K. J. Wolf

Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits

RATIONALE AND OBJECTIVES Inflammatory atherosclerotic plaques are characterized by increased endothelial permeability and multiple macrophages. Blood-pool MRI contrast agents like superparamagnetic iron oxide (SPIO) have an affinity for the monocyte-macrophage system and thus, may label inflammatory plaques. The objective was to demonstrate SPIO uptake in plaques of atherosclerotic rabbits by MRI and histology. METHODS Aortas of anesthetized Watanabe hereditable hyperlipidemic rabbits were studied with a moderately T2*-weighted gradient-echo sequence at 1.5 T. Four groups of five animals each were studied: (1) without ultrasmall SPIO (carboxydextran coating; particle size, 25 nm; estimated plasma half-life, 6 hours) or with imaging after intravenous injection of SPIO at a dose (micromol Fe/kg) and postcontrast time delay (hours) of 50/8 (2), 50/24 (3), or 200/48 (4). In vivo MRI was compared with corresponding ex vivo histological iron stains. RESULTS Animals receiving 200 micromol Fe/kg demonstrated areas of focal signal loss clearly confined to the aortic wall on a mean of 24 +/- 9 (31% +/- 11%) of 76 +/- 5 images compared with 0 +/- 0 of 76 +/- 5 images in controls (P = 0.009). The number of images with this finding in groups 2 and 3 was not significantly different compared with controls. By microscopy, SPIO-iron was seen in the endothelial cells and subendothelial intimal macrophages of atherosclerosis-prone aortic wall segments. Atherosclerotic lesions demonstrating iron uptake also showed a high macrophage content. CONCLUSIONS SPIO accumulates in aortic plaques of atherosclerotic rabbits, producing a characteristic MRI finding. As SPIO accumulates in plaques with increased endothelial permeability and a high macrophage content, two established features of plaque inflammation, it may have a potential for noninvasive assessment of inflammatory atherosclerotic plaques.

Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents

Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet.

EVALUATION OF GADOBUTROL IN A RABBIT MODEL AS A NEW LANTHANIDE CONTRAST AGENT FOR COMPUTED TOMOGRAPHY

RATIONALE AND OBJECTIVES.The efficacy of the neutral lanthanide contrast agent gadobutrol was compared to that of the iodinated contrast agent iopromide in rabbits. METHODS.The computed tomography (CT) attenuation of increasing concentrations of gadolinium (Gd) (gadobutrol) and iodine (I) (iopromide) was measured in Hounsfield units (HU) in aqueous solution at 80,120, and 137 kV. The peak enhancement (net increase in CT attenuation compared with baseline) and the time-enhancement product in the aorta and in the renal parenchyma of the outer and inner cortex were measured in rabbits over a 5-minute period after the animals were given single intravenous injections of 0.7,1.0, and 1.5 mmol Gd/kg of gadobutrol and 1.0 and 2.4 mmol I/kg of iopromide. RESULTS.In vitro, the CT attenuation of gadolinium was 40% higher than that of iodine at equivalent mass concentrations (120 kV). The mean peak enhancements in the aorta after the injections of 0.7,1.0, and 1.5 mmol Gd/kg and 1.0 and 2.4 mmol I/kg were 216,313,591, 224, and 498 HU, respectively. In addition, a 30-second injection of the high dose of gadobutrol resulted in an attenuation profile that was suitable for a three-dimensional reconstruction of the aorta and the renal vasculature. CONCLUSIONS.Because of the higher CT attenuation of gadolinium compared with that of iodine, the neutral macrocyclic chelate gadobutrol is a more effective contrast agent than iopromide for CT at lower doses of the imaging atom.

Characterisation of focal liver lesions with unenhanced and contrast enhanced low MI real time ultrasound: on-site unblinded versus off-site blinded reading.

OBJECTIVE To compare on-site and blinded off-site reading of baseline ultrasound (US) and contrast enhanced ultrasound (CEUS) for classification and characterisation of focal liver lesions. MATERIALS AND METHODS 99 patients (57 women and 42 men, age range 18-89 years, mean age: 59 years) with 53 malignant and 46 benign liver lesions were studied with unenhanced US followed by contrast enhanced US after injection of 2.4 ml SonoVue® (Bracco, Milano, Italy). Image interpretation was performed on-site with clinical information available by consensus of two readers and off-site by two independent blinded readers at two different centers. Comparison of pre and post contrast scans and of the different readers was performed. Reference examinations were histology, intraoperative US, MRI or CT. RESULTS Sensitivity for malignancy improved from 81/89/66% (on-site/off-site reader 1/2) before to 100/96/96% post contrast administration (p<0.05, except for reader 1). Specificity improved from 48/48/54% on baseline US to 89/80/76% on CEUS (p<0.05). Accuracy for specific lesion diagnosis was 62/59/50% pre and 90/77/72% post contrast (p<0.05). Classification and characterisation post contrast were mildly inferior for off-site reading. Agreement between on-site and off-site readers of unenhanced scans was fair (κ=0.29-0.39) while it was good for CEUS (κ=0.63-0.79). CONCLUSIONS CEUS improves classification and characterisation of focal liver lesions and interobserver agreement compared to conventional US. Classification and characterisation post contrast were mildly but statistically significantly better for on-site than for off-site reading.

Hepatic transit time analysis using contrast-enhanced ultrasound with BR1: A prospective study comparing patients with liver metastases from colorectal cancer with healthy volunteers.

We prospectively compared hepatic transit time (HTT) measurements in subjects with liver metastases from colorectal cancer (group a) and healthy volunteers (group b) using contrast-enhanced ultrasound with BR1. The purpose of this study was to verify our hypothesis that the hemodynamic changes of the liver, which occur during metastasis seeding, would shorten the HTT, and we expect that such changes could be used for the detection of occult liver metastases from colorectal cancer in the future. The study had institutional review board approval and all subjects gave informed written consent. Group a and group b consisted of 22 subjects each. Baseline and post contrast images were acquired starting 10 s before and ending 40 s after administration of BR1, using nonlinear imaging at a frame rate of 5/s. The baseline images were used to determine the signal intensity without contrast enhancement as the reference signal. Arrival times (AT) of the contrast agent for the hepatic artery, the portal vein and one hepatic vein were determined using (i) quantitative analysis and (ii) subjective analysis by two blinded readers. HTT was calculated based on arrival time measurements. Quantitative and subjective analysis showed significantly shorter arterial to venous and portal to venous HTT in group a compared with group b (p < 0.001). Arterial to venous HTT (quantitative analysis) was < or = 9 s in 19 of 22 subjects of group a and >9 s in 18 of 22 subjects of group b (sensitivity 86%, specificity 82%, positive predictive value 83%, negative predictive value 86%, area under the curve [AUC] 0.87). Portal to venous HTT (quantitative analysis) was < 7 s in 21 of 22 subjects of group a and > 7s in 15 of 22 subjects of group b (sensitivity 95%, specificity 68%, PPV 75%, NPV 94%, AUC 0.85). There was an inverse relation with number of liver segments involved for arterial to venous and portal to venous HTT in group a (p < 0.05), but no correlation between HTT and overall volume of metastases (group a) or subject age (group b). From the results of our study, we conclude that HTT measurements using contrast-enhanced ultrasound with BR1 can detect hemodynamic changes caused by metastatic liver disease from colorectal cancer. However, comparison with the literature suggests that the use of other contrast agents might provide better results. Comparison of different contrast agents for the purpose of transit time analysis would therefore be useful before embarking on a prospective trial looking at the detection of occult liver metastases in patients with colorectal cancer. (E-mail: jhohmann@uhbs.ch).

Detection of hepatocellular carcinoma and liver metastases with BR14: a multicenter phase IIA study.

The study was designed primarily to find the optimal dosage range of BR14 contrast-enhanced ultrasonography (CEUS) to detect malignant focal liver lesions. Secondary objectives were the evaluation of the safety profile and comparison with contrast-enhanced MRI (CE MRI). We studied 25 patients (9 females, 16 males, mean age, 66 years) with known hepatocellular carcinoma or liver metastases at 3 centers over a 3-month period. Each patient underwent a baseline examination and at least 3 CEUS examinations with ascending dose levels (0.25 mL; 1.0 mL; 4.0 mL) of BR14. CE MRI was performed 4 weeks before or after the CEUS examination. Dedicated liver maps were used to record the location, size, and type of detected lesions. Examination quality was documented and safety parameters were assessed. The number of lesions detected by BR14 CEUS increased with dosage, whereas the number of missed lesions and the lesion sizes decreased. Despite the increasing contrast enhancement, substantial differences among dosages were not seen for other image quality parameters. No significant changes were noted in safety parameters and no serious adverse events were reported. We conclude that the recommended dose level of BR14 is between 1 mL and 4 mL; at this dosage, lesion detection is comparable to that of CE MRI.

Fallgruben und Besonderheiten der modernen bildgebenden Diagnostik der oberen Halswirbelsäule

ZusammenfassungDie technischen Entwicklungen des letzten Jahrzehnts haben zu einer Veränderung der Wertigkeit bildgebender Verfahren in der gesamten Neuroradiologie und damit auch für die Darstellung des kraniozervikalen Übergangs geführt. Den Hauptbeitrag zur bildgebenden Diagnostik der oberen Halswirbelsäule (HWS) liefern heutzutage die hochauflösende Mehrzeilenspiralcomputertomografie (CT) und die Magnetresonanztomografie (MRT). Konventionelle Röntgenübersichten dienen bei Bedarf noch zu einer ersten Orientierung.AbstractRecent technical developments led to a change in the significance of the different imaging modalities in the whole spectrum of neuroradiology and thus also in the field of imaging of the cervical spine. The main part in diagnostic imaging of the upper cervical spine is taken by high-resolution multislice CT and MRI. Conventional X-rays serve as an initial screening technique if required.

USPIO-enhanced direct thrombus MRI.

Endothelial dysfunction and macrophage infiltration are basic pathomechanisms of atherosclerosis and deep vein thrombosis. Ultrasmall superparamagnetic iron oxide particles (USPIO; charge DDM43/34, IDF, Berlin, Germany) were demonstrated to accumulate in inflammatory atherosclerotic plaques of Watanabe heritable hyperlipidemic rabbits through regionally increased endothelial permeability and uptake by macrophages (1). Initial clinical observations show that AMI227 (Sinerem®, Guerbet) was taken up in plaques of pelvic arteries in 7 of 19 patients (2). Inflammatory plaques are not only indicators of progression of atherosclerosis but may also trigger occluding thrombosis through endothelial ulceration and thus lead to myocardial infarction or cerebral infarction (vulnerable plaques) (3). Endothelial dysfunction is also present in fresh thrombi, where the endothelial cover is absent or incomplete (4). Only organized thrombi undergo complete endothelialization. During inflammatory organization, macrophages eliminate decomposition products of the thrombus through phagocytosis (siderophages). The aim of the present study was to investigate whether USPIO particles diffuse into nonendothelialized fresh thrombi or organized thrombi rich in macrophages owing to the high intravascular concentration of this blood pool contrast medium and thus allow for direct thrombus MR imaging.