Diagnostic value of CT perfusion imaging for parotid neoplasms

Objectives:

To assess the value of CT perfusion imaging in the differentiation of different histological categorization of benign tumours from malignant tumours in patients with parotid neoplasms.

Methods:

CT perfusion was successfully performed in 62 patients with parotid neoplasms whose diagnoses were confirmed by surgery or biopsy. The software generated a tissue time–density curve (TDC) and measured blood volume, blood flow, mean transit time and capillary permeability surface product. One-way ANOVA and receiver operating characteristic curves were used to analyse the difference and diagnostic efficacies of all perfusion data between each one of the benign tumours and malignancies. Statistical significance was assigned at the 5% level.

Results:

Pleomorphic adenomas mainly had a gradually ascending TDC. Warthin tumours showed a fast ascent followed by a fast descent. The TDC of basal cell adenomas had a fast ascension followed by a plateau, then a gradual descent. Malignant tumours mainly showed a rapidly ascending curve with a stable plateau. Significant differences were observed in blood flow, blood volume and mean transit time between pleomorphic adenomas and malignant tumours (p < 0.05) as well as in blood flow and blood volume between the Warthin tumours, the basal cell adenomas and the malignant tumours (p < 0.05). Differences in permeability surface between the basal cell adenomas and malignant tumours were significant (p < 0.01).

Conclusion:

CT perfusion of parotid gland could provide TDC and perfusion data, which were useful in the differentiation of different histological benign tumours and malignant tumours in the parotid gland.     

Dynamic Contrast-Enhanced MRI Using a Macromolecular MR Contrast Agent (P792): Evaluation of Antivascular Drug Effect in a Rabbit VX2 Liver Tumor Model

Objective

To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models.

Materials and Methods

This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (K^trans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups.

Results

P792 group showed a more prominent decrease in K^trans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group.

Conclusion

Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.     

Assessment of Perfusion Pattern and Extent of Perfusion Defect on Dual-Energy CT Angiography: Correlations between the Causes of Pulmonary Hypertension and Vascular Parameters

Objective

To assess perfusion patterns on a dual-energy pulmonary CT angiography (DECTA) of pulmonary hypertension (PHT) with variable causes and to assess whether the extent of perfusion defect can be used in the severity assessment of PHT.

Materials and Methods

Between March 2007 and February 2011, DECTA scans of 62 consecutive patients (24 men, 38 women; mean age, 58.5 ± 17.3 [standard deviation] years; range, 19-87 years) with PHT were retrospectively included with following inclusion criteria; 1) absence of acute pulmonary thromboembolism, 2) maximal velocity of tricuspid regurgitation jet (TR Vmax) above 3 m/s on echocardiography performed within one week of the DECTA study. Perfusion patterns of iodine map were divided into normal (NL), diffuse heterogeneously decreased (DH), multifocal geographic and multiple peripheral wedging patterns. The extent of perfusion defects (PD), the diameter of main pulmonary artery (MPA) and the ratio of ascending aorta diameter/MPA (aortopulmonary ratio, APR) were measured. Pearson correlation analysis was performed between TR Vmax on echocardiography and CT imaging parameters.

Results

Common perfusion patterns of primary PHT were DH (n = 15) and NL (n = 12). The perfusion patterns of secondary PHT were variable. On the correlation analysis, in primary PHT, TR Vmax significantly correlated with PD, MPA and APR (r = 0.52, r = 0.40, r = -0.50, respectively, all p < 0.05). In secondary PHT, TR Vmax significantly correlated with PD and MPA (r = 0.38, r = 0.53, respectively, all p < 0.05).

Conclusion

Different perfusion patterns are observed on DECTA of PHT according to the causes. PD and MPA are significantly correlated with the TR Vmax.     

The evaluation of haemodynamics in cirrhotic patients with spectral CT

Objective:

To evaluate haemodynamics in cirrhotic patients with portal hypertension using spectral CT imaging.

Methods:

118 cirrhotic patients with portal hypertension were included in the study group (further divided into Child–Pugh A, B and C subgroups). The control group consisted of 21 subjects with normal liver functionality. All subjects underwent three-phase spectral CT scans. Material decomposition images with water and iodine as basis material pairs were reconstructed. The iodine concentrations for the hepatic parenchyma in both arterial and portal venous phases were measured. The arterial iodine fraction (AIF) was obtained by dividing the iodine concentration in the hepatic arterial phase by that in the portal venous phase. AIF values from the study and control groups were compared using analysis of variance and between subgroups using a post-hoc test with Bonferroni correction, with a statistical significance of p<0.05.

Results:

The AIF was 0.25±0.05 in the control group, and 0.29±0.10, 0.37±0.12 and 0.43±0.14 in the study group with Child–Pugh Grades A, B and C, respectively. The difference in AIF between the control and study groups was statistically significant. The differences were statistically significant between the subgroups with multiple comparisons except between the control group and the Child–Pugh A group (p=0.685).

Conclusion:

AIF measured in spectral CT could be used to evaluate the liver haemodynamics of cirrhotic patients.

Advances in knowledge:

The AIF, provided by spectral CT, could be used as a new parameter to observe liver haemodynamics.Portal hypertension in patients with hepatic cirrhosis usually leads to changes in not only liver morphology but also liver perfusion and haemodynamics [1]. At present, a CT liver perfusion scan is one of the imaging means to obtain liver haemodynamics. Perfusion parameters, such as liver blood volume, blood flow (BF), mean transit time (MTT) and hepatic perfusion index (HPI), can be obtained by perfusion scans using the cine mode or dynamic shuttle mode and mathematic calculations [2–4]. Liver haemodynamic changes in cirrhotic patients with portal hypertension can be detected by calculating the liver perfusion parameters, including decreasing liver BF and increasing liver HPI, that are related to decreased liver function [1,5].However, some drawbacks of CT liver perfusion scan limit its clinical usefulness. Many patients cannot endure the long breath-hold time necessary for perfusion scans. As a result, motion artefacts often occur [6–8]. Another concern is the relatively high radiation dosage involved in cine scans [9–11]. As a substitutional method for obtaining CT liver perfusion parameters, an arterial enhancement fraction (AEF) parameter was calculated from a simulated multiphasic liver CT by Kim et al [12], which was found to correlate strongly with HPI measured with perfusion CT.Recently, a new CT scanning mode, the spectral CT mode, was introduced. This scanning mode is based on the single tube fast switching between low (80 kV) and high (140 kV) energy data sets. Spectral CT produces both monochromatic and material decomposition image sets [13]. One of the properties of spectral CT is that it enables accurate assessment of the concentration of certain materials, such as iodine, the active ingredient of contrast medium, in tissues or tumours [14]. The liver has two sets of blood systems, the hepatic artery and the portal vein blood supply. In contrast-enhanced CT, liver density changes in the hepatic arterial and portal venous phases reflect the hepatic artery and portal vein perfusion. A previous study using an animal model has indicated that there is a close correlation between liver blood perfusion parameters HPI and the iodine concentration ratio in the hepatic arterial and portal venous phases in the hepatic parenchyma [hepatic arterial iodine fraction(AIF)] after contrast injection [15]. The objective of this study was to compare the AIF obtained in spectral CT imaging of cirrhotic patients with portal hypertension to that of the control group with normal liver functionality and to evaluate the possibility of estimating the liver haemodynamics of cirrhotic patients using the AIF.     

Sentinel Node Mapping of VX2 Carcinoma in Rabbit Thigh with CT Lymphography Using Ethiodized Oil

Objective

To assess the feasibility of computed tomography (CT) lymphography using ethiodized oil for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh.

Materials and Methods

This experiment received approval from the institutional animal use and care administrative advisory committee. Twenty-three rabbits with VX2 carcinoma in the thigh underwent CT before and after (1 hour, 2 hour) peritumoral injection of 2 mL ethiodized oil. After the CT examination, sentinel nodes were identified by peritumoral injection of methylene blue and subsequently removed. The retrieved sentinel and non-sentinel lymph nodes were investigated with radiographic and pathologic examinations. Based on the comparison of CT findings with those of radiographic and pathologic examinations, the diagnostic performance of CT for sentinel node identification was assessed.

Results

All 23 rabbits showed 53 ethiodized oil retention nodes on post-injection CT and specimen radiography, and 52 methylene blue-stained nodes at the right femoroiliac area. Of the 52 blue-stained sentinel nodes, 50 nodes demonstrated ethiodized oil retention. Thus, the sentinel node detection rate of CT was 96% (50 of 52). On pathologic examination, 28 sentinel nodes in 17 rabbits (nodes/rabbit, mean ± standard deviation, 1.7 ± 0.6) harbored metastasis. Twenty seven of the 28 metastatic sentinel nodes were found to have ethiodized oil retention.

Conclusion

Computed tomography lymphography using ethiodized oil may be feasible for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh.     

Quantitative dual energy CT measurements in rabbit VX2 liver tumors: Comparison to perfusion CT measurements and histopathological findings

Purpose

To evaluate the correlation between quantitative dual energy CT and perfusion CT measurements in rabbit VX2 liver tumors.

Materials and methods

This study was approved by the institutional animal care and use committee at our institution. Nine rabbits with VX2 liver tumors underwent contrast-enhanced dual energy CT and perfusion CT. CT attenuation for the tumors and normal liver parenchyma and tumor-to-liver ratio were obtained at the 140 kVp, 80 kVp, average weighted images and dual energy CT iodine maps. Quantitative parameters for the viable tumor and adjacent liver were measured with perfusion CT. The correlation between the enhancement values of the tumor in iodine maps and perfusion CT parameters of each tumor was analyzed. Radiation dose from dual energy CT and perfusion CT was measured.

Results

Enhancement values for the tumor were higher than that for normal liver parenchyma at the hepatic arterial phase (P < 0.05). The highest tumor-to-liver ratio was obtained in hepatic arterial phase iodine map. Hepatic blood flow of the tumor was higher than that for adjacent liver (P < 0.05). Enhancement values of hepatic tumors in the iodine maps positively correlated with permeability of capillary vessel surface (r = 0.913, P < 0.001), hepatic blood flow (r = 0.512, P = 0.010), and hepatic blood volume (r = 0.464, P = 0.022) at the hepatic arterial phases. The effective radiation dose from perfusion CT was higher than that from DECT (P < 0.001).

Conclusions

The enhancement values for viable tumor tissues measured in iodine maps were well correlated to perfusion CT measurements in rabbit VX2 liver tumors. Compared with perfusion CT, dual energy CT of the liver required a lower radiation dose.     

Anti-tumour effects of transcatheter arterial embolisation administered in combination with thalidomide in a rabbit VX2 liver tumour model

Objective

Using a liver tumour model we investigated whether thalidomide enhances the anti-tumour effect of transcatheter arterial embolisation (TAE).

Method

First, the viability of VX2 tumour cells co-cultured with thalidomide in a 21% and 1% O₂ atmosphere was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Second, we randomly assigned 20 rabbits bearing VX2 liver tumours to 4 groups: Group 1 (thalidomide plus TAE), Group 2 (TAE only), Group 3 (thalidomide only) and Group 4 (control). Thalidomide was orally administered for 5 days. The anti-tumour effects were assessed by the tumour proliferation rate using MRI and by immunohistochemical analysis of the area of intratumoural vessels. Analysis of variance and Tukey''s honestly significant difference test were used for statistical analysis.

Results

The viability of cells grown under hypoxic and normal conditions was not significantly different, nor was there a difference among the four groups. The tumour size increased by 55.9±29.3% in Group 1, 250.6±73.3% in Group 2, 355.2±51.7% in Group 3 and 424.7±110.7% in Group 4; the difference between Group 1 and the other three groups was significant. The area of intratumour vessels in specimens was 0.22±0.28% in Group 1, 0.42±0.29% in Group 2, 1.44±1.00% in Group 3 and 6.00±2.17% in Group 4; the difference between Group 1 and the other groups was statistically significant, as was the difference between Groups 3 and 4.

Conclusion

Thalidomide used in combination with TAE enhanced anti-tumour effects in rabbits bearing VX2 liver tumours.     

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

Objective

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

Materials and Methods

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

Results

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

Conclusion

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

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.     

Perfusion-based assessment of disease activity in untreated and treated patients with aortitis and chronic periaortitis: correlation with CT morphological,clinical and serological data

Objective:

To evaluate the role of perfusion-based assessment of inflammatory activity in patients with treated and untreated aortitis and chronic periaortitis as compared with clinical and serological markers.

Methods:

35 patients (20 females; median age 66 years) with (peri) aortitis were retrospectively evaluated. All patients had clinical symptoms prompting at the time of imaging. All patients first underwent whole-body contrast-enhanced CT and subsequently segmental volume perfusion CT for assessment of the degree of vascularization of (peri) aortitis as a surrogate marker for inflammatory activity. Blood flow, blood volume, volume transfer constant (k-trans), time to peak and mean transit time were determined. The thickness of the increased connective tissue formation was measured. Perfusion data were correlated with clinical symptoms and acute-phase inflammatory parameters such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and leukocyte number.

Results:

21 of 35 patients were untreated and 14 of 35 had previous/ongoing immunosuppression. The interobserver agreement was good (κ = 0.78) for all perfusion parameters. Average values of perfusion parameters were higher in untreated patients but remained abnormally elevated in treated patients as well. Perfusion data and ESR and CRP correlated well both in aortitis (p < 0.05) and in periaortitis (p < 0.05). In periaortitis, perfusion parameters agreed well with ESR and CRP values (p < 0.05) only in untreated patients.

Conclusion:

Perfusion CT parameters in untreated aortitis and chronic periaortitis correlate well with serological markers with respect to disease activity assessment. However, in treated periaortitis, correlations were weak, suggesting an increased role for (perfusion-based) imaging.

Advances in knowledge:

Volume perfusion CT may be used for diagnosis of aortitis/periaortitis.     

Perfusion CT to assess angiogenesis in colon cancer: technical limitations and practical challenges

Objective

Perfusion CT may have the potential to quantify the degree of angiogenesis of solid tumours in vivo. This study aims to identify the practical and technical challenges inherent to the technique, and evaluate its feasibility in colorectal tumours.

Methods

51 patients from 2 institutions prospectively underwent a single perfusion CT on 2 different multidetector scanners. The patients were advised to breath-hold as long as possible, followed by shallow breathing, and were given intravenous buscopan to reduce movement. Numerous steps were explored to identify the challenges.

Results

43 patients successfully completed the perfusion CT as per protocol. Inability to detect the tumour (n=3), misplacement of dynamic sequence co-ordinates (n=2), failure of contrast injection (n=2) and displacement of tumour (n=1) were the reasons for failure. In 14 cases excessive respiratory motion displaced the tumour out of the scanning field along the temporal sequence, leading to erroneous data capture. In nine patients, minor displacements of the tumour were corrected by repositioning the region of interest (ROI) to its original position after reviewing each dynamic sequence slice. In 20 patients the tumour was stable, and data captured from the ROI were representative, and could have been analysed by commercially available Body Tumor Perfusion 3.0® software (GE Healthcare, Waukesha, WI). Hence all data were manually analysed by MATLAB® processing software (MathWorks, Cambridge, UK).

Conclusion

Perfusion CT in tumours susceptible to motion during acquisition makes accurate data capture challenging and requires meticulous attention to detail. Motion correction software is essential if perfusion CT is to be used routinely in colorectal cancer.Perfusion CT is increasingly being used to measure the vascular perfusion in tumours to gain insight into the functional nature of the tumour. The applications for this technique in solid tumours have ranged from distinguishing the presence of malignancy in suspicious lesions in the colon and the lungs [1-3] to grading the aggressiveness of lymphomas and brain tumours [4,5]. One of the interesting aspects of perfusion CT is the potential to quantify the degree of angiogenesis in solid tumours by providing quantifiable vascular parameters [6-10]. This has gained significance owing to the development of safe neoadjuvant treatment strategies with antiangiogenesis drugs, which act by constricting tumour growth and preventing propagation of metastases [11]. There is then a possibility that perfusion CT would be able to screen patients demonstrating high angiogenic activity, who in turn would be susceptible to antiangiogenic drugs.Despite the many promising roles perfusion CT may play in the future management of solid tumours, its uptake in the clinical setting is restricted because of the complexity of the perfusion CT protocols [12]. The success of the scan is dependent on accurate capture of the contrast enhancement data from the area of interest for quantitative perfusion analysis. Also, the numerous steps involved in the perfusion CT protocol introduce areas of variability that affect the final analysis [13-15]. One of the main challenges in ensuring accurate data capture has been motion artefacts due to either respiration or peristalsis [16]. Perfusion CT in the lung has been affected by this, leading to loss of data in 6 of the 16 patients scanned in one study [17]. Thus perfusion studies in relatively fixed tumours such as pancreas, parotids or rectum have been easier to perform [4,18-20]. However, in colonic tumours the potential for motion artefacts is increased owing to mobility offered by the mesentery and, being intraperitoneal, it is also susceptible to displacement during respiration.In 2008 we undertook a prospective study to investigate the ability of perfusion CT to quantify the degree of angiogenesis in colorectal tumours. The perfusion parameters calculated were correlated with microvessel density count obtained on immunohistochemical staining of resected surgical specimen. In this paper we describe our experience of perfusion CT in colorectal tumours with an aim to identify the practical challenges inherent to the technique and to analyse the numerous technical steps in the methodology, in order to evaluate its practical feasibility in the treatment of colorectal cancer.     

Hypereosinophilic Syndrome: CT Findings in Patients with Hepatic Lobar or Segmental Involvement

Objective

The purpose of this study was to describe the CT findings of hepatic hypereosinophilic syndrome in which hepatic lobes or segments were involved.

Materials and Methods

Seven patients with hypereosinophilic syndrome with hepatic lobar or segmental involvement were included in our study. In all seven, diagnosis was based on liver biopsy and the results of corticosteroid treatment. CT findings were retrospectively reviewed by three radiologists, who reached a consensus. Biopsy specimens were examined, with special reference to portal and periportal inflammation.

Results

CT demonstrated well-defined, homogeneous or heterogeneous low attenuation with a straight margin limited to a hepatic lobe (n = 2), segments (n = 3), or subsegments (n = 2), particularly during the portal phase. Where there was subsegmental involvement, lesions were multiple, ovoid or wedge-shaped, and showed low attenuation. In two patients with lobar or segmental involvement, segmental portal vein narrowing was observed. Histopathologic examination disclosed eosinophilic infiltration in the periportal area, sinusoids and central veins, as well as portal phlebitis.

Conclusion

Hypereosinophilic syndrome may involve the presence of hepatic lobar, segmental, or subsegmental low-attenuated lesions, as seen on CT images. Their presence may be related to damage of the liver parenchyma and to portal phlebitis.     

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.     

Multiphasic Perfusion CT in Acute Middle Cerebral Artery Ischemic Stroke: Prediction of Final Infarct Volume and Correlation with Clinical Outcome

Objective

To assess the utility of multiphasic perfusion CT in the prediction of final infarct volume, and the relationship between lesion volume revealed by CT imaging and clinical outcome in acute ischemic stroke patients who have not undergone thrombolytic therapy.

Materials and Methods

Thirty-five patients underwent multiphasic perfusion CT within six hours of stroke onset. After baseline unenhanced helical CT scanning, contrast-enhanced CT scans were obtained 20, 34, 48, and 62 secs after the injection of 90 mL contrast medium at a rate of 3 mL/sec. CT peak and total perfusion maps were obtained from serial CT images, and the initial lesion volumes revealed by CT were compared with final infarct volumes and clinical scores.

Results

Overall, the lesion volumes seen on CT peak perfusion maps correlated most strongly with final infarct volumes (R²=0.819, p<0.001, slope of regression line=1.016), but individual data showed that they were less than final infarct volume in 31.4% of patients. In those who showed early clinical improvement (n=6), final infarct volume tended to be overestimated by CT peak perfusion mapping and only on total perfusion maps was there significant correlation between lesion volume and final infarct volume (R²=0.854, p=0.008). The lesion volumes depicted by CT maps showed moderate correlation with baseline clinical scores and clinical outcomes (R=0.445-0.706, p≤0.007).

Conclusion

CT peak perfusion maps demonstrate strong correlation between lesion volume and final infarct volume, and accurately predict final infarct volume in about two-thirds of the 35 patients. The lesion volume seen on CT maps shows moderate correlation with clinical outcome.     

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.     

Quantitative liver tumor blood volume measurements by a C-arm CT post-processing software before and after hepatic arterial embolization therapy: comparison with MDCT perfusion

PURPOSE

We aimed to determine whether the C-arm computed tomography (CT) blood volume (BV) imaging of hepatic tumors performed with a new prototype software is capable of measuring the BV changes in response to hepatic arterial treatments and to validate these quantitative measurements with commercially available multidetector computed tomography (MDCT) perfusion software.

METHODS

A total of 34 patients with hepatic tumors who underwent either radioembolization (RE, n=21) or transarterial chemoembolization (TACE, n=13) were included in the study. Using a prototype software by Siemens Healthcare, 74 C-arm CT BV measurements were obtained in both pre- and postembolization settings (three patients had additional BV measurements before and after work-up angiography for RE). Ten of 34 patients underwent MDCT perfusion study before embolization, enabling comparison of BV measurements using C-arm CT versus MDCT methods.

RESULTS

The mean BV of 14 tumor lesions in 10 patients on MDCT perfusion was highly correlated with the BV values on C-arm CT (r=0.97, P < 0.01). The BV values obtained by C-arm CT decreased from 140.6±28.3 mL/1000 mL to 45.9±23.5 mL/1000 mL after TACE (66.37% reduction) and from 175.6±29.4 mL/1000 mL to 84.1±22.5 mL/1000 mL after RE (53.75% reduction).

DISCUSSION

Quantitative BV measurement with C-arm CT is well-correlated with MDCT BV measurements, and it is a promising tool to monitor perfusion changes during hepatic arterial embolization.Liver perfusion with computed tomography (CT) was first described in 1991 by Miles et al. (1). It has been evolved since then parallel to the development of the CT technology and the post-processing software. However, the clinical implications of the liver perfusion studies have not been validated, and they are not considered to be a part of the routine examination yet. Compared to cerebral perfusion, the most important technical challenges of liver perfusion are the dual blood supply of the liver and the need for motion correction due to breathing movements.It has long been established that normal liver parenchyma derives most (>75%) of its blood from the portal vein whereas liver tumors derive 80%–100% of their blood supply from the hepatic artery (2, 3). Thus, several hepatic arterial embolization therapies were developed to affect mainly the tumors while preserving the normal parenchyma as much as possible. The two different hepatic arterial therapies used in this study are transarterial chemoembolization (TACE) and radioembolization (RE). The principles and mode of action of RE are fundamentally different compared with TACE (4). As a general rule, the liver tumor bed is fully embolized by chemoembolic material in TACE, while in RE optimal perfusion and blood flow is required to allow the generation of free radicals by ionization of water molecules near the tumor cell DNA (5).In both of these hepatic arterial treatment alternatives the tumor blood supply is the key factor of success: if arterial perfusion of the tumor is high, the amount of arterial therapy that is targeted to the tumor capillary bed would be high, while preserving the nontumoral liver parenchyma as much as possible. Vice versa, if tumor perfusion is closer to the rest of the normal liver parenchyma, then, the toxicity of any given treatment to the normal liver parenchyma becomes an important issue. So far, there is no real-time quantitative documentation of these vital perfusion preferences. In a pathological study, when yttrium-90 microspheres given for RE were released into the hepatic artery, they preferentially accumulated in the periphery of tumors at a ratio of at least 3:1 to 20:1 compared with the normal liver (5). Knowing the perfusion ratio between the tumor and the normal liver parenchyma is of great interest in any liver-directed therapy in order to achieve the most individualized treatment in every patient.C-arm CT (syngo DynaCT, Siemens Healthcare, Forchheim, Germany) is a recently developed tool that comes with the advanced technology of flat panel angio suites. In this method, the flat panel of the C-arm used for regular angiographies is acting like a rotational CT detector around the patient and the obtained data are reconstructed to provide a CT view. As it is essential to use the C-arm angiography table, “C-arm CT” term is used in this study. The field of view is limited to the size of the flat panel detector and the rotation speed is more limited in comparison to the multidetector CT (MDCT) technology.Herein, a novel “blood volume” (BV) measurement software utilizing C-arm CT images is used to quantify BV values in liver tumors and normal liver parenchyma, thus BV ratio of tumor to parenchyma is obtained prior to the hepatic arterial embolization therapy. Furthermore, as these patients were on the angio table for chemo- or radioembolization procedures, postembolization measurements were also obtained in order to quantify the changes in response to hepatic arterial embolization. The measurements obtained with C-arm CT via transcatheter intra-arterial injection were also compared with commercially available MDCT perfusion study with contrast injected via peripheral intravenous line in a subgroup of patients in order to validate the prototype software of C-arm CT measurements.     

Dynamic contrast-enhanced CT in suspected lung cancer: quantitative results

Objectives:

To examine whether dynamic contrast-enhanced CT (DCE-CT) could be used to characterise and safely distinguish between malignant and benign lung tumours in patients with suspected lung cancer.

Methods:

Using a quantitative approach to DCE-CT, two separate sets of regions of interest (ROIs) in tissues were placed in each tumour: large ROIs over the entire tumour and small ROIs over the maximally perfused parts of the tumour. Using mathematical modelling techniques and dedicated perfusion software, this yielded a plethora of results.

Results:

First, because of their non-normal distribution, DCE-CT measurements must be analysed using log scale data transformation. Second, there were highly significant differences between large ROI and small ROI measurements (p<0.001). Thus, the ROI method used in a given study should always be specified in advance. Third, neither quantitative parameters (blood flow and blood volume) nor semi-quantitative parameters (peak enhancement) could be used to distinguish between malignant and benign tumours. This was irrespective of the method of quantification used for large ROIs (0.13<p<0.76) and small ROIs (0.084<p<0.31). Fourth, although there were no indications of systematic reproducibility bias, the 95% limits of agreement were so broad that the risk of disagreement between the measurements could affect the clinical use of the measurements. This lack of reproducibility should be addressed.

Conclusion and advances in knowledge:

A quantitative approach to DCE-CT is not a clinically usable method for characterising lung tumours.In the Western world, lung cancer remains the leading cause of cancer-related death in both males and females. The disease has a poor prognosis with an overall 5-year mortality rate of approximately 84% [1]. In patients with suspected lung cancer, the first imaging examination is that of a chest radiograph followed by a contrast-enhanced CT of the thorax and upper abdomen. Depending on the local arrangements, this is followed by other examinations such as dynamic contrast-enhanced CT (DCE-CT).DCE-CT is a tool which, in theory, can quantify the perfusion of tissues by calculating the delivery of a contrast agent, and therefore blood, to these tissues [2–4]. This is expected to be clinically useful, and, accordingly, studies investigating the use of DCE-CT in oncology are increasingly reported in the literature [5–7].The fundamental principle of DCE-CT is based on the temporal changes in tissue density after an intravenous administration of iodinated contrast media. By obtaining, in quick succession, a series of images of a particular tissue of interest, it is possible to record the temporal changes in tissue attenuation occurring after intravenous injection of the contrast. The quantification of perfusion recorded by CT is performed using mathematical modelling techniques.In quantitative analysis, the operator places a region of interest (ROI) in the tumour, and a dedicated perfusion software is then used to calculate a numeric perfusion value for the ROI. This numeric value represents the mean of the numeric perfusion values for each voxel within the ROI, and, as such, it provides an estimate of the total perfusion of the selected tumour volume.The purpose of this study was to examine whether DCE-CT could be used to characterise and safely distinguish between malignant and benign lung tumours in patients with suspected lung cancer. For this purpose, a quantitative approach was used, by which lung tumours were measured and analysed using a dedicated computer software. Reproducibility was also verified.     

Pretreatment Evaluation with Contrast-Enhanced Ultrasonography for Percutaneous Radiofrequency Ablation of Hepatocellular Carcinomas with Poor Conspicuity on Conventional Ultrasonography

Objective

To determine whether pretreatment evaluation with contrast-enhanced ultrasonography (CEUS) is effective for percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) with poor conspicuity on conventional ultrasonography (US).

Materials and Methods

This retrospective study was approved by the institutional review board and informed consent was waived. From June 2008 to July 2011, 82 patients having HCCs (1.2 ± 0.4 cm) with poor conspicuity on planning US for RFA were evaluated with CEUS prior to percutaneous RFA. We analyzed our database, radiologic reports, and US images in order to determine whether the location of HCC candidates on planning US coincide with that on CEUS. To avoid incomplete ablation, percutaneous RFA was performed only when HCC nodules were identified on CEUS. The rate of technical success was assessed. The cumulative rate of local tumor progression was estimated with the use of the Kaplan-Meier method (mean follow-up: 24.0 ± 13.0 months).

Results

Among 82 patients, 73 (89%) HCCs were identified on CEUS, whereas 9 (11%) were not. Of 73 identifiable HCCs on CEUS, the location of HCC on planning US corresponded with that on CEUS in 64 (87.7%), whereas the location did not correspond in 9 (12.3%) HCCs. Technical success was achieved for all 73 identifiable HCCs on CEUS in a single (n = 72) or two (n = 1) RFA sessions. Cumulative rates of local tumor progression were estimated as 1.9% and 15.4% at 1 and 3 years, respectively.

Conclusion

Pretreatment evaluation with CEUS is effective for percutaneous RFA of HCCs with poor conspicuity on conventional US.     

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.     

Hepatic Sinusoidal Obstruction Syndrome Caused by Herbal Medicine: CT and MRI Features

Objective

To describe the CT and MRI features of hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal medicine Gynura segetum.

Materials and Methods

The CT and MRI features of 16 consecutive Gynura segetum induced HSOS cases (12 men, 4 women) were analyzed. Eight patients had CT; three patients had MRI, and the remaining five patients had both CT and MRI examinations. Based on their clinical presentations and outcomes, the patients were classified into three categories: mild, moderate, and severe. The severity of the disease was also evaluated radiologically based on the abnormal hepatic patchy enhancement in post-contrast CT or MRI images.

Results

Ascites, patchy liver enhancement, and main right hepatic vein narrowing or occlusion were present in all 16 cases. Hepatomegaly and gallbladder wall thickening were present in 14 cases (87.5%, 14/16). Periportal high intensity on T2-weighted images was present in 6 cases (75%, 6/8). Normal liver parenchymal enhancement surrounding the main hepatic vein forming a clover-like sign was observed in 4 cases (25%, 4/16). The extent of patchy liver enhancement was statistically associated with clinical severity classification (kappa = 0.565).

Conclusion

Ascites, patchy liver enhancement, and the main hepatic veins narrowing were the most frequent signs of herbal medicine induced HSOS. The grade of abnormal patchy liver enhancement was associated with the clinical severity.