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.     

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.     

Miliary tuberculosis: a comparison of CT findings in HIV-seropositive and HIV-seronegative patients

The aim of this study was to determine the differences in CT findings of miliary tuberculosis in patients with and without HIV infection. Two radiologists reviewed retrospectively the CT findings of 15 HIV-seropositive and 14 HIV-seronegative patients with miliary tuberculosis. The decisions on the findings were reached by consensus. Statistical analysis was performed using the χ² test, Mann–Whitney U-test and Fisher''s exact test. All of the HIV-seropositive and -seronegative patients had small nodules and micronodules distributed randomly throughout both lungs. HIV-seropositive patients had a higher prevalence of interlobular septal thickening (p = 0.017), necrotic lymph nodes (p = 0.005) and extrathoracic involvement (p = 0.040). The seropositive patients had a lower prevalence of large nodules (p = 0.031). In conclusion, recognition of the differences in the radiological findings between HIV-seropositive and -seronegative patients may help in the establishment of an earlier diagnosis of immune status in patients with miliary tuberculosis.Miliary tuberculosis (TB), which results from lympho-haematogenous dissemination of Mycobacterium tuberculosis, is a complication of both primary and post-primary TB [1, 2]. This disease results in the formation of small discrete foci of granulomatous tissue, which are uniformly distributed throughout the lung [3].An increase in TB incidence, including miliary TB, has been associated with infection by human immunodeficiency virus (HIV) [4]. In 2005, the World Health Organization estimated that 12% of HIV deaths globally were caused by TB, and that there were 630 000 new co-infections with TB and HIV [5]. Disseminated TB accounted for 5.4–8.1% of culture-confirmed TB cases, with 10–14% of patients coinfected with HIV having clinically recognisable dissemination [6, 7].Chest radiography may be helpful in the detection and final diagnosis of miliary TB. The characteristic radiographical findings consist of the presence of fine granular or numerous small nodular opacities measuring 1–3 mm in diameter scattered throughout both lungs [1, 3, 8, 9]. However, the radiograph may appear to be normal in the early stage of disease or in cases with nodules below the threshold of perceptibility; therefore, a diagnosis of miliary TB from chest radiographs can be difficult [10].Several studies have shown that CT imaging is more sensitive for the detection of parenchymal abnormalities in patients with AIDS who have active intrathoracic disease, and it has been suggested that CT may also be helpful in the differential diagnosis [11–14]. In addition, it has been reported that certain imaging techniques provided by multidetector-row CT are useful for the diagnosis of multiple micronodular infiltrative lung disease [15]. CT findings of miliary TB have been described in previous reports [16–18]; however, only a few studies on miliary TB in patients with HIV, particularly with reference to the CD4 count, have been reported [19, 20]. The radiographic manifestations of HIV-associated pulmonary TB are thought to be dependent upon the level of immunosuppression at the time of overt disease [21–23].The purpose of this study was to determine the differences in the CT findings of miliary TB for patients with and without HIV infection and to analyse any correlation between the CT features and the level of immunosuppression in patients.     

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.     

Accessory or additional renal arteries show no relevant effects on the width of the upper urinary tract: a 64-slice multidetector CT study in 1072 patients with 2132 kidneys

Objective

The aim of this study was to find out on an unselected patient group whether crossing vessels have an influence on the width of the renal pelvis and what independent predictors of these target variables exist.

Methods

In this cross-sectional study, 1072 patients with arterially contrasted CT scans were included. The 2132 kidneys were supplied by 2736 arteries.

Results

On the right side, there were 293 additional and accessory arteries in 286 patients, and on the left side there were 304 in 271 patients. 154 renal pelves were more than 15 mm wide. The greatest independent factor for hydronephrosis on one side was hydronephrosis on the contralateral side (p<0.0001 each). Independent predictors for the width of the renal pelvis on the right side were the width of the renal pelvis on the left, female gender, increasing age and height; for the left side, predictors were the width of the renal pelvis on the right, concrements, parapelvic cysts and great rotation of the upper pole of the kidney to dorsal. Crossing vessels had no influence on the development of hydronephrosis. Only anterior crossing vessels on the right side are associated with widening of the renal pelvis by 1 mm, without making it possible to identify the vessel as an independent factor in multivariate regression models.

Conclusion

The width of the renal pelvis on the contralateral side is the strongest independent predictor for hydronephrosis and the width of the renal pelvis. There is no link between crossing vessels and the width of the renal pelvis.Obstructions of the ureteropelvic junction (UPJ) can be caused by intrinsic or extrinsic factors [1]. Although there are no studies of this to date, crossing the UPJ by an aberrant crossing vessel is considered the most important [2] of the extrinsic factors [3]. Crossing vessels, which are thought to cause from 40% to over 50% of the extrinsic UPJ obstructions in adults [4, 5], are located ventral more often than dorsal to the UPJ. These are usually normal vessels of the lower pole segment [4, 6–9], which can be divided into additional renal arteries arising from the aorta, and accessoric renal arteries arising from branches of the aorta [10, 11]. The primary surgical therapy of choice is endoscopic endopyelotomy [12]. The success rate of 89–90% [12, 13] is thought to be noticeably poorer in patients with crossing vessels [12, 13]; however, this is not undisputed [14, 15]. Be that as it may, to prevent bleeding complications it is necessary to be familiar with the vascular situation around the UPJ prior to the procedure [3, 16–18]. CT angiography is used for this purpose, as it is highly accurate, quick to perform and shows all relevant anatomical structures in relation to one another [3, 19, 20]. The objective of this study was to determine whether or not there are vascular morphological patterns or other factors that influence the width of the renal collecting system, regardless of the definitions of hydronephrosis.     

Hepatocellular carcinoma in cirrhotic patients at multidetector CT: hepatic venous phase versus delayed phase for the detection of tumour washout

Objectives

Our aim was to compare retrospectively hepatic venous and delayed phase images for the detection of tumour washout during multiphasic multidetector row CT (MDCT) of the liver in patients with hepatocellular carcinoma (HCC).

Methods

30 cirrhotic patients underwent multiphasic MDCT in the 90 days before liver transplantation. MDCT was performed before contrast medium administration and during hepatic arterial hepatic venous and delayed phases, images were obtained at 12, 55 and 120 s after trigger threshold. Two radiologists qualitatively evaluated images for lesion attenuation. Tumour washout was evaluated subjectively and objectively. Tumour-to-liver contrast (TLC) was measured for all pathologically proven HCCs.

Results

48 HCCs were detected at MDCT. 46 of the 48 tumours (96%) appeared as either hyper- or isoattenuating during the hepatic arterial phase subjective washout was present in 15 HCCs (33%) during the hepatic venous phase and in 35 (76%) during the delayed phase (p<0.001, McNemar’s test). Objective washout was present in 30 of the 46 HCCs (65%) during the hepatic venous phase and in 42 of the HCCs (91%) during the delayed phase (p=0.001). The delayed phase yielded significantly higher mean TLC absolute values compared with the hepatic venous phase (−16.1±10.8 HU vs −10.5±10.2 HU; p<0.001).

Conclusions

The delayed phase is superior to the hepatic venous phase for detection of tumour washout of pathologically proven HCC in cirrhotic patients.Multiphasic contrast-enhanced multidetector row CT (MDCT) plays a pivotal role in the diagnostic work-up of cirrhotic patients, who are at increased risk of developing hepatocellular carcinoma (HCC) [1]. Increased enhancement of the tumour compared with the surrounding liver parenchyma during the hepatic arterial phase is the cornerstone for the diagnosis of HCC at multiphasic MDCT [1,2]. However, a variety of entities—dysplastic nodules [3], confluent hepatic fibrosis [4], non-tumourous arterioportal shunts [5] and haemangioma [6]—can also manifest with increased arterial enhancement and thus mimic HCC, particularly if they are smaller than 2 cm in diameter.Tumour washout, i.e. hypoattenuation relative to the adjacent hepatic parenchyma during the hepatic venous or delayed phase, has been recognised as a strong predictor of HCC [7,8]. This sign has been included, along with the presence of hypervascularity, in the latest American Association for the Study of Liver Diseases (AASLD) guidelines for the diagnosis of HCC at multiphasic MDCT, MRI or contrast-enhanced ultrasonography [1]. Although it is well known that tumour enhancement is best visualised during the late hepatic arterial phase [9,10], there is no consensus regarding the correct timing for the detection of tumour washout at multiphasic MDCT of the liver. Most commonly, the hepatic arterial phase is followed by the hepatic venous phase, acquired 60–70 s after injection of contrast material [9-12]. In addition, a delayed phase, acquired from 2–10 min after contrast material injection, can follow the hepatic venous phase [13-20] or can occur alone after the hepatic arterial phase [21-23]. Regardless of the phase sequence chosen, to the best of our knowledge, no study has yet compared the hepatic venous and delayed phases for the detection of tumour washout in patients with HCC. The purpose of our study was to compare retrospectively the hepatic venous and delayed phases for the detection of tumour washout during multiphasic MDCT of the liver in patients with HCC who underwent liver transplantation.     

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.     

Simplified rules for everyday delineation of lymph node areas for breast cancer radiotherapy

The aim of this study was to present the simplified rules of delineation of lymph node (LN) volumes in breast irradiation. Practical rules of delineation of LN areas were developed in the Department of Radiation Oncology of the Institut Curie. These practical guidelines of delineation were based on different specific publications in the field of breast and LN anatomy. The principal characteristic of these rules is their clearly established relationship with anatomical structure, which is easy to find on CT slices. The simplified rules of delineation have been published in pocket format as the illustrated atlas “Help of delineation for breast cancer treatment”. In this small pocket guide, delineation using the practical rules is illustrated, with examples from anatomical CT slices. It is shown that there is an improvement in delineation after the use of these simplified rules and the guide. In conclusion, this small guide is useful for improving everyday practice and decreasing the differences in target delineation for breast irradiation between institutions and observers.The value of lymph node irradiation has already been demonstrated by various studies and meta-analyses [1–3]. In the age of new conformal techniques, there is a real need for a clear definition of treated volumes, such as breast, tumour bed, lymph node areas and organs at risk (OAR) [4–10]. Many teams have been working for several years on the definition of treated volumes. Some delineation studies are exclusively theoretical and some provide a good anatomical atlas, but this information is difficult to use in everyday practice [4–15]. The treatment position has also been shown to be an important factor of variability in the depth and situation of lymph node volumes [5, 6]. Conformal and intensity-modulated radiotherapy (IMRT) require an exact definition of target volumes in terms of their anatomical limits for delineation on CT scans. Some authors have proposed anatomically based landmarks specific for breast cancer radiotherapy in order to delineate all regional lymph nodes and the breast [5, 6, 8, 10, 15, 16]. Despite this work, two recent papers have demonstrated the individual interobserver variability and differences in target and OAR delineation for breast irradiation, especially in lymph node areas [7, 8].This study was designed to propose a practical method to improve and facilitate the everyday delineation process for the clinicians of our department.     

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.     

Pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy

Objective:

To describe the pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy (IMRT) for oropharyngeal cancer.

Methods:

A cohort of patients undergoing weekly CT scans during dose-painted IMRT was considered. The parotid glands were contoured at the time of treatment planning (baseline) and on all subsequent scans. For a given patient, the parotid glands were labelled as higher (H) and lower (L), based on the mean dose at planning. The volume of each gland was determined for each scan and the percent change from baseline computed. Data were fit to both linear and quadratic functions. The role of selected covariates was assessed with both logistic regression and pair-wise comparison between the sides. The analyses were performed considering the whole treatment duration or each separate half.

Results:

85 patients, 170 glands and 565 scans were analysed. For all parotids except one, the quadratic function provided a better fit than the linear one. Moreover, according to both the logistic regression and pair-wise comparison, the cumulative mean dose of radiation is independently correlated with the parotid shrinkage during the first but not the second half of the treatment. Conversely, age and weight loss are predictors of relative parotid shrinkage during the entire course of the treatment.

Conclusion:

Parotid gland shrinkage during IMRT is not linear. Age, weight loss and radiation dose independently predict parotid shrinkage during a course of IMRT.

Advances in knowledge:

The present study adds to the pathophysiology of parotid shrinkage during radiotherapy.Fractionated radiotherapy is based on the assumption that the dose distribution obtained at planning is delivered during each treatment session. However, both set-up errors and tissue deformation can modify the dose that is administered. Shifts in the location of isodose levels compared with planning become critical for techniques that are highly conformal to the target(s), such as IMRT, justifying the interest in image guidance and adaptive radiotherapy [1]. Because of the sharp dose gradient around the target(s), subtle changes in the relative position or in the volume of organs at risk may alter the planned dose that the volume of an organ receives, as has been shown for the parotid glands [2–6].In a study by Ricchetti et al [7], we found that the parotid glands are the regions of interest that undergo the largest absolute and relative changes in volume during treatments. Although at least 16 articles have documented a significant percent reduction in the volume of the parotid gland during the course of fractionated radiotherapy [2,3,7–20], there are still several unanswered questions. It is unclear why some parotid glands shrink to about 50–60% during treatment, while others show only minimal changes. Studies that have investigated predictors of shrinkage have suggested weight loss during treatment, patient age and dose of radiation to the parotid as potential factors [2,9,16–19]. However, results are inconsistent [3,8,10,14]. Some studies have suggested that dosimetrically spared parotid glands undergo only minimal volume changes during treatment [16,18], whereas others describe a similar behaviour regardless of the radiation dose [7,8,10]. Furthermore, it is unclear whether the daily percent volume change is constant [8,10,16,19] or variable [7,10,13] during the course of treatment. A variable daily percent change in the volume may indicate that there are predictive factors specific to certain portions of the fractionated radiation schedule. In the present article, we attempt to clarify these points.     

Embolisation of the right gastric artery in patients undergoing hepatic arterial infusion chemotherapy using two possible approach routes

We used a retrospective non-randomised study to investigate the clinical effect of selective embolisation of the right gastric artery before hepatic arterial infusion chemotherapy (HAIC) using a port-catheter system. We evaluated whether the hepatic artery or the left gastric artery is the better approach for selecting the right gastric artery. A total of 367 patients (244 men and 123 women; mean age, 64.1 years) with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system. In 294 of these patients, right gastric arterial embolisation with microcoils was attempted before placement of the port-catheter system to prevent gastric mucosal lesions. Approach was either through the hepatic artery (175 patients) or through the left gastric artery (119 patients), with success rates in catheterising the right gastric artery of 78.3% and 77.3%, respectively. If the attempt was unsuccessful, the catheter was redirected to the alternative approach, which increased the final success rate to 96.3%. Only seven patients experienced gastroduodenal mucosal lesions acutely after HAIC, as revealed by endoscopy. Embolisation of the right gastric artery is a feasible procedure that can reduce the incidence of gastric mucosal lesions associated with HAIC. Approach through either the hepatic artery or the left gastric artery is equally acceptable.Long-term hepatic arterial infusion chemotherapy (HAIC) via an implanted port-catheter system is a treatment option for patients with unresectable advanced liver cancer [1, 2]. In the past, such catheter placement was done by surgical laparotomy under general anaesthesia [3–6], an invasive procedure. However, recent advances in interventional techniques allow the implantation of port-catheter systems percutaneously under local anaesthesia [7–14].A frequent complication is reactive gastric or duodenal mucosal lesions, which result from chemical irritation caused by infusion of chemotherapeutic agents into adjacent organs through arteries originating from the common hepatic artery [15–24]. One such complication is a gastric mucosal lesion caused by inflow of chemotherapeutic agents into the right gastric artery [15–24]. To prevent this complication, the efficacy of selectively embolising the right gastric artery with coils at the time of implantation of the port-catheter system has been noted [21, 25–27].In many cases, however, the right gastric artery is slender and angulated, with anatomical variations [26, 28–31]. Hence, it is occasionally difficult to insert a catheter selectively into the right gastric artery by antegrade catheterisation via the site of the hepatic artery. This is the approach most commonly used by interventional radiologists. Failure to embolise the right gastric artery can result [26]. As an alternative method, a retrograde approach to the right gastric artery via the left gastric artery has been introduced [32, 33].Because HAIC with an implanted port-catheter system is performed in a relatively large number of cases in our institution, we have many opportunities to embolise the right gastric artery using both approaches. The aim of the present retrospective non-randomised study, which included a large number of subjects, was to evaluate the usefulness of right gastric arterial embolisation and to determine whether the antegrade or retrograde approach is more useful.     

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.     

Vascular invasion in hepatocellular carcinoma: is there a correlation with MRI?

Objective

Hepatocellular carcinoma (HCC) is one of the commonest malignancies worldwide. Prognosis is predicted by size at diagnosis, vascular invasion and tumour proliferation markers. This study investigates if MRI features of histologically proven HCCs correlate with vascular invasion.

Methods

Between 2006 and 2008, 18 consecutive patients, with a total of 27 HCCs, had comprehensive MRI studies performed at our institution within a median of 36 days of histology sampling. Each lesion was evaluated independently on MRI by 3 radiologists (blinded to both the radiology and histopathology reports) using a 5-point confidence scale for 23 specific imaging features. The mean of the rating scores across readers was calculated to determine interobserver consistency. The most consistent features were then used to examine the value of features in predicting vascular invasion, using a χ² test for trend, having eliminated those features without sufficient variability.

Results

22 of the 23 imaging features showed sufficient variability across lesions. None of these significantly correlated with the presence of vascular invasion, although a trend was identified with the presence of washout in the portal venous phase on MRI and the median size of lesions, which was greater with vascular invasion.

Conclusion

This study suggests that no single MRI feature accurately predicts the presence of vascular invasion in HCCs, although a trend was seen with the presence of washout in the portal venous phase post gadolinium. Larger prospective studies are required to investigate this further.Hepatocellular carcinoma (HCC) is one of the commonest malignancies worldwide, either arising de novo or on a background of cirrhosis. The incidence in Western countries is rising owing to increasing rates of alcoholic liver disease and hepatitis C infection. Untreated, the 5-year survival rate for symptomatic HCC is less than 5% [1]. At present, surgery is the only potentially curative treatment for HCC with options including either a partial hepatectomy or orthotopic liver transplantation (OLT). Following resection there is a 5-year survival rate of 40–50% [2] with a cumulative 5-year recurrence rate between 75 and 100% [3]. The 5-year survival rate in patients with cirrhosis following transplantation of small (<2 cm) HCC is up to 80% [4]. However, the use of OLT is limited owing to the lack of donor livers. Regional therapies such as transcatheter arterial chemoembolisation [5] and percutaneous radiofrequency ablation [6] may improve prognosis. The value of neo-adjuvant and adjuvant chemotherapy and immunotherapy in prolonging survival remains controversial [7,8]. However, a recent study evaluating sorafenib, a multikinase inhibitor, in patients with advanced HCC has shown an increased median overall survival of 2.8 months over a placebo [9].Studies of patients with explanted liver for end-stage cirrhosis have shown that MRI, with the use of dynamic gadolinium-enhanced sequences, has a moderate sensitivity for the detection of HCC of between 55 and 91% [10-12] and specificity between 55 and 86% [11-13]. The sensitivity is lower with lesions <2 cm in size [11-13]. In patients with cirrhosis, HCC is thought to develop as part of a spectrum of de-differentiation from regenerative nodule through to low-grade dysplastic nodule, high-grade dysplastic nodule, then to frankly malignant. Early diagnosis using non-invasive imaging leads to an improved prognosis but at present, unless biopsy is performed, only lesion size is used to determine patient management in those where gross vascular involvement or metastatic spread precludes curative treatment.Several factors predicting outcome have been identified including tumour pathological factors (such as size, stage, grade, the presence of vascular invasion, portal vein tumour thrombus and intrahepatic metastases) [14,15], the patient’s hepatitis status, the patient’s functional liver reserve [16] and the serum α-fetoprotein level [17]. Overall, one of the most strongly correlated factors is the presence or absence of vascular invasion. There is a 4.4- and 15-fold increased risk of recurrence following OLT for HCC in patients with micro- or macrovascular invasion, respectively [18].The aims of this retrospective study were twofold. First to identify the interobserver variability of MRI features for patients with histologically proven HCC, and second to determine if there was a correlation between imaging features on MRI and histologically defined vascular invasion; these MRI features could then serve as a surrogate marker of prognosis. There has been little literature to date attempting to correlate MRI features with microvascular invasion.     

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.     

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.     

Bone age assessment by dual-energy X-ray absorptiometry in children: an alternative for X-ray?

Objective

The aim of the study was to validate dual-energy X-ray absorptiometry (DXA) as a method to assess bone age in children.

Methods

Paired dual-energy X-ray absorptiometry (DXA) scans and X-rays of the left hand were performed in 95 children who attended the paediatric endocrinology outpatient clinic of University Hospital Rotterdam, the Netherlands. We compared bone age assessments by DXA scan with those performed by X-ray. Bone age assessment was performed by two blinded observers according to the reference method of Greulich and Pyle. Intra-observer and interobserver reproducibility were investigated using the intraclass correlation coefficient (ICC), and agreement was tested using Bland and Altman plots.

Results

The intra-observer ICCs for both observers were 0.997 and 0.991 for X-ray and 0.993 and 0.987 for DXA assessments. The interobserver ICC was 0.993 and 0.991 for X-ray and DXA assessments, respectively. The mean difference between bone age assessed by X-ray and DXA was 0.11 years. The limits of agreement ranged from −0.82 to 1.05 years, which means that 95% of all differences between the methods were covered by this range.

Conclusions

Results of bone age assessment by DXA scan are similar to those obtained by X-ray. The DXA method seems to be an alternative for assessing bone age in a paediatric hospital-based population.Children with the same chronological age often have a different bone maturation as a consequence of various genetic and social factors [1-3]. Bone age is a useful indicator of children’s growth and biological maturation and is frequently assessed in paediatric endocrinology to determine delayed or advanced growth [4-7]. In children with growth disorders, regular hand X-rays are needed to follow skeletal development at an interval of once or twice per year [8-10]. The classical method to assess bone age is based on the recognition of changes in the maturity indicators in hand–wrist X-rays by comparison with a reference atlas (Greulich and Pyle method) [11].The main problem with this method is the exposure to a certain amount of irradiation involved in X-ray procedures [12-14]. Although the precise risk estimate of paediatric cancers due to diagnostic X-ray exposure is not known [15-17], we know that the lifetime attributable risk of cancer due to one single X-ray exposure in childhood approximates 15% per sievert [18]. To avoid detrimental effects in later life as a result of cumulative radiation exposure, dose reduction is therefore particularly important in childhood [18,19]. Consequently, methods involving less radiation would be preferable to assess bone age in children. Dual-energy X-ray absorptiometry (DXA) has been suggested as a safer method to assess bone age [20]. In both children and adults, DXA is currently widely used to measure bone mineral density for the assessment of osteoporosis [21]. When applied to assess bone age, a hand–wrist scan by DXA (0.0001 mSv) produces a 10-fold lower effective dose than a hand–wrist X-ray (0.001 mSv) [22].One previous study in a paediatric population of 60 Polish subjects (5–20 years old) suggested that results for bone age assessment by DXA are similar to those produced by X-ray [20]. However, their results were presented as correlation coefficients and t-test analysis. For methods of comparison, Bland and Altman analysis is a more appropriate analysis, since it investigates agreement [23,24]. Also, they used a reference method that applied to the Polish population [25], whereas the Greulich and Pyle method would be more generalisable [3].Thus far, the accuracy of the assessment of bone age in children using DXA scans has not been properly validated. Therefore, the aim of this study was to investigate whether hand–wrist bone age assessment by DXA produces similar results to the classical X-ray method.     

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.     

Inter- and intrascanner variability of pulmonary nodule volumetry on low-dose 64-row CT: an anthropomorphic phantom study

Objective:

To assess inter- and intrascanner variability in volumetry of solid pulmonary nodules in an anthropomorphic thoracic phantom using low-dose CT.

Methods:

Five spherical solid artificial nodules [diameters 3, 5, 8, 10 and 12 mm; CT density +100 Hounsfield units (HU)] were randomly placed inside an anthropomorphic thoracic phantom in different combinations. The phantom was examined on two 64-row multidetector CT (64-MDCT) systems (CT-A and CT-B) from different vendors with a low-dose protocol. Each CT examination was performed three times. The CT examinations were evaluated twice by independent blinded observers. Nodule volume was semi-automatically measured by dedicated software. Interscanner variability was evaluated by Bland–Altman analysis and expressed as 95% confidence interval (CI) of relative differences. Intrascanner variability was expressed as 95% CI of relative variation from the mean.

Results:

No significant difference in CT-derived volume was found between CT-A and CT-B, except for the 3-mm nodules (p<0.05). The 95% CI of interscanner variability was within ±41.6%, ±18.2% and ±4.9% for 3, 5 and ≥8 mm nodules, respectively. The 95% CI of intrascanner variability was within ±28.6%, ±13.4% and ±2.6% for 3, 5 and ≥8 mm nodules, respectively.

Conclusion:

Different 64-MDCT scanners in low-dose settings yield good agreement in volumetry of artificial pulmonary nodules between 5 mm and 12 mm in diameter. Inter- and intrascanner variability decreases at a larger nodule size to a maximum of 4.9% for ≥8 mm nodules.

Advances in knowledge:

The commonly accepted cut-off of 25% to determine nodule growth has the potential to be reduced for ≥8 mm nodules. This offers the possibility of reducing the interval for repeated CT scans in lung cancer screenings.Lung cancer is the primary cancer in males and the second most common cancer in females worldwide, causing 18% of the total number of deaths [1]. Many lung cancers are found at a relatively late stage, resulting in a 5-year survival of only 15% or less [2]. Low-dose CT is a promising screening method for early detection of lung cancer [3–7]. The first result indicates that CT lung cancer screening can reduce lung cancer-specific mortality [8].In lung cancer screening, treatment decisions usually depend on pulmonary nodule size for the nodules at first detection and on the growth rate at follow-up [4]. Therefore, it is essential to assess the nodule size and growth rate accurately and reproducibly [9,10]. Variability has been found in CT-derived nodule size assessment [11,12]. In view of the current practice of patients frequently undergoing follow-up examinations, sometimes not on the same scanner, reliable inter- and intrascanner reproducibility of nodule volumetry is important.However, previous studies reported inconsistent results regarding the reproducibility of nodule volumetry. Some in vitro studies have been performed in which artificial nodules were placed at known locations in a thoracic phantom without pulmonary vessels [13–15]. Some of these studies were based on older generation CT scanners [13,16]. These studies generally showed a small margin of variability in nodule volumetry for software from different vendors. On the other hand, in vivo studies have shown that variability can be considerable, with variability up to 25% for 15 to 500 mm³ nodules [11,17–19]. A study to investigate inter- and intrascanner variability under optimally controlled conditions, yet resembling human lungs, using a more realistic phantom, has not been performed. Nowadays, 64-row multidetector CT (64-MDCT) scanners are most commonly utilised, as well as in lung cancer screenings. The variability of nodule volumetry of these scanners impacts nodule management, e.g. the interval of repeated CT scanning. As an extension to our recent study on observer detection and accuracy of manual and semi-automated volumetry [10], the focus of this study is on reproducibility between and within 64-MDCT systems. We assessed the inter- and intrascanner variability of pulmonary nodule volumetry on low-dose 64-MDCT, using randomly placed solid nodules in an anthropomorphic thoracic phantom with a background of pulmonary vasculature.     

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].