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HS2 enhancer function is blocked by a transcriptional terminator inserted between the enhancer and the promoter.

The HS2 enhancer in the beta-globin locus control region regulates transcription of the globin genes 10-50 kb away. How the HS2 enhancer acts over this distance is not clearly understood. Earlier studies show that in erythroid cells the HS2 enhancer initiates synthesis of intergenic RNAs from sites within and downstream of the enhancer, and the enhancer-initiated RNAs are transcribed through the intervening DNA into the cis-linked promoter and gene. To investigate the functional significance of the enhancer-initiated transcription, here we inserted the lac operator sequence in the intervening DNA between the HS2 enhancer and the epsilon-globin promoter in reporter plasmids and integrated the plasmids into erythroid K562 cells expressing the lac repressor protein. We found that the interposed lac operator/repressor complex blocked the elongation of enhancer-initiated transcription through the intervening DNA and drastically reduced HS2 enhancer function as measured by the level of mRNA synthesized from the epsilon-globin promoter. The results indicate that the tracking and transcription mechanism of the HS2 enhancer-assembled transcriptional machinery from the enhancer through the intervening DNA into the cis-linked promoter can mediate enhancer-promoter interaction over a long distance.

Blotting, Northern↗

Simian virus 40 revertant enhancers exhibit restricted host ranges for enhancer function.

We have assayed the cell-specific activity of a matched set of four enhancers found in viral revertants derived from simian virus 40 (SV40) enhancer mutants. These enhancers all contain 71-base-pair duplications that span identical regions or, in one case, the same region shifted by 2 nucleotides. The four enhancers differ, however, in that each one either carries a different wild-type pair of the genetically defined SV40 enhancer A, B, or C elements, with the other two elements mutated, or carries all three elements mutated. The three enhancers carrying two copies of a wild-type element effectively enhance transcription in CV-1 and HeLa cells, but only the enhancer containing a duplicated wild-type C element exhibits activity in NIH 3T3 cells. These results show that the ability of the A, B, and C elements to compensate for one another is cell specific and that selection for enhancer function in one cell type can generate enhancers with different cell-specific activities. These results are consistent with the hypothesis that tandem duplication of multiple distinct enhancer elements, as in wild-type strains of SV40 (e.g., the 72-base-pair repeat), has the property of expanding the host range of an enhancer.

Animals↗

Posttherapeutic intraaxial brain tumor: the value of perfusion-sensitive contrast-enhanced MR imaging for differentiating tumor recurrence from nonneoplastic contrast-enhancing tissue.

BACKGROUND AND PURPOSE: Differentiation of tumor recurrence from treatment-related changes may be difficult with conventional MR imaging when newly enhancing lesions appear. Our aim was to determine the value of perfusion-sensitive contrast-enhanced MR imaging for differentiating recurrent neoplasm from nonneoplastic contrast-enhancing tissue. METHODS: Twenty patients in whom new enhancing lesions developed within irradiated regions were examined prospectively with perfusion-sensitive contrast-enhanced MR imaging. Twelve of them also underwent thallous chloride Tl 201 single-photon emission tomography (201Tl-SPECT). Normalized relative cerebral blood volume (rCBV) ratios and thallium indexes were evaluated to determine whether the new enhancing lesions were recurrent or not. Five instances of tumor recurrence and one of radiation necrosis were verified histologically; in the others, tumor recurrence was distinguished by lesions that progressively increased in size on serial MR examinations over at least 5 months, and nonneoplastic contrast-enhancing tissue was distinguished by lesions that disappeared or decreased in size on serial MR studies over at least 9 months. RESULTS: When normalized rCBV ratios were higher than 2.6 or lower than 0.6, enhancing lesions were either recurrent (n = 5) or nonneoplastic contrast-enhancing tissue (n = 3), respectively. All nonneoplastic contrast-enhancing tissue had a low thallium index, whereas three of four recurrent lesions had a high index. CONCLUSION: An enhancing lesion with a normalized rCBV ratio higher than 2.6 or lower than 0.6 may suggest tumor recurrence or nonneoplastic contrast-enhancing tissue, respectively. In these cases, further examination with 201Tl-SPECT may not be necessary. However, when the normalized rCBV ratio is between 0.6 and 2.6, 201Tl-SPECT may be useful in making the differentiation.

Adolescent↗

Detection of liver metastases: gadobenate dimeglumine-enhanced three-dimensional dynamic phases and one-hour delayed phase MR imaging versus superparamagnetic iron oxide-enhanced MR imaging.

The aim of this study was to compare the diagnostic performance of gadobenate dimeglumine (Gd-BOPTA)-enhanced MR imaging, including dynamic phases and one-hour delayed phase, versus superparamagnetic iron oxide (SPIO)-enhanced imaging for detection of liver metastases. Twenty-three patients with 59 liver metastases underwent Gd-BOPTA-enhanced MR imaging (unenhanced, arterial, portal, equilibrium and one-hour delayed phase) using three-dimensional volumetric interpolated imaging and SPIO-enhanced T2-weighted turbo spin-echo and T2*-weighted gradient-echo sequences on a 1.5-T unit. Three observers independently interpreted the three sets of images, i.e. Gd-BOPTA-enhanced dynamic MRI (set 1), delayed phase imaging (set 2) and SPIO-enhanced MRI (set 3). Diagnostic accuracy was evaluated using the alternative-free response receiver operating chracteristic (ROC) analysis. Sensitivity and positive predictive value were also evaluated. The mean accuracy (Az values) and sensitivity of Gd-BOPTA-enhanced delayed phase imaging (0.982, 95.5%) were comparable to those of SPIO-enhanced imaging (0.984, 97.2%). In addition, Az values and sensitivities of both imaging sets were significantly higher than those of Gd-BOPTA-enhanced dynamic images (0.826, 77.4%: p<0.05). There was no significant difference in the positive predictive value among the three image sets. Gd-BOPTA-enhanced delayed phase imaging showed comparable diagnostic performance to SPIO-enhanced imaging for the detection of liver metastases, and had a better diagnostic performance than Gd-BOPTA-enhanced dynamic images.

Adult↗

Breast MRI using the VIBE sequence: clustered ring enhancement in the differential diagnosis of lesions showing non-masslike enhancement.

OBJECTIVE: The purpose of this study was to assess the frequency of a finding in which minute ring enhancements are clustered (defined as clustered ring enhancement) in lesions showing non-masslike enhancement and to evaluate the clinical usefulness of this sign, in addition to that of the BI-RADS MRI descriptors, in the differentiation between benign and malignant lesions. MATERIALS AND METHODS: Retrospective review was performed of 61 consecutive lesions showing non-masslike enhancement. MRI was performed on a 1.5-T system using the volumetric interpolated breath-hold examination (VIBE) sequence. The kinetic parameter was visually assessed as follows: washout, plateau, and persistent. RESULTS: The most frequent morphologic finding among the malignant lesions was heterogeneous internal enhancement (69%) (p = 0.003), followed in frequency by segmental distribution (54%) (p < 0.001); whereas, stippled internal enhancement was the most frequent finding in benign lesions (50%) (p < 0.001). The presence of clustered ring enhancement was found in 63% of the malignant lesions and only 4% of the benign lesions (p < 0.001). The features with the highest positive predictive value for malignancy were a segmental distribution (100%), clustered ring enhancement (96%), and a washout pattern (94%). The specificity of clustered ring enhancement was 96% (25/26). In cases showing focal and regional enhancement, the combination of clumped internal architecture and clustered ring enhancement showed a statistically significant association with malignant lesions (p < 0.001). CONCLUSION: Clustered ring enhancement is thought to be a useful sign to differentiate between benign and malignant lesions, in addition to the BI-RADS MRI descriptors.

Adult↗

Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced versus mangafodipir trisodium-enhanced MR imaging.

OBJECTIVE: The purpose of our study was to compare the diagnostic accuracy and lesion conspicuity of ferumoxides-enhanced MR imaging with those of mangafodipir trisodium-enhanced MR imaging for the preoperative detection of hepatocellular carcinoma. SUBJECTS AND METHODS: Twenty-one patients with 39 hepatocellular carcinomas underwent ferumoxides-enhanced and mangafodipir trisodium-enhanced MR imaging. The diagnosis was established by pathologic examination after surgical resection in all patients. Five MR sequences were obtained 30 min after ferumoxides administration, and two MR sequences were obtained before and 15 min after mangafodipir trisodium administration. Three observers independently interpreted both MR images of all sequences on a segment-by-segment basis. The diagnostic accuracy of MR imaging was assessed using receiver operating characterizing analysis. Lesion (hepatocellular carcinoma > 10 mm in diameter)-to-liver contrast-to-noise ratio was calculated on MR images. RESULTS: Ferumoxides-enhanced MR imaging (A(z) = 0.971) was significantly more accurate (p < 0.05) than mangafodipir trisodium-enhanced MR imaging (A(z) = 0.950). The mean sensitivity of ferumoxides-enhanced MR imaging (86%) was significantly greater (p < 0.05) than that of mangafodipir trisodium-enhanced MR imaging (44%) in lesions smaller than 10 mm. The mean lesion-to-liver contrast-to-noise ratio of hepatocellular carcinoma on ferumoxides-enhanced MR imaging (13.7 +/- 8.8) was significantly greater than on mangafodipir trisodium-enhanced MR imaging (5.4 +/- 5.1) (p < 0.01). CONCLUSION: Ferumoxides-enhanced MR imaging has superior diagnostic accuracy in lesions smaller than 10 mm and superior lesion conspicuity compared with mangafodipir trisodium-enhanced MR imaging for the preoperative detection of hepatocellular carcinoma.

Adult↗

Long-range activation of transcription by SV40 enhancer is affected by "inhibitory" or "permissive" DNA sequences between enhancer and promoter.

The transcriptional enhancer effect is used in many, if not all, organisms for remote control of gene transcription. An enhancer DNA can dramatically stimulate transcription of a linked gene from positions either 5' or 3' to the gene. Both the proximal promoter and the distal enhancer sequences are binding sites for transcription factors. Interaction between promoter and enhancer is mediated by these factors, presumably via looping out of the intervening DNA. Here we report that the extent of remote activation by an enhancer depends on characteristics of that intervening DNA. Using Beta-globin and SV40 T-antigen test genes, we show that the effect of an SV40 enhancer is transmitted to the responsive promoter, with little or no loss of efficiency, through certain segments of mammalian DNA derived from rabbit beta-globin or mouse alpha-globin gene regions. By contrast, a strong reduction of enhancer activity is observed with certain spacer segments of prokaryotic DNA (from plasmid pBR322 or phage lambda) or sequences of high (G + C) content from eukaryotic genes. We have analyzed more closely sequences that are more or less permissive for transmission of the transcriptional enhancer effect. It appears that these permissive sequences generally have a high (A + T) content and notably a very low abundance of CpG dinucleotides. By contrast, (G + C)-rich DNA segments with high local densities of CpG were the most deleterious for long-range enhancer action. We note that the latter sequence composition is typical for "CpG islands" of many mammalian genes, including housekeeping genes and the human alpha-globin gene. This may be related to the finding that promoters of most cell type-specific genes, whose activity depends on a strong enhancer, do not contain CpG islands. Most likely, the spacer DNAs of typical cell type-specific genes have evolved to allow maximal transmission of the enhancer effect.

Animals↗

Identification of an Spl-like element within the immunoglobulin kappa 3' enhancer necessary for maximal enhancer activity.

A number of functional DNA sequences have been identified within the murine immunoglobulin kappa 3' enhancer (kappaE3'). These DNA sequences were identified using plasmid reporter constructs in which the centrally active core region (or mutants of that region) of the enhancer was placed directly adjacent to the promoter of a reporter construct. Functional DNA sequences thus identified were found to bind to the transcription factors PU.1, NF-EM5, E2A, ATF-1, or CREM. In the studies reported here, we show that additional enhancer sequences that lie outside of the core region are necessary for maximal enhancer activity when the core region is not directly adjacent to the promoter. A series of progressive and internal deletion constructs shows that enhancer sequences between nucleotides 275 and 329 are important for enhancer activity. Progressive deletion to nucleotide position 329 resulted in a 4-fold reduction in enhancer activity. Using electrophoretic mobility shift assays, we show that this segment of the enhancer binds to ubiquitously expressed nuclear factors. Dimethyl sulfate methylation interference assays indicated protein-DNA interactions within a G-rich sequence between positions 302 and 306 and an A-rich sequence between positions 319 and 329. Ultraviolet light protein-DNA cross-linking studies revealed nuclear factors of approximately 85 and 105 kDa that bind to the newly identified enhancer region. Oligonucleotide competition studies and binding studies with purified Sp1 or Sp1 antibodies indicate that Sp1 can bind to this sequence. These studies show that functional sequences within the kappaE3' enhancer include an Sp1-like site approximately 90 bp 5' of the central 132 bp region originally believed to account for most of the enhancer activity.

Animals↗

An IgH enhancer that drives transcription through basic helix-loop-helix and Oct transcription factor binding motifs. Functional analysis of the E(mu)3' enhancer of the catfish.

The transcriptional enhancer (E(mu)3') of the IgH locus of the channel catfish, Ictalurus punctatus, shows strong B cell-specific activity and differs from the mammalian E(mu) enhancer in both location and structure. It occurs between the mu and delta genes and contains numerous transcription factor binding sites, predominantly octamer and muE5 motifs of consensus and variant sequences. It lacks the classical muA-muE3(CBF)-muB core array of binding motifs seen within mammalian IgH E(mu) enhancers. To determine the functionally important motifs, a series of mutant enhancers was created using sequence-targeted polymerase chain reaction. Whereas the mutation of consensus and variant octamer motifs (individually or in multiples) decreased enhancer function, mutation of a single consensus muE5 motif destroyed the function of this enhancer in mammalian plasmacytomas. Mutation of this consensus muE5 site, combined with mutations of certain octamer sites, destroyed function in catfish B cells. Experiments using artificial enhancers containing multimers of motifs or short regions of the native enhancer suggested that the minimal E(mu)3' enhancer (a) contains a consensus muE5 site and two octamer sites, (b) is B cell-specific, and (c) is active across species. The dependence of an Ig enhancer on sites that bind basic helix-loop-helix and Oct transcription factors has not previously been observed and confirms large differences in structure and function between fish and mammalian IgH enhancers.

Amino Acid Motifs↗

Enhancer-dependent transcription of the epsilon-globin promoter requires promoter-bound GATA-1 and enhancer-bound AP-1/NF-E2.

We analyzed epsilon-globin transcription in erythroid cells and in erythroid extracts to determine the requirements for enhancer-dependent expression of this gene. Mutations that abolished GATA-1 binding at a single position in the promoter prevented interaction with enhancers, whereas elimination of a second more distal promoter GATA-1 site had no effect. Deletion or mutation of the GATA-1 sites in either the human beta-globin locus control region DNase-hypersensitive site II enhancer or the chicken beta A/epsilon-globin enhancer did not diminish the ability of the enhancers to interact with the promoter. In contrast, mutation of the AP-1/NF-E2 sites in these enhancers resulted in elimination of enhancement. In vitro transcription of these constructs was promoter dependent and was not sensitive to abolition of GATA-1 binding in the promoter, consistent with the role of GATA-1 solely as a mediator of the enhancer effect. Thus, GATA-1 regulates the response of the epsilon-globin gene to enhancers through a specific site in the promoter and requires enhancer AP-1/NF-E2 binding to transduce the enhancer effect on transcription.

Base Sequence↗

Transcription of the HS2 enhancer toward a cis-linked gene is independent of the orientation, position, and distance of the enhancer relative to the gene.

The locus control region (LCR) regulates transcription of the downstream beta-like globin genes 10 to 50 kb away. Among hypersensitive sites HS4, -3, -2, and -1, which define the LCR in erythroid cells, HS2 possesses prominent enhancer function. The mechanism by which the HS2 enhancer and other functional components of the LCR act over the distance is not clear. We have used reverse transcription-PCR and RNase protection assays to analyze the transcriptional statuses of both the endogenous and the transfected HS2 enhancer in erythroid K562 cells. A novel pattern of HS2 enhancer transcription was observed. The endogenous HS2 enhancer was transcribed predominantly in the direction toward the downstream globin genes. The HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids was also transcribed predominantly toward the CAT gene, regardless of whether the enhancer was placed (i) in the genomic or reverse genomic orientation, (ii) in a position 5' or 3' to the gene, or (iii) at various distances up to 6 kb from the gene. The orientation, position, and distance independence in gene-tropic transcription of the HS2 enhancer correlates with the observed orientation, position, and distance independence of HS2 enhancer function and suggests that enhancer transcription may play a role in enhancer function.

Animals↗

Labyrinthine enhancement on gadolinium-enhanced magnetic resonance imaging in sudden deafness and vertigo: correlation with audiologic and electronystagmographic studies.

Sudden deafness with or without vertigo presents a difficult diagnostic problem. This article describes 12 patients with enhancement of the cochlea and/or vestibule on gadolinium-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI), correlating the enhancement with the auditory and vestibular function. All patients were studied with T2-weighted axial images taken through the whole brain, enhanced 3-mm axial T1-weighted images taken through the temporal bone, and enhanced T1-weighted sagittal images taken through the whole brain. Cochlear enhancement on the side of hearing loss was found in all the patients. The vestibular enhancement correlated with both subjective vestibular symptoms and objective measures of vestibular function on electronystagmography. In 2 patients, the resolution of symptoms 4 to 6 months later correlated with resolution of the enhancement on MRI. No labyrinthine enhancement was seen in a series of 30 control patients studied with the same MRI protocol. Labyrinthine enhancement in patients with auditory and vestibular symptoms is a new finding and is indicative of labyrinthine disease. While abnormalities on electronystagmograms and audiograms are nonspecific and only indicate a sensorineural problem, enhanced MRI may separate patients with retrocochlear lesions, such as acoustic neuromas, from those in whom the abnormal process is in the labyrinth or the brain.

Adult↗

Rim enhancement of breast cancers on contrast-enhanced MR imaging: relationship with prognostic factors.

BACKGROUND: There is little evidence regarding associations between magnetic resonance imaging (MRI) features and other important histopathological prognostic factors of breast cancer. The purpose of our study was to investigate the relationship between rim enhancement on MRI and common histopathological prognostic factors of breast cancers. METHODS: We reviewed the contrast-enhanced MR images of 106 consecutive women with histopathologically verified invasive breast carcinomas. Three radiologists assessed the images of each lesion for the presence of rim enhancement on early and delayed images, which were classified into four patterns. Statistical analyses were performed to explore the associations of these patterns with common histopathological prognostic factors and patient age. RESULTS: Positive ratios of lymph node metastasis and blood vessel invasion and negative ratios of hormone receptors were higher in the invasive cancers with rim enhancement than those without rim enhancement. Rim enhancement was more frequent in invasive ductal cancers with a higher histological grade and larger invasive cancers. The pattern of rim enhancement with centripetal progression showed a significantly increased risk of lymph node metastasis and was associated with a larger size of invasive lesion when compared with the other patterns. Invasive cancers with rim enhancement and little change between the early and delayed images and with centrifugal progression showed significantly less hormone receptor positivity than those without rim enhancement. CONCLUSIONS: Rim enhancement patterns of breast cancers on contrast-enhanced MRI are related to common histopathological prognostic factors and these patterns may be valuable in the preoperative evaluation of breast cancers.

Adenocarcinoma, Mucinous↗

[Constructing recombinant plasmid with prostate-specific membrane antigen promoter and reverse enhancer and comparing the transcription activity of enhancers in different directions].

OBJECTIVE: To assess the specificity of prostate-specific membrane antigen(PSMA) promoter and enhancer in controlling gene expression and to compare the activity of enhancers in different directions for choosing the most suitable prostate-specific PSMA controlling elements. METHODS: PSMA enhancer gene was amplified with PCR, then the enhancer gene was subcloned into the expressing vector pEGFP-PSMA(Pro) reversely to construct the recombinant plasmid pEGFP-PSMA(E(r)-p), which was transfected into different cell lines such as LNCaP, PC-3,MCF-7,A549. Green fluorescent protein (GFP) expression was observed and compared to other recombinants constructed previously. RESULTS: The recombinant plasmid with reverse enhancer was successfully constructed, the PSMA promoter and enhancer showed modulating activity in PSMA-expressed cell line uniquely. PSMA enhancer could increase 30-fold transcriptional activity over the basal level achieved by PSMA promoter alone, and no impact of the direction on the activity of enhancer was noted. CONCLUSION: PSMA promoter/ enhancer is specific to PSMA-expressed cells. The transcriptional activity of reverse enhancer is similar to that of enhancer. PSMA promoter/enhancer has the potential for use in targeted gene therapy of prostate adenocarcinoma.

Adenocarcinoma↗

Detection of hepatocellular carcinoma by ferumoxides-enhanced MR imaging in cirrhosis: Incremental value of dynamic gadolinium-enhancement.

PURPOSE: To investigate the incremental value of dynamic gadolinium-enhancement performed immediately after ferumoxides-enhanced magnetic resonance (MR) imaging on the detection of hepatocellular carcinoma in patients with cirrhosis. MATERIALS AND METHODS: We retrospectively reviewed MR scans of 62 cirrhotic patients over a two-year period. Sequences included ferumoxides-enhanced T2-weighted fast spin echo followed by dynamic gadolinium-enhanced T1-weighted spoiled gradient echo. Two readers independently documented the presence of hepatocellular carcinoma on a three-point confidence scale, without and with gadolinium-enhanced images. The presence or absence of hepatocellular carcinoma was established by histopathology (58 patients) or follow-up imaging (four patients) over a mean period of nine months. RESULTS: A total of 71 hepatocellular carcinomas were found in 42 patients. There was no statistically significant difference in sensitivity for the diagnosis of hepatocellular carcinoma without vs. with gadolinium-enhanced images (68% vs. 74% for reader 1 and 62% vs. 73% for reader 2, respectively, P > 1.3). However, both readers showed a lower mean confidence for tumor detection without vs. with gadolinium-enhanced images (2.3 vs. 2.7 for reader 1, 2.3 vs. 2.9 for reader 2, P < 0.01). CONCLUSION: In our study, the addition of dynamic gadolinium-enhancement to ferumoxides-enhanced MR imaging did not improve hepatocellular carcinoma detection, but the addition of gadolinium-enhancement is recommended if ferumoxides-enhanced imaging is used because it increased reader confidence.

Adolescent↗

Short-term evolution of new multiple sclerosis lesions enhancing on standard and triple dose gadolinium-enhanced brain MRI scans.

We compared the short-term magnetic resonance imaging (MRI) evolution of new multiple sclerosis (MS) lesions enhancing after single dose (SD) (0.1 mmol/kg) or triple dose (TD) (0.3 mmol/kg) gadolinium-DTPA (Gd) to explore possible differences in the pathological substrates of acute MS lesions. Brain MRI scans were obtained at baseline and every 4 weeks for a 3-month period in 18 relapsing-remitting MS patients. At each time point, using two separate sessions, we obtained dual echo and T1-weighted scans before and after SD and TD of Gd. New enhancing lesions detected at month 1 and 2 were entered into the analysis. The presence of corresponding hypointense lesions on unenhanced T1-weighted scans and hyperintense lesions on T2/proton density (PD)-weighted images was assessed on the same scan and on the scans performed 1 month before and 1 month after the new lesion development. Persistence of enhancement was evaluated on the SD and TD scans obtained 1 month after new lesion appearance. One-hundred and sixty lesions were studied. Of these, 97 lesions were enhancing after both SD and TD (group A) and 63 lesions only after TD (group B). Thirty (31%) of the lesions enhancing after both SD and TD and ten (16%) of the lesions enhancing only after TD had corresponding T1-weighted lesions (P = 0.03). Of these lesions, 87% in group A and 40% in group B (P = 0.003) were not hypointense on the previous scans. No differences were found in the frequencies of corresponding T2/PD-weighted abnormalities (92% in Group A vs. 87% in Group B lesions). Of these hyperintense areas, 62% in group A and 56% in group B were not present on the previous scans. On follow-up scans, 52% of the lesions enhancing after SD and TD and 70% of the lesions enhancing only after TD did not show enhancement after the injection of both the doses of Gd (P = 0.02). The frequencies of corresponding T2/PD and T1-weighted abnormalities were higher in Group A than in Group B lesions, but the differences were not statistically significant. Our findings suggest that the pathological process is less severe in MS lesions enhancing only after TD injection than in those enhancing after the SD.

Adult↗

Hepatocellular carcinoma in cirrhosis: enhancement patterns at dynamic gadolinium- and superparamagnetic iron oxide-enhanced T1-weighted MR imaging.

PURPOSE: To prospectively compare intraindividual differences in enhancement patterns between gadolinium- and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging in patients with histologically proved hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty-two patients (18 men, four women; mean age, 58.9 years) with 36 pathologically proved HCC lesions underwent contrast material-enhanced dynamic T1-weighted gradient-echo MR imaging twice. Gadopentetate dimeglumine was used at the first session. After a mean interval of 5 days, a second session was performed with a bolus-injectable SPIO agent, ferucarbotran. Qualitative analysis of contrast enhancement patterns with each agent during hepatic arterial, portal venous, and equilibrium phases was performed by two readers who classified lesions as isointense, hypointense, or hyperintense compared with surrounding liver parenchyma and searched for presence of hyperintense peritumoral ring enhancement. Results of signal intensity analysis during different vascular phases at both sessions were compared by using the McNemar test, and kappa statistic was used to evaluate agreement between signal intensity and enhancement pattern of lesions during different vascular phases. RESULTS: On gadolinium-enhanced hepatic arterial phase images, HCC lesions (n = 36) were hyperintense in 21 (58%) cases, hypointense in 10 (28%), and isointense in five (14%). On ferucarbotran-enhanced hepatic arterial phase images, HCC lesions were isointense in 18 (50%) cases, hypointense in 11 (31%), and hyperintense in seven (19%). On gadolinium-enhanced portal venous and equilibrium phase images, respectively, HCC lesions were hypointense in 17 (47%) and 21 (58%) cases, hyperintense in 10 (28%) cases and one (3%) case, and isointense in nine (25%) and 14 (39%) cases. On ferucarbotran-enhanced portal venous and equilibrium phase images, respectively, HCC lesions were hypointense in 15 (42%) and 11 (31%) cases, hyperintense in three (8%) and three (8%) cases, and isointense in 18 (50%) and 22 (61%) cases. CONCLUSION: For HCC, contrast enhancement pattern on T1-weighted gradient-echo MR images shows marked variability with gadolinium or SPIO contrast agents.

Adult↗

Healthy premenopausal breast parenchyma in dynamic contrast-enhanced MR imaging of the breast: normal contrast medium enhancement and cyclical-phase dependency.

PURPOSE: To define the range of normal contrast medium enhancement, the variability in contrast medium enhancement patterns in healthy premenopausal breast parenchyma, and the implications for management strategies in cases with incidental contrast medium-enhancing foci on breast magnetic resonance (MR) images. MATERIALS AND METHODS: Twenty healthy volunteers (aged 21-41 years) were examined on a 1.5-T system (dynamic two-dimensional gradient-echo protocol with subtraction postprocessing) during each week of a menstrual cycle (group 1) or over 4 months (group 2). The authors evaluated changes in the number of enhancing foci and the respective enhancement patterns within a cycle and between cycles. RESULTS: Both diffuse and nodular enhancement of breast parenchyma occurred during all phases of the menstrual cycle, especially in weeks 1 and 4. Enhancement was lowest in week 2. A total of 60 enhancing foci (73% of which resolved completely during follow-up) were found in 16 of 20 volunteers. Twenty-six foci demonstrated enhancement velocities beyond the malignancy threshold (>80% increase in the 1st minute). CONCLUSION: Contrast-enhancing foci are normal in healthy premenopausal breasts, even when formal malignancy criteria of enhancement velocity are met. This has to be kept in mind to avoid false-positive results, especially in younger patients.

Adult↗