Showing papers by "Michael Hughes published in 2008"

Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data.

Abstract: The risk of stroke in atrial fibrillation (AF) needs to be assessed in each patient to determine the clinical and cost-effectiveness of thromboprophylaxis, with the aim of appropriate use of antithrombotic therapy. To achieve this, stroke risk factors in AF populations need to be identified and stroke risk stratification models have been devised on the basis of these risk factors. In this article, we firstly provide a systematic review of studies examining the attributable stroke risk of various clinical, demographic and echocardiographic patient characteristics in AF populations. Secondly, we performed a systematic review of published stroke risk stratification models, in terms of the results of the review of stroke risk factors and their ability to accurately discriminate between different levels of stroke risk. Thirdly, we review the health economic evidence relating to the cost-effectiveness of anticoagulation and antiplatelet therapy as thromboprophylaxis in AF patients. The studies included in the systematic review of stroke risk factors identified history of stroke or TIA, increasing age, hypertension and structural heart disease (left-ventricular dysfunction or hypertrophy) to be good predictors of stroke risk in AF patients. The evidence regarding diabetes mellitus, gender and other patient characteristics was less consistent. Three stroke risk stratification models were identified that were able to discriminate between different categories of stroke risk to at least 95% accuracy. Few models had addressed the cumulative nature of risk factors where a combination of risk factors would confer a greater risk than either factor alone. In patients at high risk of stroke, anticoagulation is cost effective, but not for those with a low risk of stroke. With the evidence available for stroke risk factors and the various alternative stroke risk stratification models, a review of these models in terms of the evidence on which they are devised and their performance in representative AF populations is important. The appropriate administration of thromboprophylaxis in AF patients would need to balance the risks and benefits of antithrombotic therapy with its cost-effectiveness.

In Vivo Emergence of Vicriviroc Resistance in a Human Immunodeficiency Virus Type 1 Subtype C-Infected Subject

Abstract: Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase IIb study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.

Quality assessment of dental treatments using en-face optical coherence tomography.

Abstract: The present study evaluates the potential of en-face optical coherence tomography (OCT) as a possible noninvasive high resolution method for supplying necessary information on the material defects of dental prostheses and microleakage at prosthetic interfaces. Teeth are also imaged after several treatment methods to asses material defects and microleakage at the tooth-filling interface, and the presence or absence of apical microleakage, as well as to evaluate the quality of bracket bonding on dental hard tissue. C-scan and B-scan OCT images as well as confocal images are acquired from a large range of samples. Gaps between the dental interfaces and material defects are clearly exposed.

Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week results.

Abstract: Objective: To investigate pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r)-based therapy in HIV-1-infected infants 6 weeks to 6 months of age. Methods: A prospective, multicenter, open-label trial of 21 infants with HIV-1 RNA > 10 000 copies/ml and treated with LPV/r 300/75 mg/m 2 twice daily plus two nucleoside reverse transcriptase inhibitors. Intensive pharmacokinetic sampling was performed at 2 weeks and predose concentrations were collected every 8 weeks; safety and plasma HIV-1 RNA were monitored every 4-12 weeks for 24 weeks. Results: Median age at enrollment was 14.7 weeks (range, 6.9-25.7) and 19/21 completed > 24 weeks of study. Although LPV/r apparent clearance was slightly higher than in older children, the median area under the concentration-time curve 0-12 h (67.5 μg,h/ml) was in the range reported from older children taking the recommended dose of 230/57.5 mg/m 2 . Predose concentrations stabilized at a higher level after the first 2 weeks of study. In as-treated analysis at week 24, 10/19 (53%) had plasma HIV-1 RNA <400copies/ml (median change, -3.33 log 10 copies/ml); poor adherence contributed to delayed viral suppression, which improved with longer follow-up. Three infants (14%) had transient adverse events of grade 3 or more that were possibly related to study treatment but did not require permanent treatment discontinuation. Conclusion: Despite higher clearance in infants 6 weeks to 6 months of age, a twice daily dose of 300/75 mg/m 2 LPV/r provided similar exposure to that in older children, was well tolerated and provided favorable virological and clinical efficacy.

Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy.

Abstract: Hyperlipidemia and insulin resistance have been noted to occur in HIV-infected individuals1,2 and are sometimes associated with an increase in abdominal fat and/or loss of peripheral fat3–5 These changes are seen more commonly in individuals who receive highly active antiretroviral therapy (HAART)6–9 but may also occur before treatment2,7 Individuals who experience these effects seem to be at increased risk for cardiovascular disease,10,11 a particular concern to children who may face lifetime exposure to these complications Etiologies and interrelationships of these complications are poorly understood Evidence suggests that alterations in the growth hormone axis may contribute to these metabolic abnormalities; in 1 study, for example, treatment with growth hormone (GH)-releasing factor resulting in increased insulin-like growth factor-1 (IGF-1) levels improved lipid profiles in HIV-infected individuals with central adiposity12 An increased understanding of risk factors and their relationships to adverse metabolic effects may lead to better insight into the pathophysiology and potential preventive and/or treatment strategies in childhood HIV infection Evidence from several studies of children suggests that hyperlipidemia, particularly hypercholesterolemia, is relatively common in HIV-infected children who receive antiretroviral therapy (ART);4,8,9,13,14 less evidence is available on insulin resistance in pediatric patients Metabolic abnormalities and fat redistribution are more likely to occur in postpubertal children,4,8,15 especially those who are on protease inhibitor (PI) treatment4,8,16,17 Few studies reported exclusively on prepubertal children The objectives of this study were to evaluate (1) lipid profiles and glucose homeostasis in HIV-positive prepubertal children on initiating or changing ART and (2) associations of lipid profiles and glucose homeostasis with viral, immune, ART, and growth factor parameters We hypothesized that treatment-naive patients would have an increased prevalence of lipid abnormalities compared with population-based norms and that both lipid abnormalities and subclinical insulin resistance would increase in prevalence after initiating or changing ART, particularly in children begun on PI therapy We also hypothesized that lipid profiles and insulin sensitivity would be less favorable in children with abnormalities in the GH axis as measured by IGF-1 and its binding proteins

Pharmacokinetics and safety of nelfinavir when used in combination with zidovudine and lamivudine in HIV-infected pregnant women: Pediatric AIDS Clinical Trials Group (PACTG) Protocol 353.

Abstract: Background: Combination antiretroviral regimens including nelfinavir (NFV) are commonly used in pregnancy. We studied the safety, antiviral effect, and pharmacokinetics of NFV and its M8 metabolite with two dosing regimens in combination with zidovudine (ZDV) and lamivudine (3TC) in HIV-infected pregnant women. Method: HIV-infected pregnant women between 14 and 34 weeks gestation received NFV (Cohort 1: 750 mg tid, n = 10; Cohort 2: 1250 mg bid, n = 23) with ZDV and 3TC. Serial blood sampling for NFV concentrations was performed antepartum (AP) and 6 weeks postpartum (PP). Maternal and cord blood samples were also obtained at delivery. NFV and M8 levels were determined by high-performance liquid chromatography. The pharmacokinetic (PK) target was an extrapolated NFV AUC 0–24 > 30 μg ⋅ h/mL. Mothers were followed frequently for potential clinical and laboratory toxicity. Results: Overall, NFV in combination with ZDV and 3TC was well tolerated. The PK target was met in 3/8 AP and 5/7 PP in Cohort 1 and 17/21 AP and 16/17 PP in Cohort 2. When Cohort 2 NFV PK parameters AP and PP were compared, median C max (3.90 μg/mL vs. 5.01 μg/mL, p < .05) and AUC 0–24 (56.6 vs. 86.8 μg ⋅ h/mL, p < .05) were increased PP and oral clearance (Cl/F; 44.2 vs. 28.8 L/h, p < .05) was decreased PP. The average M8/NFV ratio was increased PP compared to AP (0.085 vs. 0.29, p < .001). Placental transfer of NFV was low with a median cord blood:maternal plasma ratio at delivery of 0.05. Maternal mean CD4+ T cell counts increased significantly and plasma HIV-1 RNA levels decreased from entry to delivery and 6 to 12 weeks postpartum. Conclusion: NFV used in combination with ZDV and 3TC was well tolerated in pregnant HIV-infected women and produced a significant improvement in HIV disease parameters. NFV drug exposure is inadequate in most pregnant women receiving 750 mg tid but is much improved with 1250 mg bid. NFV crosses the placenta poorly. The AP increase in NFV oral clearance and decrease in M8/NFV ratio suggest that CYP3A activity increases relative to CYP2C19 activity during pregnancy. Key words: HIV, nelfinavir, pregnant women

Optical Coherence Tomography in archaeological and conservation science - a new emerging field

Abstract: There has been a long tradition of applying biomedical imaging techniques to the examination of historical artefacts, owing to similar demands for non-invasive methods in both fields. Optical Coherence Tomography (OCT) is no exception. We review the achievements on OCT applications to art conservation and archaeology since the publication of the first papers in 2004. Historical artefacts include a much broader range of materials than biological tissues, hence presenting a greater and somewhat different challenge to the field of OCT. New results will be presented to illustrate the various applications of OCT including both qualitative and quantitative analysis.

Associations of chemokine receptor polymorphisms With HIV-1 mother-to-child transmission in sub-Saharan Africa: possible modulation of genetic effects by antiretrovirals.

Abstract: Background HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa.

Laparoscopic-assisted small bowel resection for treatment of adult small bowel intussusception: a case report.

Abstract: Background Intussuception is a rare cause of intestinal obstruction in adults. Diagnosis is often difficult due to the variable and sometimes episodic nature of symptoms. Surgery is the recommended treatment option in adults if the diagnosis is proven.

Implant bone interface investigated with a non-invasive method: optical coherence tomography

Abstract: Bone implants insertion implies the necessity of a important primary stability. The quality of the implant insertion could be investigated by implant bone interface analysis. In this study, we demonstrate that en-face optical coherence tomography can be used to evaluate these interfaces. We have collected both C-scan OCT images (en-face) as well as B-scan OCT images (cross section). 3D analysis was possible by acquiring 30-100 C-scans which were used post-acquisition to explore the volume of the tissue around the interface. Four implants were inserted into a human mandible and their interfaces imaged. The images show gaps of different sizes and shapes between the implant and the bone at different depths.

Insulin-like growth factor-1 and lean body mass in HIV-infected children.

Abstract: Objectives: To describe insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1-binding protein-1 (IGFBP-1) and IGFBP-3 in HIV+ children before and after initiating or changing antiretroviral therapy and to evaluate association of growth and body composition to growth factors at baseline and over time. Methods: Ninety-seven prepubertal HIV+ children aged 1 month to younger than 13 years were observed over 48 weeks after beginning or changing antiretroviral therapy. Serum IGF-1, IGFBP-1, and IGFBP-3 were measured and compared with age- and sex-specific norms. Anthropometric measures were compared as follows: subjects vs matched children from (a) the National Health and Nutrition Examination Survey to generate z scores and (b) HIV-exposed, uninfected children from Women and Infants Transmission Study; and subjects with normal vs abnormal IGF-1 and IGFBP concentrations at baseline. Anthropometric changes were compared for children whose IGF-1 level normalized vs remaining subjects. Multivariate analysis adjusting for sex, race, and baseline age evaluated associations between anthropometry and IGF-1 and IGFBP concentrations. Results: In multivariate analysis, lower baseline IGF-1 and IGFBP-3 were associated with lower mean weight, height, mid-arm muscle circumference, and mid-thigh circumference z scores. Twenty-four percent of children had a low IGF-1 level at baseline, 50% of whom normalized IGF-1 on study. Children whose IGF-1 normalized had greater increases in mean mid-arm muscle circumference z score (1.00 vs −0.03, P = 0.029), but a trend toward lesser mean height increase (P = 0.082) than remaining subjects. Likewise, in comparison to controls from Women and Infants Transmission Study, mean mid-arm muscle circumference also increased more in children whose IGF-1 normalized (P = 0.024) but mean height changed less (P = 0.003). Fifty-five percent of children had elevated IGFBP-1 at baseline, 69% of whom normalized. Conclusions: IGF-1 increases and IGFBP-1 decreases in HIV-infected children upon initiation or change in antiretroviral therapy. Improved muscle mass, but not linear growth, is associated with normalized IGF-1 concentration. These findings suggest that IGF-1 may merit evaluation as a potential therapeutic strategy to improve lean body mass in HIV-infected children.

The search for data on when to start treatment for HIV infection.

Abstract: The question of when to start antiretroviral therapy (ART) for infection with HIV has been much discussed, and treatment management guidelines have oscillated from the “hit hard, hit early” philosophy to conservative approaches of deferring treatment in asymptomatic patients until CD4 cell counts are 200 cells/ L [1, 2], despite their being few data on the subject [3] In this issue of the Journal, results from a subgroup analysis [4] of a randomized trial, the Strategies for Management of Antiretroviral Therapy (SMART) study, are presented that provide some insight into this question Major reasons why, in recent years, guidelines have tended to be more conservative and have recommended deferring treatment until CD4 cell counts are 200 cells/ L include the following [5]: the low absolute risk of AIDS-defining clinical events at higher CD4 cell counts; the negative impact of side effects on quality of life as well as the occasional occurrence of life-threatening adverse effects, including ones that have been associated with long-term use of ART (such as myocardial infarction); and the inconvenience of drug regimens, leading to reduced adherence, an increased risk of drug resistance, and limitations on future drug options Revisiting these issues, Phillips et al [5] recently concluded that advances in drug development and an improved understanding of the durability and adverse effects of specific drugs has led to renewed interest in the possibility that initiation of ART at CD4 cell counts 200 cells/ L might be preferable The SMART study [6] enrolled HIVinfected subjects with CD4 cell counts 350 cells/ L (including subjects with prior AIDS events) and randomized participants to a continuous ART strategy versus a CD4 cell count– guided strategy for interrupting therapy during periods of higher CD4 cell counts The study population was predominantly and extensively ART experienced In this issue, results are presented for a subgroup of SMART participants not receiving ART at the time of enrollment [4] Specifically, participants who were ART naive (n 249) or who had not received ART for at least 6 months (n 228) were included Per the SMART study design, the subjects in the continuous ART arm were in effect randomized to (re)initiate ART immediately, and those in the CD4 cell count– guided arm were randomized to defer (re)initiation until their CD4 cell count fell to 250 cells/ L Follow-up was for a mean of 18 months In this subgroup, as in the overall SMART population, subjects who immediately (re)initiated ART experienced fewer grade 4 symptomatic adverse events than did those deferring (re)initiation In addition, also as in the overall study population, fewer subjects randomized to (re)initiate ART immediately experienced opportunistic disease (OD) events or died (5 vs 15 participants; P 02) or experienced major cardiovascular, renal, or hepatic events (the so-called serious non-AIDS events; 2 vs 12 participants; P 01) Of importance, this comparison was driven primarily by events among subjects who had previously received ART (for a median of 4 years) The data that more truly address the question of when first to start ART were limited Of the 249 ART-naive participants, 1 versus 4 participants experienced OD events or died in the immediate versus deferred ART arms, and 1 versus 4 experienced serious non-AIDS events That use of ART at higher CD4 cell counts might reduce the incidence of OD is not surprising: randomized trials conducted in the early 1990s showed a benefit [7], and observational studies have suggested that this is true for regimens in use more recently [8] What is more important is that this subgroup analysis raises Received 11 January 2008; accepted 11 January 2008; electronically published 26 March 2008 Potential conflicts of interest: MDH currently has consultancy agreements with the following companies that have anti-HIV products: Boehringer Ingelheim, Tibotec, and Virionyx HRR reports no potential conflicts Financial support: National Institutes of Health (grant AI068634) Reprints or correspondence: Dr Michael Hughes, Harvard University, School of Public Health, Center for Biostatistics in AIDS Research, 655 Huntington Ave, Boston, MA 02115 (mhughes@sdacharvardedu) The Journal of Infectious Diseases 2008; 197:1084–6 © 2008 by the Infectious Diseases Society of America All rights reserved 0022-1899/2008/19708-0003$1500 DOI: 101086/586712 E D I T O R I A L C O M M E N T A R Y

Practical issues arising in an exploratory analysis evaluating progression-free survival as a surrogate endpoint for overall survival in advanced colorectal cancer.

Abstract: This paper is based on a conference presentation in which several authors presented results from analyses of the same dataset concerning the evaluation of progression-free survival (PFS) as a surrogate endpoint for overall survival in advanced colorectal cancer clinical trials. In evaluating a potential surrogate endpoint, there is a hierarchy of information that might usually be considered desirable: 1) a biological rationale for surrogacy, 2) demonstration of the prognostic value of the surrogate endpoint in untreated patients and 3) in treated patients and 4) demonstration across randomized comparisons that differences in the effect of randomized treatments on the surrogate endpoint are associated with the corresponding differences in the effect on the clinical endpoint of interest. Results from analyses that might be used to address the third and four requirements are presented and some of the practical issues that arise in evaluating a surrogate endpoint, which would be relevant to many diseases, are illustrated. Although the results presented should not be seen as a definitive analysis of the value of PFS as a surrogate endpoint, concerns are identified about the potential lack of standardization of the definition of PFS or the frequency of evaluation of disease progression and the high leverage of one study in evaluating the association in addressing the fourth requirement.

A statistical framework for quantile equivalence clinical trials with application to pharmacokinetic studies that bridge from HIV-infected adults to children.

Abstract: Summary Bridging clinical trials are sometimes designed to evaluate whether a proposed dose for use in one population, for example, children, gives similar pharmacokinetic (PK) levels, or has similar effects on a surrogate marker as an established effective dose used in another population, for example, adults. For HIV bridging trials, because of the increased risk of viral resistance to drugs at low PK levels, the goal is often to determine whether the doses used in different populations result in similar percentages of patients with low PK levels. For example, it may be desired to evaluate that a proposed pediatric dose gives approximately 10% of children with PK levels below the 10th percentile of PK levels for the established adult dose. However, the 10th percentile for the adult dose is often imprecisely estimated in studies of relatively small size. Little attention has been given to the statistical framework for such bridging studies. In this article, a formal framework for the design and analysis of quantile-based bridging studies is proposed. The methodology is then developed for normally distributed outcome measures from both frequentist and Bayesian directions. Sample size and other design considerations are discussed.

Major Clinical Outcomes in Antiretroviral Therapy (ART)-Naive Participants and in Those Not Receiving ART at Baseline in the SMART Study. Commentary

Abstract: Background. The SMART study randomized 5472 human immunodeficiency virus (HIV)-infected patients with CD4 + cell counts >350 cells/μL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral supression [VS] group). In the DC group, participants started ART when the CD4 + cell count was 350 cells/μL compared with <250 cells/μL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial.

Fibres reinforced dentures investigated with en-face optical coherence tomography

Abstract: The complete dentures are currently made using different technologies. In order to avoid deficiencies of the prostheses made using the classical technique, several alternative procedures have been devised. In order to enhance the mechanical strength, complete denture bases are reinforced with fibres. Their material and structure vary wildly, which makes the investigation difficult. In this study, optical coherence tomography (OCT) is evaluated as a possible non-invasive technique to assess the biomechanical behaviour of the reinforcing fibres. OCT images demonstrate structural defects between fibres and the acrylic material in all dentures bases investigated. We conclude that OCT can successfully be used as a noninvasive analysis method.

Quasi-simultaneous optical coherence tomography and confocal imaging

Abstract: A new approach of acquiring quasi-simultaneous optical coherence tomography (OCT) and confocal images is presented. The two images are generated using different principles, OCT and confocal microscopy. When the system is used to image the retina, the two images have depth resolutions, at present, of <20 µm and ~1 mm, respectively. The acquisition and display of en face OCT and confocal images are quasi-simultaneous, without the need of a beamsplitter. By using a chopper to periodically obstruct the reference beam in the OCT interferometer, synchronized with the XY-transversal scanner, much higher acquisition speed is obtained than in a previous report where we flipped an opaque screen in the reference arm of the interferometer. Successful operation of the novel configuration was achieved by: (1) stable synchronization of the chopper's movement with the horizontal line scanner and (2) fast self-adjusting of the gain value of avalanche photodiodes, depending on the optical power. Images from coin, leaves, and retina in vivo have been collected to demonstrate the functionality of the system.

An optical coherence tomography investigation of materials defects in ceramic fixed partial dental prostheses

Abstract: Metal ceramic and integral ceramic fixed partial prostheses are mainly used in the frontal part of the dental arch because for esthetics reasons. The masticatory stress may induce fractures of the bridges. There are several factors that are associated with the stress state created in ceramic restorations, including: thickness of ceramic layers, mechanical properties of the materials, elastic modulus of the supporting substrate material, direction, magnitude and frequency of applied load, size and location of occlusal contact areas, residual stresses induced by processing or pores, restoration-cement interfacial defects and environmental defects. The fractures of these bridges lead to functional, esthetic and phonetic disturbances which finally render the prosthetic treatme nt inefficient. The purpose of this study is to evaluate the capability of optical coherence tomography (OCT) in detection and analysis of possible material defects in metal-ceramic and integral ceramic fixed partial dentures.

Fixed partial dentures investigated by optical coherent tomography

Abstract: Fixed partial prostheses as integral ceramics, integral polymers, metal ceramics or metal polymers bridges, are mainly used in the frontal part of the dental arch (especially the integral bridges). They have to satisfy high stress requirements as well as esthetic. The masticatory stress may induce fractures of the bridges. These may be triggered by initial materials defects or by alterations of the technological process. The fractures of these bridges lead to functional, esthetic and phonetic disturbances which finally render the prosthetic treatment inefficient. The purpose of this study is to evaluate the capability of en-face optical coherence tomography (OCT) in detection and analysis of possible fractures in several integral fixed partial dentures. The materials used were represented by several fixed partial prostheses, integral ceramics, integral polymers, metal ceramics and metal polymers bridges. In order to discover the defects, scanning was performed from incisal, vestibular, oral and cervical directions material defects such as fractures and pores were investigated using OCT. In conclusion, en-face OCT has proven as a valuable non invasive method to investigate fixed partial prostheses before their insertion in the oral cavity.

Investigations of OCT imaging performance using a unique source providing several spectral wavebands

Abstract: The authors report investigations into the suitability of a broadband supercontinuum fiber laser (SCFL) for use in Optical Coherence Tomography (OCT). The supercontinuum of light extending from 400 nm to 1800 nm can be used selectively in several spectral wavebands from 600 nm to 1700 nm in order to characterize the performance of single mode (SM) fiber OCT systems through spectral and auto-correlation measurements, dispersion measurements and image acquisition. Spectral selection and tailoring is made possible through a combination of bandpass optical filters. In addition, for the first time, given the optical bandwidth available, we perform evaluation of effective noise bandwidths which take into consideration the spectral behavior of the optical splitter in the balanced detection receiver.

Root canal filling evaluation using optical coherence tomography

Abstract: The root canal fillings are destined to seal the root canal especially in the apical areea. Invasive techniques are known which are used to assess the quality of the seal. These lead to the destruction of the probes and often no conclusion could be drawn in respect to the existence of any microleakage in the investigated areas of interest. Optical coherence tomography (OCT) is a relatively novel non-invasive imaging technique which presents potential in assessing the microleakage of the apical area in the root canal fillings with micron depth resolution. 3D reconstruction allows a complete view with obvious display of gaps in the apical root canal filling. For this study, 30 monoradicular teeth were prepared by conventional and rotative methods. Afterwards, root canal fillings were produced in each tooth. The images obtained show some microleakage in all the investigated root canal fillings. The advantages of the OCT method consist in non-invasiveness and high resolution.

Optical coherence tomography and confocal microscopy investigations of dental prostheses

Abstract: Dental prostheses are very complex systems, heterogenous in structure, made up from various materials, with different physical properties. An essential question mark is on the physical, chemical and mechanical compatibility between these materials. They have to satisfy high stress requirements as well as esthetic challenges. The masticatory stress may induce fractures of the prostheses, which may be triggered by initial materials defects or by alterations of the technological process. The failures of dental prostheses lead to functional, esthetic and phonetic disturbances which finally render the prosthetic treatment inefficient. The purpose of this study is to evaluate the capability of en-face optical coherence tomography as a possible non-invasive high resolution method in supplying the necessary information on the material defects of dental prostheses and microleakage at prosthetic interfaces. C-scan and B-scan OCT images as well as confocal images are acquired from a large range of samples. Gaps between the dental interfaces and material defects are clearly exposed. We conclude that OCT can successfully be used as a noninvasive analysis method.

Investigation of bracket bonding for orthodontic treatments using en- face optical coherence tomography

Abstract: Despite good diagnosis and treatment planning, orthodontic treatment can fail if bonding fails. It is now common practice to address the aesthetic appearance of patients using aesthetic brackets instead of metal ones. Therefore, bonding aesthetic brackets has become an issue for orthodontists today. Orthodontic bonding is mainly achieved using composite resin but can also be performed with glass ionomer or resin cements. For improving the quality of bonding, the enamel is acid etched for 30 seconds with 38% phosphoric acid and then a bonding agent is applied. In our study we investigated and compared the quality of bonding between ceramic brackets, polymeric brackets and enamel, respectively using a new investigation method - OCT. The aim of our study was to evaluate the resin layer at the bracket base - tooth interface.

A swept source OCT at 1300 nm with angular compounding for art and archaeological conservation

Abstract: We have assembled a swept source optical coherence tomography (OCT) system for use in Art & Archaeological Conservation. The system is illuminated by an in-house swept source with a central wavelength of 1300 nm. This system includes dedicated optics to allow for angular averaging for speckle noise reduction. We demonstrate that the averaging produces significant improvements in speckle SNR in art and archaeological type objects and allows easier identification of features. We further demonstrate that there is practically no loss of axial resolution.

Imaging of basal cell carcinoma tissue using en-face OCT

Abstract: We have investigated the applicability of en-face OCT in imaging freshly excised biopsies of Basal Cell Carcinoma. Encouraging results have been obtained in identifying tumor features and abnormal skin architecture.

Perfluorocarbon Nanoparticles for Molecular Imaging and Targeted Therapeutics : These particles allow very sensitive detection of the development of conditions such as cancer and heart disease and can be used to diagnose, treat and monitor therapy

Abstract: Molecular imaging is a novel tool that has allowed noninvasive diagnostic imaging to transition from gross anatomical description to identification of specific tissue epitopes and observation of biological processes at the cellular level. Until recently, this technique was confined to the field of nuclear imaging; however, advances in nanotechnology have extended this research to include magnetic resonance (MR) imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and ultrasound (US), among others. The application of nanotechnology to MR, SPECT, and US molecular imaging has generated several candidate contrast agents. We discuss the application of one multimodality platform, a targeted perfluorocarbon nanopar- ticle. Our results show that it is useful for noninvasive detection with all three imaging modalities and may additionally be used for local drug delivery.

Quasi-simultaneous OCT/confocal imaging

Abstract: A new approach of acquiring quasi-simultaneous OCT and confocal images is presented. The two images are generated using different principles, optical coherence tomography (OCT) and confocal microscopy (CM). When the system is used to image the retina, the two images have depth resolutions, at present, of less than 20 μm and approximately 1 mm respectively. The acquisition and display of en-face OCT and confocal images are quasi-simultaneous, without the need of a beam splitter. By using a chopper to periodically obstruct the reference beam in the OCT interferometer, synchronized with the XY-transversal scanner, much higher acquisition speed is obtained than in a previous report where we flipped an opaque screen in the reference arm of the interferometer. Successful operation of the novel configuration was achieved by: (1) stable synchronization of the chopper's movement with the horizontal line scanner and (2) fast self-adjusting of the gain value of avalanche photodiodes depending on the optical power. Images from coin, leafs and retina in vivo have been collected to demonstrate the functionality of the system.

An innovative approach for investigating the ceramic bracket-enamel interface - optical coherence tomography and confocal microscopy

Abstract: Bonding has become a routine procedure in several dental specialties - from prosthodontics to conservative dentistry and even orthodontics. In many of these fields it is important to be able to investigate the bonded interfaces to assess their quality. All currently employed investigative methods are invasive, meaning that samples are destroyed in the testing procedure and cannot be used again. We have investigated the interface between human enamel and bonded ceramic brackets non-invasively, introducing a combination of new investigative methods - optical coherence tomography (OCT) and confocal microscopy (CM). Brackets were conventionally bonded on conditioned buccal surfaces of teeth The bonding was assessed using these methods. Three dimensional reconstructions of the detected material defects were developed using manual and semi-automatic segmentation. The results clearly prove that OCT and CM are useful in orthodontic bonding investigations.

Quasi-Simultaneous OCT/SLO Imaging

Abstract: Quasi-simultaneous OCT and SLO images are produced without the need to split the signal from the retina. A chopper synchronized with the transverse scanner periodically blocks-off the reference beam in the OCT.