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Detection of hepatocellular carcinoma arising in cirrhotic livers: comparison of gadolinium- and ferumoxides-enhanced MR imaging.

OBJECTIVE: We prospectively compared the detectability of hepatocellular carcinoma (HCC) arising in cirrhotic livers using dynamic gadolinium-enhanced fast low-angle shot (FLASH), ferumoxides-enhanced T2-weighted turbo spin-echo, and ferumoxides-enhanced T2*-weighted FLASH MR imaging. SUBJECTS AND METHODS: Fifty-three patients with HCC (32 men and 21 women) who were 33-86 years old (mean, 63 years old) were enrolled in a prospective MR study to assess hepatic lesions using both gadopentetate dimeglumine and ferumoxides. Dynamic gadolinium-enhanced imaging was obtained before and 30, 60, and 180 sec after rapid bolus injection of gadopentetate dimeglumine (0.1 mmol/kg). Ferumoxides-enhanced T2-weighted turbo spin-echo imaging and ferumoxides-enhanced T2*-weighted FLASH imaging were performed between 30 min and 2 hr after i.v. infusion of ferumoxides (10 micromol/kg). Images were analyzed qualitatively and quantitatively. A receiver operating characteristic curve study was performed to compare the diagnostic value of gadolinium-enhanced imaging with that of ferumoxides-enhanced imaging for the detection of HCC. RESULTS: Quantitative analysis revealed a significantly higher percentage of signal-intensity loss and higher liver-lesion contrast-to-noise ratio on ferumoxides-enhanced T2*-weighted FLASH imaging than on ferumoxides-enhanced T2-weighted turbo spin-echo imaging. The percentage of signal-intensity loss and liver-lesion contrast-to-noise ratio on ferumoxides-enhanced images was significantly higher in patients with mild liver cirrhosis (Child's class A) than in patients with severe liver cirrhosis (Child's class C). Qualitative analysis showed that dynamic gadolinium-enhanced images revealed significantly higher lesion conspicuity than did ferumoxides-enhanced T2-weighted turbo spin-echo images. According to receiver operating characteristic analysis, dynamic gadolinium-enhanced FLASH imaging achieved the highest sensitivity, and ferumoxides-enhanced T2*-weighted FLASH imaging was the second most sensitive. We found that ferumoxides-enhanced turbo spin-echo imaging was the least valuable technique for revealing HCC lesions. Gadolinium-enhanced imaging revealed more HCC lesions than did ferumoxides-enhanced imaging, particularly for lesions smaller than 2 cm in diameter. CONCLUSION: Ferumoxides-enhanced imaging revealed fewer findings, such as lesion conspicuity of HCCs arising in cirrhotic livers, than did gadolinium-enhanced FLASH imaging.

Adult↗

Correlative study of angiogenesis and dynamic contrast-enhanced magnetic resonance imaging features of hepatocellular carcinoma.

PURPOSE: To explore the correlation between contrast-enhancement patterns on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and angiogenesis by analyzing microvessel density (MVD), vascular endothelial growth factor (VEGF), and P53 protein expression in hepatocellular carcinoma (HCC). MATERIAL AND METHODS: MRI was performed with a GE Signa 1.5T MR scanner using SE and FMPSPGR sequences in 30 patients (38 lesions) during the period October 1998 to March 2000. All had histopathologically proven HCC. MR images were reviewed/ analyzed retrospectively. The 30 patients were between 35 and 65 years of age (average age 58; 18 M and 12 F). SE T1WI, PDWI, and T2WI were acquired initially. The FMPSPGR sequence was acquired in the same position. The DCE-MRI was performed in the arterial, portal vein, and delay phase after a bolus injection of Gd-DTPA. The specimens were stained immunohistochemically for CD34, VEGF, and P53. MVD was highlighted by anti-CD34 antibody staining. The enhancement features of HCC lesions were studied correlatively with the tumor MVD, VEGF, and P53 expression at protein level. RESULTS: In the arterial phase, the results showed that MVD of HCC in the high-enhancement group (229.76 +/- 80.96) was higher than that in the equal-enhancement (173.09 +/- 61.38) and low-enhancement groups (153.00 +/- 108.58) (P < 0.01, respectively). VEGF expression of HCC in the high-enhancement group (68.42%) was higher than that in the equal-enhancement (36.36%) and low-enhancement groups (38.89%) (P < 0.05, respectively). In the portal vein phase, MVD of HCC in the enhancement group (259.80 +/- 93.30) was higher than that in the non-enhancement group (178.64 +/- 92.65) (P < 0.05). No significant correlation was found between VEGF expression and the enhancement feature in the portal vein phase. In the delay phase, MVD of HCC in the ring-enhancement group (269.06 +/- 57.89) was significantly higher than that in the non-ring-enhancement group (144.10 +/- 88.90) (P < 0.01). There was a significant difference in VEGF expression between the ring-enhancement group (76.47%) and the non-ring-enhancement group (42.86%) (P < 0.05). No significant correlation was detected between P53 protein expression and the enhancement feature. Relative enhancement (RE) correlated with MVD, but not with VEGF and P53 protein expression. CONCLUSION: The contrast-enhancement patterns on DCE-MRI are influenced by tumor angiogenesis, as reflected by elevated VEGF expression, and are therefore valuable indicators for accessing tumor angiogenic activity and tumor neovascularization in vivo in HCC patients.

Adult↗

Mechanistic studies of branched-chain alkanols as skin permeation enhancers.

As part of a long-term effort to understand the structure/function relationship between chemical permeation enhancers and skin permeation enhancement, the present study examined the influence of hydrocarbon chain branching on the effectiveness of skin permeation enhancers of the type that possesses a polar group (e.g., the hydroxyl group) attached to a hydrocarbon chain(s). The effects of x-hexanol, x-heptanol, x-octanol, and x-nonanol (where x is the position of the hydroxyl group ranging from 1 up to 5) on the transport of a probe permeant, corticosterone, across hairless mouse skin (HMS) were investigated. Isoenhancement concentrations are defined as the aqueous concentrations for which different enhancers induce the same extent of permeant transport enhancement, E, across the lipoidal pathway of stratum corneum (SC). The isoenhancement concentrations of 2-alkanol, 3-alkanol, 4-alkanol, and 5-alkanol to induce E = 10 were approximately 1.9-, 2.6-, 3.1-, and 3.9-fold higher, respectively, than those of the 1-alkanols of the same molecular formula. This suggested that the branched-chain alkanols have lower enhancer potency than the 1-alkanols of the same molecular formula; the potency decreases as the hydroxyl group moves from the end of the chain towards the center of the enhancer alkyl chain. To further investigate the mechanism(s) of action of the branched-chain alkanols as skin permeation enhancers, the equilibrium uptake of the enhancers into the hairless mouse skin stratum corneum (HMS SC) from aqueous enhancer solutions of E = 10 was determined. The data from these experiments provided a direct measure of the "intrinsic" potency of the enhancer. In the same experiments, the equilibrium partitioning (distribution) of a surrogate permeant, estradiol (E2beta), into the HMS SC was also determined and compared to the partitioning from PBS (no enhancer present). The uptake amounts (micromole/mg SC) for 1-alkanols into the intercellular lipids of the SC were found to be essentially the same at their isoenhancement concentrations. However, at their isoenhancement concentrations, the uptake amounts of the branched-chain alkanols into the intercellular lipids of HMS SC were higher than those of the 1-alkanols. These results support the view that: (1) the intrinsic potencies of the 1-alkanols are essentially the same and independent of their 1-alkyl chain length at their isoenhancement concentrations, (2) the intrinsic potencies of the branched-chain alkanols are lower than those of the normal alkanols, and (3) branching of the alkyl chain reduces the ability of the enhancer to effect lipid fluidization in the SC lipid lamellae at the target site(s). The enhancement effects of the branched-chain alkanols and the 1-alkanols at their isoenhancement concentrations upon E2beta partitioning into the SC intercellular lipids were found to be approximately the same and in the range of five- to eight-fold enhancement. The constancy of this enhancement for E2beta partitioning suggests that the mechanism of enhancement action for the branched-chain alkanols and the 1-alkanols are the same. Additionally, a good correlation of the intercellular lipid/PBS partition coefficients of both the branched-chain alkanols and the 1-alkanols with the n-octanol/PBS partition coefficients was found. This supports the view that the chemical microenvironment of the polar head group and the alkyl group of the studied enhancers at the site of skin permeation enhancer action in the SC lipid lamellae can be represented by water-saturated n-octanol for both the branched-chain alkanols and the 1-alkanols.

Alkanes↗

A short sequence within two purine-rich enhancers determines 5' splice site specificity.

Purine-rich enhancers are exon sequences that promote inclusion of alternative exons, usually via activation of weak upstream 3' splice sites. A recently described purine-rich enhancer from the caldesmon gene has an additional activity by which it directs selection of competing 5' splice sites within an alternative exon. In this study, we have compared the caldesmon enhancer with another purine-rich enhancer from the chicken cardiac troponin T (cTNT) gene for the ability to regulate flanking splice sites. Although similar in sequence and length, the two enhancers demonstrated strikingly different specificities towards 5' splice site choice when placed between competing 5' splice sites in an internal exon. The 32-nucleotide caldesmon enhancer caused effective usage of the exon-internal 5' splice site, whereas the 30-nucleotide cTNT enhancer caused effective usage of the exon-terminal 5' splice site. Both enhancer-mediated splicing pathways represented modulation of the default pathway in which both 5' splice sites were utilized. Each enhancer is multipartite, consisting of two purine-rich sequences of a simple (GAR)n repeat interdigitated with two enhancer-specific sequences. The entire enhancer was necessary for maximal splice site selectivity; however, a 5- to 7-nucleotide region from the 3' end of each enhancer dictated splice site selectivity. Mutations that interchanged this short region of the two enhancers switched specificity. The portion of the cTNT enhancer determinative for 5' splice site selectivity was different than that shown to be maximally important for activation of a 3' splice site, suggesting that enhancer environment can have a major impact on activity. These results are the first indication that individual purine-rich enhancers can differentiate between flanking splice sites. Furthermore, localization of the specificity of splice site choice to a short region within both enhancers indicates that subtle differences in enhancer sequence can have profound effects on the splicing pathway.

Animals↗

Enhancing patterns in multiple sclerosis: evolution and persistence.

BACKGROUND AND PURPOSE: Contrast enhancement on MR images of patients with multiple sclerosis (MS) is known to be associated with abnormalities of the blood-brain barrier (BBB). However, little is known about diagnostic patterns and common features of enhanced MS lesions. This study was designed to evaluate initial enhancement patterns, changes in these enhancing patterns, and duration of enhancement in a cohort of patients with MS. METHODS: Twenty-five patients with clinically definite MS were studied retrospectively. The appearance of enhancing lesions and sequential changes in the appearance on axial contrast-enhanced spin-echo images were evaluated. The enhancing lesions were classified as nodular, ringlike, or "other" (eg, arclike). RESULTS: Of 301 new enhancing lesions, 205 (68%) showed nodular enhancement, 70 (23%) a ring pattern, and 26 (9%) a pattern neither nodular nor ringlike (eg, arclike). Two hundred eighty (93%) of 301 enhancing lesions disappeared within 6 months, and seven (2%) lesions showed persistent enhancement longer than 6 months. The other 14 (5%) lesions, which disappeared by the time of the next scan, were excluded, because the course between two examinations was longer than 6 months. Of nine persisting nodular enhancing lesions on the follow-up images, seven were decreased in size, whereas all of two persisting ringlike enhancing lesions on the follow-up images were larger than before. CONCLUSION: Nodular enhancement is the predominant enhancement pattern for new MS lesions, and the temporal course of enhancement is usually shorter than 6 months. The appreciation of the evolution of MS-enhanced lesions aids in both identifying new MS lesions and distinguishing these lesions from other pathologic entities. This may be helpful in clinically evaluating the stage of MS lesions.

Adult↗

Distinction between cavernous hemangiomas of the liver and hepatic metastases on CT: value of contrast enhancement patterns.

OBJECTIVE: Differentiating between cavernous hemangiomas of the liver and hepatic metastases on the basis of single-pass, contrast-enhanced CT is a significant and frequently encountered diagnostic challenge. Recognition of characteristic enhancement features of cavernous hemangiomas can aid in effectively distinguishing between these lesions. The purpose of this study was to determine sensitivity and specificity of dense, globular enhancement for differentiating cavernos hemangiomas and metastases during single-pass, contrast-enhanced CT. MATERIALS AND METHODS: CT appearance of 133 lesions in 91 patients with cavernous hemangiomas (44 patients) or metastases (47 patients) was retrospectively evaluated in a blinded review. CT examinations were performed with nonhelical technique following injection of 150 ml of contrast material. All patients with metastases had pathologic proof (n = 47). Patients with cavernous hemangiomas were clinically stable for at least 2 years after CT (n = 43) or had tissue proof (n = 1). All lesions were evaluated based on the following criteria: (1) Type of enhancement: globular, linear, diffuse and homogeneous, or diffuse and heterogeneous. (Globular enhancement was considered to be present when enhancing nodules less than 1 cm in diameter were seen within lesions.) (2) Continuity of enhancing tissue: continuous or noncontinuous. (Uninterrupted collections of contrast material within at least 50% of a lesion were considered continuous. Multiple, separate collections of contrast material were considered noncontinuous.) (3) Degree of enhancement: hypo-, iso-, or hyperdense relative to the aorta. (4) Distribution of enhancement: peripheral, central, or mixed. RESULTS: Seventy-six percent of cavernous hemangiomas had globular enhancement, compared to 10% of metastases (p < .001). Seventy-two percent of cavernous hemangiomas had enhancement isodense with the aorta, and 96% of metastases were hypodense (p < .001). Sixty-seven percent of cavernous hemangiomas had peripheral enhancement, compared to 38% of metastases (p < .001). The combined finding of globular, isodense enhancement was seen in 67% of cavernous hemangiomas and none of the metastases. Only 10% of cavernous hemangiomas had nonglobular, hypodense enhancement, compared with 90% of metastases. Combining all criteria, reviewers correctly classified 122 (92%) of the lesions. Presence of globular enhancement, isodense with the aorta, was 67% sensitive and 100% specific in differentiating cavernous hemangiomas from hepatic metastases. CONCLUSION: In most cases, differentiation of cavernous hemangiomas from hepatic metastases can confidently be made with single-pass, contrast-enhanced CT. Globular enhancement, isodense with the aorta, is 67% sensitive and 100% specific in differentiating cavernous hemangiomas and hepatic metastases.

Adult↗

Schistosomiasis japonica of the liver: contrast-enhanced CT findings in 113 patients.

OBJECTIVE: The purpose of this study was to determine the findings on contrast-enhanced CT scans in patients with hepatic schistosomiasis japonica and to determine their pathologic basis. MATERIALS AND METHODS: Unenhanced and contrast-enhanced CT scans of 113 patients with histologically proved schistosomiasis were reviewed. Radiologic and pathologic findings were correlated after autopsy in 19 patients. RESULTS: Unenhanced CT scans showed septal calcification in the liver parenchyma in 53 patients (47%) and capsular calcification along the hepatic surface in 29 patients (26%). Twenty-seven patients (24%) had both types of calcification. Fifty-four patients (48%) showed one or more types of enhancement. Septal enhancement (i.e., linear enhancement of hepatic parenchyma looking like septa in the liver) was seen in 52 patients (46%). Forty-seven of the 53 patients who had septal calcification on unenhanced CT scans had septal enhancement on scans obtained after the administration of contrast material. The enhancement was found at sites of septal calcification in 44 patients and at noncalcified sites in 18 (15 had enhancement at both calcified and noncalcified sites). Five of 60 patients who did not have septal calcification on unenhanced CT scans had septal enhancement at noncalcified sites on scans obtained after the administration of contrast material. Amorphous enhancement (i.e., poorly defined and irregularly shaped enhancement) was seen in six patients (5%). Capsular enhancement (i.e., curvilinear enhancement along the hepatic surface) was seen in 12 patients (11%). Histologic studies showed broad fibrous septa at sites of septal enhancement. CONCLUSION: CT findings in patients with schistosomiasis japonica involving the liver include septal, amorphous, and capsular contrast enhancement. Septal enhancement occurs in broad fibrous septa. CT evidence of septal enhancement may suggest the diagnosis of hepatic schistosomiasis japonica, especially when no calcification is seen on unenhanced CT scans.

Adult↗

Peak contrast enhancement in CT and MR angiography: when does it occur and why? Pharmacokinetic study in a porcine model.

PURPOSE: To investigate pharmacokinetic and physiologic factors that determine the time to peak intravenous contrast medium enhancement in computed tomographic (CT) and magnetic resonance (MR) angiography in the porcine mid-abdominal aorta. MATERIALS AND METHODS: Four pigs were imaged repeatedly in seven to eight sets: For each set, 20 dynamic CT scans were obtained at a fixed aortic level after intravenous injection of contrast medium. From a physiologically based compartment model, aortic contrast enhancement curves were generated by varying contrast medium injection duration from 1 to 40 seconds. Contrast enhancement curves and times to peak aortic enhancement from the experiment and model were compared. Time to peak aortic enhancement obtained from the injection with the shortest duration was considered the time to peak test bolus contrast enhancement. Mathematic and pharmacokinetic analyses were performed to investigate factors that determine peak enhancement. RESULTS: Empiric and compartmental model times to peak aortic enhancement were in good agreement. Time to peak aortic enhancement corresponded to the weighted sum of injection duration and time to peak test bolus enhancement. With increasing injection duration, the relative contribution of injection duration to peak aortic enhancement time increased. When injection duration was longer than time to peak test bolus enhancement, time to peak aortic enhancement increased linearly with injection duration and occurred shortly after completion of injection. However, when injection duration was shorter than time to peak test bolus enhancement, time to peak aortic enhancement was determined predominantly by time to peak test bolus enhancement and only gradually increased with injection duration. CONCLUSION: Time to peak aortic enhancement is determined by the relative contributions of injection duration and contrast medium traveling time and may well be explained by contrast medium volumetric inflow and recirculation physiology.

Angiography↗

Single-pass CT of hepatic tumors: value of globular enhancement in distinguishing hemangiomas from hypervascular metastases.

OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of globular enhancement for differentiating hepatic hemangiomas from hypervascular metastases on single-pass, contrast-enhanced CT scans. Globular enhancement was defined as enhancing nodules less than 1 cm seen within a lesion. MATERIALS AND METHODS: Fifty CT examinations were retrospectively evaluated in a blinded fashion by two independent reviewers. The CT studies were done with nonhelical technique after the IV injection of 150 ml of contrast material. The series included 25 patients with histologically proven hypervascular hepatic metastases (carcinoid, islet cell carcinoma, and leiomyosarcoma) and 25 patients with clinically proven hepatic hemangiomas. Patients with hemangiomas were clinically stable for at least 2 years after the CT studies. A single lesion was isolated from the first-pass, contrast-enhanced portion of each examination; the remainder of the examination was excluded from the review to minimize reviewer bias. Each lesion was evaluated for (1) the presence or absence of globular enhancement (defined as enhancing nodules less than 1 cm seen within a lesion), (2) the density of globular enhancement relative to that of the aorta, (3) the degree of border definition (well or poorly marginated), and (4) the presence or absence of a hypodense halo. A diagnostic impression was then recorded for each lesion. RESULTS: Globular enhancement was 88% sensitive and 84-100% specific for differentiating hepatic hemangiomas from hypervascular metastases (p < .001). A mean of 62% of hemangiomas showed globular enhancement isodense relative to that of the aorta; none of the metastases showed globular, isodense enhancement. The majority of the metastases showed nonglobular enhancement (mean, 92%). The reviewers showed 84% agreement in the identification of (1) globular enhancement in hemangiomas, (2) lack of globular enhancement in metastases, and (3) globular enhancement in the combined set of all lesions. Neither the presence of a hypodense halo nor the degree of border definition was significant in distinguishing between the two groups of lesions. The reviewers showed 96% agreement in the categorization of metastases and 76% agreement in the categorization of hemangiomas. There was 86% agreement in the categorization of all lesions. Overall, reviewers diagnosed a mean of 89% of lesions correctly. A mean of 98% of metastases and a mean of 80% of hemangiomas were diagnosed correctly. CONCLUSIONS: Globular enhancement is highly sensitive (88%) and specific (84-100%) for differentiating hepatic hemangiomas from hypervascular metastases on single-pass, contrast-enhanced CT scans.

Adult↗

[Value of dynamic enhanced magnetic resonance in diagnosis of pancreatic carcinoma and endocrine tumors].

OBJECTIVE: To explore the value of dynamic enhanced magnetic resonance (MR) in diagnosis of pancreatic carcinoma and endocrine tumors. METHODS: Twenty-two patients with pancreatic carcinoma and 9 patients with pancreatic endocrine tumors underwent routine MR scanning and dynamic contrast enhanced MR examination before they underwent operation. RESULTS: No tumor image was seen in 4 of the 22 patients with pancreatic carcinoma by routine MR scanning. Fat-saturated T(1)-weighted imaging (FS-T(1) WI) showed that 11 of them were hyposignal, 6 slightly hyposignal, and 1 isosignal; and fat-saturated T(2)-weighted imaging (FS-T(2) WI) showed that 5 were hypersignal, 7 slightly hypersignal, 5 isosignal, 1 slightly hyposignal, and 13 with heterogeneous signals. After dynamic MR imaging no tumor was enhanced in the arterial phase (AP); and all the tumors were obviously enhanced during the pancreatic phase (PP) and portal venous phase (PVP), 5 of which showed isosignal intensity, 10 slightly hyposignal intensity, and 3 hyposignal intensity. Four of the 5 cases with small pancreatic carcinoma were demonstrated as isosignal and one was slightly hyposignal. During the delayed enhancement phase (DEP) the signal intensity of the tumors became slightly weaker. No tumor image was seen in 14 of the 9 patients with pancreatic endocrine tumors by routine MR scanning. FS-T(1) WI showed that 5 of them were hyposignal, and 3 slightly hyposignal; and FS-T(2) WI showed that 2 were hypersignal, 4 slightly hyposignal, and 2 isosignal. After dynamic MR imaging 2 cases were moderately enhanced and 6 cases mildly enhanced during AP, and all pancreatic endocrine tumors were obviously enhanced during PP and PVP, with isosignal intensity in 2 cases, slightly hyposignal intensity in 1 case, and slightly hypersignal intensity in 5 cases. Peritumor thin-walled enhancement was seen in 6 cases. CONCLUSION: Dynamic enhanced MR has a certain value in the diagnosis of pancreatic carcinoma and endocrine tumors. Pancreatic carcinoma shows various enhanced forms by dynamic enhanced magnetic resonance, the degree of the greatest enhanced form not surpassing that of normal pancreatic tissue. Pancreatic endocrine carcinoma shows obvious enhanced forms by dynamic enhanced magnetic resonance, the degree of the greatest enhanced form surpassing that of normal pancreatic tissue. Peritumor thin-walled enhancement is a characteristic feature of pancreatic endocrine carcinoma.

Adult↗

Evaluation of tumor angiogenesis of breast carcinoma using contrast-enhanced digital mammography.

OBJECTIVE: The purpose of this article is to assess the accuracy of contrast-enhanced digital mammography in the detection of breast carcinoma and to correlate the findings on the images with those of histologic analysis using microvessel quantification. SUBJECTS AND METHODS: Twenty patients with a suspicious breast abnormality underwent contrast-enhanced digital mammography using a full-field digital mammography unit that was modified to detect iodinated enhancement. For each patient, a total of six contrast-enhanced craniocaudal views were acquired from 30 seconds to 7 minutes after the injection of a bolus of 100 mL of an iodinated contrast agent. Image processing included a logarithmic subtraction and the analysis of enhancement kinetic curves. Contrast-enhanced digital mammography findings were compared with histologic analysis of surgical specimens, including intratumoral microvessel density quantification evaluated on CD34-immunostained histologic sections obtained from all patients. RESULTS: An area of enhancement was depicted on contrast-enhanced digital mammograms in 16 of the 20 histologically proven breast carcinomas. Excellent correlation was seen between the size of enhancement and the histologic size of tumors, which ranged from 9 to 22 mm. Early enhancement with washout was observed in four cases, early enhancement followed by a plateau in four cases, gradual enhancement in seven cases, and unexpected decrease of enhancement in one case. Intratumoral microvessel density ranged from 11.7 to 216.6 microvessels per square millimeter. A poor correlation was found between data measured on contrast-enhanced digital mammography and intratumoral microvessel density measured on CD34-immunostained histologic sections. CONCLUSION: Contrast-enhanced digital mammography is able to depict angiogenesis in breast carcinoma. Breast compression and projective images acquisition alter the quantitative assessment of enhancement parameters.

Adult↗

Prospective study of differential diagnosis of hepatic tumors by pattern-based classification of contrast-enhanced sonography.

AIM: To prospectively evaluate the usefulness of a pattern-based classification of contrast-enhanced sonographic findings for differential diagnosis of hepatic tumors. METHODS: We evaluated the enhancement pattern of the contrast-enhanced sonography images in 586 patients with 586 hepatic lesions, consisting of 383 hepatocellular carcinomas, 89 metastases, and 114 hemangiomas. After injecting a galactose-palmitic acid contrast agent, lesions were scanned by contrast-enhanced harmonic gray-scale sonography in three phases: arterial, portal, and late. The enhancement patterns of the initial 303 lesions were classified retrospectively, and multiple logistic regression analysis was used to identify enhancement patterns that allowed differentiation between hepatic tumors. We then used the pattern-based classification of enhancement we had retrospectively devised to prospectively diagnose 283 liver tumors. RESULTS: Seven enhancement patterns were found to be significant predictors of different hepatic tumors. The presence of homogeneous or heterogeneous enhancement both in the arterial and portal phase was the typical enhancement pattern for hepatocellular carcinoma, while the presence of peritumoral vessels in the arterial phase and ring enhancement or a perfusion defect in the portal phase was the typical enhancement pattern for metastases, and the presence of peripheral nodular enhancement both in the arterial and portal phase was the typical enhancement pattern for hemangioma. The sensitivity, specificity, and accuracy of prospective diagnosis based on the combinations of enhancement patterns, respectively, were 93.2%, 96.2%, and 94.0% for hepatocellular carcinoma, 87.9%, 99.6%, and 98.2% for metastasis, and 95.6%, 94.1%, and 94.3% for hemangioma. CONCLUSION: The pattern-based classification of the contrast-enhanced sonographic findings is useful for differentiating among hepatic tumors.

Aged↗

Influences of alkyl group chain length and polar head group on chemical skin permeation enhancement.

Previous investigations in our laboratory on the influence of the n-alkanols and the 1-alkyl-2-pyrrolidones as skin permeation enhancers for steroid molecules as permeants demonstrated that the enhancer potencies (based on aqueous concentration values) of these two homologous series were the same when compared at the same alkyl chain length; that is, the contribution of the hydroxyl group and that of the pyrrolidone group to enhancer potency were the same. The purpose of the present study was to further investigate what was believed to be a somewhat surprising finding, and two additional homologous series, the 1,2-alkanediols and N,N-dimethylalkanamides, were selected for study as enhancers. Corticosterone (CS) flux enhancement along the lipoidal pathway of hairless mouse skin stratum corneum was determined with 1,2-hexane-, 1,2-octane-, and 1,2-decanediol and with N,N-dimethylhexanamide, N,N- dimethylheptanamide, N,N-dimethyloctanamide, and N,N-dimethylnonanamide as enhancers. The enhancement factor (E) for the lipoidal pathway was calculated from the CS permeability coefficient and the CS solubility data over a 4 to 100 range of E values. Comparisons of the enhancer potencies of all four homologous series revealed that the enhancer potencies of all were very nearly the same when compared at equal alkyl group chain length. Moreover, the contribution of each of the polar head groups toward the enhancer potency was essentially constant, independent of the alkyl group chain length. It was reasoned that this outcome was either the result of the random selection of four polar head groups making the same contribution to enhancer potency or the result of these particular polar head groups not contributing to enhancer potency. To test the hypothesis that the former was more likely than the latter and that a suitable semipolar organic phase may mimic the microenvironment of the polar head group at the site of enhancer action, n-octanol-phosphate buffered saline (PBS) and n-hexane-PBS partition coefficients were determined for all the enhancers. The n-octanol-PBS partition coefficients for the enhancers, but not the n-hexane-PBS partition coefficients, were very nearly the same when compared at equal alkyl group chain lengths; this result supports the hypothesis that each of the four polar head groups likely contributes the same toward the enhancer potency and locates in the semipolar region of the hairless mouse skin stratum corneum lipid bilayers, which is well-approximated by water-saturated n-octanol.

Alkanes↗

Pre-B-cell colony-enhancing factor is a secreted cytokine-like protein from the human amniotic epithelium.

OBJECTIVE: The purpose of this study was to determine whether pre-B-cell colony-enhancing factor is a secreted cytokine in the human amnion and to study its chemotaxic and antiapoptotic properties. STUDY DESIGN: Pre-B-cell colony-enhancing factor secretion was studied from amniotic epithelial-like WISH cells and primary amniotic epithelial cells that were seeded on squares of immobilon-P membrane and stimulated with lipopolysaccharide or tumor necrosis factor-alpha, respectively. The pre-B-cell colony-enhancing factor protein was detected both intracellularly and after secretion, as bound to the membrane, by immunostaining and densitometry. Medium and cell lysates that were obtained from WISH cells that were treated with lipopolysaccharide alone or together with a pre-B-cell colony-enhancing factor antisense oligonucleotide to block pre-B-cell colony-enhancing factor translation were also analyzed for secreted pre-B-cell colony-enhancing factor by Western blotting and densitometry. A chemotaxic effect of pre-B-cell colony-enhancing factor on human neutrophils was compared with the chemoattractants interleukin-8 and N-Formyl-Met-Leu-Phe methyl ester in a rapid fluorescence-based neutrophil migration assay. Apoptosis was induced in primary amniotic epithelial cells and fibroblasts by actinomycin D (1 microg/mL); the antiapoptotic effects of pre-B-cell colony-enhancing factor on early apoptosis were measured by the annexin V assay, and the late effects were determined by measurement of nuclear matrix protein in the media. RESULTS: Treatment of amnion cells that adhered to immobilon-P membrane to induce the secretion of pre-B-cell colony-enhancing factor showed significantly (P<.05) more pre-B-cell colony-enhancing factor protein surrounding the cells compared with the controls. Although the addition of lipopolysaccharide to cultured WISH cells caused the secretion of pre-B-cell colony-enhancing factor into the medium, co-treatment with an antisense oligonucleotide to pre-B-cell colony-enhancing factor obliterated it. Analysis of the cell lysates showed no significant change, which suggests that most of the pre-B-cell colony-enhancing factor protein had been secreted. No significant chemotaxic effects of pre-B-cell colony-enhancing factor were observed; however, pre-B-cell colony-enhancing factor treatment (100 ng/mL), together with actinomycin D, cancelled the early induction of apoptosis, although there was a dose-dependent and significant late antiapoptotic effect on primary amnion epithelial cells (P<.001) and fibroblasts (P<.01). CONCLUSION: Pre-B-cell colony-enhancing factor is a secreted protein from amniotic epithelial cells. Although it had no chemotaxic effects, it was antiapoptotic for both amniotic epithelial cells and fibroblasts and may protect these cells against apoptosis that is induced by chronic distension, labor, or infection.

Amnion↗

Improvement of absorption enhancing effects of n-dodecyl-beta-D-maltopyranoside by its colon-specific delivery using chitosan capsules.

In general, absorption enhancing effects of various absorption enhancers were greater in the large intestine than those in the small intestinal regions. Therefore, the effectiveness of absorption enhancers is expected to be remarkably observed, if these enhancers can be delivered to the large intestine with some poorly absorbable drugs after oral administration. In this study, therefore, we examined whether chitosan capsules were effective for the colon-specific delivery of a certain absorption enhancer and can improve the absorption enhancing action of the absorption enhancer after oral administration. 5(6)-Carboxyfluorescein (CF) was used as a model drug to investigate the site-dependent effectiveness of various absorption enhancers by an in situ closed loop method. Sodium glycocholate (NaGC), n-dodecyl-beta-d-maltopyranoside (LM), sodium salicylate (NaSal) and sodium caprate (NaCap) were used as models of absorption enhancers in this study. Overall, the absorption enhancing effects of these enhancers for intestinal absorption of CF were greater in the colon than those in the jejunum and the ileum. Especially, among these enhancers tested in this study, LM showed much greater absorption enhancing effect in the colon than in the jejunum and the ileum. Therefore, LM was selected as a model absorption enhancer to examine the effect of chitosan capsules on the absorption enhancing effect of LM. When CF and LM were orally administered to rats using chitosan capsules, the plasma concentration of CF was much higher than those in other dosage forms including solution and gelatin capsules. Therefore, chitosan capsules may be useful carriers for colon-specific delivery of LM, thereby increasing its absorption enhancing effect from the intestinal membranes.

Animals↗

Prediction of radiotherapy outcome using dynamic contrast enhanced MRI of carcinoma of the cervix.

PURPOSE: To investigate whether analysis of MRI enhancement data using a pharmacokinetic model improved a previously found correlation between contrast enhancement and tumor oxygenation measured using PO2 histograph. To evaluate the prognostic value of gadolinium enhancement data for radiotherapy outcome, and to study the efficacy of combined enhancement and MRI volume data. METHODS AND MATERIALS: Fifty patients underwent dynamic gadolinium-enhanced MRI as part of their initial staging investigations before treatment. Gadolinium enhancement was analyzed using the Brix pharmacokinetic model to obtain the parameters amplitude and rate of contrast enhancement. Pretreatment tumor oxygen measurements (Eppendorf PO2 histograph) were available for 35 patients. RESULTS: Both standard and pharmacokinetic-derived enhancement data correlated with tumor oxygenation measurements, and poorly enhancing tumors had low tumor oxygen levels. However, only the pharmacokinetic-analyzed data correlated with patient outcome and patients with poorly (amplitude less than median) vs. well-enhancing tumors had significantly worse disease-specific survival (p = 0.024). For the 50 patients studied, no relationship was found between enhancement and volume data. Combining MRI volume and enhancement information highlighted large differences in outcome (p = 0.0054). At the time of analysis, only 55% of patients with large, poorly enhanced tumors were alive compared with 92% of patients with small, well-enhanced tumors. CONCLUSION: These preliminary results suggest that pharmacokinetic modeling of dynamic contrast-enhanced MRI provides data that reflect tumor oxygenation and yields useful prognostic information in patients with locally advanced carcinoma of the cervix. Combining MRI-derived enhancement and volume data delineates large differences in radiotherapy outcome.

Adenocarcinoma↗

Patterns of uterine enhancement with helical CT.

OBJECTIVE: The purpose of this study was to evaluate the enhancement characteristics of the normal uterine body and cervix using dynamic contrast-enhanced helical CT. METHODS: Thirty-eight women scheduled for pelvic CT for non-gynecologic malignancies underwent dynamic contrast-enhanced helical CT of the pelvis. Data acquisition was during the arterial phase (30-45 s after the start of injection), the parenchymal phase (90-120 s after the start of injection), and delayed phase (3-9 min after the start of injection). The images were evaluated by four radiologists for the pattern of myometrial and cervical enhancement. Correlation was made with the age and menstrual status of the patients. RESULTS: In the uterine body, three types of enhancement were observed. Type 1 enhancement, seen in 16 patients (42%), was characterized by the visualization of a subendometrial zone of enhancement, 30-120 s after the start of injection. Eight of these patients also showed an enhancing zone in the outer myometrium. Both zones were transitory, and in all cases, the uterus became homogeneous in the delayed phase. This pattern was seen predominantly in premenopausal women with a mean age of 34 years. Type 2 enhancement, seen in 17 cases (45%), was defined by the absence of subendometrial enhancement in the early phase. Enhancement was either diffuse from the outset or originated in the outer myometrium. This pattern was seen nearly equally in premenopausal and postmenopausal women with a mean age of 40 years. Type 3 enhancement was seen in five postmenopausal patients (13%) with a mean age of 53 years and was characterized by faint diffuse enhancement. In the cervix, a zonal pattern of enhancement defining inner and outer stroma was seen in 23 patients (61%). Fifteen patients were premenopausal and eight were postmenopausal. CONCLUSION: In this study, we have shown a transitory zonal distribution of the contrast in the myometrium and cervix using dynamic contrast-enhanced helical CT. The demonstration of these patterns is not constant and depends on individual variables. Of these, the menopausal status and/or age of the patient appear to be most important. While CT is not the primary imaging modality to evaluate the uterus, knowledge of these normal findings might help when confronted with unusual uterine enhancement during routine studies obtained with spiral CT.

Adult↗

MRI evolution of new MS lesions enhancing after different doses of gadolinium.

OBJECTIVE: To investigate the evolution of multiple sclerosis (MS) lesions enhancing after single dose (SD) or triple dose (TD) of gadolinium-DTPA (Gd). MATERIAL AND METHODS: For 3 months, 30 relapsing-remitting MS patients underwent 2 monthly MRI sessions, consisting of Gd-enhanced T1-weighted scans, after SD (i.e., 0.1 mmol/kg) in one session and TD (i.e., 0.3 mmol/kg) in the other. New enhancing lesions on month 1 and month 2 follow-up scans were studied and for them any persistence of enhancement was evaluated on the scans obtained the next month. RESULTS: In all, 151 lesions enhancing after both SD and TD and 91 lesions enhancing only after TD entered the analysis. After 1 month, for the 151 lesions enhancing after both SD and TD, 73 (48%) were not enhancing, 50 (33%) were still enhancing after both SD and TD and 28 (19%) were enhancing only after TD. For the 91 lesions enhancing only after TD, 61 (67%; P<0.005) were not enhancing, 16 (18%; P<0.01) were still enhancing only after TD and 14 (15%; P=NS) showed enhancement after both SD and TD. CONCLUSION: Enhancing lesions in patients with MS are heterogeneous. Those enhancing only after TD of Gd are characterized by a milder and shorter opening of the blood-brain barrier.

Blood-Brain Barrier↗