoms, but MCN should be resected because of a potential for malignant degeneration [5,7,8]. Endoscopic ultrasound and cyst fluid aspiration have a role in distinguishing mucinous and serous lesions, but it is an invasive procedure with a risk of complications such as pancreatitis [10]. Therefore, it is clinically valuable to determine characteristic imaging findings that can distinguish SOA from MCN.Recently, Kim et al [6] and Cohen-Scali et al [5] described characteristic CT findings that can be used to differentiate SOA from MCN. MRI can demonstrate septa within a lesion with greater sensitivity than CT; therefore, MRI provides a better evaluation of tissue characteristics than CT [1,11]. However, few studies have described the MRI features of SOA [1,2]. The purpose of this study was to describe the differences in the MRI features of SOA and MCN in the pancreas.     

Correlation between computerised findings and Newman's scaling on vascularity using power Doppler ultrasonography imaging and its predictive value in patients with plantar fasciitis

Objectives

The purpose of this study was to correlate findings on small vessel vascularity between computerised findings and Newman''s scaling using power Doppler ultrasonography (PDU) imaging and its predictive value in patients with plantar fasciitis.

Methods

PDU was performed on 44 patients (age range 30–66 years; mean age 48 years) with plantar fasciitis and 46 healthy subjects (age range 18–61 years; mean age 36 years). The vascularity was quantified using ultrasound images by a customised software program and graded by Newman''s grading scale. Vascular index (VI) was calculated from the software program as the ratio of the number of colour pixels to the total number of pixels within a standardised selected area of proximal plantar fascia. The 46 healthy subjects were examined on 2 occasions 7–10 days apart, and 18 of them were assessed by 2 examiners. Statistical analyses were performed using intraclass correlation coefficient and linear regression analysis.

Results

Good correlation was found between the averaged VI ratios and Newman''s qualitative scale (ρ = 0.70; p<0.001). Intratester and intertester reliability were 0.89 and 0.61, respectively. Furthermore, higher VI was correlated with less reduction in pain after physiotherapeutic intervention.

Conclusions

The computerised VI not only has a high level of concordance with the Newman grading scale but is also reliable in reflecting the vascularity of proximal plantar fascia, and can predict pain reduction after intervention. This index can be used to characterise the changes in vascularity of patients with plantar fasciitis, and it may also be helpful for evaluating treatment and monitoring the progress after intervention in future studies.Plantar fasciitis is the most common cause of heel pain, and about 2 000 000 patients in the USA receive treatment every year because of this condition [1]. Besides mechanical loading, vascular disturbance with consequent metabolic impairment and hypoxia is thought to play an important role [2]. Indeed, fibrovascular hyperplasia and vascular proliferation were observed from microscopic specimens obtained from operative resection [3-5]. Walther et al [6] were the first group to evaluate plantar fascia vascularity non-invasively using power Doppler ultrasonography (PDU).PDU is one of the colour flow imaging techniques that encodes the amplitude of the power spectral density of the Doppler signals [7]. This method has been used to assess soft-tissue vascularity and treatment efficacy with a variety of musculoskeletal and related problems. Changes in vascularity in synovial tissues in patients with rheumatoid arthritis [8-11], osteoarthritis [12,13], tendinopathy [6,14-21] and plantar fasciitis [6] have been reported. Modulation in vascularity was observed in patients with tendinopathy after a course of intervention [14-21]. Most of these studies used the Newman''s grading scale to grade the tissue vascularity [19-21]. This qualitative grading for the PDU images had high correlation with the histopathological grading of vascularity of the synovial membrane in patients with arthritis [11]. Nevertheless, Newman''s grading system may not be objective and sensitive enough to differentiate subtle vascularity changes.Recently, computerised methods were used to quantify tissue vascularity with ultrasonography. Tissue vascularity was quantified by computing a vascular index (VI), which is calculated as the ratio of the number of colour pixels to the total number of pixels within the region of interest in patients with soft-tissue problems [8,9,11,17]. Note that most of these studies were conducted using colour Doppler ultrasonography. In this connection, PDU is superior to frequency-based colour Doppler ultrasonography, especially in tissues with low blood flow, such as the plantar fascia [6,22,23]. Ying et al [24] reported the feasibility of computerised quantification of vascularity in thyroid tissues with PDU. We were interested in evaluating whether the computerised quantification of vascularity could be applied on musculoskeletal tissue, such as the plantar fascia. Therefore, the purpose of the present study was to correlate the computerised VI and Newman''s qualitative grading scale in quantifying plantar fascia vascularity using PDU, to evaluate the intra- and intertester reliability of the computerised quantitative method and its predictive ability of recovery in patients with plantar fasciitis. Proximal plantar fascia, which is the most commonly affected area in individuals with plantar fasciitis, according to clinical examination [25,26] and previous B-mode ultrasonography [26-28], was chosen as the target testing area.     

Iron overload: accuracy of in-phase and out-of-phase MRI as a quick method to evaluate liver iron load in haematological malignancies and chronic liver disease

Objectives

The purpose of this prospective study was to evaluate the accuracy of in-phase and out-of-phase imaging to assess hepatic iron concentration in patients with haematological malignancies and chronic liver disease.

Methods

MRI-based hepatic iron concentration (M-HIC, μmol g^–1) was used as a reference standard. 42 patients suspected of having iron overload and 12 control subjects underwent 1.5 T in- and out-of-phase and M-HIC liver imaging. Two methods, semi-quantitative visual grading made by two independent readers and quantitative relative signal intensity (rSI) grading from the signal intensity differences of in-phase and out-of-phase images, were used. Statistical analyses were performed using the Spearman and Kruskal–Wallis tests, receiver operator curves and κ coefficients.

Results

The correlations between M-HIC and visual gradings of Reader 1 (r=0.9534, p<0.0001) and Reader 2 (r=0.9456, p<0.0001) were higher than the correlations of the rSI method (r=0.7719, p<0.0001). There was excellent agreement between the readers (weighted κ=0.9619). Both visual grading and rSI were similar in detecting liver iron overload: rSI had 84.85% sensitivity and 100% specificity; visual grading had 85% sensitivity and 100% specificity. The differences between the grades of visual grading were significant (p<0.0001) and the method was able to distinguish different degrees of iron overload at the threshold of 151 μmol g^–1 with 100% positive predictive value and negative predictive value.

Conclusion

Detection and grading of liver iron can be performed reliably with in-phase and out-of-phase imaging. Liver fat is a potential pitfall, which limits the use of rSI.Iron overload is a clinically recognised condition with variety of aetiologies and clinical manifestations [1-4]. Liver iron concentration correlates closely with the total body iron stores [5]. The excess iron accumulates mainly in the liver and the progressive accumulation of toxic iron can lead to organ failure if untreated [2,4]. Several diseases causing iron overload, such as transfusion-dependent anaemia, haematological malignancies, thalassaemia, haemochromatosis and chronic liver disease, result in a large number of patients with a potentially treatable iron overload [1,2,4].Several quantitative MRI methods for iron overload measurement by multiple sequences have been established, such as proportional signal intensity (SI) methods and proton transverse relaxation rates (R₂, R₂*) [4,6,7]. A gradient echo liver-to-muscle SI-based algorithm [8] has been widely validated and used for quantitative liver iron measurement [8-11]. MRI-based hepatic iron concentration (M-HIC, μmol g^–1 liver dry weight) with corresponding R₂* [9] can be calculated with this method which is a directly proportional linear iron indicator, virtually independent of the fat fraction, as the echo times are taken in-phase [8,9]. This method showed a high accuracy in calibrations with the biochemical analysis of liver biopsies (3–375 μmol g^–1) of 174 patients. The mean difference of 0.8 μmol g^–1 (95% confidence interval of –6.3 to 7.9) between this method and the biochemical analysis is quite similar [8] to the intra-individual variability found in histological samples [12].The quantitative MRI methods are based on progressive SI decay, with the longer echo times due to relaxing properties of iron. Interestingly, this iron-induced effect is seen in MR images with multiple echoes [4,6-11], but also in dual-echo images, namely in-phase and out-of-phase imaging [13,14]. In-phase and out-of-phase imaging has become a routine part of liver MRI, performed initially for liver fat detection [6,13,15]. Quite recently some investigators have noticed an alternative approach of the sequence to detect liver iron overload due to the more pronounced SI decrease on in-phase images with the longer echo time [13,14]. Yet, to our knowledge, this is the first prospective study evaluating the accuracy of in-phase and out-of-phase imaging to assess hepatic iron concentration.The purpose of the study was to evaluate the capability and accuracy of dual-echo in-phase and out-of-phase imaging to assess hepatic iron concentration at 1.5 T in patients with haematological malignancies and chronic liver disease. MRI-based hepatic iron concentration (M-HIC, μmol g^–1) was used as a reference standard [8,9].