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PubMed1989

A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes.

Exposure of skeletal myoblasts to growth factor-deficient medium results in transcriptional activation of muscle-specific genes, including the muscle creatine kinase gene (mck). Tissue specificity, developmental regulation, and high-level expression of mck are conferred primarily by a muscle-specific enhancer located between base pairs (bp) -1350 and -1048 relative to the transcription initiation site (E. A. Sternberg, G. Spizz, W. M. Perry, D. Vizard, T. Weil, and E. N. Olson, Mol. Cell. Biol. 8:2896-2909, 1988). To begin to define the regulatory mechanisms that mediate the selective activation of the mck enhancer in differentiating muscle cells, we have further delimited the boundaries of this enhancer and analyzed its interactions with nuclear factors from a variety of myogenic and nonmyogenic cell types. Deletion mutagenesis showed that the region between 1,204 and 1,095 bp upstream of mck functions as a weak muscle-specific enhancer that is dependent on an adjacent enhancer element for strong activity. This adjacent activating element does not exhibit enhancer activity in single copy but acts as a strong enhancer when multimerized. Gel retardation assays combined with DNase I footprinting and diethyl pyrocarbonate interference showed that a nuclear factor from differentiated C2 myotubes and BC3H1 myocytes recognized a conserved A + T-rich sequence within the peripheral activating region. This myocyte-specific enhancer-binding factor, designated MEF-2, was undetectable in nuclear extracts from C2 or BC3H1 myoblasts or several nonmyogenic cell lines. MEF-2 was first detectable within 2 h after exposure of myoblasts to mitogen-deficient medium and increased in abundance for 24 to 48 h thereafter. The appearance of MEF-2 required ongoing protein synthesis and was prevented by fibroblast growth factor and type beta transforming growth factor, which block the induction of muscle-specific genes. A myoblast-specific factor that is down regulated within 4 h after removal of growth factors was also found to bind to the MEF-2 recognition site. A 10-bp sequence, which was shown by DNase I footprinting and diethyl pyrocarbonate interference to interact directly with MEF-2, was identified within the rat and human mck enhancers, the rat myosin light-chain (mlc)-1/3 enhancer, and the chicken cardiac mlc-2A promoter. Oligomers corresponding to the region of the mlc-1/3 enhancer, which encompasses this conserved sequence, bound MEF-2 and competed for its binding to the mck enhancer. These results thus provide evidence for a novel myocyte-specific enhancer-binding factor, MEF-2, that is expressed early in the differentiation program and is suppressed by specific polypeptide growth factors. The ability of MEF-2 to recognize conserved activating elements associated with multiple-specific genes suggests that this factor may participate in the coordinate regulation of genes during myogenesis.

Animals↗

PubMed2006

A weakened transcriptional enhancer yields variegated gene expression.

Identical genes in the same cellular environment are sometimes expressed differently. In some cases, including the immunoglobulin heavy chain (IgH) locus, this type of differential gene expression has been related to the absence of a transcriptional enhancer. To gain additional information on the role of the IgH enhancer, we examined expression driven by enhancers that were merely weakened, rather than fully deleted, using both mutations and insulators to impair enhancer activity. For this purpose we used a LoxP/Cre system to place a reporter gene at the same genomic site of a stable cell line. Whereas expression of the reporter gene was uniformly high in the presence of the normal, uninsulated enhancer and undetectable in its absence, weakened enhancers yielded variegated expression of the reporter gene; i.e., the average level of expression of the same gene differed in different clones, and expression varied significantly among cells within individual clones. These results indicate that the weakened enhancer allows the reporter gene to exist in at least two states. Subtle aspects of the variegation suggest that the IgH enhancer decreases the average duration (half-life) of the silent state. This analysis has also tested the conventional wisdom that enhancer activity is independent of distance and orientation. Thus, our analysis of mutant (truncated) forms of the IgH enhancer revealed that the 250 bp core enhancer was active in its normal position, approximately 1.4 kb 3' of the promoter, but inactive approximately 6 kb 3', indicating that the activity of the core enhancer was distance-dependent. A longer segment--the core enhancer plus approximately 1 kb of 3' flanking material, including the 3' matrix attachment region--was active, and the activity of this longer segment was orientation-dependent. Our data suggest that this 3' flank includes binding sites for at least two activators.

3' Flanking Region↗

PubMed1992

Dynamic MR imaging of the abdomen with gadopentetate dimeglumine: normal enhancement patterns of the liver, spleen, stomach, and pancreas.

To show the normal contrast enhancement patterns of the upper abdominal organs, dynamic gadopentetate dimeglumine-enhanced MR imaging of the upper abdomen was performed in 48 patients. Although all patients were originally examined for focal hepatic lesions, none of them had diffuse parenchymal disease of any of the examined organs. Dynamic gadopentetate dimeglumine-enhanced MR imaging was done by using a heavily T1-weighted gradient-echo sequence (100/5 [TR/TE], 80 degrees flip angle) performed before, and repeatedly for a period of 10 min after, an IV bolus injection of gadopentetate dimeglumine (0.1 mmol/kg). Signal enhancement in each of the organs was calculated by measuring the signal intensity before and after administration of contrast medium. All organs showed signal enhancement within the first 2 min (p less than .001) and a continuous decline thereafter. The enhancement of the pancreas, liver, stomach wall, spleen, and renal cortex reached peaks of 75%, 78%, 96%, 144%, and 216%, respectively, 45 sec after administration of contrast medium. Liver and pancreas showed a homogeneous enhancement pattern throughout the examination. The spleen appeared heterogeneous during the first 60 sec and homogeneous thereafter. Two zones could be distinguished on the contrast-enhanced images of the stomach wall: an enhanced inner zone and an unenhanced outer zone. We conclude that homogeneous enhancement of the liver and pancreas, early heterogeneous enhancement of the spleen, and enhancement of the inner gastric wall are normal patterns on dynamic gadopentetate dimeglumine-enhanced MR images.

Contrast Media↗

PubMed1998

Usefulness of optimized gadolinium-enhanced fast fluid-attenuated inversion recovery MR imaging in revealing lesions of the brain.

OBJECTIVE: The purpose of this study was to compare the contrast enhancement of lesions of the brain revealed by gadolinium-enhanced optimized fast fluid-attenuated inversion recovery (FLAIR) MR imaging with that of lesions on gadolinium-enhanced optimized T1-weighted spin-echo MR imaging. SUBJECTS AND METHODS: Using computer simulations, we optimized the fast FLAIR parameters (TR, TEeff, and inversion time) and the T1-weighted spin-echo parameters (TR and TE) to provide maximum difference in signal intensity between enhancing lesions of the brain and white matter. Seventy-six consecutive patients referred for single-dose gadolinium-enhanced MR imaging of the brain underwent both optimized techniques, which were matched for spatial resolution, bandwidth, and number of excitations. The gadolinium-enhanced fast FLAIR and T -weighted spin-echo MR images were evaluated independently by two observers for number and size of enhancing lesions and for the degree of gray-white matter differentiation. Contrast-to-noise ratios were measured for enhancing lesions 1.0 cm or larger in diameter using 8 x 8 pixel regions of interest in the enhancing lesions and normal white matter. RESULTS: The most revealing parameters for fast FLAIR MR imaging proved to be a TR of 1500 msec, an inversion time of 683 msec, and a TEeff of 16 msec. For T1-weighted spin-echo MR imaging, the optimized parameters were a TR of 550 msec and a TE of 16 msec. In 28 patients, we saw enhancing lesions of the brain with at least one MR imaging technique. More lesions were seen on the T1-weighted spin-echo sequence (n = 141) than on the fast FLAIR sequence (n = 94) (p < .03). Gray-white matter differentiation was significantly better on the fast FLAIR sequence (p < .001). Contrast-to-noise ratios of enhancing lesions were greater on the T1-weighted spin-echo sequence (p < .001). CONCLUSION: In this study, optimized gadolinium-enhanced conventional T1-weighted spin-echo MR imaging proved superior to gadolinium-enhanced fast FLAIR MR imaging in revealing lesions of the brain.

Adult↗

PubMed2003

Contrast-enhanced agent detection imaging: value in the characterization of focal hepatic lesions.

OBJECTIVE: To assess the value of SH U 508A-enhanced agent detection imaging in the characterization of focal hepatic lesions. METHODS: Contrast-enhanced agent detection imaging was performed on 78 focal hepatic lesions: 34 hepatocellular carcinomas, 22 metastases, 9 hemangiomas, 9 abscesses, 3 cysts, and 1 focal nodular hyperplasia. After administration of SH U 508A, interval delay scanning with agent detection imaging was performed with intervals of approximately 7 seconds (phase I), 30 seconds (phase II), and 90 seconds (phase III) after the first arrival of the contrast agent to the liver. Two observers blinded to the final diagnosis reviewed selected images and assessed the enhancement patterns of the lesions. For quantitative analysis, we calculated the enhancement ratio of the lesions and the difference of enhancement between the lesions and the liver parenchyma. RESULTS: Agent detection imaging showed a distinctive enhancement pattern in focal liver lesions compared with that in the liver. Hepatocellular carcinomas were characterized by early enhancement (phase I) and washout (phases II and III; sensitivity, 94.1%; specificity, 93.2%; positive predictive value, 91.4%). Metastases showed peripheral rim or targetlike enhancement (phase I, phase II, or both) and a defect (phase III) and had sensitivity of 77.3%, specificity of 100%, and a positive predictive value of 100%. Hemangiomas showed peripheral nodular or inhomogeneous (phase I, phase II, or both) and gradually centripetal (phase II, phase III, or both) enhancement (sensitivity, 88.9%; specificity, 100%; positive predictive value, 100%). Abscesses were partially enhanced from phase I to phase III (sensitivity, 66.7%; specificity, 95%; positive predictive value, 85.7%). The results of the quantitative analysis of lesion enhancement were compatible with those of the qualitative analysis. CONCLUSIONS: SH U 508A-enhanced agent detection imaging may yield distinctive enhancement characteristics in focal liver lesions that would contribute positively to the characterization of these hepatic lesions.

Adult↗

PubMed1991

Identification and localization of an enhancer for the human lambda L chain Ig gene complex.

A strong transcriptional enhancer was identified for the human lambda L chain Ig gene complex. Enhancer activity was measured by activation of the chloramphenicol acetyl transferase (CAT) gene in a transient assay using both mouse and human B lymphoid cell lines. The smallest fragment identified with enhancer activity was 111 bp, which resides 11.7 kb downstream (3') of C lambda 7, a constant region gene we have recently isolated and identified as functional in the human population. Enhancer activity is orientation independent, tissue specific (active in all B cell lines tested and not in a T cell line), and independent of NF kappa B, similar to the mouse lambda enhancers recently reported. The human lambda enhancer is active in both mouse and human B cell lines; interestingly, the mouse lambda enhancers are active in mouse lines but not in a human B cell line. DNA sequence comparison of the mouse and human lambda enhancers indicates a higher degree of homology (average of 72.5%) within the 111-bp enhancer core region identified here than for the remaining flanking sequence compared (average of 42%). This discovery of an enhancer in the human lambda locus (HuE lambda), which is clearly distinct from that of the H and L chain loci, will help to determine the mechanism for the ordered expression and rearrangement of these gene complexes in B cell ontogeny. The presence of only one enhancer in the human C lambda complex 3' of all the C genes suggests that the evolutionary duplication of the L locus differs from that seen in mouse; in mouse the duplication unit was JCJC-enhancer, whereas the human JC lambda s duplicated without the enhancer.

Animals↗

PubMedDate not supplied

Multiple sclerosis lesions: relationship between MR enhancement pattern and magnetization transfer effect.

PURPOSE: To investigate the relationship between the enhancement pattern of a multiple sclerosis lesion and its magnetization transfer effect. METHODS: Fifty-four lesions were chosen from 29 patients with multiple sclerosis on the basis of enhancement pattern on contrast-enhanced T1-weighted MR images. They included 14 homogeneously enhancing lesions, 26 nonenhancing lesions, and 14 ring-enhancing lesions. Magnetization transfer ratios of the homogeneously enhancing lesions, nonenhancing lesions, and central portion of the ring-enhancing lesions were measured. Means were calculated and compared. RESULTS: The magnetization transfer ratios for homogeneously enhancing lesions were higher (mean, 32.2%; SD, 3.4%) than those for nonenhancing lesions (mean 29.4%; SD, 4.3%) and for the central portion of ring-enhancing lesions (mean, 24.5%; SD, 4.0%). Significant differences were found between the ring-enhancing lesions and the homogeneously enhancing lesions and between the ring-enhancing lesions and the nonenhancing lesions. CONCLUSION: We found a relationship between decreased magnetization transfer ratios and those enhancement patterns in which myelin is known to be decreased histopathologically. Thus, use of the magnetization transfer technique may increase the specificity of MR imaging in assessing the extent of residual myelination in multiple sclerosis lesions.

Blood-Brain Barrier↗

PubMed1997

Computer-assisted quantitation of enhancing lesions in multiple sclerosis: correlation with clinical classification.

PURPOSE: To study the utility of a computer-assisted method of quantitating enhancing multiple sclerosis (MS) lesions and to correlate this quantitation with the type and duration of disease. METHODS: Forty untreated patients with MS were studied. The patients had been classified clinically as having either relapsing-remitting (n = 27) or chronic-progressive (n = 13) disease. Postcontrast contiguous 3-mm-thick MR images of the brain were obtained for up to 3 years. The computer program selected potential lesion sites automatically on the basis of the theory of "fuzzy connectedness," which was incorporated into 3DVIEWNIX software. True lesions were selected from these previously detected potential lesions by means of yes/no responses to the program query. The number of enhancing lesions and the enhancing lesions volume were subsequently computed. RESULTS: The enhancing lesion volume in patients with relapsing-remitting disease was statistically significantly higher than that of patients with chronic-progressive disease. There was a strong positive correlation between the number of enhancing lesions and the enhancing lesion volume. No significant correlation was noted between the change in score on the expanded disability status scale (EDSS) and the change in the number of enhancing lesions, or between the change in EDSS score and the change in enhancing lesion volume. A negative correlation was found between enhancing lesion volume and duration of disease, and between the number of enhancing lesions and duration of disease in the patients who had enhancing lesions. CONCLUSIONS: Our data suggest that enhancing lesion volume reflects differences in the classification of clinical MS and in the disease activity over time. Computer-assisted quantitation of enhancing lesion volume is a robust, practical, and objective measure of MS activity.

Adult↗

PubMed2003

Structure-activity relationship for chemical skin permeation enhancers: probing the chemical microenvironment of the site of action.

Studies were previously conducted in our laboratory on the influence of n-alkanols, 1-alkyl-2-pyrrolidones, N,N-dimethlyalkanamides, and 1,2-alkanediols as skin permeation enhancers on the transport of a model permeant, corticosterone (CS). The experiments were conducted with hairless mouse skin (HMS) in a side-by-side, two-chamber diffusion cell, with enhancer present in an aqueous buffer in both chambers. The purpose of the present study was to extend these studies and investigate in greater detail the hypothesis that a suitable semipolar organic phase may mimic the microenvironment of the site of enhancer action, and that the enhancer partitioning tendency into this organic phase may be used to predict the enhancer potency. CS flux enhancement along the lipoidal pathway of HMS stratum corneum was determined with the 1-alkyl-2-azacycloheptanones, 1-alkyl-2-piperidinones, 1,2-dihydroxypropyl decanoate, 1,2-dihydroxypropyl octanoate, n-alkyl-beta-D-glucopyranosides, 2-(1-alkyl)-2-methyl-1,3-dioxolanes, 1,2,3-nonanetriol, and trans-hydroxyproline-N-decanamide-C-ethylamide as enhancers. Enhancement factors (E values) were calculated from the permeability coefficient and solubility data over a range of E values. Comparisons of the enhancer potencies for all studied homologous series and the carbon number of the n-alkyl group revealed a nearly semilogarithmic linear relationship with a slope of approximately 0.55, which is consistent with the hydrophobic effect. Moreover, comparisons of the enhancer potencies of all the enhancers with the n-hexanol-phosphate buffered saline (PBS), n-octanol-PBS, n-decanol-PBS, and n-hexane-PBS partition coefficients showed very good correlations for the n-alkanol solvents but not for n-hexane. This result supports the interpretation that the enhancer potency is directly related to the ability of the enhancer molecule to translocate to a site of action via its free energy of transfer from the bulk aqueous phase to a semipolar microenvironment in the stratum corneum lipid lamella that is well mimicked by water-saturated n-alkanols.

Adjuvants, Pharmaceutic↗

PubMed1997

Early postoperative MRI findings following surgery for herniated lumbar disc. Part II: A gadolinium-enhanced study.

The aim of our study was to evaluate the contrast-enhanced MR imaging (MRI) findings, in the early postoperative period, in unselected patients undergoing lumbar microdiscectomy (15/16 had total resolution of their symptoms). Contrast-enhanced imaging studies were performed, in all 16 patients of our series, before surgery, and at the third postoperative day and, two months after surgery. Postoperative paraspinal muscles enhancement was present in all patients. In the postoperative period, nerve root enhancement was present in 5/16 patients at the early survey and persisted in one after two months. A pseudohernia depicted as epidural intermediate signal intensity tissue, was seen in 13 patients at the third day MRI, and only in eight after two months. This pseudohernia enhanced peripherally in 8/13 patients and enhanced homogeneously in the remaining five at the first postsurgical examination; in the late MRI the peripheral enhancement was appreciable in only two patients while a homogeneous enhancement was observed in six. Clinical symptoms resolved completely in 14/16 patients on clinical evaluation at the third postoperative day, while the remaining two patients showed residual symptoms and signs of radicular compression. At the early MRI these two patients showed intradural nerve root enhancement. Two months later, one patient did not show the previously described nerve root enhancement and improved clinically, while the other had a positive Straight Leg Raising Sign with persistent intradural nerve root enhancement. In conclusion, no correlation between clinical course and contrast-enhancement of pseudohernia and extradural nerve root was appreciable, although intradural nerve root enhancement seems to represent a clinically relevant finding.

Adult↗

PubMed1999

Transcellular and lipophilic complex-enhanced intestinal absorption of human growth hormone.

PURPOSE: To evaluate the transcellular mechanism of novel enhancers absorption enhancement of human growth hormone (hGH), by examining the involvement of a P-glycoprotein-like efflux system, changes in membrane fluidity, and membrane damage. METHODS: Caco-2 cell monolayers were grown on Snapwell filter supports and placed in a side-by-side diffusion apparatus. Transport in both the apical to basolateral (AP to BL) and basolateral to apical (BL to AP) direction was measured at different temperatures and in the presence of potential inhibitors. Fluorescence anisotropy measurement was used to measure membrane fluidity. The fluorescence anisotropy of DPH- and TMA-DPH-labeled cell suspensions was measured at room temperature. LDH (a measure of cytosolic lactate dehydrogenase) leakage assay was used to evaluate cytotoxicity. RESULTS: The bi-directional transepithelial fluxes of hGH in the presence of these novel enhancers across Caco-2 cells showed marked asymmetry. Average permeability coefficient values obtained in the apical to basolateral (AP to BL) direction were lower than those of the reverse (BL to AP) direction. On the other hand, the fluxes for hGH alone were symmetric. When P-gp-like efflux inhibitors were included in the transport medium, the permeability coefficient value of BL to AP direction was significantly decreased while the transport was increased in the reverse direction in the presence of novel enhancers. In addition, lowering the temperature to 25 degrees C completely eliminated the asymmetry of hGH transport in the presence of novel enhancers. It was also shown by fluorescence anisotropy that these novel enhancers alone only slightly increased membrane fluidity. On the other hand, upon addition of hGH to the novel enhancers, the cell membrane showed a dramatic change as compared to treatment with novel enhancers alone. The results from the LDH assay showed that the novel enhancers and/or hGH did not cause cell damage, at least up to 1 hour, and the damage seen at the 2 hour point is also much lower than other known enhancers. CONCLUSIONS: This study shows that human growth hormone alone cannot be transported across Caco-2 cells, except in small quantities, by passive diffusion, but in the presence of novel enhancers, human growth hormone permeation is substantial. In addition, the asymmetry of transport of the complexed hGH appears to be due to a P-gp-like efflux system. Assuming that the present substrate specificity of the P-gp-like efflux system shows the same preference for hydrophobic molecules as p-gp, the present work also indirectly shows that human growth hormone has become more lipophilic in the presence of these novel enhancers. Furthermore, membrane fluidity data also supports the premise that these novel enhancers interact and stabilize hGH, to make them more hydrophobic and easier to be transported through cell membranes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Soy-enhanced lunch acceptance by preschoolers.

OBJECTIVE: To evaluate acceptance of soy-enhanced compared with traditional menus by preschool children. Soy-enhanced foods were substituted on a traditional cycle menu, and the amount eaten, energy, and nutrient values for traditional and soy-enhanced lunches were compared. DESIGN: A traditional three-week cycle menu, using the Child and Adult Care Food Program (CACFP) meal pattern guidelines, was used to develop a comparable soy-enhanced menu. Traditional and soy-enhanced lunches were randomly assigned to respective days. Foods were portioned onto individual plates using standardized measuring utensils. Individual plate waste techniques were used to collect food waste. Subjects/setting Participants were preschool children, three to six years of age and of white and Hispanic origin, attending a part-day Head Start program. Statistical analyses performed Analysis of covariance was used to adjust lunch and food intakes for differences in average amounts of foods served. The Nutrient Data System was used to calculate energy and nutrient content of lunches. Analysis of variance was used to calculate differences in amounts eaten, energy values, and nutrient values of traditional and soy-enhanced lunches and foods. Data analyses were performed with the Statistical Analysis Software (version 8.0, 1999, SAS Institute, Cary, NC). RESULTS: Soy-enhanced foods were successfully substituted for 23 traditional foods included in the cycle menus. Soy-enhanced foods tended to be higher in energy, protein, and iron. Traditional lunches tended to be higher in fat, saturated fat, and vitamin A. Consumption was significantly less for energy, protein, fiber, and iron from foods eaten from traditional compared with soy-enhanced lunch menus. Applications/conclusions Acceptance of soy-enhanced lunches was shown because there were no significant differences in the average amount eaten (grams per meal) between traditional and soy-enhanced lunches. Preschool programs can substitute soy-enhanced for traditional foods, which will add variety to the diet without sacrificing taste, energy, or nutrient value. The fat and energy content of the lunches was higher than recommended, and soy-enhanced foods were not always lower in fat. There is a need for the food industry and foodservice personnel to address the energy and fat content of all foods served in lunches to preschool children because a few extra calories added to the daily intakes can contribute to weight gain.

Analysis of Variance↗

PubMed2002

Dynamic enhancement features of gadophrin-2 on magnetic resonance imaging: an experimental model of VX2 carcinoma and bacterial abscess in rabbit thigh.

RATIONALE AND OBJECTIVES: To determine the dynamic enhancement features of malignant tumor and bacterial abscess in rabbits on magnetic resonance imaging (MRI) after injection of gadolinium mesoporphyrin (gadophrin-2) and to correlate them with histopathologic findings. METHODS: Six VX2 carcinomas and six bacterial abscesses were experimentally induced in either thigh of six rabbits. Dynamic T1-weighted MRI was performed before and 1, 3, 5, 10, 30 minutes and 16, 21, 72 hours after intravenous injection of gadophrin-2 (0.05 mmol/kg). The enhancement ratios of lesions were calculated for each time point. All tumors and abscesses were sectioned along the same plane of MR images for a detailed MRI-histopathologic correlation. RESULTS: In tumors and abscesses, peripheral-rim enhancement appeared on MRI at 1, 3, 5, 10, 30 minutes after injection of gadophrin-2. The lesions showed peripheral enhancement with irregular central enhancement or diffuse enhancement after 16 and 21 hours, and there was diffuse enhancement of the entire lesion after 72 hours. Enhancement ratios in tumor-necrosis mixed area and the pure necrotic area in VX2 carcinoma and the central cavity in bacterial abscess were significantly lower than that in the compact cellular portion in VX2 carcinoma and the wall of abscess at early phase (P < 0.01). On delayed phase MRI, there was no statistical significance in enhancement ratio of three histologic parts of VX2 carcinoma (P > 0.05) and two histologic parts of abscess (P > 0.05). Rapid enhancement at early phase with diminishing signal intensity at delayed phase is indicative of viable compact tumor and delayed strong enhancement is indicative of necrosis. CONCLUSION: It is difficult to distinguish an abscess from a tumor on gadophrin-2 enhanced MRI especially when intratumoral necrosis is prominent. However, the trend and degree of enhancement by gadophrin-2 could be helpful in discrimination between viable tumor and tumor necrosis.

Abscess↗

PubMed1998

Contrast-enhanced magnetic resonance imaging in conservative management of lumbar disc herniation.

STUDY DESIGN: This study was designed to investigate the morphologic changes in contrast-enhanced magnetic resonance imaging that occur during conservative treatment of patients with unilateral leg pain resulting from herniated nucleus pulposus without significant lumbar canal stenosis. OBJECTIVES: To compare the morphologic results with clinical outcomes to ascertain whether enhanced magnetic resonance imaging contributes to the management of lumbar disc herniation. SUMMARY OF BACKGROUND DATA: Contrast-enhanced magnetic resonance imaging has already been reported to be useful in the postoperative examination of the lumbar spine and in visualization of symptomatic nerve roots. However, there have been few reports about its usefulness in the conservative management of herniated nucleus pulposus or about the correlation between herniated nucleus pulposus regression and enhanced effect. The study population consisted of 48 patients with radiculopathy. All patients primarily reported unilateral leg pain, and 94% had positive tension signs. Additionally, 38% exhibited muscle weakness corresponding to the symptomatic nerve root. METHODS: All patients were studied twice or more using gadolinium-magnetic resonance imaging during conservative therapy, at a mean interval of 191 days. Changes in the size of the herniated nucleus pulposus on precontrast images fell into four categories, with changes in enhancement on postcontrast images classified into two categories: "enlargement" and "no change." RESULTS: In all cases of migrating type herniated nucleus pulposus, circular enhancement was seen on postcontrast images. In 17 of 22 cases, the enhanced area gradually thickened and intruded into the migrated disc materials as the size of the herniated nucleus pulposus decreased; the herniated nucleus pulposus disappeared in nine cases and showed a marked decrease in seven cases. These cases showed good clinical courses of sciatica. In the other five patients, in whom there were no changes in the enhanced area, there was less of a tendency for the herniated nucleus pulposus to decrease in size, and there were poorer clinical results. In six cases of extruding-type herniated nucleus pulposus, no enhanced effects were observed throughout the follow-up period. The other 20 cases showed enhancement that was relatively weaker than that of migrating disc herniation. Extension or expansion of the enhanced area was observed in the follow-up images of 15 cases, though only four showed obvious changes in the size of the herniated nucleus pulposus. These 15 cases had better clinical results than the other cases, in which enhanced effects did not change or were not observed. CONCLUSION: Contrast-enhanced magnetic resonance imaging is a useful prognostic parameter, and multiple use contributes to the proper management of lumbar disc herniation.

Adult↗

PubMed1997

Normal placenta: gadolinium-enhanced dynamic MR imaging.

PURPOSE: To establish the appearance of the normal placenta on dynamic, gadolinium-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: Eleven patients underwent MR imaging for suspected uterine (four patients) or placental (seven patients) abnormalities (but not placental insufficiency or intrauterine growth retardation). Unenhanced or gadolinium-enhanced, T1-weighted, fat suppressed, spoiled gradient-recalled-echo MR images and T2-weighted, half-Fourier, single-shot, spin-echo-train MR images were obtained. Two investigators retrospectively evaluated the images to determine the rate, pattern, and degree of placental contrast material enhancement with myometrial enhancement as a reference. RESULTS: The diagnoses were normal placenta (six patients), abnormal placental position (four patients), and subchorionic hematoma (one patient). The placenta rapidly and intensely enhanced on images acquired immediately after contrast material administration and preceded substantial enhancement of the myometrium. Immediately postcontrast images showed closely packed 2-3-cm lobules of placental enhancement in third-trimester pregnancies and heterogeneous placental enhancement in second-trimester pregnancies. In all cases, placental enhancement became more homogeneous over time. The placenta could be readily distinguished from the myometrium. All neonates were healthy with no evidence of intrauterine growth retardation. CONCLUSION: Normal placental enhancement is intense on immediately postcontrast images and precedes substantial myometrial enhancement. Third-trimester placentas exhibit a lobular pattern of enhancement, while second-trimester placentas exhibit heterogeneous enhancement.

Adult↗

PubMed1996

Prospective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain-Barré syndrome.

Nerve root enhancement of the cauda equina occurs in Guillain-Barré syndrome (GBS), but the frequency, diagnostic value, and meaning of this finding is unknown. We prospectively obtained gadolinium-enhanced lumbosacral spine MRIs in 24 consecutive patients with acute GBS and blindly rated nerve root enhancement as absent, mild, or prominent. The MRIs were obtained 13 days, mean, after onset of symptoms (range 2 to 42 days). Twenty of 24 patients had cauda equina nerve root enhancement, which was mild in 6 and prominent in 14. Eighteen of 19 with "typical" GBS had enhancement, compared with 2 of 5 with a variant presentation. Sixty percent of patients with prominent enhancement had severe back or leg pain in contrast to 10% of patients with mild or no enhancement. The GBS disability grade (0 to 5 scale) was higher in patients with prominent enhancement, and significantly fewer patients with prominent nerve root enhancement could walk independently by 2 months. There was no relationship between nerve root enhancement and the timing of the MRI, CSF protein, any of several EMG abnormalities, duration of hospitalization, mean disability grade at 2 months, or the time required for patients to improve to grade 2. In two patients, the EMGs at 11 and 20 days, respectively, were normal except for slightly prolonged F-responses and neurogenic recruitment, but there were prominent nerve root enhancement and an elevated CSF protein. Enhancement of the cauda equina nerve roots with gadolinium on lumbosacral MRI is 83% sensitive of acute GBS and was present in 95% of typical cases. This finding may be useful when electrophysiologic abnormalities are equivocal. In addition, conspicuous nerve root enhancement correlates with pain, GBS disability grade, and duration of recovery.

Acute Disease↗

PubMed2006

Evaluation of primary malignancies of the liver using contrast-enhanced sonography: correlation with pathology.

OBJECTIVE: Our purpose was to investigate the correlation of contrast-enhanced sonographic patterns with the histopathology of primary malignancies of the liver. MATERIAL AND METHODS: Of the 318 contrast-enhanced sonographic examinations performed between April and September 2004, 95 patients with 117 lesions confirmed by surgery or biopsy pathology were reviewed in this study. We analyzed the enhancement time and patterns according to the types and degrees of pathologic differentiation. RESULTS: All 65 moderately to poorly differentiated hepatocellular carcinomas (HCCs) enhanced in the arterial phase, and 96.9% (63 lesions) of them quickly washed out in the portal venous phase. All 32 well-differentiated HCCs enhanced in the arterial phase, and 50.0% (16 lesions) washed out slowly during the late phase. The washout time of the two differentiated types was significantly different (p < 0.05). Seventy-five percent of the clear cell carcinomas (12/16) enhanced in the arterial phase, 25% (4/16) did not enhance until the portal venous phase, and 31.3% (5/16) of the clear cell carcinomas washed out slowly during the late phase. The enhancement and washout times of clear cell carcinomas were significantly different than those of moderately to poorly differentiated HCCs (p < 0.05). All four intrahepatic cholangiocarcinomas presented the same patterns as moderately to poorly differentiated HCCs: enhanced in the arterial phase and quickly washed out in the portal venous phase. Among the 72 lesions enhanced homogeneously, 46 lesions (63.9%) were smaller than 3 cm. Thirty-seven lesions (82.2%) of the 45 lesions that enhanced heterogeneously were larger than 3 cm (including the four cholangiocarcinomas). Larger lesions were mainly less differentiated. There were significant differences in tumor sizes in regard to cellular differentiations and types. CONCLUSION: Our study showed that the enhancement manifestations of primary malignancies of the liver are related to pathologic types and grades. Contrast-enhanced sonograms may provide the histopathologic information for malignant tumors of the liver.

Adult↗

PubMedDate not supplied

Contrast-enhanced MR angiography of intracranial giant aneurysms.

BACKGROUND AND PURPOSE: Intravoxel phase dispersion and flow saturation often prevent adequate depiction of intracranial giant aneurysms on 3D time-of-flight (3D-TOF) MR angiography (MRA). Additional diagnostic difficulties may arise from T1 contamination artifact of an associated blood clot. Our aim was to assess whether contrast-enhanced MRA could improve the evaluation of giant aneurysms and to compare two different types of contrast-enhanced MRA. METHODS: We studied 11 aneurysms in 10 patients (age range, 31-77 years) with giant aneurysms of the anterior (n = 9) and posterior (n = 2) cerebral circulation by comparing 3D-TOF, first-pass dynamic contrast-enhanced MRA, and steady-state contrast-enhanced 3D-TOF sequences. Additional comparison with digital subtraction angiography (DSA) was performed in eight aneurysms. RESULTS: In nine of 11 aneurysms, 3D-TOF did not adequately show the lumen and exiting vessels. Contrast-enhanced 3D-TOF and dynamic contrast-enhanced MRA showed the aneurysm sac and exiting vessels in all of these cases. Dynamic contrast-enhanced MRA showed a better intravascular contrast than did contrast-enhanced 3D-TOF, which led to better delineation of the aneurysms. T1 contamination artifact from intra- or extraluminal blood clot was evident on the 3D-TOF images in four cases. The artifact was less marked on the contrast-enhanced 3D-TOF image and was completely eliminated on the dynamic contrast-enhanced MRA image by subtraction of precontrast images. The diagnostic information provided by dynamic contrast-enhanced MRA was comparable to that provided by DSA. CONCLUSION: Precontrast 3D-TOF is inadequate for the assessment of giant cerebral aneurysms. Both contrast-enhanced 3D-TOF and dynamic contrast-enhanced MRA reliably show the aneurysm sac and connected vessels. Dynamic MRA provides a superior contrast between flow and background and eliminates T1 contamination artifact. It should therefore be considered as the MRA sequence of choice.

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