ABSTRACT
Radiolabeling of nanobodies with radiometals by chelation has the advantage of being simple, fast and easy to implement in clinical routine. In this study, we validated 68Ga/111In-labeled anti-VCAM-1 nanobodies as potential radiometal-based tracers for molecular imaging of atherosclerosis. Both showed specific targeting of atherosclerotic lesions in ApoE-/- mice. Nevertheless, uptake in lesions and constitutively VCAM-1 expressing organs was lower than previously reported for the 99mTc-labeled analog. We further investigated the impact of different radiolabeling strategies on the in vivo biodistribution of nanobody-based tracers. Comparison of the pharmacokinetics between 68Ga-, 18F-, 111In- and 99mTc-labeled anti-VCAM-1 nanobodies showed highest specific uptake for 99mTc-nanobody at all time-points, followed by the 68Ga-, 111In- and 18F-labeled tracer. No correlation was found with the estimated number of radioisotopes per nanobody, and mimicking specific activity of other radiolabeling methods did not result in an analogous biodistribution. We also demonstrated specificity of the tracer using mice with a VCAM-1 knocked-down phenotype, while showing for the first time the in vivo visualization of a protein knock-down using intrabodies. Conclusively, the chosen radiochemistry does have an important impact on the biodistribution of nanobodies, in particular on the specific targeting, but differences are not purely due to the tracer's specific activity.
Subject(s)
Atherosclerosis/diagnostic imaging , Molecular Imaging , Single-Domain Antibodies/chemistry , Vascular Cell Adhesion Molecule-1/immunology , Animals , Gallium Radioisotopes , Indium Radioisotopes , Isotope Labeling , Mice , Mice, Inbred C57BL , Mice, Knockout , Single-Domain Antibodies/immunology , Single-Domain Antibodies/metabolismABSTRACT
PURPOSE: To determine whether the assessment of regional wall thickening (WT) in addition to myocardial perfusion from stress supine acquisitions could compensate for the lack of prone acquisition and the corresponding decrease in the diagnostic performance of SPECT myocardial perfusion imaging (MPI) in patients with known or suspected coronary artery disease (CAD). METHODS: The study group comprised 41 patients (123 vessels) with known or suspected CAD prospectively recruited for systematic prone and supine 201Tl stress SPECT MPI. The diagnostic performance of SPECT MPI was determined for various image sets including nongated supine images (supine NG), nongated combined prone and supine images (prone and supine NG) and gated supine images, allowing WT evaluation from NG images in addition to perfusion (supine NG + WT) using invasive coronary angiography and fractional flow reserve as the gold standards. RESULTS: The rate of false positives was significantly higher among the supine NG images (20.8%) than among either the prone and supine NG or the supine NG + WT images (3.3% and 2.7%, respectively, P < 0.05 vs. supine NG). Consequently, specificity was higher for the prone and supine NG images than for the supine NG images (96.1% vs. 76.1%, P < 0.01) and was highest for the supine NG + WT images (96.8%, P not significant vs. prone and supine NG), without significant differences in sensitivity (80.0%, 86.6% and 73.3%, respectively, P not significant for all comparisons). CONCLUSION: The diagnostic performance of supine stress SPECT MPI is improved when WT assessment of ischaemic segments is used as an additional diagnostic criterion to values not significantly different from those with combined prone and supine acquisitions.
Subject(s)
Coronary Artery Disease/diagnostic imaging , Myocardial Perfusion Imaging/methods , Patient Positioning/methods , Tomography, Emission-Computed, Single-Photon/methods , Aged , Female , Humans , Male , Middle Aged , Myocardial Perfusion Imaging/instrumentation , Myocardial Perfusion Imaging/standards , Patient Positioning/standards , Predictive Value of Tests , Prone Position , Radiopharmaceuticals , Semiconductors , Supine Position , Thallium Radioisotopes , Tomography, Emission-Computed, Single-Photon/instrumentation , Tomography, Emission-Computed, Single-Photon/standardsABSTRACT
Zernike circle polynomials are in widespread use for wavefront analysis because of their orthogonality over a circular pupil and their representation of balanced classical aberrations. However, some of the higher-order modes contain linear and quadratic terms. A new aberration series is proposed to better separate the low- versus higher-order aberration components. Because its higher-order modes are devoid of linear and quadratic terms, our new basis can be used to better fit the low- and higher-order components of the wavefront. This new basis may quantify the aberrations more accurately and provide clinicians with coefficient magnitudes which better underline the impact of clinically significant aberration modes.
Subject(s)
Refraction, Ocular , Humans , Keratoconus/physiopathology , Keratomileusis, Laser In Situ , Models, Theoretical , Refractive Errors/physiopathology , Refractive Surgical ProceduresABSTRACT
Cardiovascular diseases are currently the leading cause of mortality in the population of developed countries, due to the constant increase in cardiovascular risk factors, such as high blood pressure, cholesterol, overweight, tobacco use, lack of physical activity, etc. Numerous prospective and retrospective studies have shown that arterial stiffening is a relevant predictor of these diseases. Unfortunately, the arterial stiffness distribution across the human body is difficult to measure experimentally. We propose a numerical approach to determine the arterial stiffness distribution of an arterial network using a subject-specific one-dimensional model. The proposed approach calibrates the optimal parameters of the reduced-order model, including the arterial stiffness, by solving an inverse problem associated with the noninvasive in vivo measurements. An uncertainty quantification analysis has also been carried out to measure the contribution of the model input parameters variability, alone or by interaction with other inputs, to the variation of clinically relevant hemodynamic indices, here the arterial pulse pressure. The results obtained for a lower limb model, demonstrate that the numerical approach presented here can provide a robust and subject-specific tool to the practitioner, allowing an early and reliable diagnosis of cardiovascular diseases based on a noninvasive clinical examination.
Subject(s)
Arteries/physiology , Lower Extremity/blood supply , Lower Extremity/physiology , Models, Cardiovascular , Patient-Specific Modeling , Vascular Stiffness/physiology , Blood Flow Velocity/physiology , Blood Pressure/physiology , Computer Simulation , HumansABSTRACT
PURPOSE: To evaluate the theoretical influence of the change in corneal asphericity (ΔQ) on the change in fourth-order Zernike spherical aberration coefficient (ΔC(4)0) with customized aspheric refractive correction of myopia and hyperopia. METHODS: The initial anterior corneal surface profile was modeled as a conic section of apical radius of curvature R0 and asphericity Q0. The postoperative corneal profile was modeled as a conic section of apical curvature R1 and asphericity Q1, where R1 was computed from defocus D, and Q1 selected for controlling the postoperative asphericity. The corresponding change in fourth-order spherical aberration (ΔC(0)4) was computed within a 6-mm optical zone using inner products applied to the incurred optical path changes. These calculations were repeated for different values of D, R0, Q0, and various intended ΔC(4)0 values. RESULTS: Increasing negative spherical aberration (ΔC(4)(0) < 0) requires a change toward more negative values of asphericity (increased prolateness; ΔQ < 0) for hyperopic and low myopic corrections, but more positive values (ΔQ < 0) for high myopic correction. The larger the intended change in corneal spherical aberration (ΔC(4)(0)), the more myopic the threshold value for which the required change in asphericity, ΔQ, becomes positive. The influence of the magnitude of paraxial defocus correction is less pronounced when larger changes in C(4)(0) are intended. CONCLUSIONS: These results provide a basis for controlling the direction (sign) and the magnitude of spherical aberration changes when using customized aspheric profiles of ablation.
Subject(s)
Cornea/pathology , Corneal Surgery, Laser/methods , Corneal Wavefront Aberration/physiopathology , Hyperopia/surgery , Myopia/surgery , Humans , Hyperopia/physiopathology , Models, Theoretical , Myopia/physiopathologyABSTRACT
The third window syndrome, often associated with the Tullio phenomenon, is currently most often observed in patients with a superior semicircular-canal dehiscence (SCD) but is not specific to this pathology. Clinical and vestibular tests suggestive of this pathology are not always concomitantly observed and have been recently complemented by the skull-vibration-induced nystagmus test, which constitutes a bone-conducted Tullio phenomenon (BCTP). The aim of this work was to collect from the literature the insights given by this bedside test performed with bone-conducted stimulations in SCD. The PRISMA guidelines were used, and 10 publications were included and analyzed. Skull vibration-induced nystagmus (SVIN), as observed in 55 to 100% of SCD patients, usually signals SCD with greater sensitivity than the air-conducted Tullio phenomenon (ACTP) or the Hennebert sign. The SVIN direction when the test is performed on the vertex location at 100 Hz is most often ipsilaterally beating in 82% of cases for the horizontal and torsional components and down-beating for the vertical component. Vertex stimulations are more efficient than mastoid stimulations at 100 Hz but are equivalent at higher frequencies. SVIN efficiency may depend on stimulus location, order, and duration. In SCD, SVIN frequency sensitivity is extended toward high frequencies, with around 400 Hz being optimal. SVIN direction may depend in 25% on stimulus frequency and in 50% on stimulus location. Mastoid stimulations show frequently diverging results following the side of stimulation. An after-nystagmus observed in 25% of cases can be interpreted in light of recent physiological data showing two modes of activation: (1) cycle-by-cycle phase-locked activation of action potentials in SCC afferents with irregular resting discharge; (2) cupula deflection by fluid streaming caused by the travelling waves of fluid displacement initiated by sound or vibration at the point of the dehiscence. The SVIN direction and intensity may result from these two mechanisms' competition. This instability explains the SVIN variability following stimulus location and frequency observed in some patients but also discrepancies between investigators. SVIN is a recent useful insight among other bedside examination tests for the diagnosis of SCD in clinical practice.
ABSTRACT
Botulinum neurotoxins are the most popular non-surgical treatments for aesthetic indications, but there is uncertainty about whether certain formulations are comparable in efficacy and safety and can be substituted for one another by a simple one to one dose conversion ratio. An expert panel of French practitioners was convened to establish a consensus on the clinical equivalence in efficacy and safety of OnabotulinumtoxinA (900 KDa) and IncobotulinumtoxinA (neurotoxin free from complexing proteins - 150 KDa). The consensus was divided into three sections incorporating a biological, bibliographic and clinical analysis of the two toxins. This included a review of the published data that have directly compared the two toxins for aesthetic indications and a survey of the panel's extensive clinical experience with the two toxins in terms of efficacy and safety. All panel members reviewed and endorsed the content of each section. Among this expert panel of French aesthetic physicians and biologists there was consensus that OnabotulinumtoxinA and IncobotulinumtoxinA are clinically equivalent in terms of efficacy and safety, and that a switch from one drug to the other can be made using a simple 1:1 conversion ratio.
Subject(s)
Botulinum Toxins, Type A/administration & dosage , Cosmetic Techniques , Botulinum Toxins, Type A/adverse effects , Consensus , France , Humans , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/adverse effects , Therapeutic EquivalencyABSTRACT
Nystagmus produced in response to air-conducted sound (ACS) stimulation-the Tullio phenomenon-is well known in patients with a semicircular canal (SCC) dehiscence (SCD). Here we consider the evidence that bone-conducted vibration (BCV) is also an effective stimulus for generating the Tullio phenomenon. We relate the clinical evidence based on clinical data extracted from literature to the recent evidence about the physical mechanism by which BCV may cause this nystagmus and the neural evidence confirming the likely mechanism. The hypothetical physical mechanism by which BCV activates SCC afferent neurons in SCD patients is that traveling waves are generated in the endolymph, initiated at the site of the dehiscence. We contend that the nystagmus and symptoms observed after cranial BCV in SCD patients is a variant of Skull Vibration Induced Nystagmus (SVIN) used to identify unilateral vestibular loss (uVL) with the major difference being that in uVL the nystagmus beats away from the affected ear whereas in Tullio to BCV the nystagmus beats usually toward the affected ear with the SCD. We suggest that the cause of this difference is a cycle-by-cycle activation of SCC afferents from the remaining ear, which are not canceled centrally by simultaneous afferent input from the opposite ear, because of its reduced or absent function in uVL. In the Tullio phenomenon, this cycle-by-cycle neural activation is complemented by fluid streaming and thus cupula deflection caused by the repeated compression of each cycle of the stimuli. In this way, the Tullio phenomenon to BCV is a version of skull vibration-induced nystagmus.
ABSTRACT
Extremely low frequency electromagnetic stimulation (ELF-EMS) has been considered as a neuroprotective therapy for ischemic stroke based on its capacity to induce nitric oxide (NO) signaling. Here, we examined whether ELF-EMS reduces ischemic stroke volume by stimulating cerebral collateral perfusion. Moreover, the pathway responsible for ELF-EMS-induced NO production was investigated. ELF-EMS diminished infarct growth following experimental stroke in collateral-rich C57BL/6 mice, but not in collateral-scarce BALB/c mice, suggesting that decreased lesion sizes after ELF-EMS results from improved collateral blood flow. In vitro analysis demonstrated that ELF-EMS increased endothelial NO levels by stimulating the Akt-/eNOS pathway. Furthermore, ELF-EMS augmented perfusion in the hind limb of healthy mice, which was mediated by enhanced Akt-/eNOS signaling. In healthy C57BL/6 mouse brains, ELF-EMS treatment increased cerebral blood flow in a NOS-dependent manner, whereas no improvement in cerebrovascular perfusion was observed in collateral-sparse BALB/c mice. In addition, ELF-EMS enhanced cerebral blood flow in both the contra- and ipsilateral hemispheres of C57BL/6 mice subjected to experimental ischemic stroke. In conclusion, we showed that ELF-EMS enhances (cerebro)vascular perfusion by stimulating NO production, indicating that ELF-EMS could be an attractive therapeutic strategy for acute ischemic stroke by improving cerebral collateral blood flow.
Subject(s)
Brain Ischemia , Ischemic Stroke , Animals , Brain Ischemia/therapy , Cerebrovascular Circulation , Collateral Circulation/physiology , Electromagnetic Phenomena , Ischemia , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nitric Oxide , Proto-Oncogene Proteins c-aktABSTRACT
Purpose: The purpose of this study was to compare the low degree/high degree (LD/HD) and Zernike Expansion simulation outcomes evaluating the corneal wavefront changes after theoretical conventional and customized aspheric photorefractive ablations. Methods: Initial anterior corneal surface profiles were modeled as conic sections with pre-operative apical curvature, R0, and asphericity, Q0. Postoperative apical curvature, R1, was computed from intended defocus correction, D, diameter zone, S, and target postoperative asphericity, Q1. Coefficients of both Zernike and LD/HD polynomial expansions of the rotationally symmetrical corneal profile were computed using scalar products. We modeled different values of D, R0, Q0, S, and ΔQ = Q1 to Q0. The corresponding postoperative changes in defocus (Δz20 vs. Δg20), fourth order (Δz40 vs. Δg40) and sixth order (Δz60 vs. Δg60) Zernike and LD/HD spherical aberrations (SAs) were compared. In addition, retrospective clinical data and wavefront measurements were obtained from two examples of two patient eyes before and after corneal laser photoablation. Results: The z20, varied with both R0 and Q0, whereas the LD/HD defocus coefficient, g20, was relatively robust to changes in asphericity. Variations of apical curvature better correlated with defocus and ΔQ with SA coefficients in the LD/HD classification. The impact of ΔQ was null on g20 but induced significant linear variations in z20 and fourth order SA coefficients. LD/HD coefficients provided a good correlation with the visual performances of the operated eyes. Conclusions: Simulated variations in postoperative corneal profile and wavefront expansion using the LD/HD approach showed good correlations between defocus and asphericity variations with variations in corneal curvature and SA coefficients, respectively. Translational Relevance: The relevance of this study was to provide a clinically relevant alternative to Zernike polynomials for the interpretation of wavefront changes after customized aspheric corrections.
Subject(s)
Cornea , Light , Computer Simulation , Humans , Lasers , Retrospective StudiesABSTRACT
We are in the midst of a shift towards using novel polynomials to decompose wavefront aberrations in a more ophthalmologically relevant way. Zernike polynomials have useful mathematical properties but fail to provide clinically relevant wavefront interpretation and predictions. We compared the distribution of the eye's aberrations and demonstrate some clinical applications of this using case studies comparing the results produced by the Zernike decomposition and evaluating them against the lower degree/higher degree (LD/HD) polynomial decomposition basis which clearly dissociates the higher and lower aberrations. In addition, innovative applications validate the LD/HD polynomial basis. Absence of artificial reduction of some higher order aberrations coefficients lead to a more realistic analysis. Here we summarize how wavefront analysis has evolved and demonstrate some of its new clinical applications.
Subject(s)
Refraction, Ocular , Refractive Errors , Algorithms , Corneal Topography , Humans , Vision DisordersABSTRACT
PURPOSE: To expand upon and clinically demonstrate the results of a new polynomial decomposition method. METHODS: To discuss the theoretical considerations comparing the qualitative and quantitative information produced by the Zernike coefficients and a new polynomial decomposition basis, in a comparative series of theoretical and clinical case studies. RESULTS: These comparative studies validate the novel polynomial basis that decomposes the wavefront, with clear segregation of the higher and lower aberrations. There is no artifactual reduction of some of the higher order aberration coefficients, providing a more clinically relevant retinal image quality prediction. CONCLUSIONS: Some of the inherent limitations of the Zernike polynomials in clinical ophthalmic applications can be solved by a novel set of polynomials forming an alternative higher order basis. The new basis provides a clear separation between modes containing lower order terms versus higher order terms and offers clinicians a more clinically realistic wavefront analysis. [J Refract Surg. 2020;36(2):74-81.].
Subject(s)
Aberrometry/methods , Corneal Wavefront Aberration/diagnosis , Models, Statistical , Refractive Errors/diagnosis , Vision Disorders/diagnosis , Adult , Algorithms , Corneal Wavefront Aberration/physiopathology , Humans , Male , Models, Theoretical , Refraction, Ocular/physiology , Refractive Errors/physiopathology , Vision Disorders/physiopathology , Visual Acuity/physiologyABSTRACT
Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using 99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, 99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, 99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of 99mTc-Ctl (p < 0.05). 99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.
ABSTRACT
This work aims at quantifying the effect of inherent uncertainties from cardiac output on the sensitivity of a human compliant arterial network response based on stochastic simulations of a reduced-order pulse wave propagation model. A simple pulsatile output form is used to reproduce the most relevant cardiac features with a minimum number of parameters associated with left ventricle dynamics. Another source of significant uncertainty is the spatial heterogeneity of the aortic compliance, which plays a key role in the propagation and damping of pulse waves generated at each cardiac cycle. A continuous representation of the aortic stiffness in the form of a generic random field of prescribed spatial correlation is then considered. Making use of a stochastic sparse pseudospectral method, we investigate the sensitivity of the pulse pressure and waves reflection magnitude over the arterial tree with respect to the different model uncertainties. Results indicate that uncertainties related to the shape and magnitude of the prescribed inlet flow in the proximal aorta can lead to potent variation of both the mean value and standard deviation of blood flow velocity and pressure dynamics due to the interaction of different wave propagation and reflection features. Lack of accurate knowledge in the stiffness properties of the aorta, resulting in uncertainty in the pulse wave velocity in that region, strongly modifies the statistical response, with a global increase in the variability of the quantities of interest and a spatial redistribution of the regions of higher sensitivity. These results will provide some guidance in clinical data acquisition and future coupling of arterial pulse wave propagation reduced-order model with more complex beating heart models.
Subject(s)
Aorta/physiology , Vascular Stiffness/physiology , Blood Flow Velocity , Hemodynamics , Humans , Models, Cardiovascular , Pulse Wave AnalysisABSTRACT
BACKGROUND: Jawline reshaping by replacing volume has become an indispensable component of modern facial rejuvenation. AIM: To evaluate calcium hydroxylapatite (CaHA) for the treatment of an aging jawline in a routine setting. METHODS: Five investigators enrolled 35 subjects requesting jawline rejuvenation with CaHA. Injections were performed according to investigators usual practice. Baseline and post-treatment scores were evaluated using Merz Aesthetics Scales®. Follow-up visits took place at Day 30 (Day 60 for those with touch-up at Day 30), 180, and 360. Physician and patient satisfaction, esthetic impact of treatment, and adverse events were recorded. RESULTS: Improvements in jawline contour compared with baseline were statistically significant at each visit, with scores of 2.42 (moderate to severe sagging) at baseline, 1.02 (mild) at Day 30/60 (P≤.0001), 1.11 at Day 180 (P≤.0001), and 1.45 at Day 360 (P=.0015). Statistically significant improvements in marionette line scores were also observed. Investigators rated results as "improved" to "very much improved" in all subjects up to Day 180, and in 81% of subjects at Day 360. Satisfaction with treatment was very high. Adverse events were mostly mild and related to either the procedure or injection technique. CONCLUSION: CaHA is a very effective agent for restoring jawline contour in routine practice and is associated with high levels of physician and patient satisfaction.
Subject(s)
Cosmetic Techniques , Dermatologic Agents/administration & dosage , Durapatite/administration & dosage , Jaw , Skin Aging/drug effects , Adult , Aged , Contusions/etiology , Cosmetic Techniques/adverse effects , Edema/etiology , Esthetics , Female , Hematoma/etiology , Humans , Injections, Intradermal , Middle Aged , Pain/etiology , Patient Satisfaction , Prospective Studies , RejuvenationABSTRACT
The addition of ezetimibe, an intestinal cholesterol absorption inhibitor, to statin therapy has recently shown clinical benefits in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial by reducing low-density-lipoprotein (LDL) cholesterol levels more than statin therapy alone. Here, we investigated the mechanisms by which inhibition of intestinal cholesterol absorption might contribute to the clinically observed reduction in cardiovascular events by evaluating its effect on inflammatory plaque development in apolipoprotein E-/- mice. Methods: Apolipoprotein E-/- mice were fed the Paigen diet (1.25% cholesterol, 0.5% cholic acid, and 15% fat) without or with ezetimibe (7 mg/kg/d) for 6 wk. In a first set of mice (n = 15), we intravenously injected 3H-cholesteryl oleate-labeled human LDL to test whether ezetimibe promotes LDL-derived cholesterol fecal excretion. In a second set (n = 20), we used the imaging agent 99mTc-cAbVCAM1-5 to evaluate expression of an inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1), in atherosclerotic plaques. In a third set (n = 21), we compared VCAM-1 expression with 99mTc-cAbVCAM1-5 uptake in various tissues. Results: Mice treated with ezetimibe showed a 173% higher LDL-cholesteryl ester plasma disappearance rate (P < 0.001 vs. control) after 3H-cholesteryl oleate-labeled LDL injection. At 96 h after injection, the hepatic fraction of 3H-tracer was 61% lower in mice treated with ezetimibe (P < 0.001). Meanwhile, LDL-derived 3H-cholesterol excretion in the feces was 107% higher (P < 0.001). The antiatherogenic effect of ezetimibe monitored by 99mTc-cAbVCAM1-5 SPECT showed a 49% reduction in aortic tracer uptake (percentage injected dose per cubic centimeter, 0.95 ± 0.04 vs. 1.87 ± 0.11; P < 0.01). In addition to hypercholesterolemia, the proinflammatory Paigen diet significantly increased VCAM-1 expression with respect to the control group in various tissues, including the aorta, and this expression correlated strongly with 99mTc-cAbVCAM1-5 uptake (r = 0.75; P < 0.05). Conclusion: Inhibition of intestinal cholesterol absorption with ezetimibe promotes antiatherosclerotic effects through increased LDL cholesterol catabolism and LDL-derived cholesterol fecal excretion and reduces inflamed atherosclerotic plaques. These mechanisms may contribute to the benefits of adding ezetimibe to a statin therapy.
Subject(s)
Atherosclerosis/diagnostic imaging , Atherosclerosis/drug therapy , Cholesterol, LDL , Diet, High-Fat , Ezetimibe/administration & dosage , Animals , Anticholesteremic Agents/administration & dosage , Apolipoproteins E/genetics , Atherosclerosis/metabolism , Drug Monitoring , Feces , Female , Isotope Labeling , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Reproducibility of Results , Sensitivity and Specificity , Technetium , Tomography, Emission-Computed, Single-Photon , Treatment Outcome , TritiumABSTRACT
BACKGROUND: Age-associated volume loss is now known to play an important role in the structural changes of the aging face. In the lower face, this manifests as drooping of the corners of the mouth and jowl leading to a loss of the oval jawline of youth. Jawline reshaping by replacing volume has therefore become an indispensable component of modern facial rejuvenation. AIM: Calcium hydroxylapatite (CaHA; Radiesse® , Merz Pharmaceuticals GmbH, Frankfurt, Germany) is an injectable filler with a cosmetic indication for tissue augmentation. The ability of calcium hydroxylapatite to provide immediate and long-lasting volume enhancement makes it an ideal agent for restoring an oval jawline. METHOD: This consensus statement has been developed to assist clinicians who would like to gain more experience in the use of volumizing agents to achieve an optimal outcome with this procedure. RESULTS: Using the recently developed Merz Aesthetics Scale® for jawline, the consensus provides a treatment protocol for individuals at each stage of oval loss and presents a series of before and after images to illustrate the improvements that can be achieved. Specific recommendations for calcium hydroxylapatite including type of anesthesia, injection techniques, volume for injection, use in combination with other procedures, and expected duration of corrections are provided. Techniques for minimizing and managing expected problems and potential complications are also described. CONCLUSION: Calcium hydroxylapatite is appropriate for treating patients at any stage of oval loss.
Subject(s)
Dermatologic Agents/administration & dosage , Durapatite/administration & dosage , Face , Rejuvenation , Skin Aging , Consensus , Esthetics , Humans , Injections, Intradermal , Practice Guidelines as TopicABSTRACT
UNLABELLED: (99m)Tc-cAbVCAM1-5, a single-domain antibody fragment directed against mouse or human vascular cell adhesion molecule 1 (VCAM-1), recently has been proposed as a new imaging agent for the detection of inflamed atherosclerotic lesions. Indeed, in a mouse model of atherosclerosis, (99m)Tc-cAbVCAM1-5 specifically bound to VCAM-1-positive lesions, thereby allowing their identification on SPECT images. The purpose of the present study was to investigate (99m)Tc-cAbVCAM1-5 imaging sensitivity using a reference statin therapy. METHODS: Thirty apolipoprotein E-deficient mice were fed a western-type diet. First, the relationship between the level of VCAM-1 expression and (99m)Tc-cAbVCAM1-5 uptake was evaluated in 18 mice using immunohistochemistry and autoradiography. Second, longitudinal SPECT/CT imaging was performed on control (n = 9) or atorvastatin-treated mice (0.01% w/w, n = 9). RESULTS: (99m)Tc-cAbVCAM1-5 uptake in atherosclerotic lesions correlated with the level of VCAM-1 expression (P < 0.05). Atorvastatin exerted significant antiatherogenic effects, and (99m)Tc-cAbVCAM1-5 lesion uptake was significantly reduced in 35-wk-old atorvastatin-treated mice, as indicated by ex vivo γ-well counting and autoradiography (P < 0.05). SPECT imaging quantification based on contrast-enhanced CT was reproducible (interexperimenter intraclass correlation coefficient, 0.97; intraexperimenter intraclass correlation coefficient, 0.90), and yielded results that were highly correlated with tracer biodistribution (r = 0.83; P < 0.0001). Therefore, reduced (99m)Tc-cAbVCAM1-5 uptake in atorvastatin-treated mice was successfully monitored noninvasively by SPECT/CT imaging (0.87 ± 0.06 vs. 1.11 ± 0.09 percentage injected dose per cubic centimeter in control group, P < 0.05). CONCLUSION: (99m)Tc-cAbVCAM1-5 imaging allowed the specific, sensitive, and reproducible quantification of VCAM-1 expression in mouse atherosclerotic lesions. (99m)Tc-cAbVCAM1-5 therefore exhibits suitable characteristics for the evaluation of novel antiatherogenic agents.