Focal hepatic masses: enhancement patterns with SH U 508A and pulse-inversion US.

PURPOSE: To evaluate the role of SH U 508A-enhanced ultrasonography (US) in the differentiation of focal hepatic masses. MATERIALS AND METHODS: Contrast material-enhanced pulse inversion US was performed on 58 unknown hepatic lesions: 23 hepatocellular carcinomas, 10 focal nodular hyperplasias, 16 hemangiomas, and nine metastases. Selected images were sequentially reviewed by readers blinded to the final diagnosis. On a baseline image, they determined lesion echogenicity, and on a vascular image, the presence or absence of distinct vascularity. On an arterial phase interval-delay flash image and a postvascular image, they assessed enhancement of the lesion and liver. Responses were compared with confirmed diagnoses. RESULTS: Focal nodular hyperplasia was characterized by detectable vascularity and positive enhancement on interval-delay and postvascular scans (sensitivity, 83% [eight of 10 lesions]; specificity, 98% [40 of 41 lesions]). Hepatocellular carcinoma also showed detectable vascularity and positive enhancement on interval-delay images but no postvascular enhancement (sensitivity, 68% [14 of 20 lesions]; specificity, 74% [23 of 31 lesions]). Vascular imaging with SH U 508A did not contribute to the diagnosis of metastasis or hemangioma. However, no or weak enhancement during the arterial phase flash without postvascular enhancement produced a sensitivity of 83% (seven of eight lesions) and sensitivity of 77% (33 of 43 lesions) for metastasis. Peripheral nodular enhancement on arterial phase flash images was highly specific (98% [37 of 38 lesions]) but not sensitive (44% [six of 13 lesions]) for hemangioma. CONCLUSION: SH U 508A-enhanced pulse-inversion interval-delay flash and postvascular phase imaging are helpful in differential diagnosis of focal hepatic lesions.     

Hepatic malignancies: improved detection with pulse-inversion US in late phase of enhancement with SH U 508A-early experience

Twenty consecutive patients with known liver malignancies underwent ultrasonography (US) in conventional B mode and in pulse-inversion mode in the late hepatic-specific parenchymal phase after intravenous administration of SH U 508A, a microbubble US contrast agent. Two experienced readers assessed subjective and objective conspicuity, number of lesions, and smallest lesion diameter in each mode. Subjective and objective conspicuity were improved with pulse-inversion mode, and smaller lesions were depicted with pulse-inversion mode than with conventional B mode, improving the detection of metastases less than 1 cm in size.     

Atypical liver hemangiomas: contrast-enhancement patterns with SH U 508A and pulse-inversion US

AIM: To describe the enhancement patterns of atypical hepatic haemangiomas with Pulse Inversion Harmonic Imaging (PIHI) using SH U 508A (Levovist). MATERIALS AND METHODS: Twenty-five patients (15 women, 10 men; age range: 29-65 years, mean: 48.2 years) with 28 hepatic haemangiomas (size: 1.5 - 11.5 cm; mean: 4.6 cm) underwent PIHI before and after i.v. administration of Levovist. Selected images obtained at baseline and 25-30s, 55-60s and 240s after Levovist injection were sequentially reviewed to determine the changes in echogenicity of haemangiomas in comparison to surrounding liver parenchyma. RESULTS: At the baseline US study, 22/28 (79%) haemangiomas revealed highly inhomogeneous echotexture; 5/28 (18%) were homogeneously hypoechoic and 1/28 (3%) was isoechoic with respect to hepatic parenchyma. After Levovist administration, 16/28 (57%) haemangiomas showed peripheral hyperechoic nodules in the arterial phase with progressive centripetal fill-in in portal and late phases; such fill-in was complete in 14/16 cases and incomplete in 2/16. Four of twenty-eight (14%) haemangiomas revealed a rapid and complete homogeneous fill-in on arterial phase that lasted throughout the portal and late phases. Finally, 8/28 (29%) showed a rim-like enhancement with progressive and complete centripetal fill-in on portal and late phases. CONCLUSIONS: According to our results, PIHI with Levovist allows demonstration of typical enhancement patterns in most of atypical haemangiomas, thus providing useful diagnostic information for their characterization.     

Improved imaging of liver metastases with stimulated acoustic emission in the late phase of enhancement with the US contrast agent SH U 508A: early experience

PURPOSE: To see whether stimulated acoustic emission (SAE) in the liver parenchyma in the late phase of enhancement with SH U 508A increases the conspicuity of occult metastases at ultrasonography (US). MATERIALS AND METHODS: Eighteen patients with known hypo- or hypervascular hepatic metastases underwent US after SH U 508A administration, after a delay of at least 5 minutes, to ensure decay of blood pool enhancement. In 16 patients with visible metastases, conspicuity was compared on registered SAE and gray-scale scans by two blinded readers and by using computerized analysis of relative gray-scale and color Doppler conspicuity scores inside and outside the lesion. In nine patients, areas suspected of being involved but without definite gray-scale masses were imaged in the same way. Paired sections were analyzed by two blinded readers looking for parenchymal color defects without corresponding gray-scale masses; nine control images from three healthy volunteers were also included. RESULTS: Intense, transient parenchymal SAE was seen in all subjects. All metastases appeared as areas of reduced or absent signal. The conspicuity score was 80% for SAE versus 9% for gray-scale US (P < .001, Wilcoxon signed rank test). SAE-specific defects were seen in all patients but in none of the volunteers. Metastases seen on SAE but undetectable on gray-scale images were proved in three patients. CONCLUSION: SAE with SH U 508A improves the conspicuity of metastases. SAE-specific defects may reveal isoechoic or subtle metastases.     

Assessment of the vascularization of neuroendocrine tumors by stimulated acoustic emission of SH U 508A ultrasound contrast agent and color or power Doppler sonography

RATIONALE AND OBJECTIVES: To assess the vascularization of neuroendocrine tumors by stimulated acoustic emission (SAE) of SH U 508A during the blood pool phase in comparison with contrast-enhanced Doppler sonography. METHODS: Thirty-six patients with neuroendocrine tumors received contrast-enhanced Doppler sonography and 21, an additional SAE. To classify tumor perfusion on Doppler sonography, a 4-step rating score was introduced: (1) no vessels (hypoperfusion); (2) one feeding or central vessel (hypoperfusion); (3) some vessels (hyperperfusion); and (4) disseminated vessels (hyperperfusion). In 36 patients, 1 pancreatic primary tumor, 33 liver metastases, 1 splenic metastasis, and 1 lymph node metastasis were examined. Results were correlated with biphasic spiral CT (n = 35) and angiography (n = 2). RESULTS: Arterial-phase CT and digital subtraction angiography revealed 18 hyper- and 18 hypoperfused lesions. Contrast-enhanced Doppler correctly classified 15 of 18 patients (83%) with hyperperfused lesions as well as 16 of 18 (89%) hypoperfused tumors by applying the rating score. SAE correctly identified 4 of 9 hyperperfused lesions (44%), 2 were isoperfused compared with normal liver tissue (22%), and 3 were hypoperfused (33%). Of 12 hypoperfused lesions, 11 were classified correctly (92%), and 1 showed isoperfusion. Hence, the positive and negative predictive values for SAE were 80% and 69%, respectively. For contrast-enhanced Doppler sonography, positive and negative predictive values were 88% and 84%, respectively. CONCLUSIONS: Blood pool SAE failed to determine subtle tumor perfusion correctly. The rating score for contrast-enhanced Doppler sonography characterized tumor perfusion with high accuracy. The use of a contrast agent significantly improved perfusion characterization.     

Echo-enhanced transcranial color-coded US: clinical usefulness of intravenous infusion versus bolus injection of SH U 508A

Twelve patients with insufficient transcranial Doppler signal underwent transcranial color-coded ultrasonography before and after administration of SH U 508A with different modes of administration. Clinically useful enhancement time after bolus injection was surpassed by that after standard infusion (1 mL/min), whereas further prolongation was observed after individualized infusion. Intravenous infusion of SH U 508A provides a prolonged useful enhancement compared with that after bolus injection.     

Renal arteries in patients at risk of renal arterial stenosis: multicenter evaluation of the echo-enhancer SH U 508A at color and spectral Doppler US. Levovist Renal Artery Stenosis Study Group

PURPOSE: To assess SH U 508A in the diagnosis of suspected renal arterial stenosis by means of ultrasonography (US) and to confirm the safety of SH U 508A in a clinical setting. MATERIALS AND METHODS: A randomized crossover study was performed in 198 patients from 14 European centers who were referred for renal arterial angiography because they were suspected of having renal arterial stenosis. All patients underwent nonenhanced and SH U 508A-enhanced Doppler US of the renal arteries. Doppler criteria included measurement of renal arterial peak systolic velocity (threshold, 1.4-2.0 m/sec) in all centers and renoaortic ratio (threshold, 3.0-3.5) in nine. RESULTS: The number of examinations with successful results increased following enhanced Doppler US examination--160 (83.8%) compared with 122 (63.9%) with nonenhanced Doppler US (P = .001), including patients with obesity or renal dysfunction. Renal arterial stenosis (> or =50%) was detected at angiography in 72 patients. Results at enhanced Doppler US were in agreement with results at angiography more often than with results at nonenhanced Doppler US in the diagnosis or exclusion of renal arterial stenosis (P = .001). For patients examined with nonenhanced and enhanced Doppler US, sensitivity (80.0% and 83.7%, respectively) and specificity (80.8% and 83.6%, respectively) remained unchanged. There were no clinically important adverse events following use of SH U 508A. CONCLUSION: In patients suspected of having renal arterial stenosis, SH U 508A increased the number of diagnostic renal arterial Doppler studies.     

Gynecologic vascular abnormalities: diagnosis with Doppler US

The authors describe the use of duplex and/or color Doppler ultrasonography of the pelvis in three women to demonstrate the presence of venous malformations. One patient with a pulsatile vaginal mass was shown to have an arteriovenous malformation of the vaginal wall. The second patient was shown to have an unsuspected venous angioma in the endometrial cavity. The third patient was shown to have adnexal varices that closely mimicked hydrosalpinx. In the latter two cases, the duplex and color flow capabilities of an endovaginal probe were especially important.     

Contrast-enhanced 3D-MRA of the upper abdomen with a bolus-injectable SPIO (SH U 555 A).

The purpose of this study was to study temporal changes in signal intensity of liver, spleen, abdominal vessels, and focal liver lesions following iv bolus injection of a superparamagnetic iron oxide (SPIO) using a breath-held three-dimensional magnetic resonance angiography (3D-MRA) sequence. Dynamic SH U 555 A-enhanced 3D-MRA studies were performed in 20 patients with focal liver lesions. Sequential coronal 3D-MRA-FISP scans were acquired (TR 5.0 msec, TE 2.0 msec, flip angle 25 degrees, 140 x 256 matrix, and 80 mm slab) within 15 seconds. Scanning was started immediately after bolus injection of 10 micromol Fe/kg bodyweight and was repeated at multiple time points (baseline and 30, 60, 90, 120, 180, 240, 300, 360, and 420 seconds). Signal intensity values of liver, focal liver lesions, spleen, the portal venous system, the abdominal aorta, and the inferior vena cava were obtained to calculate relative enhancement (ENH = [SI post - SI pre]/SI pre x 100). Visibility of vessels was assessed by consensus of two readers. Signal enhancement within abdominal vessels peaked during the first pass; however, significant signal enhancement was still present 420 seconds following injection. The liver and the spleen also demonstrated a biphasic enhancement pattern with prolonged parenchymal enhancement. Dynamic MRA with bolus injectable SH U 555 A is clinically feasible, and significant vessel enhancement can be achieved even at the dose of 10 micromol Fe/kg bodyweight. However, further refinements are required to improve contrast effects.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

Efficacy of dynamic MRI with superparamagnetic iron oxide (SH U 555 A): vascularity evaluation in hepatocellular carcinoma.

PURPOSE: A study was conducted to determine the possibility of evaluating the blood flow in cases of hypervascular hepatocellular carcinoma (HCC) by employing dynamic MRI with superparamagnetic iron oxide (SH U 555 A), which can be rapidly injected via an intravenous route. METHODS: Six patients with hypervascular HCC (23 nodules) served as the subjects. Dynamic MRI includes images obtained at precontrast and at 10 (perfusion phase), 60, 120, 180, 240, 300 and 600 s after the start of injection of SH U 555 A. CT hepatic arteriography (CTHA) and CT during arterial portography (CTAP) were used as the standards of reference, and these were performed in all patients three days after dynamic MRI. The signal changes were evaluated at each phase, especially at the perfusion phase from the viewpoints of a lesion-to-liver contrast-to-noise ratio (CNR) and visual examination. RESULTS: A total of 23 hypervascular HCC were detected on CTHA and CTAP. Of the 23 lesions, 17 were detected on SH U 555 A enhanced MRI. Incorrect timing during acquisition of the perfusion phase was considered in two cases with three lesions. Of 14 lesions, excluding two cases with incorrect timing, a reduction in the transient signal in the lesions at the perfusion phase was visually recognized in 10 lesions (71%). Significant differences were seen in tumor size between visible and non-visible tumors involving transient signal reduction (p< 0.05). CNR gradually increased after rapidly decreasing in the perfusion phase. CONCLUSION: SH U 555 A enhanced MRI is valuable in limited cases. Evaluation of tumor blood flow employing dynamic MRI with SH U 555 A is affected by tumor size and requires optimal timing of the perfusion phase.     

Colour Doppler signal enhancement of intrarenal vasculature of the rabbit with Perflubron

The colour Doppler signal enhancement of the intrarenal vasculature of the kidney was studied after intravenous infusion of Perflubron. This enhancement was evaluated qualitatively and semi-quantitatively. Nine rabbits received 1 g/kg of a 100% w/v Perflubron emulsion [perfluorooctylbromide (PFOB), Alliance Pharmaceutical] intravenously. Then, two groups of 2 rabbits received 2 and 3 g/kg respectively, and 1 rabbit received 4 g/kg. The kidneys were imaged longitudinally on a colour Doppler unit with a 7.5 MHz transducer. Signal enhancement was evaluated semi-quantitatively by counting the levels of signal threshold that had to be subtracted to reproduce the baseline image. This measurement was performed 1, 3, 5, 10, 30, 45, 60, 90 and 120 min after infusion. We found that detection of very small vessels deep into the parenchyma was possible with Perflubron. In the group that received 1 g/kg Perflubron significant variations in signal enhancement were noted. The curve of mean signal enhancement showed a maximum Doppler signal at about 15 min, which slightly and progressively decreased during the next hour. With the 2, 3 and 4 g/kg doses, enhancement was constant and proportional to the infused dose. Perflubron emulsion allows significant Doppler enhancement on colour flow imaging, providing better visualisation of deep parenchymal small vessels. A dose of 1 g/kg seems adequate for this purpose.Correspondence to: N. Grenier     

Dose investigation of superparamagnetic iron oxide (SPIO) SH U 555 A in liver MR imaging

SH U 555 A, a new superparamagnetic iron oxide (SPIO) contrast agent for liver MR imaging, was investigated in terms of safety and efficacy. Eighty-four patients with suspected malignant liver tumor were randomly allocated to two groups: the L dose group (8 mumol Fe/kg) and H dose group (12 mumol Fe/kg). Efficacy was qualitatively evaluated through blinded reading of the MR images. Assessment of the images revealed no consistent differences between the L and H dose groups. During the 3- to 4-day observation period, a total of 16 adverse events were observed in 11 patients: 8 patients in the L dose group and 3 patients in the H dose group. Nasal bleeding occurred in 2 of these cases in the H dose group 2 and 4 days, respectively, after injection. Although patients in the H dose group showed a significantly larger transient decrease in Coagulation Factor XI at 4-6 hr post-injection (p.i.) than patients in the L dose group, analysis of covariance revealed an estimated 6.5% difference. There was no prolongation of APTT or change in Factor XI at 72-96 hr p.i. Because there were no clinically significant differences between the L and H doses, both were considered to be safe and effective.     

Detection of vascular complications in renal allografts with color Doppler flow imaging

One hundred ninety-five color Doppler flow (CDF) examinations were performed in 146 renal allografts to assess the capabilities of this technique in detecting intra- or extrarenal vascular complications. Conventional angiography was also performed in 44 transplants. In the group of transplants with angiographic correlation, CDF sonography enabled correct identification of 30 of 34 vascular complications. CDF showed 10 of 11 significant stenoses of the renal artery or of one of its main branches. There were two false-positive renal artery stenoses (one normal artery and one 40% stenosis). Nine of nine renal artery thromboses and the single pseudoaneurysm were also identified. Within the parenchyma, CDF sonography demonstrated five of five segmental infarcts, two of two postbiopsy arteriovenous fistulas, and three of six segmental or interlobar artery stenoses. Measurement of peak systolic velocity showed a significant difference (P less than .05) between a group (n = 8) with significant stenosis of the renal artery or one of its main branches (mean, 215.2 cm/sec +/- 32) and a group (n = 14) without stenosis (mean, 99.2 cm/sec +/- 19).     

Lower-extremity vascular grafts placed for peripheral vascular disease: prospective evaluation with duplex Doppler sonography

Eighty-five men with 92 vascular grafts placed for peripheral vascular disease of the lower extremity underwent a total of 264 examinations with duplex Doppler over a 2.5-year period. In 64 patients who underwent more than one examination, the total follow-up encompassed 740 months. In 220 native femoral arteries (96.0%) the peak systolic velocity (PSV) was higher than that in the graft. Arteriovenous shunting was associated with a normal PSV and a markedly elevated diastolic component at spectral analysis. Focal fluid collections were common initially near the graft and usually disappeared uneventfully. An average PSV of 32 cm/sec or less was always associated with impending occlusion. The sensitivity of an average PSV of 40 cm/sec or less to indicate impending graft occlusion by the next visit was only 33%; the specificity, 94%. At initial examination, stenoses were associated with high PSV focally in the graft or low PSV with absent diastolic flow.     

Diagnostic efficacy and safety of MRI of the liver with superparamagnetic iron oxide particles (SH U 555 A).

The purpose of this study was to evaluate the diagnostic efficacy and safety of an intravenous injection of magnetic resonance imaging (MRI) contrast agent, SH U 555 A, in adult patients with known focal liver lesions. Pre- and post-contrast image sets were obtained in 19 patients after injection of SH U 555 A as a part of a phase III clinical trial (patients <60 kg body weight received 0.9 mL and patients >60 kg received 1.4 mL). Three blinded readers evaluated the post-contrast images. Blood pressure and heart rate were recorded and laboratory tests were performed at baseline, during and immediately after the procedure, and four and 24 hours after the MR procedure. On post-contrast MRI, there was statistically significant improvement in diagnostic confidence, visualization, delineation, and contrast between the lesions and the healthy parenchyma in comparison to precontrast. Twenty more lesions were detected on post-contrast images. The management in six patients (31.7%) was changed after post-contrast imaging. Changes in vital signs and laboratory tests were minimal and did not affect the patients' clinical condition. Only a moderate allergic reaction (diffuse erythematous rash) was recorded. SH U 555 A is an effective and safe contrast agent for MRI of the liver.     

Peripheral third cranial nerve enhancement in multiple sclerosis

Cranial nerve III dysfunction in multiple sclerosis (MS) is uncommon. Seven cases of isolated cranial nerve III paresis associated with MS have been reported in the English-language literature. MR imaging was obtained in five cases demonstrating lesions within the midbrain. We present the detailed clinical and MR imaging findings of a young woman with MS and an isolated, painful pupil involving complete left cranial nerve III palsy. Initial MR imaging showed isolated enhancement of the cisternal portion of the cranial nerve III, suggesting that peripheral nervous system involvement may develop as part of the disease process in some patients with MS.