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Normal abdominal enhancement patterns with dynamic gadolinium-enhanced MR imaging.

The objective of this study was to quantitatively and qualitatively determine contrast enhancement patterns of normal abdominal organs with dynamic gadolinium-enhanced magnetic resonance (MR) imaging. Dynamic gadolinium-enhanced, T1-weighted, spin-echo imaging was performed during a 23-second breath hold in 38 patients, with images acquired before, during, and at 1,2, and 5 minutes after bolus injection of gadopentetate dimeglumine. Enhancement patterns of normal liver, spleen, pancreas, adrenal gland, kidney, aorta, inferior vena cava, and fat were determined by visual evaluation and by performance of signal intensity measurements with an electronic cursor. Time-intensity curves demonstrated peak enhancement of all abdominal organs during or immediately after bolus injection of gadopentetate dimeglumine. MR enhancement patterns included visualization of renal cortical nephrogram and heterogeneous enhancement of the spleen during the bolus phase of contrast material administration. Peak enhancement of normal liver was 72%; spleen, 172%; pancreas, 82%; adrenal gland, 85%; and kidney, 291%. This study established reference data regarding abdominal organ enhancement that will be useful as dynamic gadolinium-enhanced MR imaging becomes clinically implemented.

Abdomen↗

Superparamagnetic iron oxide--enhanced versus gadolinium-enhanced MR imaging for differential diagnosis of focal liver lesions.

PURPOSE: To assess AMI-25- versus gadolinium-enhanced magnetic resonance (MR) imaging in the differential diagnosis of liver tumors. MATERIALS AND METHODS: Twenty-nine patients with liver tumors underwent unenhanced, AMI-25-enhanced (15 micromol/kg), and gadolinium-enhanced(0.1 mmol/kg) imaging within 2 weeks. RESULTS: A significant (P< .05) difference in percentage signal intensity loss (PSIL) was seen in benign tumors on AMI-25-enhanced proton-density-weighted images (nine focal nodular hyperplasia [FNH], 41%; one adenoma, 32.4%) versus malignant tumors. Gadolinium-enhanced T1-weighted gradient-echo images showed strong enhancement in benign lesions (seven FNH, 147.5%; one adenoma, 91.3%) and moderate enhancement in malignant tumors (eight hepatocellular carcinomas, 116.2%, 11 metastases, 39.7%). Receiver operating characteristic analysis revealed a threshold PSIL of 10% on AMI-25-enhanced images as the most essential criteria to distinguish benign from malignant lesions (sensitivity, 88%; specificity. 89%). Interobserver analysis for two observers revealed specificity of 93% for AMI-25-enhanced imaging versus 81.5% for gadolinium-enhanced MR imaging. CONCLUSION: AMI-25 decreased the SI of benign tumors and helped differentiate benign from malignant tumors.

Adenoma↗

Ferumoxtran-10-enhanced MR lymphangiography: does contrast-enhanced imaging alone suffice for accurate lymph node characterization?

OBJECTIVE: Ferumoxtran-10 is a lymphotropic MR contrast agent that is currently under investigation. It has been shown to be effective in staging lymph nodes of patients with various primary malignancies. The current technique with ferumoxtran-10 involves imaging before and 24 hr after contrast administration. The purpose of this study was to evaluate the accuracy of ferumoxtran-10-enhanced images alone in characterizing lymph nodes for oncologic staging 24 hr after contrast enhancement. MATERIALS AND METHODS: Seventy-seven patients (58 men, 19 women) with proven primary cancer (bladder [n = 20], breast [n = 10], endometrial [n = 1], renal [n = 3], penile [n = 4], prostate [n = 31], rectal [n = 1], testicular [n = 5], and ureteral [n = 2]) who were scheduled for surgical lymph node dissection were enrolled in the study. In these patients, 169 lymph nodes (mean size, 11.2 mm) were evaluated on T2*-weighted gradient-refocused echo MRI at l.5 T both before and 24-36 hr after the IV administration of ferumoxtran-10 (2.6 mg Fe/kg). Two blinded reviewers with differing levels of interpreting experience separately performed qualitative image evaluation. A 6-point scale was used to characterize lymph nodes on contrast-enhanced images alone and on combined unenhanced and contrast-enhanced images. Receiver operating characteristic (ROC) analysis was performed separately for both reviewers. RESULTS: Of the 169 lymph nodes evaluated, 55 were benign and 114 malignant by histopathologic analysis. The results of the ROC analysis comparing contrast-enhanced images ([A(z) = area under ROC curve] reviewer 1, A(z) = 0.92; reviewer 2, A(z) = 0.94) alone with combined unenhanced and contrast-enhanced images (reviewer 1, A(z) = 0.94; reviewer 2, A(z) = 0.93) showed a statistically significant difference (p = 0.01) for reviewer 1 but no difference for reviewer 2 (p = 0.88). Reviewer 2 was more experienced in interpreting ferumoxtran-10-enhanced images than reviewer 1. CONCLUSION: On ferumoxtran-10-enhanced MR lymphangiography, contrast-enhanced images alone may suffice for lymph node characterization. However, a certain level of interpretation experience may be required before contrast-enhanced images can be used alone.

Adult↗

Sequence of enhancement of various portions of the pituitary gland on gadolinium-enhanced MR images: correlation with regional blood supply.

In an effort to study the blood supply of the pituitary gland, we determined the sequence in which various portions of the gland enhanced on MR images obtained after administration of gadopentetate dimeglumine in seven healthy volunteers. The pituitary gland has a unique blood supply: the pars nervosa is supplied by the inferior hypophyseal arteries; the infundibular stem is supplied by the superior hypophyseal arteries, which are more distal than the inferior hypophyseal arteries; and the pars distalis is supplied indirectly by portal systems from the infundibular stem. Therefore, the expected sequence of contrast enhancement of the pituitary gland is: the pars nervosa first, the infundibular stem second, and the pars distalis last. However, it is difficult to evaluate the temporal sequence of contrast enhancement with "slow" conventional MR techniques, such as routine enhanced images acquired minutes after contrast administration. Accordingly, we used rapid enhanced gradient-echo sequences (14 sec/image) and the region-of-interest method to determine contrast enhancement for various portions of the gland. Enhancement-time curves were then plotted for each portion and compared to determine the sequence of enhancement. Our results show that the timing of contrast enhancement of various parts of the pituitary gland as demonstrated on MR imaging correlates closely with the expected perfusion sequence based on knowledge of regional vascular anatomy. Normal enhancement-time curves of different portions of the pituitary gland were established. This technique and baseline data can be used to evaluate patients with hypopituitarism caused by ischemia.

Adult↗

Half-dose gadolinium-enhanced MR imaging with magnetization transfer technique in brain tumors: comparison with conventional contrast-enhanced MR imaging.

OBJECTIVE: The purpose of this study was to determine whether half-dose enhanced MR imaging with magnetization transfer (MT) saturation can replace standard-dose enhanced MR imaging without MT saturation in patients who have brain tumors. SUBJECTS AND METHODS: Three sets of enhanced T1-weighted MR images were prospectively obtained for each of 25 patients with 32 brain tumors; the first conventional MR images without MT were obtained after administration of standard-dose (0.1-mmol/kg) gadopentetate dimeglumine. Within 1 week, patients underwent administration of one half-dose (0.05 mmol/kg) of the contrast medium, and then two sets of enhanced T1-weighted images were obtained with and then without MT. The degree of contrast enhancement was assessed qualitatively for all 32 tumors and quantitatively for 26 tumors. In the quantitative analysis, we compared mean values for tumor-brain contrast-to-noise ratios in three sets of images. RESULTS: The visual conspicuity of enhancing lesions in half-dose T1-weighted MR images with MT was comparable with that of standard-dose conventional T1-weighted MR images in 43% of cases including most extraaxial tumors. In approximately 75% of cases, the degree of enhancement of the lesions was similar for half-dose T1-weighted images obtained with and without MT. Overall, mean values for tumor-brain contrast-to-noise ratios were significantly lower in half-dose T1-weighted images with MT than in standard-dose T1-weighted images. Also, mean values for tumor-brain contrast-to-noise ratios were significantly higher in half-dose T1-weighted images with MT than in half-dose T1-weighted images without MT. CONCLUSION: Because half-dose enhanced MR imaging with MT yields enhancement comparable with that of standard-dose enhanced conventional MR imaging in less than 50% of cases, the former technique would replace the latter in only limited cases such as selected extraaxial tumors.

Adult↗

Hepatocellular carcinoma treated with radiofrequency ablation: comparison of pulse inversion contrast-enhanced harmonic sonography, contrast-enhanced power Doppler sonography, and helical CT.

OBJECTIVE: The purpose of this study was to compare the efficacy of contrast-enhanced pulse inversion harmonic imaging with contrast-enhanced power Doppler sonography and helical CT to determine incomplete local treatment after radiofrequency ablation in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Thirty-five consecutive patients (24 men and 11 women; mean age, 64 years) with 43 hepatocellular carcinomas (3.6 +/- 1.1 cm) were treated using internally cooled radiofrequency ablation therapy. Therapeutic response was evaluated at 4 months with dual-phase contrast-enhanced helical CT, conventional power Doppler Sonography, and pulse inversion harmonic imaging using a sonographic contrast agent (SH-508). CT and sonographic studies were reviewed separately in random order by four radiologists at different consensus conferences. Sensitivity and specificity of the sonographic methods were determined using CT as a gold standard and results were compared using the McNemar test. RESULTS: CT examinations identified residual tumor in 12 lesions (27.9%). Although conventional contrast-enhanced power Doppler sonography identified residual viable tumor foci in four incompletely treated lesions (9.3%), contrast-enhanced pulse inversion harmonic imaging identified residual tumoral enhancement in 10 lesions (23.3%). Thus, the sensitivity of pulse inversion harmonic imaging (83.3%) was significantly greater (p < 0.05) for detecting residual nonablated tumor compared with conventional contrast-enhanced power Doppler sonography. CONCLUSION: Our study suggests that contrast-enhanced pulse inversion harmonic imaging may enable the detection of residual nonablated tumor in more cases than contrast-enhanced power Doppler sonography and may ultimately prove to be a useful adjunct for percutaneous ablation therapies. Nevertheless, contrast-enhanced axial imaging (CT or MR imaging) is currently the most sensitive test for managing thermal ablation for patients with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Hepatic enhancement in multiphasic contrast-enhanced MDCT: comparison of high- and low-iodine-concentration contrast medium in same patients with chronic liver disease.

OBJECTIVE: The aim of this study was to evaluate the degree of hepatic enhancement and image quality in patients with cirrhosis or chronic hepatitis who underwent multiphasic contrast-enhanced dynamic imaging on MDCT at least twice using standard (300 mg I/mL) and higher (370 mg I/mL) iodine concentrations in contrast medium during follow-up periods. MATERIALS AND METHODS: This study included 20 patients with chronic liver diseases who underwent at least two multiphasic contrast-enhanced dynamic MDCT examinations using 100 mL of standard (300 mg I/mL = group A) and higher (370 mg I/mL = group B) iodine concentrations in contrast medium. After we obtained unenhanced CT scans, we performed multiphasic scanning at 30 sec (arterial phase), 60 sec (portal phase), and 180 sec (late phase) after the start of contrast medium injection. The CT values of hepatic parenchyma, abdominal aorta, and portal vein were measured. The mean enhancement value was defined as the difference in CT values between unenhanced and contrast-enhanced images. Visual image quality was also assessed on the basis of the degree of hepatic and vascular enhancement, rated on a 4-point scale. RESULTS: The mean hepatic parenchyma enhancement values in group B was significantly greater (p < 0.001) than those in group A during the portal phase (43.8 +/- 8.2 H vs 36.2 +/- 7.3 H) and the late phase (33.7 +/- 7.0 H vs 27.3 +/- 3.9 H), but the difference on the arterial phase images between the two groups (9.4 +/- 3.2 H vs 8.3 +/- 2.5 H) was not significant. The mean aorta-to-liver contrast during the arterial phase in group B was significantly higher (p < 0.001) than that in group A (236 +/- 40 H vs 193 +/- 32 H). For qualitative analysis, the mean visual scores for hepatic parenchyma and vasculature enhancement in group B were significantly higher than those in group A in arterial phase (p < 0.018), portal phase (p < 0.0001), and late phase (p < 0.0001). CONCLUSION: In the same patients with chronic liver diseases, a higher iodine concentration (370 mg I/mL) in the contrast medium improves contrast enhancement of liver parenchyma in the portal phase and late phase images, improves overall image quality, and helps improve diagnostic accuracy for liver diseases on multiphasic contrast-enhanced dynamic MDCT.

Aorta, Abdominal↗

Discrete elements within the SV40 enhancer region display different cell-specific enhancer activities.

The SV40 enhancer contains three genetically defined elements, called A, B and C, that can functionally compensate for one another. By using short, synthetic DNA oligonucleotides, we show that each of these elements can act autonomously as an enhancer when present as multiple tandem copies. Analysis of a progressive series of B element oligomers shows a single element is ineffective as an enhancer and that the activity of two or more elements increases with copy number. Assay in five different cell lines of two separate enhancers containing six tandem copies of either the B or C element shows that these elements possess different cell-specific activities. Parallel oligomer enhancer constructs containing closely spaced double point mutations display no enhancer activity in any of the cell lines tested, indicating that these elements represent single units of enhancer function. These elements contain either a 'core' or 'octamer' consensus sequence but these consensus sequences alone are not sufficient for enhancer activity. The different cell-specific activities of the B and C elements are consistent with functional interactions with different trans-acting factors. We discuss how tandem duplication of such dissimilar elements, as in the wild-type SV40 72-bp repeats, can serve to expand the conditions under which an enhancer can function.

Animals↗

Modulatory subdomains of the HS2 enhancer differentially regulate enhancer activity in erythroid cells at different developmental stages.

The HS2 enhancer in the locus control region of human beta-like globin genes displays developmental-stage-independent enhancer function. The mechanism by which it regulates the transcription of the globin genes in erythroid cells throughout development is not fully understood. In this paper we dissect the HS2 enhancer into an enhancer core and five modulatory subdomains M1 to M5. The enhancer core possesses developmental-stage-independent enhancer activity. The modulatory subdomains by themselves do not possess such enhancer activity, but they apparently respond to environmental signals and modulate enhancer core activity in a developmental-stage specific manner. M1 located 5' of the core strongly stimulates core activity in K562 cells at the embryonic stage. M2 and M3 located 3' of the core strongly stimulate core activity in MEL cells at the adult stage. Moreover, M3 suppresses core activity at the embryonic stage and exhibits an adult-stage-selector activity. These findings indicate that the apparent developmental-stage-independence of the HS2 enhancer is a result of multiple interactions between the core and the modulatory subdomains located both near and far from the core.

Adult↗

The effect of MR contrast medium dose on pituitary gland enhancement, microlesion enhancement and pituitary gland-to-lesion contrast conspicuity.

INTRODUCTION: The purpose of this study was to compare the differences in gland enhancement, microlesion enhancement and gland-lesion contrast ratio in patient groups in which half-dose (HD), standard-dose (SD) and double-dose (DD) contrast medium was used in pituitary MR imaging. METHODS: Pituitary gland enhancement and microlesion enhancement were measured and gland-lesion contrast ratios were calculated in 18 patients receiving HD (0.05 mmol/kg), 9 receiving SD (0.1 mmol/kg) and 13 receiving DD (0.2 mmol/kg) contrast medium. Gland enhancement and microlesion enhancement over baseline were determined employing DICOM region of interest measurements and compared after normalization to temporal lobe white matter. Contrast ratios and differences were also calculated and compared. RESULTS: Gland enhancement and lesion enhancement were greater with larger contrast medium doses (gland: HD 50%, SD 99%, DD 132%; microlesion: HD 19%, SD 54%, DD 86%). The gland-lesion contrast ratios were similar with the three doses (25.6%), reflecting expected similar fractional contrast medium distributions in spite of different doses. The signal difference between gland and microlesion, therefore, was a fixed percentage of gland enhancement (DeltaS approximately 26%) with greater signal differences with larger contrast medium doses. CONCLUSION: Greater gland-to-lesion signal differences with larger contrast medium doses would likely improve pituitary microlesion visualization and margin characterization aiding in microlesion detection as well as preoperative planning.

Adolescent↗

Subendocardial enhancement in gadolinium-diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging in aortic stenosis.

We investigated the usefulness of magnetic resonance imaging (MRI) with gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) in assessing myocardial damage from valvular aortic stenosis (AS). Cardiac catheterization and echocardiography were performed in 17 patients with AS. T1-weighted spin-echo sequence was used to obtain magnetic resonance images of short-axis planes of the left ventricle before and after intravenous Gd-DTPA injection in all patients using a 1.5 Tesla imager. Patients were divided into 2 groups according to the presence or absence of regional myocardial enhancement in the images. The Gd-DTPA-enhanced magnetic resonance images of 7 patients showed circumferential subendocardial enhancement. All patients with enhancement had a history of heart failure and were in New York Heart Association functional class III or IV, whereas patients without enhancement were in New York Heart Association functional class I or II. Patients with enhancement had a smaller aortic valve area (0.28 +/- 0.09 vs 0.38 +/- 0.07 cm2/m2, p <0.05), a higher transvalvular pressure gradient (109 +/- 40 vs 68 +/- 18 mm Hg, p <0.05), greater elevation of left ventricular end-diastolic pressure (22 +/- 11 vs 12 +/- 2 mm Hg, p <0.05), and greater reduction in left ventricular ejection fraction (40 +/- 9 vs 59 +/- 10%, p <0.05). Subendocardial enhancement by Gd-DTPA-enhanced MRI was thus shown to be closely related to the severity of AS. In conclusion, Gd-DTPA-enhanced MRI is a new noninvasive tool that can provide useful information about myocardial damage in AS.

Adult↗

Muscle-specific enhancement of gene expression by incorporation of SV40 enhancer in the expression plasmid.

Skeletal muscle is established as an ideal tissue for gene delivery to treat systemic diseases. However, the relatively low levels of gene expression obtained from using naturally occurring promoters, including the strong cytomegalovirus (CMV) enhancer/promoter (E/P), have limited the use of muscle as a target tissue. The relatively weak simian virus 40 (SV40) enhancer is known to have dual functions promoting localization of DNA to the nucleus and activating transcription. An SV40 enhancer incorporated either at the 5' end of CMV E/P or the 3' end of the polyadenylation site gave as much as a 20-fold increase in the level of exogenous gene expression in muscle in vivo, compared with expression observed with CMV E/P alone. The minimum requirement for this enhancement is a single copy of a 72-bp element of the SV40 enhancer, in combination with either the CMV E/P or skeletal actin (SkA) promoter. Enhancement of gene expression in muscle by this SV40 enhancer was also observed by using the powerful electroporation delivery. However, the SV40 enhancer does not increase the level of CMV E/P driven reporter gene expression in dividing tumor cells in vivo and in the dividing myoblast cell C2C12 in vitro. The data suggest that including this enhancer in the plasmid will enhance the level of gene production for muscle-based gene therapy.

Animals↗

Ribosomal gene promoter domains can function as artificial enhancers of RNA polymerase I transcription, supporting a promoter origin for natural enhancers in Xenopus.

Enhancers of RNA polymerase I transcription in higher eukaryotes are repetitive elements within the intergenic spacers of rRNA genes. In Xenopus and mouse, enhancers and the gene promoter bind the activator protein, upstream binding factor, and in Xenopus, enhancers also share sequence similarity with an upstream domain of the promoter. This upstream promoter domain can act as an efficient enhancer when polymerized and cloned adjacent to a ribosomal gene promoter injected into oocytes. A core promoter domain lacking similarity with spacer sequences in Xenopus laevis but analogous to a repeated sequence in Xenopus borealis can also function as an enhancer. These data demonstrate functional relatedness between the promoter and enhancers, supporting the hypothesis that enhancers could have evolved from duplicated promoter domains that bind essential transcription factors. The ability of upstream binding factor to bind enhancers inactivated by mutation suggests that upstream binding factor binding alone cannot explain enhancer function.

Animals↗

Developmental regulation of the kappa locus involves both positive and negative sequence elements in the 3' enhancer that affect synergy with the intron enhancer.

Expression of the mouse immunoglobulin kappa locus is regulated by the intron and 3' enhancers. Previously, we have reported that these enhancers can synergize at mature B cell stages. Here we present our recent studies on the identification and characterization of the 3' enhancer sequences that play important roles in this synergy. By performing mutational analyses with novel reporter constructs, we find that the 5' region of the cAMP response element (CRE), the PU. 1/PIP, and the E2A motifs of the 3' enhancer are critical for the synergy. These motifs are known to contribute to the enhancer activity. However, we also show that mutating other functionally important sequences has no significant effect on the synergy. Those sequences include the 3' region of the CRE motif, the BSAP motif, and the region 3' of the E2A motif. We have further demonstrated that either the 5'-CRE, the PU.1/PIP, or the E2A motif alone is sufficient to synergize with the intron enhancer. Moreover, the PU.1 motif appears to act as a negative element at pre-B cell stages but as a positive element at mature B cell stages. We have also identified a novel negative regulatory sequence within the 3' enhancer that contributes to the regulation of synergy, as well as developmental stage and tissue specificity of expression. While the levels of many of the 3' enhancer binding factors change very little in cell lines representing different B cell stages, the intron enhancer binding factors significantly increase at more mature B cell stages.

Animals↗

Specific nuclear proteins interact with the Rous sarcoma virus internal enhancer and share a common element with the enhancer located in the long terminal repeat of the virus.

We have documented that the Rous sarcoma virus (RSV) internal enhancer functions in the nontransformed Baby Hamster Kidney (BHK) cell line. The sequences within this region were assayed for their ability to bind to specific factors present in BHK nuclear extracts using the gel retardation assay and DNAse I footprinting. At least two sequences within the internal enhancer which can specifically bind nuclear factors in vitro have been identified. These regions are located between nucleotides 813-850 and 856-877. These sites map within the overall region of the internal enhancer which has been shown to be essential for enhancer activity and within the specific region which can function as an orientation independent enhancer. Using the DNase I footprinting and binding data to design an oligonucleotide, we have demonstrated that an oligonucleotide extending from nucleotides 804-877 will substitute efficiently as an enhancer. We also demonstrate that the SV40 enhancer does not compete for the factors which bind to the RSV internal enhancer, whereas an oligonucleotide to the binding site for EFII in the LTR can compete for factor binding to the internal enhancer.

Animals↗

Enhancer requirement for murine cytomegalovirus growth and genetic complementation by the human cytomegalovirus enhancer.

The cytomegalovirus (CMV) enhancer is a highly complex regulatory region containing multiple elements that interact with a variety of host-encoded transcription factors. Many of these sequence elements are conserved among the different species strains of CMV, although the arrangement of the various elements and overall sequence composition of the CMV enhancers differ remarkably. To delineate the importance of this region to a productive infection and to explore the possibility of generating a murine CMV (MCMV) under the control of human CMV (HCMV) genetic elements, the MCMV enhancer was resected and replaced either with nonregulatory sequences or with paralogous sequences from HCMV. The effects of these various deletions and substitutions on viral growth in transfected or infected tissue-culture cells were evaluated. We found that mutations in MCMV that eliminate or substitute for the enhancer with nonregulatory sequences showed a severe deficiency in virus synthesis. This growth defect is effectively complemented by the homologous MCMV enhancer as well as the HCMV enhancer. In the latter case, the chimeric viruses (hybrid MCMV strains) containing the molecularly shuffled human enhancer exhibit infectious kinetics similar to that of parental wild-type and wild-type revertant MCMV. These results also show that open reading frames m124, m124.1, and m125 located within the enhancer region are nonessential for growth of MCMV in cells. Most importantly, we conclude that the enhancer of MCMV is required for optimal infection and that its diverged human counterpart can advantageously replace its role in promoting viral infectivity.

3T3 Cells↗

Dissecting a locus control region: facilitation of enhancer function by extended enhancer-flanking sequences.

Using transgenic mice, we have defined novel gene regulatory elements, termed "facilitators." These elements bilaterally flank, by up to 1 kb, a 200-bp T-cell-specific enhancer domain in the human adenosine deaminase (ADA) gene. Facilitators were essential for gene copy-proportional and integration site-independent reporter expression in transgenic thymocytes, but they had no effect on the enhancer in transfected T cells. Both segments were required. Individual segments had no activity. A lack of facilitator function caused positional susceptibility and prevented DNase I-hypersensitive site formation at the enhancer. The segments were required to be at opposed ends of the enhancer, and they could not be grouped together. Reversing the orientation of a facilitator segment caused a partial loss of function, suggesting involvement of a stereospecific chromatin structure. trans-acting factor access to enhancer elements was modeled by exposing nuclei to a restriction endonuclease. The enhancer domain was accessible to the 4-cutter DpnII in a tissue- and cell-type-specific fashion. However, unlike DNase I hypersensitivity and gene expression, accessibility to the endonuclease could occur without the facilitator segments, suggesting that an accessible chromatin domain is an intermediate state in the activational pathway. These results suggest that facilitators (i) are distinct from yet positionally constrained to the enhancer, (ii) participate in a chromatin structure transition that is necessary for the DNase I hypersensitivity and the transcriptional activating function of the enhancer, and (iii) act after cell-type-specific accessibility to the enhancer sequences is established by factors that do not require the facilitators to be present.

Adenosine Deaminase↗

Focal liver masses: enhancement patterns on contrast-enhanced images--concordance of US scans with CT scans and MR images.

PURPOSE: To assess prospectively the concordance of enhancement patterns of focal liver masses on contrast material-enhanced ultrasonographic (US) scans with patterns on contrast-enhanced computed tomographic (CT) scans or magnetic resonance (MR) images. MATERIALS AND METHODS: This study was approved by the institutional review board; patients gave informed consent. Contrast-enhanced US and contrast-enhanced CT or MR imaging were performed in 135 patients (62 men, 73 women; mean age, 51 years) with 144 confirmed liver masses. Masses included 49 hepatocellular carcinomas, 13 metastases, 30 hemangiomas, 41 lesions of focal nodular hyperplasia, and 11 others. Randomized image sets from each modality were shown independently to three blinded readers, who answered identical questions about enhancement of the lesion and liver in the arterial and portal venous phases and changes with time. Concordance for modalities was calculated from answers of readers and consensus answers between readers, with 95% confidence intervals (CIs). The kappa values were calculated for interreader agreement. RESULTS: Features of arterial phase enhancement showed concordance of more than 76% for modalities. The highest concordance of 92% (132 of 144), with 95% CI of 86% and 95% (kappa>0.84), was for the presence of peripheral pools and centripetal progression. Concordance in the portal venous phase was lower, with agreement for predominant enhancement of the lesion in 61% (86 of 142), with 95% CI of 52% and 68% (kappa>0.83). Portal venous phase washout occurred in 75% (106 of 142), with 95% CI of 67% and 81% (kappa>0.81). The majority of discordances were for malignancies for which only US depicted no sustained enhancement in the portal venous phase. CONCLUSION: US shows high concordance with CT or MR imaging, especially for the arterial phase. Discordance in the portal venous phase may reflect the tendency of CT and MR contrast agents, unlike microbubbles, to diffuse into interstitium.

Adult↗