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Uniform vascular contrast enhancement and reduced contrast medium volume achieved by using exponentially decelerated contrast material injection method.

PURPOSE: To investigate in computed tomographic (CT) angiography whether an exponentially decelerated contrast medium injection, as compared with a standard constant-rate injection, can facilitate uniform vascular contrast enhancement with a reduced contrast material volume. MATERIALS AND METHODS: CT angiography of the abdominal aorta was performed in 46 subjects by using an exponentially decelerated injection method: 134 mL of contrast medium was injected for 40 seconds, starting at 4.0 mL/sec and decreasing exponentially to 2.7 mL/sec by the end of the injection. Twenty-one of these subjects also underwent CT angiography with a constant-rate injection: 160 mL of contrast medium was injected for 40 seconds at a constant rate of 4 mL/sec. Time-enhancement curves and the magnitude of peak vascular enhancement were measured. Enhancement uniformity was evaluated by using three indexes: (a) duration of contrast enhancement achieved within 80% of the peak (80% DCE), (b) SD of the normalized contrast enhancement (SDNCE) measured from the beginning of spiral CT scanning to the time when the enhancement decreased to a level lower than the beginning level, and (c) slope of the enhancement curve calculated by using linear regression analysis. RESULTS: Exponentially decelerated injection resulted in more uniform enhancement. Mean values generated by using exponentially decelerated versus constant-rate injection in 21 paired comparisons were, respectively, 30.8 seconds +/- 5.0 versus 22.6 seconds +/- 7.6 for 80% DCE, 0.052 +/- 0.017 versus 0.086 +/- 0.031 for SDNCE, and 0.47 HU/sec +/- 0.70 versus 2.27 HU/sec +/- 0.87 for slope (P <.001 for all indexes). Compared with the peak enhancement resulting from the constant-rate injection, that resulting from the exponentially decelerated injection was reduced by a mean of 17.2% +/- 10.0. CONCLUSION: Uniform vascular contrast enhancement and reduced contrast medium volume, which are desirable in CT angiography, can be achieved with exponentially decelerated injection.

Abdomen↗

VX2 carcinoma in rabbits after radiofrequency ablation: comparison of MR contrast agents for help in differentiating benign periablational enhancement from residual tumor.

PURPOSE: To prospectively compare the accuracy of a blood pool agent, SH L 643A, with that of gadopentetate dimeglumine in differentiating benign periablational enhancement from residual tumor in VX2 carcinomas in rabbits after radiofrequency (RF) ablation. MATERIALS AND METHODS: Experiment was approved by the animal care committee. Sequential MR images were obtained before and with SH L 643A (17 000 Da, 0.05 mmol/kg) and, after a 24-hour interval, gadopentetate dimeglumine (546 Da, 0.1 mmol/kg) in 12 rabbits with VX2 carcinoma in the back muscle prior to (n = 12) and early (n = 12), 1 week (n = 8), and 4 weeks (n = 4) after RF ablation. RF ablation was performed with output of 90 W but at less than 300 seconds to ensure incomplete tumor ablation. The pathologic specimens were sectioned in the same plane as MR imaging, and the enhancement ratios (ie, the ratios of postcontrast to precontrast signal intensity) and the microvessel densities of residual tumor and benign periablational enhancement were assessed. RESULTS: With SH L 643A, the peak enhancement ratios of residual tumor (1.64 +/- 0.31 [standard deviation]) were significantly higher than those of benign periablational enhancement (0.97 +/- 0.16) (P < .001). With gadopentetate dimeglumine, the peak enhancement ratios of residual tumor (1.82 +/- 0.33) were not different from those of benign periablational enhancement (1.71 +/- 0.36). In benign periablational enhancement, enhancement ratios with injection of SH L 643A were lower than those with injection of gadopentetate dimeglumine for all time points up to 30 minutes (P < .05). The microvessel density was 25.72 +/- 5.43 vessels per field of view for residual tumor and 10.37 +/- 2.88 vessels per field of view for benign periablational enhancement (P < .001). CONCLUSION: Blood pool contrast agent SH L 643A permits more accurate differentiation of benign periablational enhancement from residual tumor compared with the extracellular agent gadopentetate dimeglumine.

Animals↗

Peripheral arterial disease: comparison of color duplex US and contrast-enhanced MR angiography for diagnosis.

PURPOSE: To prospectively compare the diagnostic accuracies of color duplex ultrasonography (US) and contrast material-enhanced magnetic resonance (MR) angiography and to assess interobserver agreement regarding contrast-enhanced MR angiographic findings in patients suspected of having peripheral arterial disease (PAD). MATERIALS AND METHODS: The institutional review board approved the study, and all patients provided signed informed consent. Two hundred ninety-five patients referred for diagnostic and preinterventional work-up of PAD with duplex US also underwent gadolinium-enhanced MR angiography. Data sets were reviewed for presence or absence of 50% or greater luminal reduction, which indicated hemodynamically significant stenosis, and to determine interobserver agreement. At duplex US, a peak systolic velocity ratio of 2.5 or greater indicated significant stenosis. Primary outcome measures were differences between duplex US and contrast-enhanced MR angiography in sensitivity and specificity for detection of significant stenosis, as assessed with the McNemar test, and interobserver agreement between the two contrast-enhanced MR angiogram readings, expressed as quadratic weighted kappa values. Intraarterial digital subtraction angiography (DSA) was the reference standard. RESULTS: Two hundred forty-nine patients had at least one hemodynamically significant stenotic lesion at contrast-enhanced MR angiography, duplex US, or both examinations. One hundred fifty-two patients underwent intraarterial DSA. The quadratic weighted kappa for agreement regarding the presence of 50% or greater stenosis at contrast-enhanced MR angiography was 0.89 (95% confidence interval [CI]: 0.87, 0.91). Sensitivity of duplex US was 76% (95% CI: 69%, 82%); specificity, 93% (95% CI: 91%, 95%); and accuracy, 89%. Sensitivity and specificity of contrast-enhanced MR angiography were 84% (95% CI: 78%, 89%) and 97% (95% CI: 95%, 98%), respectively; accuracy was 94%. Sensitivity (P = .002) and specificity (P = .03) of contrast-enhanced MR angiography were significantly higher. CONCLUSION: Results of this prospective comparison between contrast-enhanced MR angiography and duplex US provide evidence that contrast-enhanced MR angiography is more sensitive and specific for diagnosis and preinterventional work-up of PAD.

Adult↗

Carotid artery stenosis: intraindividual correlations of 3D time-of-flight MR angiography, contrast-enhanced MR angiography, conventional DSA, and rotational angiography for detection and grading.

PURPOSE: To compare three-dimensional (3D) time-of-flight (TOF) MR angiography, contrast-enhanced MR angiography, digital subtraction angiography (DSA), and rotational angiography for depiction of stenosis. MATERIALS AND METHODS: The study had Ethics Committee approval, and each patient gave written informed consent. Forty-nine patients (18 women, mean age, 67.2 years +/- 9.1 [+/- standard deviation], and 31 men, mean age, 63.1 years +/- 8.0) with symptomatic stenosis of internal carotid artery (ICA) diagnosed at duplex ultrasonography underwent transverse 3D TOF MR angiography with sliding interleaved kY acquisition and coronal contrast-enhanced MR angiography, followed by DSA and rotational angiography within 48 hours. MR angiography was performed at 1.5-T with a cervical coil. Contrast-enhanced MR angiograms were obtained after a bolus injection of 20 mL of gadobenate dimeglumine. Maximum ICA stenosis on maximum intensity projection and source images was quantified according to NASCET criteria. Correlations for 3D TOF MR angiography, contrast-enhanced MR angiography, DSA, and rotational angiography were determined by means of cross tabulation, and accuracy for detection and grading of stenoses were calculated. Data were evaluated with analysis of variance, Wilcoxon signed rank test, and McNemar test, all at significance of P < .05. RESULTS: Ninety-eight ICAs were evaluated at contrast-enhanced MR angiography, DSA, and rotational angiography, and 97 were evaluated at 3D TOF MR angiography. Correlations for contrast-enhanced MR angiography, 3D TOF MR angiography, and DSA relative to rotational angiography were r2 = 0.9332, r2 = 0.9048, and r2 = 0.9255, respectively. Lower correlation (r2 = 0.8593) was noted for contrast-enhanced MR angiography and DSA. Respective sensitivity and specificity for detection of hemodynamically relevant stenosis relative to rotational angiography were 100% and 90% for contrast-enhanced MR angiography, 95.5% and 87.2% for 3D TOF MR angiography, and 88.6% and 100% for DSA. Four of 31 severe stenoses were underestimated at DSA, and three were underestimated at contrast-enhanced MR angiography. Three severe stenoses were underestimated at 3D TOF MR angiography, and one was misclassified as occluded. Of 13 moderate (50%-69%) stenoses, one was overestimated at contrast-enhanced MR angiography, two were underestimated and three overestimated at 3D TOF MR angiography, and two were underestimated at DSA. CONCLUSION: DSA results in an underestimation of ICA stenosis compared with rotational angiography. Contrast-enhanced MR angiography correlates best with rotational angiography.

Aged↗

Contrast-enhanced MR imaging for evaluation of coronary artery disease before elective repair of aortic aneurysm.

PURPOSE: To prospectively evaluate the accuracy of first-pass contrast material-enhanced magnetic resonance (MR) imaging during stress and delayed contrast-enhanced MR imaging in the detection of significant coronary artery disease in patients before elective repair of aortic aneurysm. MATERIALS AND METHODS: The study was approved by the institutional ethics committee, and informed consent was obtained from all patients. MR imaging was performed in 49 patients (42 men and seven women; mean age, 72.2 years; age range, 58-85 years) before the elective repair of atherosclerotic aortic aneurysms. Thirty-two patients had an abdominal aneurysm, 12 had a thoracic aneurysm, and five had a thoracoabdominal aneurysm. First-pass contrast-enhanced MR images were obtained with short-axis sections encompassing the entire left ventricular myocardium in the resting state and during pharmacologic stress. Inversion-recovery-prepared delayed contrast-enhanced MR images were obtained with breath holding to evaluate for the presence of infarction. All patients underwent coronary angiography within 2 weeks of MR imaging, and these findings were used as the standard of reference. The diagnostic results of first-pass contrast-enhanced MR imaging, delayed contrast-enhanced MR imaging, and a combination of both MR imaging methods in the detection of significant coronary artery disease were expressed as sensitivity, specificity, and accuracy. RESULTS: Coronary angiography depicted a clinically significant stenosis (>70% luminal diameter narrowing) in the coronary artery in 34 of the 49 patients (69%). First-pass contrast-enhanced MR imaging depicted stress-induced hypoenhancement in 27 of those 34 patients (79%). Delayed myocardial enhancement was observed in 17 of the 34 patients (50%). The overall sensitivity of rest-stress first-pass contrast-enhanced MR imaging and delayed contrast-enhanced MR imaging combined in the prediction of at least one coronary artery with significant stenosis was 88% (30 of 34 patients). The specificity and accuracy of MR imaging were 87% (13 of 15 patients) and 88% (43 of 49 patients), respectively. CONCLUSION: Contrast-enhanced MR imaging had an accuracy of 88% in the detection of significant coronary artery disease in patients with aortic aneurysm.

Aged↗

Cholangiocarcinoma: delayed CT contrast enhancement patterns.

PURPOSE: To determine the usefulness of delayed post-equilibrium-phase contrast material-enhanced images in evaluation of intrahepatic cholangiocarcinoma. MATERIALS AND METHODS: Review of surgical, pathologic, and radiologic records revealed 47 patients with proved cholangiocarcinoma with delayed (6-36 minutes) post-equilibrium-phase contrast-enhanced computed tomographic (CT) scans. Unenhanced, dynamic contrast-enhanced, and delayed images were retrospectively reviewed, and enhancement patterns for cholangiocarcinoma lesions were recorded. Degree of delayed enhancement was compared with that of surrounding liver parenchyma. Patterns of delayed enhancement were characterized as homogeneous or heterogeneous. Enhancement characteristics were correlated with histologic findings. RESULTS: Thirty-five (74%) of 47 patients had tumors with mild or marked hyperattenuating delayed contrast enhancement, of which 18 had tumors with homogeneous hyperattenuating enhancement. In three patients, the only evidence of tumor was on the delayed images. In one patient, the tumor was not definable at any imaging phase. Tumors with delayed enhancement tended to be fibrous; however, degree of contrast material retention did not always correlate with the fibrous content of tumors at histopathologic analysis. CONCLUSION: Delayed tumoral contrast enhancement is a typical feature of intrahepatic cholangiocarcinoma and may aid in the detection and characterization of such lesions at CT.

Adult↗

Dynamic helical CT of the abdomen: prospective comparison of pre- and postprandial contrast enhancement.

PURPOSE: To investigate effects of a liquid meal on contrast material enhancement at dynamic helical computed tomography (CT). MATERIALS AND METHODS: Twenty healthy, fasting subjects underwent intravenous injection of nonionic contrast material at 4 mL/sec. Axial CT sections were obtained at a single level 15 seconds after injection, then every 5 seconds for 2 minutes. This protocol was repeated 1 week later, after ingestion of a 360-calorie liquid meal. Hepatic, splenic, and aortic attenuation were measured before and after contrast material administration. Peak enhancement level, time to peak enhancement, slope of hepatic enhancement, and hepatic, splenic, and aortic enhancement ratios were determined. RESULTS: Postprandial time to peak enhancement was 4.4 seconds earlier than preprandial (59.6 seconds +/- 9.0 [1 standard deviation] vs 64.0 seconds +/- 9.5; P < .02). No differences in maximum attenuation were found (P > .27). Postprandial maximum slope of hepatic enhancement and temporal and quantitative enhancement characteristics in aorta and spleen did not significantly differ. Postprandial hepatic-to-splenic enhancement ratios increased (P = .04), and aortic-to-hepatic ratios decreased (P = .01). Aortic-to-splenic ratios did not differ (P = .45). CONCLUSION: A liquid meal before intravenous injection of contrast material produces more rapid peak hepatic enhancement, with slightly increased relative hepatic enhancement. A patient's dietary status, however, should not influence the CT protocol.

Adult↗

Aortic and hepatic peak enhancement at CT: effect of contrast medium injection rate--pharmacokinetic analysis and experimental porcine model.

PURPOSE: To investigate the effect of injection rate of contrast medium on aortic and hepatic peak enhancement at computed tomography. MATERIALS AND METHODS: Early pharmacokinetics of contrast enhancement was analyzed theoretically and simulated with a compartment model. Contrast enhancement curves were generated from the model at different injection rates (0.5-10.0 mL/sec). Time-enhancement curves were measured. The effect of contrast medium injection rate on the time and magnitude of peak enhancement was evaluated and validated empirically in pigs. RESULTS: Theoretic predictions and experimental results were in good agreement. Time to aortic peak enhancement was the sum of injection duration and bolus transfer time of contrast medium from the injection site to the aorta. Time to hepatic peak enhancement was the sum of injection duration and time to equilibrium. The magnitude of peak enhancement increased with the injection rate, but the increase was different in the aorta and liver. CONCLUSION: Use of injection rates above 2 mL/sec did not substantially increase hepatic peak enhancement but helped increase the magnitude of arterial enhancement and temporal separation of arterial and venous phases of enhancement for dual-phase spiral CT.

Animals↗

Avulsion injury of cervical nerve roots: enhanced intradural nerve roots at MR imaging.

PURPOSE: To study the magnetic resonance (MR) imaging features of intradural nerve roots in avulsion injury of the cervical nerve roots. MATERIALS AND METHODS: Presurgical gadolinium-enhanced MR imaging was performed in 27 consecutive patients. The images were evaluated for enhancement of the intradural nerve roots and enhancement of the spinal cord surface at the root entry zone ("root stump" enhancement) by two radiologists, who were blinded to the clinical information. Intradural nerve roots were classified as enhanced, normal, or not visible. Root stumps were classified as enhanced or normal. The results were compared with the results of nerve root continuity studies (exploratory surgery with intraoperative recording of somatosensory evoked potentials or neurologic examination). RESULTS: At the 250 nerve levels (500 nerve roots) studied, 12 enhanced nerve roots and 42 enhanced root stumps were found. Seven enhanced nerve roots and 38 enhanced root stumps were related to preganglionic injury. Results of the kappa test for interobserver concordance on findings of intradural nerve roots and root stumps were 0.55 and 0.93, respectively. CONCLUSION: Although visualization of nerve roots is a problem, enhanced MR imaging is a noninvasive means of obtaining anatomic information and unique physiologic information on injured intradural nerve roots.

Adolescent↗

Arachidonic acid reversibly enhances N-type calcium current at an extracellular site.

We examined the effects of arachidonic acid (AA) on whole cell Ca(2+) channel activity in rat superior cervical ganglion neurons. Our companion paper (Liu L, Barrett CF, and Rittenhouse AR. Am J Physiol Cell Physiol 280: C1293-C1305, 2001) demonstrates that AA induces several effects, including enhancement of current amplitude at negative voltages, and increased activation kinetics. This study examines the mechanisms underlying these effects. First, enhancement is rapidly reversible by bath application of BSA. Second, enhancement appears to occur extracellularly, since intracellular albumin was without effect on enhancement, and bath-applied arachidonoyl coenzyme A, an amphiphilic AA analog that cannot cross the cell membrane, mimicked enhancement. In addition, enhancement is voltage dependent, in that currents were enhanced to the greatest degree at -10 mV, whereas virtually no enhancement occurred positive of +30 mV. We also demonstrate that AA-induced increases in activation kinetics are correlated with enhancement of current amplitude. An observed increase in the voltage sensitivity may underlie these effects. Finally, the majority of enhancement is mediated through N-type current, thus providing the first demonstration that this current type can be enhanced by AA.

Animals↗

Down-regulation of protein kinase C and kinase inhibitors dissociate short- and long-term enhancement produced by one-trial conditioning of Hermissenda.

1. The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. Previous research has shown that one-trial conditioning, consisting of light paired with serotonin (5-HT) results in short- and long-term enhancement of light-elicited generator potentials in identified type B-photoreceptors. Recent evidence suggests that 5-HT exerts its effects on the induction of short-term enhancement by activation of protein kinase C (PKC), a Ca(2+)-activated and phospholipid-dependent protein kinase. However, the contribution of protein kinases in general, and specifically PKC in long-term enhancement has not been established. 2. The protein kinase inhibitors H-7 and sphingosine blocked the induction of short-term enhancement when applied before one-trial conditioning. However, the conditions that are sufficient to block the induction of short-term enhancement do not block long-term enhancement. Sphingosine and H-7 do not block the induction and expression of long-term enhancement when applied before one-trial conditioning. 3. Pretreatment before conditioning with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which leads to down-regulation of PKC, also did not block long-term enhancement. Down-regulation by itself did not produce enhancement, although the transient peak of light-elicited generator potentials was reduced by pretreatment with TPA. 4. The results suggest that the induction of short- and long-term enhancement involve parallel processes, and thus the expression of long-term cellular plasticity produced by one-trial conditioning does not depend on the induction or expression of short-term enhancement.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

The pretreatment effect of chemical skin penetration enhancers in transdermal drug delivery using iontophoresis.

The transdermal drug delivery (TDD) system has largely been divided into physical, biochemical and chemical methods. Recently, combinations of these methods were introduced for more effective delivery with less side effects. We performed this study to identify the effectiveness and mechanism of TDD using the physical method, 'iontophoresis', plus the chemical method, 'pretreatment with chemical enhancer'. The action sites of chemical enhancers in the stratum corneum (SC) were observed by electron microscope. We also studied whether this combined method synergistically impaired the skin barrier. To confirm the synergistic effect on skin penetration by this combined method, we measured the blood glucose level after insulin iontophoresis following a chemical enhancer pretreatment in rabbits. The results were that (1) dilatation of the intercellular lipid layers of the SC and lacunae was prominent in pretreatment with chemical enhancers inducing high transepidermal water loss (TEWL); (2) the skin barrier impairment, with repeated treatments showing an increased TEWL and also epidermal proliferation, was increased with the chemical enhancers that showed a high TEWL immediately after treatment; (3) the combination of chemical enhancer pretreatment and iontophoresis showed no synergistic impairment of the skin barrier, and (4) the chemical enhancer pretreatment with greater impairment of the skin barrier could increase the delivery of insulin by iontophoresis. The results showed that a combination of chemical enhancer pretreatment and iontophoresis could deliver drugs more effectively than iontophoresis alone. Our proposed theory is that iontophoretic drug delivery may be easier through the dilated intercellular spaces of the SC which have a lower electrical impedance following the chemical enhancer pretreatment. Because the effect and the side effects in the combination are decided by the chemical enhancer rather than iontophoresis, the development of proper chemical enhancers is important in future plans.

Administration, Cutaneous↗

Distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120.

There is increasing evidence that sera from HIV-1-infected individuals contain antibodies that enhance infection by HIV-1 in vitro. Previous work has demonstrated that complement receptors on T lymphoid cells and Fc receptors for IgG (Fc gamma R) on monocytic cells are required for enhanced infection by antibody-complexed HIV-1. Characterization of such infection-enhancing antibodies is essential because immunogenic epitopes which induce enhancing antibodies should be excluded from HIV-1 vaccines. This study was conducted to identify enhancing antibodies involved in Fc R-mediated enhancement of HIV-1 infection employing IgG human monoclonal antibodies (HMAbs) reactive against gp120 of HIV-1, which were produced by B cell lines derived from an HIV-1-infected individual. A potent neutralizing HMAb N70-1.5e did not enhance infection by HIV-1 (IIIB and MN strains), whereas HMAb N70-2.3a mediated enhancement of HIV-1 infection, but had little neutralizing activity. A competition radio immunoassay demonstrated that the two antibodies bind to distinct epitopes. These results indicated that enhancing and neutralizing antibodies can be induced by different epitopes on gp120, suggesting the potential for development of safe vaccines against HIV-1 by exclusion of immunogenic epitopes for enhancing antibodies. We made attempts to identify the epitope on gp120 that is recognized by the enhancing antibody N70-2.3a by using recombinant HIV-1 proteins and found that the antibody binds to a conformational site of nonvariable sequences in the carboxyl half (aa 272-509) of gp120.

Animals↗

Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin.

Curcumin is a predominant compound derived from the rhizomes of Curcuma longa L., and shows antibacterial, anti-inflammatory and antineoplastic activity. The in-vitro and in-vivo skin absorption of curcumin was investigated after application of enhancers using Wistar rat as an animal model. The enhancers selected in this study included terpenes, flavonoids and cholestanol. The irritant profiles of these enhancers were also established by transepidermal water loss (TEWL) and histological observations. Cyclic monoterpenes generally showed stronger enhancement of curcumin permeation than the other enhancers. Modulation of concentration and pretreatment duration of enhancers possibly indicated that the enhancers have varied ability and mechanisms to enhance curcumin permeation. Terpineol produced the highest TEWL values among the enhancers tested, whereas ketocholestanol produced no, or only a negligible, increase in TEWL as compared with control. The results showed that skin disruption and inflammation did not necessarily correspond to the enhancing efficiency of the enhancers.

Administration, Cutaneous↗

Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery.

Transdermal drug delivery (TDD) is the administration of therapeutic agents through intact skin for systemic effect. TDD offers several advantages over the conventional dosage forms such as tablets, capsules and injections. Currently there are about eight drugs marketed as transdermal patches. Examples of such products include nitroglycerin (angina pectoris), clonidine (hypertension), scopolamine (motion sickness), nicotine (smoking cessation), fentanil (pain) and estradiol (estrogen deficiency). Since skin is an excellent barrier for drug transport, only potent drugs with appropriate physicochemical properties (low molecular weight, adequate solubility in aqueous and non-aqueous solvents, etc) are suitable candidates for transdermal delivery. Penetration enhancement technology is a challenging development that would increase significantly the number of drugs available for transdermal administration. The permeation of drugs through skin can be enhanced by physical methods such as iontophoresis (application of low level electric current) and phonophoresis (use of ultra sound energy) and by chemical penetration enhancers (CPE). In this review, we have discussed about the CPE which have been investigated for TDD. CPE are compounds that enhance the permeation of drugs across the skin. The CPE increase skin permeability by reversibly altering the physicochemical nature of the stratum corneum, the outer most layer of skin, to reduce its diffusional resistance. These compounds increase skin permeability also by increasing the partition coefficient of the drug into the skin and by increasing the thermodynamic activity of the drug in the vehicle. This review compiles the various CPE used for the enhancement of TDD, the mechanism of action of different chemical enhancers and the structure-activity relationship of selected and extensively studied enhancers such as fatty acids, fatty alcohols and terpenes. Based on the chemical structure of penetration enhancers (such as chain length, polarity, level of unsaturation and presence of some special groups such as ketones), the interaction between the stratum corneum and penetration enhancers may vary which will result in significant differences in penetration enhancement. Our review also discusses the various factors to be considered in the selection of an appropriate penetration enhancer for the development of transdermal delivery systems.

Administration, Cutaneous↗

Simulation of aortic peak enhancement on MDCT using a contrast material flow phantom: feasibility study.

OBJECTIVE: The objective of our study was to develop a flow phantom simulating aortic peak enhancement after the injection of contrast material on CT and to investigate the validity of the flow phantom by comparing the time-enhancement curves obtained for the flow phantom and humans. MATERIALS AND METHODS: We developed a flow phantom simulating the enhancement pattern of the aorta after the injection of contrast material. In protocols 1, 2, and 3 of the phantom study, 90, 102, and 150 mL of iohexol, respectively, was administered over 35 sec. In protocol 4, 102 mL of iohexol was administered over 25 sec. In phantom protocols 1', 2', and 3', the dose and contrast injection duration were the same as in protocols 1, 2, and 3; however, saline (10 mL) was injected during the 20 sec after contrast delivery. In the human study, 20 patients were randomized into four groups: Groups A, B, and C received 1.5, 1.7, and 2.5 mL of iohexol per kilogram of body weight, respectively, over 35 sec; and group D received 1.7 mL/kg over 25 sec. In patient groups A, B, C, and D, phantom protocols 1, 2, 3, and 4 were used, respectively. Single-level serial CT scans were obtained using a 16-MDCT scanner on the simulated and real aortas after the injection of contrast material. Time-enhancement curves of simulated and real aortas were generated, and aortic peak times and aortic peak enhancement values were calculated. RESULTS: Aortic peak enhancement and aortic peak times in protocols 1-4 and 1'-3' of the phantom study were 2-8% larger and 6-18% longer, respectively, than in the corresponding patient study. The shape of the time-enhancement curves before aortic peak time in protocols 1-3 and 1'-3' of the phantom study closely resembled that of the corresponding patient study. After the aortic peak time, the shape of time-enhancement curves in protocols 1, 2, and 3 of the phantom study was different from the corresponding patient study; however, it was similar in phantom protocols 1'-3' and the corresponding patient study. In all four phantom protocols, the difference between maximal and minimal aortic peak enhancement was less than the SD of the corresponding patient study. CONCLUSION: The level of peak aortic enhancement and the time to peak aortic enhancement were similar in the phantom and human studies when we used our different contrast injection protocols for MDCT.

Aged↗

Relapsing-remitting multiple sclerosis: sequential enhanced MR imaging vs clinical findings in determining disease activity.

OBJECTIVE: Sequential MR imaging frequently shows disease activity (clinically silent new brain lesions) in subgroups of patients with multiple sclerosis and therefore is valuable in monitoring the effects of treatment. Monitoring of disease activity in patients being treated for relapsing-remitting multiple sclerosis will increase in importance as new and safe therapies are developed. We studied sequential enhanced MR images of patients with early relapsing-remitting multiple sclerosis to define the MR features that indicate disease activity in this subgroup of patients and to compare MR imaging and clinical findings for this purpose. SUBJECTS AND METHODS: Seven patients with relapsing-remitting definite multiple sclerosis were examined monthly for 4-12 months. For each image, a standard repositioning protocol consisting of three images was used to ensure reproducibility of axial (double oblique) image planes, planned according to internal landmarks. A total of 58 unenhanced T2-weighted and enhanced T1-weighted MR images were obtained. RESULTS: MR images showed new enhancing lesions in six of the seven patients. On 25 (43%) of the 58 enhanced T1-weighted MR images, a total of 50 new enhancing lesions were observed, and on one image a reenhancing lesion was seen. The unenhanced T2-weighted images showed corresponding abnormalities for 92% of the new enhancing lesions. At follow-up, most lesions (86%) were enhanced on only one occasion: 4% were enhanced on more than two consecutive monthly MR examinations. Forty-nine percent of the lesions seen on T2-weighted images "disappeared" (beyond the resolution of the imaging system) after a mean follow-up of 3.5 months, especially lesions that were initially smaller than 5 mm. During the study, only five clinical relapses occurred in three patients (all at times when MR images showed contrast-enhancing lesions), and fixed disability did not increase. On 21 additional occasions, MR images showed new enhancing or reenhancing lesions in patients who were clinically stable at the time (4.2 times more clinically silent disease activity). CONCLUSION: Our results suggest that contrast-enhanced MR imaging is more sensitive than clinical monitoring for detecting new disease activity in patients with relapsing-remitting multiple sclerosis and that MR imaging might be useful in the evaluation of therapeutic regimens.

Adult↗

Hepatocellular carcinoma in North America: a multiinstitutional study of appearance on T1-weighted, T2-weighted, and serial gadolinium-enhanced gradient-echo images.

OBJECTIVE: The purpose of this study was to define the common appearances of hepatocellular carcinoma (HCC) in patients in North America by analyzing T1-weighted, T2-weighted, and serial gadolinium-enhanced gradient-echo images interpreted by radiologists at multiple institutions in North America. MATERIALS AND METHODS: One hundred thirteen consecutive patients with HCC from eight institutions were included in this retrospective case series. Inclusion criteria included MR imaging examinations performed on 1.5-T MR imagers using T1-weighted breath-hold spoiled gradient-echo images, T2-weighted images, and serial gadolinium-enhanced spoiled gradient-echo images. Diagnosis was established by histology in all patients. Images were analyzed retrospectively for lesion count, lesion diameter as less than or equal to 1.5 cm and greater than 1.5 cm, and signal intensity, by individual experienced radiologists at each institution. RESULTS: We found 354 HCC lesions in the 113 patients. Tumors were solitary in 63 patients, multifocal in 45 patients, and diffuse in five patients. Lesion appearance on combined T1-weighted, T2-weighted, and immediate gadolinium-enhanced spoiled gradient-echo images was as follows: 102 lesions (29%) were hypointense on T1-weighted images, were hyperintense on T2-weighted images, and exhibited diffuse heterogeneous enhancement; 52 lesions (15%) were isointense on both T1- and T2-weighted images and exhibited diffuse homogeneous enhancement (all of these lesions measured < or = 1.5 cm in diameter); 50 lesions (14%) were hypointense on T1-weighted images, were hyperintense on T2-weighted images, and exhibited diffuse homogeneous enhancement; 33 lesions (9%) were hypointense on T1-weighted images, were hyperintense on T2-weighted images, and exhibited predominantly peripheral rim enhancement; and 27 lesions (8%) were hypointense on T1-weighted images, were isointense on T2-weighted images, and exhibited diffuse homogeneous enhancement. The remaining 90 lesions showed less common patterns. The appearance of HCCs greater than 1.5 cm and of HCCs less than or equal to 1.5 cm was significantly different (p = .001). The appearance of histologically proven HCCs is separately described. CONCLUSION: The combination of hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and diffuse heterogeneous enhancement was the most common appearance of HCC on MR images in a multiinstitutional patient population in North America. Small HCCs measuring less than or equal to 1.5 cm were frequently isointense on both T1-weighted and T2-weighted images and may be detected on immediate gadolinium-enhanced images only as diffuse homogeneously enhancing lesions.

Adolescent↗