Healing of sub-critical femoral osteotomies in mice is unaffected by tacrolimus and deletion of recombination activating gene 1.

Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or duration. A comparison of healed C57BL/6 and Rag1-/- femora by µCT and ex vivo torsion testing showed no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions.

Ubiquitous formation of bulk Dirac cones and topological surface states from a single orbital manifold in transition-metal dichalcogenides.

Transition-metal dichalcogenides (TMDs) are renowned for their rich and varied bulk properties, while their single-layer variants have become one of the most prominent examples of two-dimensional materials beyond graphene. Their disparate ground states largely depend on transition metal d-electron-derived electronic states, on which the vast majority of attention has been concentrated to date. Here, we focus on the chalcogen-derived states. From density-functional theory calculations together with spin- and angle-resolved photoemission, we find that these generically host a co-existence of type-I and type-II three-dimensional bulk Dirac fermions as well as ladders of topological surface states and surface resonances. We demonstrate how these naturally arise within a single p-orbital manifold as a general consequence of a trigonal crystal field, and as such can be expected across a large number of compounds. Already, we demonstrate their existence in six separate TMDs, opening routes to tune, and ultimately exploit, their topological physics.

Simultaneous Conduction and Valence Band Quantization in Ultrashallow High-Density Doping Profiles in Semiconductors.

We demonstrate simultaneous quantization of conduction band (CB) and valence band (VB) states in silicon using ultrashallow, high-density, phosphorus doping profiles (so-called Si:P δ layers). We show that, in addition to the well-known quantization of CB states within the dopant plane, the confinement of VB-derived states between the subsurface P dopant layer and the Si surface gives rise to a simultaneous quantization of VB states in this narrow region. We also show that the VB quantization can be explained using a simple particle-in-a-box model, and that the number and energy separation of the quantized VB states depend on the depth of the P dopant layer beneath the Si surface. Since the quantized CB states do not show a strong dependence on the dopant depth (but rather on the dopant density), it is straightforward to exhibit control over the properties of the quantized CB and VB states independently of each other by choosing the dopant density and depth accordingly, thus offering new possibilities for engineering quantum matter.

Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle.

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials.

Excitation of coherent phonons in the one-dimensional Bi(114) surface.

We present time-resolved photoemission experiments from a peculiar bismuth surface, Bi(114). The strong one-dimensional character of this surface is reflected in the Fermi surface, which consists of spin-polarized straight lines. Our results show that the depletion of the surface state and the population of the bulk conduction band after the initial optical excitation persist for very long times. The disequilibrium within the hot electron gas along with strong electron-phonon coupling cause a displacive excitation of coherent phonons, which in turn are reflected in coherent modulations of the electronic states. Beside the well-known A(1g) bulk phonon mode at 2.76 THz, the time-resolved photoelectron spectra reveal a second mode at 0.72 THz which can be attributed to an optical surface phonon mode along the atomic rows of the Bi(114) surface.

The occupied electronic structure of ultrathin boron doped diamond.

Using angle-resolved photoelectron spectroscopy, we compare the electronic band structure of an ultrathin (1.8 nm) δ-layer of boron-doped diamond with a bulk-like boron doped diamond film (3 µm). Surprisingly, the measurements indicate that except for a small change in the effective mass, there is no significant difference between the electronic structure of these samples, irrespective of their physical dimensionality, except for a small modification of the effective mass. While this suggests that, at the current time, it is not possible to fabricate boron-doped diamond structures with quantum properties, it also means that nanoscale boron doped diamond structures can be fabricated which retain the classical electronic properties of bulk-doped diamond, without a need to consider the influence of quantum confinement.

Use of genetically modified muscle and fat grafts to repair defects in bone and cartilage.

We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad.BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified ("gene activated") tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.

Surface-sensitive conductance measurements.

Several approaches for surface-sensitive conductance measurements are reviewed. Particular emphasis is placed on nanoscale multi-point probe techniques. The results for two model systems, which have given rise to some dispute, are discussed in detail: Si(111)(7 × 7) and ([Formula: see text])Ag-Si(111). Other recent examples are also given, such as phase transitions in quasi-one-dimensional structures on semiconductor surfaces and the surface sheet conductivity of Bi(111), the surface of a semimetal.

Thermal switching of the electrical conductivity of Si(111)([Formula: see text])Ag due to a surface phase transition.

The temperature-dependent surface conductivity of the Si(111)([Formula: see text])Ag surface was measured using a microscopic four-point probe. The conductivity was found to undergo a sharp increase of about three orders of magnitude when the system was heated above about 220 K. This strong conductivity change is reversible and attributed to the phase transition which is generally believed to occur on this surface. It is also shown that, in order to find the true surface conductivity, it is necessary to separate it from the contribution of the bulk and space charge layer. In this work, this is achieved by using a finite-element model. A percolating network of Ag islands on Si(111) was also studied and a much simpler behaviour (compared to that of Si(111)([Formula: see text])Ag) was found. The temperature-dependent conductivity of this system was found to display typical metallic behaviour. The absolute value of the conductivity is comparable to the value expected by modelling the Ag film as exhibiting the bulk Ag transport properties.

Spin-valley locking in the normal state of a transition-metal dichalcogenide superconductor.

Metallic transition-metal dichalcogenides (TMDCs) are benchmark systems for studying and controlling intertwined electronic orders in solids, with superconductivity developing from a charge-density wave state. The interplay between such phases is thought to play a critical role in the unconventional superconductivity of cuprates, Fe-based and heavy-fermion systems, yet even for the more moderately-correlated TMDCs, their nature and origins have proved controversial. Here, we study a prototypical example, 2H-NbSe2, by spin- and angle-resolved photoemission and first-principles theory. We find that the normal state, from which its hallmark collective phases emerge, is characterized by quasiparticles whose spin is locked to their valley pseudospin. This results from a combination of strong spin-orbit interactions and local inversion symmetry breaking, while interlayer coupling further drives a rich three-dimensional momentum dependence of the underlying Fermi-surface spin texture. These findings necessitate a re-investigation of the nature of charge order and superconducting pairing in NbSe2 and related TMDCs.

Competitive binding studies with multiple sites. Effects arising from depletion of the free radioligand.

Apparently anomalous behaviour arises if a radiolabelled drug and a non-radioactive drug compete for binding to a membrane-bound receptor when (a) there is severe depletion of the radiolabelled drug and (b) the non-radioactive drug binds to a heterogeneous population of binding sites. In extreme cases, binding of the non-radioactive drug to the sites of high affinity can be obscured completely. This phenomenon is illustrated by the binding of carbachol to muscarinic receptors, estimated by inhibition of a radiolabelled antagonist.

Management of pterygium with surgery and radiation therapy. The North Florida Pterygium Study Group.

PURPOSE: To compare our results in the management of pterygium using a higher total dose with other reported results. METHODS AND MATERIALS: Between 1971 and 1991, 690 patients were treated with complete surgical excision followed by beta irradiation for primary or recurrent pterygium. Of these patients, 129 had two or more areas involving both eyes for a total of 825 lesions treated. Only 17 patients (2%) had temporal lesions with the rest of the patients having nasal pterygia. All patients underwent complete surgical resection of the pterygium before undergoing radiation therapy. One hundred forty-nine patients had undergone previous surgical resection alone but developed recurrence. After surgical excision, all patients were treated with Strontium-90 applicators starting immediately within 24 hr of surgery. Our standard policy was six weekly applications, each delivering a surface dose of 1000 cGy. The total dose delivered was 6000 cGy. Minimum follow-up was 1 year with a median of greater than 8 years. RESULTS: There were only fourteen recurrences (1.7%) out of a total of 825 lesions treated. Nine of the fourteen patients received suboptimal therapy undergoing less than five applications of Strontium-90. There were no major complications. CONCLUSION: The combination of surgical excision followed by adequate Strontium-90 applications is highly effective in the management of pterygium. The optimal total dose appears to be in the range of 2000 cGy to 6000 cGy.

The effects of ions on the binding of agonists and antagonists to muscarinic receptors.

1 There are no selective effects of Na+, K+, Ca2+, Mg2+ or Cl- on the binding of antagonists or agonists to muscarinic receptors in rat brain. A decrease in affinity related to ionic strength is found for all these ions. 2 Larger effects were produced by T1+, La3+, and some transition metal ions.

Aspects of the adrenal function in the domestic fowl.

Chromatographic purification of extracts of hen peripheral plasma on Florisil columns before measurement by spectrofluorometry showed a basal level for corticosterone of 1-3 mug/100 ml, which is much lower than concentrations previously reported using acid fluorescence. Neither handling, restraint nor repeated bleeding affected the concentration of this hormone or of glucose. Adrenal function tests with two preparations of synthetic corticotrophin showed that they caused a rapid rise in blood corticosterone and eventually of glucose. Results of studies using insulin or tolbutamide i.v. suggest that there is a threshold concentration of plasma glucose (about 70 mg/100 ml) below which hypoglycaemia stimulates the hypothalamic-pituitary-adrenal system in fowls. Prolonged treatment of laying hens with protamine zinc insulin led to aphagia and cessation of egg-laying; increased concentrations of corticosterone were observed 2 days after the administration of insulin ceased, coinciding with the return to normal plasma levels of glucose. 'Chemical adrenalectomy' with metyrapone showed that the restoration of plasma glucose to a normal concentration after insulin treatment is dependent upon fully functional adrenal cortical tissue. It appears likely that the adrenal medulla is a target for corticosterone which probably regulates the tissue levels of phenylethanolamine-N-methyltransferase, one of the enzymes necessary for the biosynthesis of adrenaline.

Effect of luteinizing hormone on progesterone secretion in vitro by the granulosa cells of the domestic fowl (Gallus domesticus).

During short periods of incubation (3 h) the secretion of progesterone by granulosa cells from the largest preovulatory follicle of the fowl was higher (160 pmol/micrograms DNA) with ovine LH in the medium than without it (60 pmol/micrograms DNA). Granulosa cells from follicles collected 24 and 48 h before their expected ovulation secreted progesterone at similar rates to cells from the largest follicle which was likely to ovulate within 5 h. The identity of progesterone was confirmed by physicochemical methods. After granulosa cells had been incubated with LH in Medium 199 for 24 h, the concentration of progesterone in the medium was 1.65 mumol/l whereas oestrone and oestradiol were present at concentrations of 254 and 199 pmol/l respectively. The results indicate that the larger yellow yolk-filled follicles of the ovarian hierarchy in the domestic fowl contribute to the preovulatory surge of progesterone which has been observed in the peripheral blood.

Apparent capacity of cardiac muscarinic receptors for different radiolabeled antagonists.

Muscarinic receptors in sarcolemmal membranes, digitonin-solubilized extracts, and purified preparations from porcine atria have revealed a shortfall in the apparent capacity for N-[3H]methylscopolamine, which was only about 75% of that for [3H]quinuclidinylbenzilate. Since binding at near-saturating concentrations of [3H]quinuclidinylbenzilate was inhibited fully at comparatively low concentrations of unlabeled N-methylscopolamine, the data are inconsistent with the notion that [3H]quinuclidinylbenzilate binds selectively to a subclass of distinct, non-interconverting, and mutually independent sites. The discrepancy is resolved by adjusting the specific activity of N-[3H]methylscopolamine to account for unlabeled scopolamine that was identified in some batches of the radioligand. Also, there was no shortfall in capacity when N-[3H]methylscopolamine was devoid of scopolamine, and the predicted effect was obtained when pure N-[3H]methylscopolamine was supplemented with known amounts of scopolamine. A small discrepancy in the levels of scopolamine estimated pharmacologically and by mass spectrometry can be attributed largely to a difference in the efficiency of ionization between scopolamine and N-methylscopolamine. Different capacities for different radioligands are not uncommon with muscarinic and other G protein-coupled receptors, and in some cases the effect may have been due wholly or in part to an unlabeled impurity. Binding data can be mechanistically ambiguous, particularly when acquired only at graded concentrations of the radioligand. The predicted effects of an unlabeled impurity mimic or resemble those of alternative scenarios such as sequestration behind a hydrophobic barrier, a nucleotide-regulated interconversion from one state of affinity to another, and cooperativity between interacting sites.

Choice of metal ion and formulation concentration for first-pass brain perfusion studies with magnetic resonance imaging at 1.5 tesla.

RATIONALE AND OBJECTIVES: Gadolinium (Gd) and dysprosium (Dy) analogues, chelated with HP-DO3A, were compared at both 0.5- and 1.0-mol/L concentrations for efficacy in first-pass brain studies on magnetic resonance (MR) imaging at 1.5 tesla (T). METHODS: Ten healthy cats were examined with a dose of 0.3 mmol/kg, using two concentrations of each agent (0.5 mol/L and 1.0 mol/L, 20 examinations). Gadolinium-HP-DO3A (gadoteridol or ProHance) or Dy-HP-DO3A was injected at 9 mL/second, with acquisition of 64 sequential steady-state free precession (SSFP) images at a rate of one each 0.6 second. RESULTS: The change in white matter signal intensity, at the peak of the first pass of the contrast agent bolus in the brain, was -231 +/- 68 for the 0.5-mol/L formulation of Gd-HP-DO3A, compared with -267 +/- 57 for the 1.0-mol/L formulation. Using the 0.5-mol/L formulation of Dy-HP-DO3A, the change at peak was -318 +/- 42, a result statistically improved compared with both the 0.5-mol/L (P < 0.02) and 1.0-mol/L (P < 0.04) Gd-HP-DO3A formulations. A further improvement was observed with the 1.0-mol/L Dy-HP-DO3A formulation, with the change being -368 +/- 33. CONCLUSIONS: First-pass brain MR studies at 1.5 T are improved by use of higher concentration Gd chelate formulations (1.0 versus 0.5 mol/L) and by substitution of the Dy ion for the Gd ion in the chelate. Injection of higher-concentration formulations results in higher initial arterial metal ion concentration. Incomplete blood mixing on transit during first pass causes the higher initial concentration, which then results in a greater susceptibility effect on imaging. The superiority of the Dy formulation compared with the Gd formulation is anticipated because of the higher magnetic moment of Dy. The curves for tissue signal intensity versus time during first pass return artifactually to near baseline after Gd chelate injection (when SSFP imaging techniques are used), a differentiating feature from results with the Dy chelate. This difference can be explained by a substantial T1 effect of the Gd chelate, despite acquisition of images that are predominantly susceptibility weighted.

Magnetic resonance imaging of an experimental model of intracranial metastatic disease. A study of lesion detectability.

RATIONALE AND OBJECTIVES: The detectability of brain metastases was evaluated in a rabbit model, with attention to magnetic resonance contrast dose and timing of image acquisition after injection of contrast medium. METHODS: Five New Zealand white rabbits were studied at 1.5 T 6 to 7 days and 11 to 12 days after surgical implantation of an adenocarcinoma tumor nidus. T1- and T2-weighted spin-echo images (0.9 x 0.9 x 2 mm3 voxel size) were obtained before administration of contrast medium. T1-weighted images were repeated 5, 15, and 30 minutes after intravenous injection of 0.1 mmol/kg gadoteridol. At 40 minutes, a supplemental dose of 0.2 mmol/kg (0.3 mmol/kg cumulative dose) was administered, with T1-weighted images repeated at 5, 15, and 30 minutes after the second injection. RESULTS: Six to 7 days after tumor implantation, lesion enhancement (percent change, with normalization to baseline and equilibrium values) was 42 +/- 9% at 5 minutes, 48 +/- 9% at 15 minutes, and 42 +/- 10% at 30 minutes after administration of 0.1 mmol/kg gadoteridol. After administration of 0.3 mmol/kg gadoteridol, lesion enhancement was 111 +/- 13% at 5 minutes, 116 +/- 8% at 15 minutes, and 100% at 30 minutes. On film review, 2 of 5 lesions were not detectable at 6 to 7 days after tumor implantation with 0.1 mmol/kg gadoteridol. Administration of 0.3 mmol/kg gadoteridol provided for lesion identification in each instance. Eleven to 12 days after tumor implantation, one lesion was not detectable with 0.1 mmol/kg gadoteridol. Administration of 0.3 mmol/kg gadoteridol again provided for lesion identification in all cases. Mean lesion enhancement increased from 39 +/- 15% to 104 +/- 10%. CONCLUSIONS: The administration of 0.3 mmol/kg gadoteridol (high dose) compared with 0.1 mmol/kg gadoteridol (conventional dose) improves metastatic lesion detectability in the brain. The lesions identified only at high dose were confirmed by histopathology. Smaller lesions were not detected at a dose of 0.1 mmol/kg.

Early dynamic magnetic resonance imaging of liver metastases with 0.3 and 0.6 mmol/kg gadoteridol injection.

RATIONALE AND OBJECTIVES: The potential for improvement in liver-lesion conspicuity on early dynamic scans after bolus intravenous gadolinium (Gd) chelate administration was evaluated using gadoteridol (Gd-HP-DO3A; Prohance) at doses of 0.3 and 0.6 mmol/kg. METHODS: Five New Zealand white rabbits with focal VX-2 adenocarcinoma liver metastases were studied on a 1.5-tesla Siemens Vision scanner. Each rabbit was imaged twice (on two separate days), after injections of 0.3 mmol/kg and 0.6 mmol/ kg Gd-HP-DO3A. The contrast dose (0.3 or 0.6 mmol/kg) was given as a single intravenous injection. The order of injection for the two doses was randomized, with the two studies (in any one rabbit) separated by 24 hours to allow for clearance. Contrast was administered using an autoinjector at a rate of 1.5 mL/second. Turbo-fast low-angle shot scans were obtained before and at 6, 12, 19, 25, 31, 60, 120, 180, 240, 300, and 600 seconds after contrast injection. The lesions were confirmed, after killing the rabbit, by gross and microscopic examination. RESULTS: The enhancement of normal liver parenchyma, assessed by (SIt-SIo)/SIo.100, (SI = signal intensity) peaked at 32% +/- 4% 19 seconds after injection of 0.3 mmol/kg and at 38% +/- 5% 31 seconds after injection of 0.6 mmol/kg. The difference in maximum parenchymal enhancement achieved, comparing the 0.3 and 0.6 mmol/kg doses, was statistically significant (P < 0.03). Lesion conspicuity, specifically (SIliver-SIlesion/noise), increased from 4.5 +/- 2.3 precontrast to a maximum of 6.8 +/- 1.2 at 19 seconds postcontrast using a dose of 0.3 mmol/kg, with the difference statistically significant (P < 0.03). The increase with a dose of 0.6 mmol/kg was from 4.2 +/- 0.7 to 6.5 +/- 1.9 with this difference also statistically significant (P < 0.02). There was no statistically significant difference in lesion conspicuity between the doses of 0.3 and 0.6 mmol/kg. CONCLUSIONS: Conspicuity of liver metastases can be improved substantially with dynamic magnetic resonance imaging and rapid intravenous bolus contrast injection with a dose of 0.3 mmol/kg. No further improvement is noted at a dose of 0.6 mmol/kg, despite greater positive contrast enhancement of normal liver parenchyma.

Evaluation of gadolinium 2,5-BPA-DO3A, a new macrocyclic hepatobiliary chelate, in normal liver and metastatic disease on high field magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A new hepatobiliary gadolinium chelate, gadolinium (Gd) 2,5-BPA-DO3A, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved extracellular contrast agent, and Gd Cy2-DOTA, a second hepatobiliary chelate in preclinical development. The ligand in Gd 2,5-BPA-DO3A is macrocyclic in nature, as opposed to the linear structure of Gd DTPA. Gadolinium 2,5-BPA-DO3A was evaluated on magnetic resonance imaging at 1.5 T, examining specifically liver parenchymal enhancement and lesion delineation, the latter in metastatic disease. METHODS: Gadolinium 2,5-BPA-DO3A was evaluated in five normal rhesus monkeys and four New Zealand White rabbits with implanted VX-2 liver tumors. These studies were compared with magnetic resonance exams in the same animals using Gd HP-DO3A and Gd Cy2-DOTA. A contrast dose of 0.1 mmol/kg intravenous was employed in each instance, with the sequence of administration (for the three agents) randomized and at least 72 hours between injections. Spin echo breathhold T1-weighted scans were obtained before and at multiple times after contrast administration. Postcontrast scans were acquired from 1 to 60 minutes after injection in the monkeys and from 1 to 240 minutes in the rabbits. RESULTS: Enhancement of normal liver parenchyma was markedly superior with Gd 2,5-BPA-DO3A compared with Gd HP-DO3A and Gd Cy2-DOTA in both monkeys and rabbits. At 2 and 60 minutes after contrast administration, the liver signal intensity in the monkey was 452 +/- 56 and 440 +/- 69 with Gd 2,5-BPA-DO3A compared with 295 +/- 34 and 256 +/- 38 with Gd HP-DO3A. The difference between agents was statistically significant at all postcontrast time points in the rhesus monkey. Excretion of contrast into the gall bladder was consistently observed after Gd 2,5-BPA-DO3A injection in both animal species. Maximum lesion conspicuity occurred in the rabbit at 45 minutes after Gd 2,5-BPA-DO3A administration. At 45 minutes postinjection, liver-lesion contrast was 0.60 +/- 0.15 with Gd 2,5-BPA-DO3A, 0.35 +/- 0.11 with Gd Cy2-DOTA, and 0.12 +/- 0.04 with Gd HP-DO3A, with the differences between agents being statistically significant. CONCLUSIONS: Gadolinium 2,5-BPA-DO3A is superior to both Gd Cy2-DOTA and Gd HP-DO3A in the degree of enhancement of normal liver parenchyma achieved after intravenous injection. This leads to improved liver lesion delineation with Gd 2,5-BPA-DO3A on delayed postcontrast magnetic resonance scans.