Detection of Ablation Boundaries Using Different MR Sequences in a Swine Liver Model.

PURPOSE: To determine the magnetic resonance (MR) sequences best suited for the assessment of ablation zones after radiofrequency ablation (RFA). METHODS: Three percutaneous MR-guided RFA of the liver were performed on three swine. Four pre-contrast and two hepatobiliary post-contrast sequences were obtained after ablation. Tissue samples were extracted and stained for nicotinamide adenine dinucleotide diaphorase hydride (NADH) and with hematoxylin and eosin. Post-ablation MR images and NADH slides were segmented to determine the total ablation zone, their Dice similarity coefficient (DSC), and the contrast-to-noise ratio (CNR) of the visible ablation boundary to normal liver tissue. RESULTS: Two distinct layers were combined to determine the ablation zone: an inner layer of coagulation necrosis and an outer layer defined as the peripheral transition zone. Corresponding zones could be found in the MR images as well. Compared to histology, the total area of the MR ablation zone was significantly smaller on the pre-contrast T1 images (p < 0.01) and significantly larger with T2 turbo spin-echo (p = 0.025). No significant difference in size of the ablation zone depiction could be found between histology, post-contrast T1 volumetric interpolated breath-hold examination (VIBE), and post-contrast T1 3D Turboflash (TFL) as well as T2 SPACE images. All sequences but the pre-contrast T1 VIBE sequence showed a DSC above 80% and a high CNR. CONCLUSIONS: Post-contrast T1 3DTFL performs best when assessing ablation zones after RFA. Since the sequence requires a long acquisition time, T1 VIBE post-contrast offers the best compromise between acquisition time and estimation accuracy.

Two case reports: Breast schwannoma and a rare case of an axillary schwannoma imitating an axillary lymph node metastasis.

A 79-year-old woman with a newly detected oval circumscribed lump in subcutaneous location on mammography and ultrasound turned out to be a Schwannoma after ultrasound-guided core needle biopsy. A 72-year-old woman with breast cancer in medical history demonstrated a new axillary mass in follow up, initially regarded as a lymph node metastasis. Core needle biopsy did not lead to a sufficient diagnosis. Pathologic examination after intraoperative sampling revealed a Schwannoma. These 2 case reports illustrate the importance of diagnostic imaging and remind to include Schwannomas in the differential diagnosis of breast and axillary masses.

Periportal fields cause stronger cooling effects than veins in hepatic microwave ablation: an in vivo porcine study.

BACKGROUND: Vascular cooling effects are a well-known source for tumor recurrence in thermal in situ ablation techniques for hepatic malignancies. Microwave ablation (MWA) is an ablation technique to be considered in the treatment of malignant liver tumors. The impact of vascular cooling in MWA is still controversial. PURPOSE: To evaluate the influence of different intrahepatic vessel types, vessel sizes, and vessel-to-antenna-distances on MWA geometry in vivo. MATERIAL AND METHODS: Five MWAs (902-928 MHz) were performed with an energy input of 24.0 kJ in three porcine livers in vivo. MWA lesions were cut into 2-mm slices. The minimum and maximum radius of the ablation area was measured for each slice. Distances were measured from ablation center toward all adjacent hepatic vessels with a diameter of ≥1 mm and within a perimeter of 20 mm around the antenna. The respective vascular cooling effect relative to the maximum ablation radius was calculated. RESULTS: In total, 707 vessels (489 veins, 218 portal fields) were detected; 370 (76%) hepatic veins and 185 (85%) portal fields caused a cooling effect. Portal fields resulted in higher cooling effects (37%) than hepatic veins (26%, P < 0.01). No cooling effect could be observed in close proximity of vessels within the central ablation zone. CONCLUSION: Hepatic vessels influenced MWA zones and caused a distinct cooling effect. Portal fields resulted in more pronounced cooling effect than hepatic veins. No cooling effect was observed around vessels situated within the central white zone.

Abuse as a Cause of Childhood Fractures.

BACKGROUND: It is well known that physical abuse of children all too often escapes detection. Fractures are among the potential consequences of physical abuse but are also com- mon in childhood because of accidents. A question frequently addressed to the Medical Child Protection Hotline (Medizini- sche Kinderschutzhotline) is how fractures due to abuse can be distinguished from accidental fractures. METHODS: This review is based on pertinent publications retrieved by a search in PubMed and in the Cochrane Data- base, as well as on the authors' experience in a pediatric emergency department with ca. 29 000 consultations per year and in a child protection outpatient clinic with ca. 100 consultations per year. RESULTS: Fractures due to abuse are especially common among infants; their incidence is estimated at 56.8/100 000 among infants less than six months old and 39.8/100 000 among infants aged 6 to 11 months. In consideration of the age of the child, the type of fracture, the history, and other factors, a high probability of abuse can be suspected in many cases, so that further measures can be initiated. CONCLUSION: All physicians involved in the care of children (even if only occasionally) should be aware of the major indicators of likely physical abuse and of the available oppor- tunities for counseling and intervention. Failures to diagnose child abuse are associated with high rates of recurrence and mortality.

Minimal vascular flows cause strong heat sink effects in hepatic radiofrequency ablation ex vivo.

BACKGROUND: The present paper aims to assess the lower threshold of vascular flow rate on the heat sink effect in bipolar radiofrequency ablation (RFA) ex vivo. METHODS: Glass tubes (vessels) of 3.4 mm inner diameter were introduced in parallel to bipolar RFA applicators into porcine liver ex vivo. Vessels were perfused with flow rates of 0 to 1,500 ml/min. RFA (30 W power, 15 kJ energy input) was carried out at room temperature and 37°C. Heat sink effects were assessed in RFA cross sections by the decrease in ablation radius, area and by a high-resolution sector planimetry. RESULTS: Flow rates of 1 ml/min already caused a significant cooling effect (P ≤ 0.001). The heat sink effect reached a maximum at 10 ml/min (18.4 mm/s) and remained stable for flow rates up to 1,500 ml/min. CONCLUSIONS: Minimal vascular flows of ≥1 ml/min cause a significant heat sink effect in hepatic RFA ex vivo. A lower limit for volumetric flow rate was not found. The maximum of the heat sink effect was reached at a flow rate of 10 ml/min and remained stable for flow rates up to 1,500 ml/min. Hepatic inflow occlusion should be considered in RFA close to hepatic vessels.

(90)Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II clinical trial.

PURPOSE: We report on a multicenter phase II trial of (90)yttrium-ibritumomab-tiuxetan ((90)YIT) as first-line stand-alone therapy for patients with follicular lymphoma (FL). PATIENTS AND METHODS: Fifty-nine patients with CD20(+) FL grade 1 to 3a in stages II, III, or IV, age 50 years old or older requiring therapy were enrolled. They received (90)YIT according to standard procedure. If complete response (CR) or unconfirmed complete response (CRu) without evidence for minimal residual disease (MRD) 6 months after application of (90)YIT was achieved, patients were observed without further intervention. The same applied to patients with partial response (PR) or with stable disease (SD). Patients with CR but with persisting MRD were to receive a consolidation treatment with rituximab. Primary end point was the clinical and molecular response rate. Secondary end points were time to progression, safety, and tolerability. RESULTS: Six months after treatment with (90)YIT, 56% of the patients showed a CR or CRu and 31% achieved a PR. After a median follow-up of 30.6 months, the progression-free survival (PFS) was 26 months. There was a trend for shorter PFS in patients with increased lactate dehydrogenase (LDH). Of the 26 patients who had CR 12 months after (90)YIT, only three had relapsed. Median time to next treatment has not been reached. The most common toxicities were transient thrombocytopenia and leukocytopenia. Nonhematologic toxicities never exceeded grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE v2.0). CONCLUSION: (90)YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after (90)YIT appear to have long- lasting responses.

Hepatic transit time analysis using contrast enhanced MRI with Gd-BOPTA: A prospective study comparing patients with liver metastases from colorectal cancer and healthy volunteers.

PURPOSE: To find out if the hepatic transit time (HTT) shortening, which was already proven in patients with liver metastases by other modalities, can also be detected with MRI. MATERIALS AND METHODS: The Patient group consisted of 20 subjects with liver metastases from colorectal cancer and the control group of 21 healthy subjects. Baseline and post contrast images were acquired before and after administration of Gd-BOPTA, using a T1-weighted bolus test sequence. Arrival times (AT) of the contrast agent for the aorta, the hepatic artery, the portal vein and one hepatic vein were determined. Based on arrival time measurements HTT were calculated. RESULTS: All analyses showed significantly shorter HTT in patients with metastases compared with healthy volunteers (P < 0.05). There were no false positives using a threshold of 10.4 s for arterial to venous HTT. For aortal to venous and portal to venous HTT a threshold of 12.5 s and 4 s was calculated, respectively. No significant correlation between HTT and involved liver segments, overall volume of metastases or subject age was found. CONCLUSION: We conclude that HTT measurements using contrast enhanced MRI with Gd-BOPTA can detect hemodynamic changes due to metastatic liver disease from colorectal cancer.

Post-processing central k-space subtraction for high-resolution arterial peripheral MR angiography.

Peripheral MR angiography requires high resolution and arterial contrast. Neither can be obtained simultaneously due to the short arterial phase of the contrast agent. To improve temporal resolution, keyhole imaging was developed, which combines high resolution and arterial k-spaces at the time of image acquisition. Here, a related approach is introduced for image post-processing in the Fourier domain. It is demonstrated that simple substitution of the central k-space with low-resolution data leads to severe distortion. Hence, a dedicated calculation scheme is necessary for composite k-space post-processing. A solution is presented for high-resolution arterial peripheral MR angiography that uses subtraction of venous intensities from the central high-resolution k-space. The calculations in the Fourier domain do not require interpolations between the different resolutions. High-resolution steady-state MR angiography, which exhibits contrast-enhanced arteries and veins at an isotropic resolution of 0.65 mm, and standard resolution arterial first-pass MR angiography were combined to obtain images with the resolution of the steady-state images and arterial contrast. Numerical simulations on software phantoms are presented. The operation of the method is demonstrated in five patients.

Gadofluorine M-enhanced magnetic resonance imaging of inflammatory bowel disease: quantitative analysis and histologic correlation in a rat model.

OBJECTIVES: : To determine the colonic mural enhancement in a rat model of inflammatory bowel disease (IBD) using gadofluorine M- and diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance (MR) imaging, and to correlate the degree of enhancement with the histopathologic severity of the disease. MATERIALS AND METHODS: : This study was approved by our hospital's institutional animal care and use committee. A total of 44 rats with 2 grades (mild, n = 17; and severe, n = 27) of dinitrobenzene sulfonic acid (DNBS)-induced IBD and 13 rats without IBD, were examined using a 2.4-T, small animal MR scanner. T2- and T1-weighted MR images were acquired, and sequential T1-weighted MR imaging was then performed immediately and again 15, 45, 60, and 90 minutes, and 24 hours after intravenous -injection of either gadofluorine M- or Gd-DTPA (0.1 mmol Gd/kg body weight). The signal-to-noise ratios and enhancement ratios (ER) of the colon wall were measured. For paired and group comparisons of the histopathology and MR imaging data, the Wilcoxon- and the Mann-Whitney U tests were used, and the multifactorial analysis of variance test was used to compare the time courses of the ERs. RESULTS: : Gadofluorine M injection resulted in significant differences in the ER of noninflamed, mildly inflamed, and severely inflamed colon wall at any time up to 24 hours after contrast injection (ER at 24 hours 2.0 ± 1.2; 10.1 ± 4.3; and 49.7 ± 10.8, respectively; P < 0.01). After Gd-DTPA injection, significant differences were observed in the ER of inflamed and noninflamed bowel at 15, 45, and 60 minutes (P < 0.01); however, no significant differences in mildly and severely inflamed bowel were observed at any time. In contrast to Gadofluorine M, there was no prolonged contrast enhancement in the inflamed colon wall after intravenous injection of Gd-DTPA (ER at 24 hours 1.6 ± 1.3; 3.4 ± 2.7; and 3.3 ± 1.6, respectively; n.s.). CONCLUSIONS: : Gadofluorine M-enhanced MR imaging shows a higher correlation of the wall enhancement and histopathology grading in an IBD rat model than does Gd-DTPA-enhanced imaging.

In vivo validation of a therapy planning system for laser-induced thermotherapy (LITT) of liver malignancies.

PURPOSE: In situ ablation is increasingly being used for the treatment of liver malignancies. The application of these techniques is limited by the lack of a precise prediction of the destruction volume. This holds especially true in anatomically difficult situations, such as metastases in the vicinity of larger liver vessels. We developed a three-dimensional (3D) planning system for laser-induced thermotherapy (LITT) of liver tumors. The aim of the study was to validate the system for calculation of the destruction volume. METHODS: LITT (28 W, 20 min) was performed in close contact to major hepatic vessels in six pigs. After explantation of the liver, the coagulation area was documented. The liver and its vascular structures were segmented from a pre-interventional CT scan. Therapy planning was carried out including the cooling effect of adjacent liver vessels. The lesions in vivo and the simulated lesions were compared with a morphometric analysis. RESULTS: The volume of lesions in vivo was 6,568.3 ± 3,245.9 mm(3), which was not different to the simulation result of 6,935.2 ± 2,538.5 mm(3) (P = 0.937). The morphometric analysis showed a sensitivity of the system of 0.896 ± 0.093 (correct prediction of destructed tissue). The specificity was 0.858 ± 0.090 (correct prediction of vital tissue). CONCLUSIONS: A 3D computer planning system for the prediction of thermal lesions in LITT was developed. The calculation of the directional cooling effect of intrahepatic vessels is possible for the first time. The morphometric analysis showed a good correlation under clinical conditions. The pre-therapeutic calculation of the ablation zone might be a valuable tool for procedure planning.

Evaluation of possible drug-drug interaction between gadoxetic acid and erythromycin as an inhibitor of organic anion transporting peptides (OATP).

PURPOSE: To evaluate if erythromycin compromises liver-specific enhancement of gadoxetic acid; both compounds competing in organic anion transporting peptides (OATP) -mediated hepatocytic uptake. MATERIALS AND METHODS: The study was approved by institutional review board. Twelve healthy subjects (nine men, three woman; mean age, 38.7 years) were examined twice by MR imaging with prior administration of NaCl solution (placebo) or 1000 mg of erythromycin following a randomized sequence. Gadoxetic acid (0.025 mmol/kg body weight) was administered 15 min after the end of infusions. Pre- and 20 min postcontrast two-dimensional gradient-recalled-echo sequences were acquired. Relative enhancements of liver parenchyma and ratio of means were calculated from signal intensity measurements. Plasma levels of gadoxetic acid and erythromycin were determined and given in geometric means and coefficients of variation (CV). RESULTS: Concentration of erythromycin directly after end of infusion was 13.9 mg/L (CV 14.9%). Gadolinium plasma concentrations 5 min after gadoxetic acid administration were 138.7 µmol/L (CV 20.4%) after erythromycin infusion and 129.6 µmol/L (CV 22.8%) after placebo. Mean relative enhancements of liver parenchyma were 88.1 (SD 24.9%) after erythromycin infusion and 92.6 (SD 17.9%) after placebo. Ratio of relative enhancements was 0.951 (95% confidence interval, 0.833; 1.061; statistically not significant). CONCLUSION: Coadministration of erythromycin has no effect on gadoxetic acid enhanced liver MR imaging.

Bipolar radiofrequency ablation for nodular thyroid disease--ex vivo and in vivo evaluation of a dose-response relationship.

BACKGROUND: The prevalence of thyroid nodules ranges between 2% and 60% depending on the population studied. However, minimally invasive procedures like radiofrequency ablation (rfA) are increasingly used to treat tumors of parenchymatous organs, and seem to be suitable for singular thyroid nodules as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose-response relationship for rfA of thyroid nodules. MATERIAL AND METHODS: Thermal lesions were induced in healthy porcine thyroid glands ex vivo (n=110) and in vivo (n=10) using a bipolar radiofrequency system; rf was applied in a power range of 10-20 watts. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The transversal and axial lesion diameters were measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. RESULTS: The inducible lesion volumes were between 0.91±0.71 cm(3) at 20W and 2.80±0.85 cm(3) at 14W. The maximum temperatures after rf ablation were between 44.0±9.7°C and 61.6±13.9°C at a distance of 5 mm and between 30.0±8.6°C and 53.5±8.6°C at a distance of 10 mm from the applicator. The histochemical analysis demonstrates a complete loss of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. CONCLUSION: This study is the first to demonstrate a dose-response relationship for rfA of thyroid tissue. rfA is suitable for singular thyroid nodules and induces reproducible, clinically relevant lesions with irreversible cell damage in an appropriate application time.

Outcome of patients with acute sigmoid diverticulitis: multivariate analysis of risk factors for free perforation.

BACKGROUND: Sigmoid diverticulitis (SD) is common in the West; its incidence is increasing as the average age of the population increases. The aim of this study was to assess the clinical outcomes of patients with acute SD and to determine whether emergency operation was associated more often with previous episodes of acute diverticulitis. METHODS: All consecutive patients admitted for acute SD were recruited prospectively over an 11-year period from January 1998 to December 2008. Multiple logistic regression was used to identify risk factors for free perforation. RESULTS: We included 934 patients (490 men and 444 women; median age, 59.2 years): 450 (48.2%) presented for their first SD episode and 484 (51.8%) had a prior history of SD. Free perforation occurred in 152 patients: during the first episode of SD in 114 patients (25.3%), during the second in 29 (12.7%), during the third in 8 (5.9%), and during the fifth in 1 patient (0.9%; P < .001). No patient with >5 previous episodes of SD had free perforation. All 152 patients with free perforation required emergent operative intervention. After initial conservative therapy in 782 patients, 82 required early elective operative intervention owing to exacerbation of infection under antibiotic treatment. Late elective colectomy was performed in 299 patients during the inflammation-free interval, and operative intervention was recommended in 345 patients owing to complicated diverticulitis. Uncomplicated SD in 56 patients was managed conservatively. Comorbidity (>1 disorder) and the first episode of SD were identified as risk factors for free perforation on multiple logistic regression. CONCLUSION: The risk of free perforation in acute SD decreases with the number of previous episodes of SD. The first episode thus is the most dangerous for a free perforation. The indication for colectomy should not be made based on the potential risk of free perforation.

Preoperative CT staging in sigmoid diverticulitis--does it correlate with intraoperative and histological findings?

PURPOSE: This study was designed to evaluate whether the computed tomography (CT) reflects the extent of the inflammation in sigmoid diverticulitis (SD) in order to draw conclusions for selecting the appropriate treatment. METHODS: Two hundred four patients who underwent resection for SD from January 2003 to December 2008 were included. The preoperative CT stage was compared with intraoperative and histological findings. Patients were classified into phlegmonous (Hansen-Stock IIa), abscess-forming (HS IIb), and free perforated (HS IIc) forms of SD. Patients with a recurrent type of diverticulitis were excluded. RESULTS: In the phlegmonous type (HS IIa; n = 75), we found a correlation with the preoperative stage in 52% (intraoperative) and 56% (histological), an understaging in 12% (intraoperative) and 11% (histological), and an overstaging in 36% (intraoperative) and 33% (histological). In the abscess-forming type (HS IIb, Hinchey I/II; n = 87), we found conformity in 92% (intraoperative) and 90% (histological), understaging in 3% (intraoperative) and 0% (histological), and overstaging in 5% (intraoperative) and 10% (histological). In the presence of a free perforation (HS IIc, Hinchey III/IV; n = 42), we saw conformity in 100% (intraoperative and histological). The positive predictive value for correctly diagnosing of phlegmonous type (HS IIa), abscess-forming type (HS IIb), and free perforation (HS IIc) by CT was intraoperatively (histologically) 52% (56), 92% (90), and 100% (100), respectively. CONCLUSIONS: The CT is one of the most accurate methods for staging in SD. However, in the phlegmonous type (HS IIa), it leads to an overestimation of the findings in every third patient. It must be clarified whether this pronounced low inflammation should really be regarded as a complicated form of SD. In contrast, the abscess-forming (HS IIb) and free perforated (HS IIc) type of complicated SD is very well reflected by CT.

[A young man with chronic diarrhea and epigastric pain]. / Junger Mann mit chronischer Diarrhö und Oberbauchschmerzen.

CASE REPORT: A 26-year-old man was admitted to hospital with a 6-month history of diarrhea and abdominal pain. Before admission, upper and lower gastrointestinal endoscopy had shown a mild erosive duodenitis and the patient was started on a proton pump inhibitor. Physical examination and laboratory tests on admission were not constructive. In addition, repeated gastrointestinal endoscopy, cross-sectional imaging and neuroendocrine markers did not point to a specific etiology. Therefore, as a provocation test, the proton pump inhibitor therapy was discontinued. Discontinuation resulted in a progression of the patient's symptoms and an endoscopic detection of duodenal ulcers. Except for the normal serum gastrin levels, this constellation was suggestive of a gastrinoma, so that further investigations were initiated. Subsequently, the diagnosis could be confirmed and the gastrinoma located. After successful pancreaticoduodenectomy, the patient was symptom-free. CONCLUSION: As part of a systematic investigation on chronic diarrhea, the work-up for neuroendocrine causes can play an important role. In this context, it should be kept in mind that some gastrinoma patients present without an elevation of serum gastrin levels. Regardless of a negative gastrin test, a typical symptom constellation should therefore prompt further investigations.

Microscopic findings in sigmoid diverticulitis--changes after conservative therapy.

INTRODUCTION: The indications for prophylactic surgery for phlegmonous and covered perforated type of acute sigmoid diverticulitis (SD) are currently matters of debate, and a more conservative approach has been advocated. However, it has not yet been clarified to what extent CT findings indicative of acute SD correlate with histological findings, and it is still uncertain how these findings change in the time interval between initial antibiotic treatment and late elective surgery. The aim of this study was to record time-course changes of inflammation in phlegmonous and abscess-forming diverticulitis after conservative treatment in order to check the indication for surgery. MATERIAL AND METHODS: This study included all patients who underwent surgery for CT morphologically phlegmonous and covered perforated SD from January 2002 to June 2007. Two groups were formed to record time-course changes: early elective surgery (7-10 days after antibiotic treatment) and late elective surgery (4-6 weeks after conservative treatment). Exclusion criteria were emergency interventions, free perforations (Hinchey III and IV), recurrent inflammations, and contrast allergy. The extent of the inflammation recorded preoperatively by CT scan was compared with histological findings. RESULTS: A total of 257 patients (142 male and 115 female; mean age, 56.6 years) underwent surgery (116 early elective and 141 late elective) for phlegmonous and covered perforated SD. Phlegmonous SD was seen in 127 cases and covered perforated SD in 130 cases. In the phlegmonous type of SD, early surgery led to conformity with the preoperative stage in 56%, to more extensive findings in 11%, and to subsided inflammation in 33%. Late surgery led to conformity in 0% and to signs of subsided inflammation in 100%. In the covered perforated type of SD, early surgery led to conformity in 90%, to subsided inflammation in 10%, and to milder manifestation in 0%. In contrast, late surgery here led to conformity in 26% of the cases and to subsided inflammation in 74%. Considerable histological changes can be detected under conservative therapy. The acute inflammation subsides under antibiotic therapy as awaited. It must be clarified whether the phlegmonous form of SD should, in principal, be regarded as an indication for surgery, since it shows early and nearly complete regression of the inflammation. Otherwise, the covered perforated type of SD still shows marked inflammatory changes after conservative therapy in a high percentage of patients and should thus preferably be treated by surgery. However, the clinical appearance of the patient with sigmoid diverticulitis still remains the most important part of decision making.

Qualitative and quantitative evaluation of hepatocellular carcinoma and cirrhotic liver enhancement using Gd-EOB-DTPA.

OBJECTIVE: The objective of our study was to prospectively evaluate quantitatively and qualitatively the enhancement patterns of cirrhotic liver tissue and hepatocellular carcinoma (HCC) after administration of the hepatocyte-specific contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) on dynamic MRI and to determine the time point of maximum liver-to-lesion contrast. SUBJECTS AND METHODS: Twenty-five patients with HCC in liver cirrhosis underwent 1.5-T MRI. T2-weighted turbo spin-echo and T1-weighted 3D gradient-echo sequences before and between 15 seconds and 20 minutes after the injection of 10 mL of Gd-EOB-DTPA were performed. Signal-to-noise ratios (SNRs) of liver parenchyma and liver-to-lesion contrast-to-noise ratios (CNRs) were calculated and plotted over time. Enhancement patterns of HCC were characterized qualitatively by two radiologists. RESULTS: The SNR of liver parenchyma increased significantly at 15 seconds and 60 seconds after contrast injection and remained stable thereafter. HCC showed positive CNR during the arterial phase and increasingly negative CNR during the further time course (p < 0.05). The maximum absolute CNR was found at 20 minutes after contrast injection. There was no correlation between the degree of enhancement at any time point and tumor grade. On qualitative evaluation, 16 HCCs showed arterial enhancement with early washout, and five showed arterial enhancement with late washout. In the remaining four HCCs, enhancement persisted until 20 minutes. Lesion conspicuity at 20 minutes after contrast injection was at least equal to or higher than it was on the remaining sequences in 19 of the 25 patients. CONCLUSION: After Gd-EOB-DTPA injection, most HCCs showed typical arterial enhancement with early washout. Liver-to-lesion contrast was best at 20 minutes.

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).

Interspecies difference in liver-specific functions and biotransformation of testosterone of primary rat, porcine and human hepatocyte in an organotypical sandwich culture.

Interspecies difference is an important issue in toxicology research. We compared the potential in vitro metabolism of human, porcine and rat hepatocytes over 2 weeks in culture in an organotypical culture model which reflects the in vivo situation. All three species show similar LDH-rates. Albumin measurements showed that rat cells are about twice as active as human and porcine hepatocytes. The ethoxyresorufin-O-deethylase (EROD) activity of the rat hepatocytes is with about 14 microU/10(6)cells distinctly higher than those of porcine and human cells (1.8 and 0.5 microU/10(6)cells respectively), furthermore, the activity of the rat EROD increases slightly during the prolonged time in culture, whereas those of porcine and human enzymes slightly decrease. Concerning ethoxycoumarin-O-deethylase (ECOD), the enzyme activities are found to be in three different ranges where rat cells show the highest activity with 66 microU/10(6)cells, porcine hepatocytes exhibit an activity of about 23 microU/10(6)cells, and human activity is lowest with 0.7 microU/10(6)cells. All three species show a similar decreasing trend of ECOD during the period of study. Regarding the biotransformation of testosterone, human and porcine liver cells form three major metabolites whereas rat cells form a mixture of all measured metabolites. Hence, in vitro metabolism using porcine hepatocytes would be much more scientific sense than one using rat hepatocytes since the metabolic pathways are much closer to human metabolism.