Integrin αvß3-targeted dynamic contrast-enhanced magnetic resonance imaging using a gadolinium-loaded polyethylene gycol-dendrimer-cyclic RGD conjugate to evaluate tumor angiogenesis and to assess early antiangiogenic treatment response in a mouse xenograft tumor model.

The purpose of this study was to validate an integrin αvß3-targeted magnetic resonance contrast agent, PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2, for its ability to detect tumor angiogenesis and assess early response to antiangiogenic therapy using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Integrin αvß3-positive U87 cells and control groups were incubated with fluorescein-labeled cRGD-conjugated dendrimer, and the cellular attachment of the dendrimer was observed. DCE MRI was performed on mice bearing KB xenograft tumors using either PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 or PEG-G3-(Gd-DTPA)6-(cRAD-DTPA)2. DCE MRI was also performed 2 hours after anti-integrin αvß3 monoclonal antibody treatment and after bevacizumab treatment on days 3 and 6t. Using DCE MRI, the 30-minute contrast washout percentage was significantly lower in the cRGD-conjugate injection groups. The enhancement patterns were different between the two contrast injection groups. In the antiangiogenic therapy groups, a rapid increase in 30-minute contrast washout percentage was observed in both the LM609 and bevacizumab treatment groups, and this occurred before there was an observable decrease in tumor size. The integrin αvß3 targeting ability of PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 in vitro and in vivo was demonstrated. The 30-minute contrast washout percentage is a useful parameter for examining tumor angiogenesis and for the early assessment of antiangiogenic treatment response.

Delineation of the watershed between right and left hepatic arterial territories with carbon dioxide-enhanced ultrasonography.

PURPOSE: To delineate the watersheds between hepatic arterial territories and their variations with the use of CO(2)-enhanced ultrasonography (US) and to compare the results with segmental anatomy as described by Couinaud. MATERIALS AND METHODS: From March 2004 to January 2005, this study recruited 31 patients (18 men and 13 women; mean age, 63 years; range, 47-77 y) with hepatocellular carcinoma (HCC) who were scheduled to receive transarterial chemoembolization. After serial angiography, CO(2)-enhanced US was performed with catheters superselectively inserted into the hepatic arteries. The territorial divisions between hepatic arteries were compared with the anatomic courses of the middle and left hepatic veins. Data from 17 patients were used to assess the vascular territories of the right and left lobe and data from the remaining 14 patients were used to assess those of the left medial and left lateral segments. RESULTS: Mapped arterial territories exactly matched Couinaud segments in 17 of 31 patients (54.8%). They did not coincide with Couinaud segments in 45.2% of patients with HCC. Crossover enhancement was noted over the right and left lobes and over the left medial and lateral segments in seven patients each. Two tumors located exactly in watershed areas showed CO(2) enhancement across the hepatic vein. CONCLUSIONS: CO(2)-enhanced US is useful to delineate arterial territories of hepatic segments and show crossover arterial supply compared with Couinaud segments. Awareness of crossover arterial supply is important for chemoembolization, segmental chemoembolization, hepatic arterial infusion, sonography, and surgery.

Use of two-dimensional multiple-slice magnetic resonance hydrography for diagnosis of hepatic hemangiomas and cysts.

BACKGROUND/PURPOSE: Although hepatic hemangiomas and cysts display very high signal intensities on conventional T2 images, their appearances are quite distinct using magnetic resonance hydrography (MRH). We examined the feasibility of using MRH in distinguishing hepatic cysts from hemangiomas. METHODS: We recruited 97 patients with hepatic hemangiomas and 65 with hepatic cysts. All patients underwent magnetic resonance imaging (including two-dimensional multiple slice MRH, TR/TE: 8000/800) and the results were reviewed independently by two radiologists. The signal intensities of the lesions were measured. For each lesion, the variation in signal to noise ratio between MRH and the fat-saturated T2-weighted images was calculated, and the results were validated using a receiver operating characteristic curve. RESULTS: There was a significant difference between the signal to noise ratio of hepatic hemangiomas and cysts using MRH (p < 0.001). This difference could be identified by visual inspection. The receiver operating characteristic curve revealed that the ideal cut-off value for the signal intensity reduction ratio between hepatic cysts and hemangiomas was -0.1. Using this ratio, the derived sensitivity was 95.4%, specificity 99.0%, and accuracy 99.7%. CONCLUSION: Hepatic hemangiomas and cysts have significantly different signal intensities on non-contrast two-dimensional multiple-slice MRH. This approach uses a non-invasive, reliable, and accurate imaging technique to differentiate the two diagnoses.

Differentiation of soft tissue benign and malignant peripheral nerve sheath tumors with magnetic resonance imaging.

PURPOSE: The objective of this study was to differentiate the magnetic resonance (MR) imaging appearance of benign peripheral nerve sheath tumors (PNSTs) from that of malignant PNSTs. MATERIALS AND METHODS: Twenty-six patients who underwent MR imaging and had a histologic diagnosis of benign (schwannoma, n=16; neurofibroma, n=1) or malignant (n=9) PNST were retrospectively reviewed. The size, location, shape, margin, and signal intensities of the tumors on precontrast and gadolinium-enhanced MR imaging were analyzed. In each patient, the presence or absence of split fat, target, and fascicular signs was determined. RESULTS: The mean size of the benign PNSTs (3.4 cm, S.D.=2.5 cm) was significantly smaller than that of the malignant tumors (8.2 cm, S.D.=3.1 cm) (P<.001). Seventeen (65.4%) of the 26 tumors were spindle shaped or ovoid (12 benign and 5 malignant tumors). Contiguity with specific nerves was identified in 15 (88.2%) of the 17 benign PNSTs but in none of the malignant tumors (P<.05). Well-defined margins were noted in all 17 benign PNSTs but in only 3 (33.3%) of the 9 malignant tumors (P<.001). Five (55.6%) of the 9 malignant PNSTs but none of the benign tumors showed signal intensity change in adjacent soft tissue (P<.05). There was no significant difference in signal intensity between the benign and malignant tumors on T(1)-weighted, T(2)-weighted, and contrast-enhanced MR images. The split fat and target signs were present more frequently in the benign PNSTs than in the malignant PNSTs (P<.05). CONCLUSIONS: Benign and malignant PNSTs are often spindle shaped. Recognition of contiguity with adjacent nerves, a well-defined margin, and the presence of the split fat sign may suggest benignity. Imaging features suggestive of malignancy can be a larger size and an infiltrative margin.

T2-weighted and T1-weighted dynamic superparamagnetic iron oxide (ferucarbotran) enhanced MRI of hepatocellular carcinoma and hyperplastic nodules.

BACKGROUND/PURPOSE: Iron oxide contrast medium (ferucarbotran) shortens both T1 and T2 relaxation time. We used the T2- and the T1-weighted dynamic ferucarbotran-enhanced magnetic resonance (MR) imaging to predict the histologic grade of hepatocellular carcinoma (HCC) and to distinguish HCC from hyperplastic nodules. METHODS: Forty-three patients with 48 representative hepatic lesions (13 well differentiated HCC, 19 moderately differentiated HCC, 4 poorly differentiated HCC, 12 hyperplastic nodules) were included in the study. T1-weighted image, T2-weighted turbo spin echo, and T2*EPI (echo-planar) images were obtained before and after ferucarbotran injection. The percentage T2 signal intensity loss (T2 PSIL) of the tumors was calculated at 5 minutes and 25 minutes after contrast injection. The enhancement in dynamic T1 images was interpreted by two independent radiologists. RESULTS: The T2 PSIL of well differentiated HCC was 39.5 +/- 8.23%, moderately differentiated HCC was 26.4 +/- 13.78%, poorly differentiated HCC was 4.4 +/- 9.42%, and hyperplastic nodules was 44.3 +/- 11.04%. Comparison of T2 PSIL showed significant differences in the three histologically graded HCCs (p < 0.001), but not between the well differentiated HCCs and hyperplastic nodules (p > 0.05). Delayed post-contrast (25 minutes) T2-weighted images were not necessary and shortened the examination time. In the post contrast dynamic T1 study, no significant differences between all the groups was seen. CONCLUSION: Ferucarbotran MR images help in differentiating the different histologic grades of HCC but T2 PSIL could not differentiate hyperplastic nodules from well differentiated HCC. Dynamic post contrast T1-weighted images provide no additional information.

Targeted tumor theranostics using folate-conjugated and camptothecin-loaded acoustic nanodroplets in a mouse xenograft model.

In this study, we aimed to validate the feasibility of receptor-targeted tumor theranostics with folate-conjugated (FA) and camptothecin-loaded (CPT) acoustic nanodroplets (NDs) (collectively termed FA-CPT-NDs). The ND formulation was based on lipid-stabilized low-boiling perfluorocarbon that can undergo acoustic droplet vaporization (ADV) under ultrasound (US) exposure. Conjugation of folate enhanced the selective delivery to tumors expressing high levels of folate receptor (FR) under mediation by the enhanced permeability and retention effect. In vitro and in vivo studies were performed using FR-positive KB and FR-negative HT-1080 cell lines and mouse xenograft tumor models. Simultaneous therapy and imaging were conducted with a clinical US imaging system at mechanical indices of up to 1.4 at a center frequency of 10 MHz. The results demonstrated that FA-CPT-NDs selectively attached to KB cells, but not HT-1080 cells. The targeted ADV caused instant and delayed damage via mechanical disruption and chemical toxicity to decrease the viability of KB cells by up to 45%, a much higher decrease than that achieved by the NDs without folate conjugation. The in vivo experiments showed that FR-mediated targeting successfully enhanced the EPR of FA-CPT-NDs in KB tumors mainly on the tumor periphery as indicated by immunofluorescence microscopy and US B-mode imaging. Treatments with FA-CPT-NDs at a CPT dose of 50 µg/kg inhibited the growth of KB tumors for up to six weeks, whereas treatment with NDs lacking folate produced a 4.6-fold increase in tumor volume. For HT-1080 tumors, neither the treatments with FA-CPT-NDs nor those with the NDs lacking folate presented tumor growth inhibition. In summary, FR-targeted tumor theranostics has been successfully implemented with FA-CPT-NDs and a clinical US unit. The ligand-directed and EPR-mediated accumulation provides active and passive targeting capabilities, permitting the antitumor effects of FA-CPT-NDs to be exerted selectively to FR-positive tumors and simultaneously providing targeted US imaging capabilities.

MR cholangiopancreatography: prospective comparison of 3-dimensional turbo spin echo and single-shot turbo spin echo with ERCP.

BACKGROUND AND PURPOSE: Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive technique for examination of the biliopancreatic tract. Respiratory-triggered 3-dimensional turbo spin echo (3DTSE RT) and breath-hold thick slab single-shot turbo spin echo (ssTSE BH) are both useful MRCP techniques. The purpose of this study was to compare these 2 sequences with endoscopic retrograde cholangiopancreatography (ERCP) in patients with biliary tract disease. METHODS: Forty four patients with suspected biliary obstruction were recruited to receive MRCP within 3 days before ERCP. MRCP was performed using both 3DTSE RT with maximum intensity projection images and ssTSE BH. ERCP was performed and assessed by 2 endoscopists. RESULTS: MRCP was successfully performed in all patients, whereas ERCP failed in 6 patients (13.6%). MRCP was effective in detecting the presence of choledocholithiasis in 13 of 14 patients, ERCP in 12 of 12, and 2 failed ERCP. MRCP was effective in detecting benign biliary obstruction in 18 of 19 patients, and ERCP in 15 of 15, but 4 patients failed ERCP and choledocholithiasis was misdiagnosed by MRCP in 1 patient. Both MRCP and ERCP correctly diagnosed malignant bile duct obstruction in 10 of 11 patients, and both misdiagnosed that condition as benign obstruction in 1 patient. There was no significant difference between MRCP and successful ERCP in detecting lesions. MRCP was significantly better than ERCP when both successful and failed ERCP were encountered (p = 0.0498). Both 3DTSE RT and ssTSE BH produced the same results in depicting the biliary ducts and lesions in 37 patients (84.1%). Four patients (9.1%) showed better images on 3DTSE RT, whereas 3 patients (6.8%) showed better images on ssTSE BH. CONCLUSIONS: 3DTSE RT and the ssTSE BH were complementary to each other in MRCP studies. Using these 2 techniques, MRCP has a high successful rate and diagnostic accuracy when compared with ERCP in detecting bile duct disease.

Characterization of hyperintense nodules on T1-weighted liver magnetic resonance imaging: comparison of Ferucarbotran-enhanced MRI with accumulation-phase FS-T1WI and gadolinium-enhanced MRI.

BACKGROUND: T1-weighted (T1W) hyperintense nodules against a background of cirrhosis are diagnostically challenging in daily practice. All regenerative nodules, dysplastic nodules and hepatocellular carcinoma (HCC) might present hyperintense on T1W imaging (T1WI), so T1W hyperintense nodules cannot be definitively characterized as dysplastic nodules or HCC before biopsy, resection or transplantation. The purpose of our study was to evaluate Ferucarbotran-enhanced Magnetic Resonance Imaging (MRI) with accumulation-phase fat suppression T1-weighted imaging (FS-T1WI) in comparison with gadolinium-enhanced MRI for characterization of hyperintense nodules on unenhanced T1WI within cirrhotic liver. METHODS: Two separate groups of patients with histologically-proven T1W hyperintense nodule on MRI were retrospectively identified. The Ferucarbotran group consisted of 17 T1W hyperintense nodules in 12 patients. The gadolinium group consisted of 22 T1W hyperintense nodules in 21 patients. All of the patients had liver cirrhosis. Finally, 11 HCC nodules, and six benign nodules were included in the Ferucarbotran group; 15 HCC nodules and seven benign nodules were included in the gadolinium group. RESULTS: With the conventional criteria, in the gadolinium-enhanced group, the sensitivity, specificity, and accuracy were 53%, 100%, and 73%, respectively. Using the conventional criteria in the Ferucarbotran group, the sensitivity, specificity, and accuracy were 73%, 100%, 82%, respectively. Using the conventional criteria plus hyperintense on the accumulation-phase FS-T1WI in the Ferucarbotran group for characterization of the T1W hyperintense nodules, the sensitivity, specificity, and accuracy were 100%, 83%, 94%, respectively. The sensitivity of Ferucarbotran-enhanced MR with accumulation-phase FS-T1WI was better than that of gadolinium-enhanced MRI (p=0.01). CONCLUSION: Ferucarbotran-enhanced MR imaging with accumulation-phase FS-T1WI is superior to gadolinium-enhanced MRI in characterization of T1W hyperintense nodules within cirrhotic liver. T1W hyperintense nodule within cirrhotic liver depicting hyperintense on Ferucarbotran-enhanced accumulation-phase FS-T1WI should be investigated aggressively.

Dynamic contrast-enhanced folate-receptor-targeted MR imaging using a Gd-loaded PEG-dendrimer-folate conjugate in a mouse xenograft tumor model.

PURPOSE: The purpose of this study is to validate a folate-receptor (FR)-targeted dendrimer, PEG-G3-(Gd-DTPA)11-(folate)5, for its ability to detect FR-positive tumors, by using dynamic contrast-enhanced MRI. PROCEDURES: KB cells, FR siRNA knockdown KB cells, and FR negative HT-1080 cells, were incubated with fluorescein-labeled dendrimer and their cellular uptake was observed. Dynamic contrast-enhanced MRI was performed on mice-bearing KB and HT-1080 tumors and the enhancement patterns and parameters were analyzed. RESULTS: Green fluorescence was found in the KB cells in the cellular uptake experiment, but was not seen in other settings. In the dynamic contrast-enhanced MRI, the 30-min washout percentage was -4 +/- 18% in the KB tumors and 39 +/- 23% in the HT-1080 tumors. A 17% cut-off point gave a sensitivity of 94.4% and a specificity of 93.8%. CONCLUSIONS: We have demonstrated the targeting ability of PEG-G3-(Gd-DTPA)11-(folate)5 in vitro and in vivo. A 17% cut-off point for a 30-min washout percentage can be a useful parameter for the diagnosis of FR-positive tumors.

Correlation between the bone marrow blood perfusion and lipid water content on the lumbar spine in female subjects.

PURPOSE: To assess the marrow lipid water ratio (LWR) and spectral line width (LW) of lumbar vertebra by proton MR spectroscopy ((1)H MRS) and correlate with the marrow blood perfusion (MBP) by contrast-enhanced dynamic MRI (dMRI) in female subjects. MATERIALS AND METHODS: A total of 50 female subjects were included. Single-voxel (1)H MRS was measured at the L3 vertebrae. In the dMRI study, the maximum enhancement percentage (E(max)) and enhancement slope were calculated from time-intensity curves. Pearson's correlation was calculated to explore the association of (1)H MRS, age, and perfusion parameters. Partial correlation was then used to control confounder effect. RESULTS: LWR was negatively correlated with E(max) (r = -0.72; P < 0.0001), but positively correlated with age (r = 0.63; P < 0.0001). Lipid LW was negatively correlated with age (r = -0.33; P <0.05), but positively correlated with E(max) (r = 0.4; P < 0.05). After adjusting for the age effect by partial correlation, marrow LWR still negatively correlated with E(max) (r = -0.63; P < 0.0001). After adjusting for the E(max) effect, marrow LWR still positively correlated with age (r = 0.37; P < 0.05). CONCLUSION: After controlling the age factor, the LWR and water LW has significant negative correlation with vertebral BMP. Further investigation is needed to explore the relationship between bone marrow fat metabolism and angiogenesis.

Transcatheter arterial chemoembolization in patients with hepatocellular carcinoma and coexisting hepatic cavernous hemangioma.

We investigated the consequence of repeated transcatheter arterial chemoembolization (TACE) for coexisting small hepatic hemangioma in the treatment of patients with hepatocellular carcinomas and describe the imaging features of embolized hemangioma on the follow-up Lipiodol CT and MR. Six of 431 patients with biopsy-confirmed hepatocellular carcinomas, who underwent TACE, also had seven small hepatic cavernous hemangiomas (0.8 approximately 2.3 cm) in the same area of embolization. All six patients underwent repeated TACE All lesions were evaluated with CT and/or MR for the post-treatment follow-up. The outcomes and imaging features of these embolized hemangiomas were reviewed for the change of tumor size, Lipiodol deposition, enhancing pattern as well as embolization complications. Six of the seven hemangiomas did not depict changes in the size or enhancement pattern without being ablated. One hemangioma showed a decrease in size, but still persisted after TACE. All of the hemangiomas showed Lipiodol deposition for 2 approximately 15 months, in which five hemangiomas depicted irregular rim patterns. There is no complication caused by the procedures. The differentiation of small hepatic hemangiomas from viable HCC is important in the post-TACE follow-up to avoid unnecessary repeated embolization.

Magnetic resonance imaging appearance of well-differentiated hepatocellular carcinoma.

OBJECTIVE: To investigate the magnetic resonance imaging (MRI) features of well-differentiated hepatocellular carcinoma (HCC). METHODS: We reviewed the MRI of 32 patients with 33 pathologically confirmed well-differentiated HCC. The MRI protocol included T2-weighted imaging with and without fat saturation, dual-phase T1-weighted imaging, and gadolinium-enhanced dynamic study. The signal intensity of each lesion was categorized as hyperintense, isointense, and hypointense with reference to the surrounding liver parenchyma. RESULTS: Thirty-one (93.9%) of 33 well-differentiated HCC were demonstrated on the MRI. The remaining 2 were isointense in all magnetic resonance sequences and, therefore, could not be identified. Most of them were hyperintense (n = 15 [45.4%]) or isointense (n = 16 [48.5%]) on T1-weighted imaging, and hyperintense (n = 12 [36.4%]) or isointense (n = 17 [51.5%]) on T2-weighted imaging. On the dynamic study, 17 lesions (51.5%) were enhanced. CONCLUSIONS: MRI may identify most well-differentiated HCC; however, the imaging appearance is diverse. Biopsy should be performed if magnetic resonance study is inconclusive.

Arthritis imaging using a near-infrared fluorescence folate-targeted probe.

A recently developed near-infrared fluorescence-labeled folate probe (NIR2-folate) was tested for in vivo imaging of arthritis using a lipopolysaccharide intra-articular injection model and a KRN transgenic mice serum induction mouse model. In the lipopolysaccharide injection model, the fluorescence signal intensity of NIR2-folate (n = 12) and of free NIR2 (n = 5) was compared between lipopolysaccharide-treated and control joints. The fluorescence signal intensity of the NIR2-folate probe at the inflammatory joints was found to be significantly higher than the control normal joints (up to 2.3-fold, P < 0.001). The NIR2-free dye injection group showed a persistent lower enhancement ratio than the NIR2-folate probe injection group. Excessive folic acid was also given to demonstrate a competitive effect with the NIR2-folate. In the KRN serum transfer model (n = 4), NIR2-folate was applied at different time points after serum transfer, and the inflamed joints could be detected as early as 30 hours after arthritogenic antibody transfer (1.8-fold increase in signal intensity). Fluorescence microscopy, histology, and immunohistochemistry validated the optical imaging results. We conclude that in vivo arthritis detection was feasible using a folate-targeted near-infrared fluorescence probe. This receptor-targeted imaging method may facilitate improved arthritis diagnosis and early assessment of the disease progress by providing an in vivo characterization of active macrophage status in inflammatory joint diseases.

Detection of dysplastic intestinal adenomas using a fluorescent folate imaging probe.

Macrophages have long been recognized as a prominent component of tumors. Activated macrophages overexpress folate receptors and we used this phenomenon to image inflammatory reactions in colon dysplasia using a fluorescent folate probe (FFP). APC(Delta468) mice injected with FFP showed fluorescent adenomas (target-to-background ratio, adenoma vs. adjacent normal mucosa, of 2.46 +/- 0.41), significantly higher (p < .001) than adenomas in animals injected with a non-folate-containing control probe. Fluorescence-activated cell-sorting analysis revealed a 3-fold higher content of Mac1-positive cells in colonic adenomas compared with normal adjacent mucosa (6.8% vs. 2.2%), and confirmed the source of FFP-positive cells to be primarily an F4/80-positive macrophage subpopulation. Taken together, these results indicate that probe potentially can be used to image dysplastic intestinal adenomas in vivo.

Peritumoral fat-spared area is well correlated with the presence of temporal peritumoral enhancement in hepatic hemangioma in fatty liver.

PURPOSE: To assess the relationship between temporal peritumoral enhancement and peritumoral focal fat sparing adjacent to hepatic hemangiomas. MATERIALS AND METHODS: On the basis of MRI and sonographic imaging follow-up, 51 hepatic hemangiomas were identified in 37 patients, who had both hepatic hemangiomas and focal fat-sparing areas in fatty liver. Among them, 36 tumors were associated with peritumoral focal fat spares. The association between the temporal peritumoral enhancement in the early arterial phase of dynamic MRI and peritumoral fat sparing in the same hemangioma was investigated. Furthermore, the configuration of the temporal peritumoral enhancement was correlated with that of the peritumoral focal fat-sparing area. We used Chi square and Fisher's exact test for statistic analysis. RESULTS: A total of 31 out of 36 hemangiomas (86.1%) showed both peritumoral focal fat spares and temporal peritumoral enhancement. The presence of temporal peritumoral enhancement is significantly related to that of peritumoral focal fat-sparing (P < 0.001). A total of 21 of the 31 tumors (67.7%) presented with similar configuration of the peritumoral focal fat-sparing area and temporal peritumoral enhancement area with respect to size and shape. The remaining 10 hemangiomas showed similar shape but slightly different size in these two imaging characteristics. CONCLUSION: Temporal peritumoral enhancement seen in hepatic hemangioma might be related to focal fatty sparing adjacent to the hemangiomas.

Imaging reactive oxygen species in arthritis.

Reactive oxygen species (ROS) have been shown to play a role in the pathogenesis of arthritides. Luminol was used as the primary reporter of ROS and photons resulting from the chemiluminescence reaction were detected using a super-cooled CCD photon counting system. Luminol was injected intravenously into groups of animals with different models of arthritis. Imaging signal correlated well with the severity of arthritis in focal and pan-arthritis as determined by histological measurement of ROS by formazan. Measurements were highly reproducible, sensitive, and repeatable. In vivo chemiluminescence imaging is expected to become a useful modality to elucidate the role of ROS in the pathogenesis of arthritides and in determining therapeutic efficacy of protective therapies.

Portal hemodynamic changes after hepatocyte transplantation in acute hepatic failure.

Hepatocyte transplantation has been proposed as an alternative for rescuing patients with acute hepatic failure. However, portal hemodynamic changes and issues of safety after hepatocyte transplantation in acute hepatic failure have not been systemically evaluated because of the lack of a suitable experimentation system. In this study, we created a novel spring-guidewire introducer needle to simplify the technique for long-term portal cannulation in F-344 rats. The portal cannula was capable of being used for blood sampling, infusion of hepatocytes, and measurement of portal hemodynamic changes. One week after portal cannulation, rats were injected with D-galactosamine (1.35 g/kg, i.p.) to induce hepatic failure. Hepatocytes (2 x 10(7)) were infused intraportally 24-26 h after induction of liver injury. Portal pressures were recorded for up to 60 min after hepatocyte transplantation. Intraportal infusion of 2 x 10(7) hepatocytes caused an instantaneous onset of portal hypertension. The magnitude of the rise in portal pressure was similar in both normal rats and rats with acute hepatic failure (33.0 +/- 7.1 vs. 37.7 +/- 0.5 mm Hg; p = 0.23). However, the resolution rate of portal hypertension was remarkably delayed in rats with acute hepatic failure, and the portal pressure was significantly higher than that in normal rats 60 min after hepatocyte transplantation (25.0 +/- 2.8 vs. 14.5 +/- 2.4 mm Hg; p = 0.007). In conclusion, we have established a simple new technique for long-term portal cannulation of rats. Our studies provide critical insights into the delayed resolution of portal hemodynamics after hepatocyte transplantation in subjects with acute hepatic failure.

Relationship between vertebral bone marrow blood perfusion and common carotid intima-media thickness in aging adults.

PURPOSE: To evaluate the relationship between vertebral marrow blood perfusion and common carotid intima-media thickness (IMT) in aging adults. MATERIALS AND METHODS: An age- and sex-matched case control study was conducted. Subjects were contacted and enrolled voluntarily according to a database containing 2,258 cases that received carotid ultrasonography examination at our hospital in the previous two years. Forty-three pairs of subjects (56 male, 30 female; aged 44-85 years, average 63 years) underwent dynamic contrast-enhanced magnetic resonance (MR) study of the lumbar spine. The average peak enhancement percentage of the second to fourth lumbar vertebrae was used to represent the vertebral marrow perfusion status for each subject. The common carotid IMT, presence of plaque, peak enhancement percentage, body mass index (BMI), systolic and diastolic blood pressure, serum total cholesterol, high-density lipoprotein (HDL), and triglycerol levels were acquired for statistical analysis. RESULTS: The average peak enhancement percentage was significantly lower in thickened IMT group compared to the normal IMT group (73 +/- 23 vs. 90 +/- 27, P=0.0023). The carotid IMT inversely correlated with vertebral peak enhancement percentage (r=-0.33, P=0.0018). The vertebral peak enhancement percentage was significantly lower in subjects with presence of any carotid plaque (P=0.032). Common carotid IMT was the only significant variable that was negatively associated with vertebral marrow perfusion after adjusting for the effect of sex, age, blood pressure, BMI, total cholesterol, HDL, and triglycerol level in linear regression model (P=0.008). CONCLUSION: Our data demonstrate the negative association between vertebral marrow blood perfusion and common carotid IMT. These results suggest that common carotid IMT may provide the information of tissue perfusion status of the vertebral bone marrow.

Temporal peritumoral enhancement of hepatic cavernous hemangioma: findings at multiphase dynamic magnetic resonance imaging.

OBJECTIVE: To evaluate the occurrence rate of temporal peritumoral enhancement associated with hepatic cavernous hemangiomas and to correlate that with the speed of intratumoral contrast enhancement and tumor volume. METHODS: Dynamic magnetic resonance imaging (MRI) of 69 consecutive patients with 136 hemangiomas was reviewed for peritumoral enhancement. Tumor volume was estimated by the largest diameter on T2-weighted images. Speed of intratumoral contrast enhancement was determined by portal phase image and was categorized as rapid (>75% of tumor volume), intermediate (25%-75% of tumor volume), or slow (<25% of tumor volume). RESULTS: Temporal peritumoral enhancement was found in 37 (26.6%) of 136 hemangiomas. It was more common in hemangiomas with rapid enhancement (30 of 67 cases [44.8%]) than in those with intermediate (3 of 22 cases [13.6%]) and slow (4 of 47 cases [8.5%]) enhancement (P < 0.05). There was no statistically significant relation between lesion size and presence of temporal peritumoral enhancement (P > 0.05). CONCLUSIONS: Temporal peritumoral enhancement is not uncommonly seen in hepatic cavernous hemangiomas at dynamic MRI. It is most commonly encountered in rapidly enhancing small lesions. There is no statistically significant relation between temporal peritumoral enhancement and tumor volume, however.