On the Design of a Comprehensive Authorisation Framework for Service Oriented Architecture (SOA)

DTIC Science & Technology

2013-07-01

Authentication Server AZM Authorisation Manager AZS Authorisation Server BP Business Process BPAA Business Process Authorisation Architecture BPAD Business...Internet Protocol Security JAAS Java Authentication and Authorisation Service MAC Mandatory Access Control RBAC Role Based Access Control RCA Regional...the authentication process, make authorisation decisions using application specific access control functions that results in the practice of

The regulatory acceptance of alternatives in the European Union.

PubMed

Warbrick, E Vicky; Evans, Peter F

2004-06-01

Recently, progress has been made toward the regulatory acceptance of replacements in the European Union (EU), particularly with the introduction of in vitro methods for the prediction of skin corrosivity, dermal penetration, phototoxicity and embryotoxicity. In vitro genotoxicity tests are well established, and testing for this endpoint can be completed without animals, provided that clear negative outcomes are obtained. Tiered approaches including in vitro tests can also be used to address skin and eye irritation endpoints. Reductions and/or refinements in animal use are being achieved following the replacement of the oral LD50 test with alternative methods and the adoption of reduced test packages for materials, such as closed-system intermediates and certain polymers. Furthermore, the use of a "read-across" approach has reduced animal testing. Substantial gains in refinement will also be made with the recent acceptance of the local lymph node assay for skin sensitisation and the development of an acute inhalation toxicity method that avoids lethality as the endpoint. For the future, under the proposed EU Registration, Evaluation and Authorisation of Chemicals (REACH) scheme, it is envisaged that, where suitable in vitro methods exist, these should be used to support registration of substances produced at up to ten tonnes per annum. This proposal can only accelerate the further development, validation and regulatory acceptance of such alternative methods.

Integrated testing strategy (ITS) for bioaccumulation assessment under REACH.

PubMed

Lombardo, Anna; Roncaglioni, Alessandra; Benfentati, Emilio; Nendza, Monika; Segner, Helmut; Fernández, Alberto; Kühne, Ralph; Franco, Antonio; Pauné, Eduard; Schüürmann, Gerrit

2014-08-01

REACH (registration, evaluation, authorisation and restriction of chemicals) regulation requires that all the chemicals produced or imported in Europe above 1 tonne/year are registered. To register a chemical, physicochemical, toxicological and ecotoxicological information needs to be reported in a dossier. REACH promotes the use of alternative methods to replace, refine and reduce the use of animal (eco)toxicity testing. Within the EU OSIRIS project, integrated testing strategies (ITSs) have been developed for the rational use of non-animal testing approaches in chemical hazard assessment. Here we present an ITS for evaluating the bioaccumulation potential of organic chemicals. The scheme includes the use of all available data (also the non-optimal ones), waiving schemes, analysis of physicochemical properties related to the end point and alternative methods (both in silico and in vitro). In vivo methods are used only as last resort. Using the ITS, in vivo testing could be waived for about 67% of the examined compounds, but bioaccumulation potential could be estimated on the basis of non-animal methods. The presented ITS is freely available through a web tool. Copyright © 2014 Elsevier Ltd. All rights reserved.

European regulatory use and impact of subgroup evaluation in marketing authorisation applications.

PubMed

Tanniou, Julien; Teerenstra, Steven; Hassan, Sagal; Elferink, Andre; van der Tweel, Ingeborg; Gispen-de Wied, Christine; Roes, Kit C B

2017-12-01

Marketing authorisation application dossiers relating to medicinal products containing new active substances and evaluated by the European Medicines Agency (EMA) over the period 2012-2015 were examined. Major objections and other concerns relating to efficacy and safety of the day 80 assessment reports were reviewed. Overall, approved products have more subgroup concerns than nonapproved products, which seems to be a consistent pattern. Subgroup analyses are mainly assessed to have the insurance that subgroups of patients that might lack a positive benefit: risk ratio will not be wrongly included in the approved treatment indication. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Quality Issues Identified During the Evaluation of Biosimilars by the European Medicines Agency's Committee for Medicinal Products for Human Use.

PubMed

Cilia, Mark; Ruiz, Sol; Richardson, Peter; Salmonson, Tomas; Serracino-Inglott, Anthony; Wirth, Francesca; Borg, John Joseph

2018-02-01

The aim of this study was to identify trends in deficiencies raised during the EU evaluation of the quality part of dossiers for marketing authorisation applications of biosimilar medicinal products. All adopted day 120 list of questions on the quality module of 22 marketing authorisation applications for biosimilars submitted to the European Medicines Agency and concluded by the end of October 2015 was analysed. Frequencies of common deficiencies identified were calculated and summarised descriptions included. Frequencies and trends on quality deficiencies were recorded and presented for 22 biosimilar applications. Thirty-two 'major objections' for 9 products were identified from 14 marketing authorisation applications with 15 raised for drug substance and 17 for drug product. In addition, 547 'other concerns' for drug substance and 495 for drug product were also adopted. The frequencies and trends of the identified deficiencies together with their impact were discussed from a regulatory perspective and how these impact key manufacturing processes and key materials used in the production of biosimilars. This study provides an insight to the regulatory challenges prospective companies need to consider when developing biosimilars; it also helps elucidate common pitfalls in the development and production of biosimilars and in the submission of dossiers for their marketing authorisations. The results are expected to be of interest to pharmaceutical companies but also to regulators to obtain consistent information on medicinal products based on transparent rules safeguarding the necessary pharmaceutical quality of medicinal products.

Grouping of Petroleum Substances as Example UVCBs by Ion Mobility-Mass Spectrometry to Enable Chemical Composition-Based Read-Across.

PubMed

Grimm, Fabian A; Russell, William K; Luo, Yu-Syuan; Iwata, Yasuhiro; Chiu, Weihsueh A; Roy, Tim; Boogaard, Peter J; Ketelslegers, Hans B; Rusyn, Ivan

2017-06-20

Substances of Unknown or Variable composition, Complex reaction products, and Biological materials (UVCBs), including many refined petroleum products, present a major challenge in regulatory submissions under the EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and US High Production Volume regulatory regimes. The inherent complexity of these substances, as well as variability in composition obfuscates detailed chemical characterization of each individual substance and their grouping for human and environmental health evaluation through read-across. In this study, we applied ion mobility mass spectrometry in conjunction with cheminformatics-based data integration and visualization to derive substance-specific signatures based on the distribution and abundance of various heteroatom classes. We used petroleum substances from four petroleum substance manufacturing streams and evaluated their chemical composition similarity based on high-dimensional substance-specific quantitative parameters including m/z distribution, drift time, carbon number range, and associated double bond equivalents and hydrogen-to-carbon ratios. Data integration and visualization revealed group-specific similarities for petroleum substances. Observed differences within a product group were indicative of batch- or manufacturer-dependent variation. We demonstrate how high-resolution analytical chemistry approaches can be used effectively to support categorization of UVCBs based on their heteroatom composition and how such data can be used in regulatory decision-making.

Health economics of market access for biopharmaceuticals and biosimilars.

PubMed

Simoens, Steven

2009-09-01

This article discusses health economic challenges of research and development, registration, pricing and reimbursement of biopharmaceuticals and biosimilars. A literature search was carried out of PubMed, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews and EconLit up to March 2009. The development process of biopharmaceuticals is risky, lengthy, complex and expensive. Registration is complicated by the inherent variation between biopharmaceuticals. Also, as biopharmaceuticals are likely to be efficacious in a subgroup of the patient population, there is a need to select the most responsive target population and to identify biomarkers. To inform pricing and reimbursement decisions, the development process needs to collect comparative data to calculate the incremental cost effectiveness and budget impact of biopharmaceuticals. There is a role for innovative mechanisms such as risk-sharing arrangements to reimburse biopharmaceuticals. Given that biosimilars are similar, but not identical to the reference biopharmaceutical, the development process needs to generate clinical trial data in order to gain marketing authorisation. From a health economic perspective, the question arises whether inherent differences between biopharmaceuticals and biosimilars produce differences in safety, effectiveness and costs: to date, this question is unresolved. The early inclusion of health economics in the process of developing biopharmaceuticals and biosimilars is imperative with a view to demonstrating their relative (cost) effectiveness and informing registration, pricing and reimbursement decisions.

[When state authorisation was introduced for medical doctors in Norway].

PubMed

Haave, Per

2007-12-13

In 1927, a law was implemented in Norway that for the first time required medical students to be state authorised before they could practice medicine and use the title medical doctor. The question of authorisation split the professional elite, both the Norwegian Medical Association and the Medical Faculty at the University of Oslo. Those very few members of the professional elite that advocated authorisation did, however, convince the government as well as the parliament that authorisation should be given and recalled by the state. State authorisation was first of all aimed at protecting the medical profession against "unfit" members; it was not a question of monopolising medical work or preventing other groups from working within the healthcare services. To put this into context, one should know that there had been a transition from a bureaucratic to a free labour market and most doctors were no longer engaged by the State, but had to practise in a private market. One feared that this would undermine the doctors' authority and status. In this situation, authorisation by the state was considered necessary to safeguard the public's confidence in doctors and their work.

Study protocol for a transversal study to develop a screening model for excessive gambling behaviours on a representative sample of users of French authorised gambling websites

PubMed Central

Hardouin, Jean-Benoit; Grall-Bronnec, Marie; Challet-Bouju, Gaëlle

2017-01-01

Introduction Since the legalisation of online gambling in France in 2010, gambling operators must implement responsible gambling measures to prevent excessive gambling practices. However, actually there is no screening procedure for identifying problematic gamblers. Although several studies have already been performed using several data sets from online gambling operators, the authors deplored several methodological and clinical limits that prevent scientifically validating the existence of problematic gambling behaviour. The aim of this study is to develop a model for screening excessive gambling practices based on the gambling behaviours observed on French gambling websites, coupled with a clinical validation. Methods and analysis The research is divided into three successive stages. All analyses will be performed for each major type of authorised online gambling in France. The first stage aims at defining a typology of users of French authorised gambling websites based on their gambling behaviour. This analysis will be based on data from the Authority for Regulating Online Gambling (ARJEL) and the Française Des Jeux (FDJ). For the second stage aiming at determining a score to predict whether a gambler is problematic or not, we will cross answers from the Canadian Problem Gambling Index with real gambling data. The objective of the third stage is to clinically validate the score previously developed. Results from the screening model will be compared (using sensitivity, specificity, area under the curve, and positive and negative predictive values) with the diagnosis obtained with a telephone clinical interview, including diagnostic criteria for gambling addiction. Ethics and dissemination This study was approved by the local Research Ethics Committee (GNEDS) on 25 March 2015. Results will be presented in national and international conferences, submitted to peer-reviewed journals and will be part of a PhD thesis. A final report with the study results will be presented to the ARJEL, especially the final screening model. Trial registration number NCT02415296. PMID:28515192

[Safety monitoring of cell-based medicinal products (CBMPs)].

PubMed

Funk, Markus B; Frech, Marion; Spranger, Robert; Keller-Stanislawski, Brigitte

2015-11-01

Cell-based medicinal products (CBMPs), a category of advanced-therapy medicinal products (ATMPs), are authorised for the European market by the European Commission by means of the centralized marketing authorisation. By conforming to the German Medicinal Products Act (Sec. 4b AMG), national authorisation can be granted by the Paul-Ehrlich-Institut in Germany exclusively for ATMPs not based on a routine manufacturing procedure. In both procedures, quality, efficacy, and safety are evaluated and the risk-benefit balance is assessed. For the centralised procedure, mainly controlled clinical trial data must be submitted, whereas the requirements for national procedures could be modified corresponding to the stage of development of the ATMP. After marketing authorization, the marketing authorization/license holder is obligated to report all serious adverse reactions to the competent authority and to provide periodic safety update reports. If necessary, post-authorization safety studies could be imposed. On the basis of these regulatory measures, the safety of advanced therapies can be monitored and improved.

Banking (on) the brain: from consent to authorisation and the transformative potential of solidarity.

PubMed

Harmon, Shawn H E; Mcmahon, Aisling

2014-01-01

Modern technologies and biomedicine ambitions have given rise to new models of medical research, including population biobanking. One example of biobanking is brain banking, which refers to the collection and storage of brain and spinal cord samples for research into neurological diseases. Obviously, brain banking involves taking brains and tissue from deceased people, a fact which complicates the role of recruiters and makes consent a poor tool for stakeholders. After contextualising brain banking and considering the public health issues at stake, this article explores the legal definitions and demands of, and actual processes around, consent in England/Wales/Northern Ireland and authorisation in Scotland, articulating and evaluating their conceptual and practical differences. It then argues for an expanded but improved operation of 'authorisation' in the brain banking (and broader biobanking) setting, adopting 'solidarity' as our foundation and the improvement of the 'public good' our objective. © The Author [2014]. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

Applications of AOPs to ecotoxicology | Science Inventory | US ...

EPA Pesticide Factsheets

Toxicologists conducting safety assessments for either human or ecological health are responsible for generating data for possible adverse effects of a rapidly increasing number of substances. For example, the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) program in Europe, and the recent reauthorization of the Toxic Substances Control Act (TSCA) in the United States (US) both explicitly mandate consideration of the potential toxicity of many thousands of chemicals that, in the past, would not have been assessed. There also is an increasing emphasis on understanding the effects of existing chemical mixtures on human health and the environment; for example in North America, the Great Lakes Restoration Initiative, sponsored by the Office of the President of the US, has identified complex mixtures of chemicals of emerging concern as one of the highest priority stressors in the lakes. These types of new regulatory programs and monitoring initiatives highlight the necessity of identifying and developing novel, rapid approaches for assessing the potential toxicity of substances, to augment (or, in some instances, replace) the more costly, long-term in vivo test methods that historically have supported chemical risk assessments. Fortunately, these chemical evaluation challenges are occurring against a backdrop of evolving data collection and analysis techniques that enable generation of biological information in manners previously conside

QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation†

PubMed Central

Jensen, G.E.; Niemelä, J.R.; Wedebye, E.B.; Nikolov, N.G.

2008-01-01

A special challenge in the new European Union chemicals legislation, Registration, Evaluation and Authorisation of Chemicals, will be the toxicological evaluation of chemicals for reproductive toxicity. Use of valid quantitative structure–activity relationships (QSARs) is a possibility under the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data and epidemiological human studies), dominant lethal effect in rodents (in vivo) and Drosophila melanogaster sex-linked recessive lethal effect. A structure set of 57,014 European Inventory of Existing Chemical Substances (EINECS) chemicals was screened. A total of 5240 EINECS chemicals, corresponding to 9.2%, were predicted as reproductive toxicants by one or more of the models. The chemicals predicted positive for reproductive toxicity will be submitted to the Danish Environmental Protection Agency as scientific input for a future updated advisory classification list with advisory classifications for concern for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption. PMID:19061080

Compliance of LC50 and NOEC data with Benford's Law: an indication of reliability?

PubMed

de Vries, Pepijn; Murk, Albertinka J

2013-12-01

Reliability of research data is essential, especially when potentially far-reaching conclusions will be based on them. This is also, amongst others, the case for ecotoxicological data used in risk assessment. Currently, several approaches are available to classify the reliability of ecotoxicological data. The process of classification, such as using the Klimisch score, is time-consuming and focuses on the application of standardised protocols and the documentation of the study. The presence of irregularities and the integrity of the performed work, however, are not addressed. The present study shows that Benford's Law, based on the occurrence of first digits following a logarithmic scale, can be applied to ecotoxicity test data for identifying irregularities. This approach is already successfully applied in accounting. Benford's Law can be used as reliability indicator, in addition to existing reliability classifications. The law can be used to efficiently trace irregularities in large data sets of interpolated (no) effect concentrations such as LC50s (possibly the result of data manipulation), without having to evaluate the source of each individual record. Application of the law to systems in which large amounts of toxicity data are registered (e.g., European Commission Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals) can therefore be valuable. © 2013 Elsevier Inc. All rights reserved.

Authentication and Authorisation Infrastructure for the Mobility of Users of Academic Libraries: An Overview of Developments

ERIC Educational Resources Information Center

Hudomalj, Emil; Jauk, Avgust

2006-01-01

Purpose: To give an overview of the current state and trends in authentication and authorisation in satisfying academic library users' mobility and instant access to digital information resources, and to propose that libraries strongly support efforts to establish a global authentication and authorisation infrastructure.…

Service Oriented Architecture Security Risks and their Mitigation

DTIC Science & Technology

2012-10-01

this section can be mitigated by making use of suitable authentication , confidentiality, integrity, and authorisation standards such as Security...for authorisation . Machines/non-human users should be clearly identified and authenticated by the identity provision and authentication services... authentication , any security related attributes for the subject, and the authorisation decisions given based on the security and privilege attributes

Endocrine Disruptors

PubMed Central

2015-01-01

Law and science combine in the estimation of risks from endocrine disruptors (EDs) and actions for their regulation. For both, dose–response models are the causal link between exposure and probability (or percentage change) of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU) has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation and other regulations or directives. The integration of a vast (in kind and in scope) number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices. PMID:26740809

SVHC in imported articles: REACH authorisation requirement justified under WTO rules.

PubMed

Schenten, Julian; Führ, Martin

2016-01-01

The purpose of the REACH Regulation is to ensure a high level of protection of human health and the environment as well as the free circulation of substances on the internal market while enhancing competitiveness and innovation. To this end, REACH introduces, among other instruments, the authorisation regime for substances of very high concern (SVHC) that are listed on Annex XIV of the regulation. After expiration of the transitional period for each Annex XIV-SVHC, articles, such as most products of daily use, produced in the European Economic Area (EEA) may not contain such substances unless an authorisation was granted for the specific use or this use falls within the scope of an exemption from the authorisation requirement. The authorisation scheme does, however, only apply to SVHC used in the EEA. As a consequence, REACH does not regulate SVHC entering the European market as part of imported articles which burden human health and the environment. Moreover, from an economic perspective, domestic articles are subject to stricter requirements than those which are produced abroad, putting actors from within the EEA at competitive disadvantage and thus impeding the intention of REACH to enhance competitiveness and innovation. One option to close this regulatory gap could be to extend the authorisation requirement to SVHC present in imported articles. A legal appraisal on behalf of the German Environment Agency (UBA) assesses whether such option would be in accordance with the specifications of WTO world trade law. It concludes that, measured by the standards of the WTO dispute settlement practice, such an extended authorisation scheme would neither violate the principles of national treatment and most-favoured nation treatment. Also, such regulation would not constitute an unnecessary obstacle to trade, since the extended authorisation requirement would pursue a legitimate objective covered by the regulatory autonomy of the EU and, furthermore, the regulation would not be more trade-restrictive than necessary. The contribution at hand summarises the main findings while taking into account first reactions to the legal appraisal.

Comparing the Advanced REACH Tool's (ART) Estimates With Switzerland's Occupational Exposure Data.

PubMed

Savic, Nenad; Gasic, Bojan; Schinkel, Jody; Vernez, David

2017-10-01

The Advanced REACH Tool (ART) is the most sophisticated tool used for evaluating exposure levels under the European Union's Registration, Evaluation, Authorisation and restriction of CHemicals (REACH) regulations. ART provides estimates at different percentiles of exposure and within different confidence intervals (CIs). However, its performance has only been tested on a limited number of exposure data. The present study compares ART's estimates with exposure measurements collected over many years in Switzerland. Measurements from 584 cases of exposure to vapours, mists, powders, and abrasive dusts (wood/stone and metal) were extracted from a Swiss database. The corresponding exposures at the 50th and 90th percentiles were calculated in ART. To characterize the model's performance, the 90% CI of the estimates was considered. ART's performance at the 50th percentile was only found to be insufficiently conservative with regard to exposure to wood/stone dusts, whereas the 90th percentile showed sufficient conservatism for all the types of exposure processed. However, a trend was observed with the residuals, where ART overestimated lower exposures and underestimated higher ones. The median was more precise, however, and the majority (≥60%) of real-world measurements were within a factor of 10 from ART's estimates. We provide recommendations based on the results and suggest further, more comprehensive, investigations. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Authorised allergen products for intracutaneous testing may no longer be available in Germany: Allergy textbooks have to be re-written.

PubMed

Klimek, Ludger; Werfel, Thomas; Vogelberg, Christian; Jung, Kirsten

Beside the skin prick test, the intracutaneous test represents the most important skin test method for detecting type-1 allergies. With the incorporation of European directives into national law, test allergens used for allergy diagnosis are deemed medicinal products within the meaning of the German Medicinal Products Act (Arzneimittelgesetz) and therefore require marketing authorisation for distribution in Germany. The high costs of acquiring and maintaining these authorisations have lead to no new finished intracutaneous test products being authorized in Germany for more than 20 years. Instead, most manufacturers have voluntarily withdrawn their existing marketing authorisations for intracutaneous test extracts. The last manufacturer to offer approved finished allergen products for intracutaneous tests recently announced that it would now cease production and distribution of these solutions. Research on the current European and German legislation; selective literature search in Medline, including national and international guidelines and Cochrane meta-analyses; licensing information on the Paul-Ehrlich-Institute homepage (www.pei.de) as well as in the Bundesanzeiger (Federal Gazette). According to information on www.pei.de, marketing authorisations still existed as of 31.01.2015 for intracutaneous test solutions of six grass/cereal/herbal pollens, seven tree pollens, ten food allergens, twelve moulds and yeasts as well as two fungal mixtures, five house dust and storage mites and five animal epithelia/danders, all held by only one company in Germany. These marketing authorisations were granted between 16th March 1987 and 17th January 1992; more recent marketing authorisations do not exist. European legislation and the associated increase in production and licensing costs have already lead to numerous suppliers withdrawing their marketing authorisation for diagnostic test allergens - marketing authorisations for 443 diagnostic allergens were voluntarily withdrawn by manufacturers in 2013 alone. If the announced restrictions on the allergen portfolio go ahead, considerable problems in the management of allergy patients in Germany due to the discontinuation of the intracutaneous test are likely to be encountered. Moreover, the fact that a diagnostic procedure that has been established for decades seems set to disappear quite simply because all the requisite substances vanish from the market in one fell swoop may well be without parallel in modern medicine. The situation for skin prick test allergens is less dramatic, although, here again, the available range is becoming increasingly limited.

Time matters: A stock-pollution approach to authorisation decision-making for PBT/vPvB chemicals under REACH.

PubMed

Gabbert, Silke; Hilber, Isabel

2016-12-01

A core aim of the European chemicals legislation REACH is to ensure that the risks caused by substances of very high concern (SVHC) are adequately controlled. Authorisation - i.e. the formal approval of certain uses of SVHC for a limited time - is a key regulatory instrument in order to achieve this goal. For SVHC which are, in addition to their toxicity, (very) persistent and/or (very) bioaccumulative (PBT/vPvB chemicals), decision-making on the authorisation is conditional on a socio-economic analysis (SEA). In a SEA companies must demonstrate that the gains from keeping a chemical in use outweigh expected damage costs for society. The current setup of the REACH authorisation process, including existing guidance on performing a SEA, ignores that PBT/vPvB chemicals are stock pollutants. This paper explores the implications of incorporating stock pollution effects of these chemicals into a SEA on authorisation decision-making. We develop a cost-benefit approach which includes stock dynamics of PBT/vPvB chemicals. This allows identifying the decision rules for granting or refusing an authorisation. Furthermore, we generalize the model to an entire set of damage functions. We show that ignoring stock pollution effects in a SEA may lead to erroneous decisions on the use of PBT/vPvB chemicals because long-term impacts are not adequately captured. Using a historic case of DDT soil contamination as an illustrative example we discuss information requirements and challenges for authorisation decisions on the use of PBT/vPvB chemicals under REACH. Copyright © 2016 Elsevier Ltd. All rights reserved.

New active substances authorized in the United Kingdom between 1972 and 1994

PubMed Central

Jefferys, David B; Leakey, Diane; Lewis, John A; Payne, Sandra; Rawlins, Michael D

1998-01-01

Aims The study was undertaken to assemble a list of all new active medicinal substances authorised in the United Kingdom between 1972 and 1994; to assess whether the pattern of introductions had changed; and to examine withdrawal rates and the reasons for withdrawal. Methods The identities of those new active substances whose manufacturers had obtained Product Licences between 1972 and 1994 were sought from the Medicines Control Agency's product data-base. For each substance relevant information was retrieved including the year of granting the Product Licence, its therapeutic class, whether currently authorised (and, if not, reason for withdrawal), and its nature (chemical, biological etc.). Results The Medicines Control Agency's data-base was cross-checked against two other data-bases for completeness. A total of 583 new active substances (in 579 products) were found to have been authorised over the study period. The annual rates of authorisation varied widely (9 to 40 per year). Whilst there was no evidence for any overall change in the annual rates of authorising new chemical entities, there has been a trend for increasing numbers of new products of biological origin to be authorised in recent years. Fifty-nine of the 583 new active substances have been withdrawn (1 each for quality and efficacy, 22 for safety, and 35 for commercial reasons). Conclusions For reasons that are unclear there is marked heterogeneity in the annual rates of authorisation of new active substances. Their 10 year survival is approximately 88% with withdrawals being, predominantly, for commercial or safety reasons. This confirms the provisional nature of assessments about safety at the time when a new active substance is introduced into routine clinical practice, and emphasises the importance of pharmacovigilance. PMID:9491828

Evaluation of the ’Mentor’ Assessment and Feedback System for Air Battle Management Team Training

DTIC Science & Technology

2006-11-01

authorised properly All aircraft entering ADIZ are identified in a timely manner Challenge procedures issued Unauthorised aircraft...maintained Effective low-level sanitisation Tactical Employment Pre-emptive Inter-FEZ Co- ordination Authentication procedures enforced

[European Marketing Authorisation: a long process. Experiences of small biotech companies with the ATMP regulation].

PubMed

Buljovčić, Z

2011-07-01

On 30 December 2008, the Regulation (EC) 1394/2007 on advanced therapy medicinal products (ATMPs) entered into force. Herewith the first EU-wide regulatory framework for ATMPs was established. It requires a central marketing authorisation application to the EMA (European Medicinal Agency). This new framework especially changes the code of regulatory practice for tissue engineered products (TEPs), as no registration procedure had been previously required for autologous TEPs. This also meant that no clinical proof of efficacy achieved by a pivotal clinical trial was necessary. Difficulties and their background as well as the vast requirements for product development that have to be addressed by small companies within a very short time frame are presented. Hereby, it is obvious that regulatory experience which is required to identify and implement the resulting implications was not in place yet and still had to be established. The lack of regulatory experience also resulted in difficulties with scientific advice preparation, expectations toward regulatory agencies, consultants, and transformation of regulatory requirements. Addressing the regulatory requirements within the transition period is even more difficult for entrepreneurs with products which are assigned for indications resulting in complex challenges to the trial design. Due to the enormous time pressure to generate data and due to the implied financial pressure, different adaptation strategies are evolving. In Germany the "hospital exemption" according to §4b AMG (German Medicinal Products Law) is of major importance. A reorientation toward acellular products and a slow down in development of new ATMP products is expected.

[Regulatory control of new medicines: help or hindrance?].

PubMed

Vozeh, S

1999-04-15

To answer the question of the benefit and the cost/benefit ratio of the activities of a drug regulatory agency, the most important, clinically relevant "products" of a licensing authority in general, and the Swiss licensing authority (IKS) in particular are discussed. The activities of the medicines licensing authority assure that: For all new substances the efficacy and a positive benefit/risk ratio have been demonstrated before a marketing authorisation. For all marketed medicines an information for professionals and patients is available that has been evaluated and approved by an independent and competent reviewer. An independent post marketing surveillance of the side effects profile continues after a medicine has been put on the market. All clinical trials investigating medicinal products are performed according to GCP rules corresponding to international ethical and scientific standards. An international comparison of the time needed for the evaluation of a marketing authorisation application for a new medicine reveals that the IKS is one of the most efficient agencies. This is illustrated with an example showing the evaluation times of the EMEA and the IKS for products approved in 1997.

Economic Evaluations of Pharmaceuticals Granted a Marketing Authorisation Without the Results of Randomised Trials: A Systematic Review and Taxonomy.

PubMed

Hatswell, Anthony J; Freemantle, Nick; Baio, Gianluca

2017-02-01

Pharmaceuticals are usually granted a marketing authorisation on the basis of randomised controlled trials (RCTs). Occasionally the efficacy of a treatment is assessed without a randomised comparator group (either active or placebo). To identify and develop a taxonomic account of economic modelling approaches for pharmaceuticals licensed without RCT data. We searched PubMed, the websites of UK health technology assessment bodies and the International Society for Pharmacoeconomics and Outcomes Research Scientific Presentations Database for assessments of treatments granted a marketing authorisation by the US Food and Drug Administration or European Medicines Agency from January 1999 to May 2014 without RCT data (74 indications). The outcome of interest was the approach to modelling efficacy data. Fifty-one unique models were identified in 29 peer-reviewed articles, 30 health technology appraisals, and 15 International Society for Pharmacoeconomics and Outcomes Research abstracts concerning 30 indications (44 indications had not been modelled). We noted the high rate of non-submission to health technology assessment agencies (28/98). The majority of models (43/51) were based on 'historical controls'-comparisons to previous meta-analysis or pooling of trials (5), individual trials (16), registries/case series (15), or expert opinion (7). Other approaches used the patient as their own control, performed threshold analysis, assumed time on treatment was added to overall survival, or performed cost-minimisation analysis. There is considerable variation in the quality and approach of models constructed for drugs granted a marketing authorisation without a RCT. The most common approach is of a naive comparison to historical data (using other trials/registry data as a control group), which has considerable scope for bias.

[Immunogenicity of biosimilars].

PubMed

van Aerts, L A G J M; Franken, A A M; Leufkens, H G M

2016-01-01

Biosimilars of more complex recombinant protein drugs, such as monoclonal antibodies and fusion proteins, are entering the market. The manufacturer should demonstrate that its product does not show any relevant differences in terms of quality characteristics, biological activity, safety and efficacy compared to the reference product, as outlined in EMA guidelines. This should be established with an extensive comparability exercise. One aspect that is subject to particular scrutiny is the immunogenicity of the biosimilar and the reference medicinal product. For three cases, one etanercept and two infliximab biosimilars, we describe how data are assessed and an opinion is reached by authorities. Not in all cases unanimity exists whether all remaining uncertainties on biosimilarity have been resolved satisfactorily before marketing authorisation. The Dutch Medicines Evaluation Board therefore emphasises that even after marketing authorisation, biosimilars and other biologicals should be properly monitored.

Regulatory landscape for cell therapy--EU view.

PubMed

McBlane, James W

2015-09-01

This article addresses regulation of cell therapies in the European Union (EU), covering cell sourcing and applications for clinical trials and marketing authorisation applications. Regulatory oversight of cell sourcing and review of applications for clinical trials with cell therapies are handled at national level, that is, separately with each country making its own decisions. For clinical trials, this can lead to different decisions in different countries for the same trial. A regulation is soon to come into force that will address this and introduce a more efficient clinical trial application process. However, at the marketing authorisation stage, the process is pan-national: the Committee for Human Medicinal Products (CHMP) is responsible for giving the final scientific opinion on all EU marketing authorisation applications for cell therapies: favourable scientific opinions are passed to the European Commission (EC) for further consultation and, if successful, grant of a marketing authorisation valid in all 28 EU countries. In its review of applications for marketing authorisations (MAAs) for cell therapies, the CHMP is obliged to consult the Committee for Advanced Therapies (CAT), who conduct detailed scientific assessments of these applications, with assessment by staff from national regulatory authorities and specialist advisors to the regulators. Copyright © 2015.

The new European legislation on traditional herbal medicines: main features and perspectives.

PubMed

Silano, Marco; De Vincenzi, Massimo; De Vincenzi, Alessandro; Silano, Vittorio

2004-03-01

Under the Italian Presidency of the Council of the European Union (July 2003-December 2003) an agreement has been reached by the European Parliament and the Council on the approval of the proposal of Directive of the European Parliament and the Council amending the Directive 2001/83/EC as regards traditional herbal medicinal products. Once implemented in the E.U. Member States, this new Directive will remove the constraints that have made it difficult granting marketing authorisations of herbal substances and preparations as traditional medicinal products under the pre-existing Community legislation. The main features (i.e. traditional herbal medicine definition, simplified registration procedure, provisions for Community herbal monographs and Community list of herbal substances and preparations and establishment of the Committee for Herbal Medicinal Products) of this new Community legislation are analysed and discussed in the present paper together with some expected positive public health impacts.

An assessment of the compliance with good pharmacy practice in an urban and rural district in Sri Lanka.

PubMed

Wijesinghe, P R; Jayakody, R L; De A Seneviratne, R

2007-02-01

To evaluate the compliance of private pharmacies to good pharmacy practice (GPP) in an urban and rural district in Sri Lanka and identify deficiencies with a view to improving supply of safe and effective drugs to consumers. Lot quality assurance sampling (LQAS) method was used to determine the number of pharmacies that need to be studied and the threshold limit of defective elements. An inspection of 20 pharmacies in the urban and all 18 pharmacies in the rural district was carried out using a structured checklist. Compliance to seven subsystems of GPP was studied. Storage of drugs, maintenance of cold chain, dispensing and documentation were comprehensively substandard in both districts. Individual items of supervision in registration, physical environment and order of the pharmacy were also found to be substandard in both districts. This study shows that the LQAS method can be used to identify inadequate pharmacy services in the community as a whole. There was poor compliance to GPP by the private pharmacies in both districts. There are concerns about the quality of drugs and the safety of private pharmacy services to the community. Some of the deficiencies could be easily corrected by educating the pharmacists and authorised officers, and more effective and streamlined supervision.

Challenges to orphan drugs access in Eastern Europe: the case of Bulgaria.

PubMed

Iskrov, Georgi; Miteva-Katrandzhieva, Tsonka; Stefanov, Rumen

2012-11-01

This article explores how an Eastern European country could deal with orphan drugs access, combining EU policies with its own national settings. The cross-sectional observational study takes the total number of orphan drugs (61) available on EU level by March 2011, and then consecutively filters it through the requirements and criteria of relevant Bulgarian legislation on registration, pricing and reimbursement of medicinal products, obtaining the final number of accessible orphan drugs (16) in Bulgaria. The study further evaluates the average time period from market authorisation to positive reimbursement decision by Bulgarian health authorities (43±29.1 months). Access to orphan drugs should be provided on a reasonable and justified basis. Having in mind the limited availability of resources, it is not a question whether to prioritise rarity, but to create legitimate mechanisms for properly assessing orphan drugs' value and optimally using this value, according to the society's needs and views. The analysis identifies four important challenges to orphan drugs' access in Eastern Europe: (1) elaboration of new orphan drugs pricing approaches, (2) further interaction of cost-effectiveness analysis with medical criteria, (3) active introduction of epidemiological registries for rare diseases, and (4) research of societal preferences and raising public awareness. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Use of genotoxicity information in the development of integrated testing strategies (ITS) for skin sensitization.

PubMed

Mekenyan, Ovanes; Patlewicz, Grace; Dimitrova, Gergana; Kuseva, Chanita; Todorov, Milen; Stoeva, Stoyanka; Kotov, Stefan; Donner, E Maria

2010-10-18

Skin sensitization is an end point of concern for various legislation in the EU, including the seventh Amendment to the Cosmetics Directive and Registration Evaluation, Authorisation and Restriction of Chemicals (REACH). Since animal testing is a last resort for REACH or banned (from 2013 onward) for the Cosmetics Directive, the use of intelligent/integrated testing strategies (ITS) as an efficient means of gathering necessary information from alternative sources (e.g., in vitro, (Q)SARs, etc.) is gaining widespread interest. Previous studies have explored correlations between mutagenicity data and skin sensitization data as a means of exploiting information from surrogate end points. The work here compares the underlying chemical mechanisms for mutagenicity and skin sensitization in an effort to evaluate the role mutagenicity information can play as a predictor of skin sensitization potential. The Tissue Metabolism Simulator (TIMES) hybrid expert system was used to compare chemical mechanisms of both end points since it houses a comprehensive set of established structure-activity relationships for both skin sensitization and mutagenicity. The evaluation demonstrated that there is a great deal of overlap between skin sensitization and mutagenicity structural alerts and their underlying chemical mechanisms. The similarities and differences in chemical mechanisms are discussed in light of available experimental data. A number of new alerts for mutagenicity were also postulated for inclusion into TIMES. The results presented show that mutagenicity information can provide useful insights on skin sensitization potential as part of an ITS and should be considered prior to any in vivo skin sensitization testing being initiated.

Granting marketing authorisation for medicines in South East European countries: the point of view of the authority.

PubMed

Tomić, Sinisa; Sucić, Anita Filipović; Martinac, Adrijana Ilić

2010-01-01

European legislation for medicines places the emphasis on an assessment of quality, safety and efficacy during the procedure for the granting of marketing authorisations for medicines, in order to protect patient health. The integrated European regulatory system involves the participation of a network of experts from the agencies of the member states that takes part in the European procedures for the authorisation of medicines. On the way to full membership in the EU, candidate countries and potential candidates have to transpose and implement the European directives for medicinal products; they must also strengthen their scientific and administrative capacities. Croatia acquired good experience in implementing the simplified marketing authorisation procedure for medicines authorised in the EU pursuant to the New Collaboration Agreement between Drug Regulatory Authorities in Central and East European Countries (nCADREAC), which helps it to exchange information and prepare for the implementation of European procedures. However, there are still some provisions to transpose before actual full membership, and also dossier upgrading, in which the marketing authorisation holder has to harmonise its documentation about a medicinal product with the requirements of the directives, if a product already on the market was not previously approved in line with current European legislation. Collaboration with the European Medicines Agency (EMA) through an Instrument for Pre-Accession (IPA) provides candidate countries and potential candidates the opportunity for education and training in some regulatory activities as well as the participation of their representatives as observers in some EMA committees and working groups. Some characteristics of the national regulatory frameworks of the countries of South East Europe in their efforts to achieve harmonisation with EU legislation are presented in this paper. Copyright 2010 Elsevier Inc. All rights reserved.

Authorisation within the European Union of vaccines against antigenically variable viruses responsible for major epizootic diseases.

PubMed

Mackay, D K J

2007-08-01

Antigenically variable viruses are responsible for some of the most contagious and economically important diseases that affect domestic livestock. The serious consequences of such diseases in terms of economic loss, and human and animal health, were clearly demonstrated by recent epizootics of foot and mouth disease, and outbreaks of avian influenza and bluetongue in the European Union (EU). For such diseases, government authorities need to be able to respond, if appropriate, by making use of vaccines that are suited to the epidemiological situation. The current EU regulatory framework is not well adapted for approval and maintenance of vaccines where the antigens included have to be chosen to reflect the epidemiological need. An extensive revision of the technical requirements for authorisation of veterinary medicinal products within the EU is currently underway. Additionally, a major revision of the regulations that control how such authorisations are kept up-to-date is about to start. This provides an ideal opportunity to introduce into EU legislation the concept of the 'multistrain dossier' whereby a potentially large number of approved strains may be included within a marketing authorisation and the final vaccines may be blended to include strains according to need. In addition, new strains may be added onto the marketing authorisation by means of a rapid regulatory procedure should new antigenic variants actually or potentially threaten the EU.

[The role of the Committee for Medicinal Products for Human Use (CHMP) in the European centralised procedure].

PubMed

Enzmann, Harald; Schneider, C

2008-07-01

The centralised procedure for marketing authorisation at the European Medicines Agency (EMEA) started more than 10 years ago, offering marketing authorisation for all member states of the European Union in a single procedure. Originally it was a purely optional alternative to the established national procedures; however, its importance has been growing ever since. The introduction of the mandatory scope for several important indications was a crucial step. The increasing importance of the centralised procedure was paralleled by the increasing weight of the EMEA and of the Committee for Human Medicinal Products (CHMP) who is responsible for scientific evaluation in the centralised procedure. This paper describes the basic principles of the centralised procedure including the definitions of the mandatory and optional scope, and how the CHMP works including its responsibility in European referrals that provide a link to national procedures.

Chemicals in Household Products: Problems with Solutions

NASA Astrophysics Data System (ADS)

Glegg, Gillian A.; Richards, Jonathan P.

2007-12-01

The success of a regulatory regime in decreasing point-source emissions of some harmful chemicals has highlighted the significance of other sources. A growing number of potentially harmful chemicals have been incorporated into an expanding range of domestic household products and are sold worldwide. Tighter regulation has been proposed, and the European Commission has introduced the Regulation on the Registration, Evaluation, and Authorisation of Chemicals to address this concern. However, it is clear that in addition to the regulation, there is a potential to effect change through retailer and consumer attitudes and behaviours. Interviews were conducted with 7 key stakeholder groups to identify critical issues, which were then explored using a public survey questionnaire (1,008 respondents) and 8 subsequent focus groups. The findings demonstrated that the issue of chemicals in products is of concern to consumers for reasons of personal health rather than environmental protection. Key obstacles to the wider purchase of “green-alternative” products included perceived high cost and poor performance, lack of availability of products, and poor information concerning such products. Although improved regulation was seen as part of the solution, consumers must also play a role. It was clear from this study that consumers are not currently able to make informed choices about the chemicals they use but that they would be receptive to moving toward a more sustainable use of chemicals in the future if empowered to do so.

Chemicals in household products: problems with solutions.

PubMed

Glegg, Gillian A; Richards, Jonathan P

2007-12-01

The success of a regulatory regime in decreasing point-source emissions of some harmful chemicals has highlighted the significance of other sources. A growing number of potentially harmful chemicals have been incorporated into an expanding range of domestic household products and are sold worldwide. Tighter regulation has been proposed, and the European Commission has introduced the Regulation on the Registration, Evaluation, and Authorisation of Chemicals to address this concern. However, it is clear that in addition to the regulation, there is a potential to effect change through retailer and consumer attitudes and behaviours. Interviews were conducted with 7 key stakeholder groups to identify critical issues, which were then explored using a public survey questionnaire (1,008 respondents) and 8 subsequent focus groups. The findings demonstrated that the issue of chemicals in products is of concern to consumers for reasons of personal health rather than environmental protection. Key obstacles to the wider purchase of "green-alternative" products included perceived high cost and poor performance, lack of availability of products, and poor information concerning such products. Although improved regulation was seen as part of the solution, consumers must also play a role. It was clear from this study that consumers are not currently able to make informed choices about the chemicals they use but that they would be receptive to moving toward a more sustainable use of chemicals in the future if empowered to do so.

[Products toxic to reproduction used in the occupational environment: Definition, risk assessment, classification].

PubMed

Lafon, D

2006-10-01

European regulations (transcribed into French law) aimed at protecting employees from chemicals toxic to reproduction enable classification and labelling of such substances, if they are liable to cause an alteration of male or female reproductive functions or capacity, or to induce non-hereditary harmful effects on their offspring. Three categories can be used to classify these substances in two areas, namely their impairment of fertility and their effects on development. This classification is rarely based on epidemiological study results, but most often on those of experimental toxicological studies conducted by substance manufacturers. These reproduction toxicological studies are only compulsory above a certain tonnage placed on the market. The high level of this tonnage means that these tests are effectively only conducted on rare occasions. It is reckoned that there is no reproduction experimental data for over 95% of substances newly placed on the market. These products therefore appear to be reproduction non-toxic only because they have not been tested. This is a major fault in the current labelling system, which does not allow non-toxic products to be differentiated from non-tested products. The future EU regulatory framework for Registration, Evaluation and Authorisation of CHemicals (REACH) will only slightly enhance information in this area. It can be estimated that over 80% of chemical products will not be exhaustively tested for reproduction and nearly 75% will not be tested to any degree.

[Cancer: Is it really so different? Particularities of oncologic drugs from the perspective of the pharmaceutical regulatory agency].

PubMed

Enzmann, Harald; Broich, Karl

2013-01-01

For innovative oncological medicines the centralised procedure at the European Medicines Agency is mandatory for a marketing authorisation application for the European Union. As with other medical drugs, the marketing authorisation decision is based on the assessment of its efficacy, safety and pharmaceutical quality but does not consider price or reimbursement. More sophisticated diagnostic methods drive an increasing stratification of cancer into a multitude of different diseases. Regardless of their different pathogenesis and therapeutic options the most relevant clinical endpoints remain cure, overall survival and progression free survival. These endpoints include both efficacy and safety, as patient survival reflects the sum of the beneficial anti-tumour effects (increasing survival) AND the adverse effects (decreasing survival). The benefit of an anticancer medicine should be evident from both overall survival and progression free survival (e.g. used as primary and secondary endpoints). Mature data on overall survival may not be needed for marketing authorisation if a clear increase in progression free survival convincingly predicts a beneficial effect on overall survival. In these exceptional cases treatment of patients with an obviously beneficial medicine must not be delayed - possibly for years - until the exact size of the benefit has been established. The continued stratification of the disease cancer results in a lower prevalence for each of the newly distinguished disease entities and an ever increasing number of orphan designations for medicines for rare diseases. Incentives for the development of orphan medicines include market exclusivity for up to ten years. In specific circumstances, however, the orphan legislation may restrict the authorisation and marketing of competing generic products even beyond these ten years. Conditional approval and approval under exceptional circumstances may accelerate patients' access to a new medicine. Both postulate that the extent of the benefit cannot be determined with sufficient certainty at the time of marketing authorisation. This uncertainty may have a negative impact on price and reimbursement as these decisions may consider data or assessments from the marketing authorisation procedure. Therefore, marketing authorisation applications and subsequent pricing and reimbursement negotiations should not be regarded as completely independent processes, but be included in an overall strategy for the development of oncologic drugs. (As supplied by publisher). Copyright © 2013. Published by Elsevier GmbH.

Classification of sensitizing and irritative potential in a combined in-vitro assay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wanner, Reinhard, E-mail: reinhard.wanner@charite.d; Sonnenburg, Anna; Quatchadze, Maria

2010-06-01

We have developed a coculture system which in parallel indicates the sensitizing and irritative potential of xenobiotics. The assay is named loose-fit coculture-based sensitization assay (LCSA) and may be performed within 5 days. The system is composed of human monocytes that differentiate to a kind of dendritic cells by 2-day culturing in the presence of allogenic keratinocytes. The culture medium is enriched by a cocktail of recombinant cytokines. On day 3, concentration series of probes are added. On day 5, cells are harvested and analyzed for expression range of CD86 as a marker of sensitizing potential and for uptake ofmore » the viability stain 7-AAD as a marker of irritative potential. Estimation of the concentration required to cause a half-maximal increase in CD86 expression allowed quantification of sensitizing potential, and estimation of the concentration required to reduce viability to 50% allowed quantification of irritative potential. Examination of substances with known potential resulted in categorization of test scores. To evaluate our data, we have compared results with those of the validated animal-based sensitization test, the murine local lymph node assay (LLNA, OECD TG 429). To a large extent, results from LCSA and from LLNA achieved analogous grouping of allergens into categories like weak-moderate-strong. However, the new assay showed an improved capacity to distinguish sensitizers from non-sensitizers and irritants. In conclusion, the LCSA contains potential to fulfil the requirements of the EU's programme for the safety of chemicals 'Registration, Evaluation, Authorisation and Restriction of chemical substances' (REACH, 2006) to replace animal models.« less

Exploring REACH as a potential data source for characterizing ecotoxicity in life cycle assessment.

PubMed

Müller, Nienke; de Zwart, Dick; Hauschild, Michael; Kijko, Gaël; Fantke, Peter

2017-02-01

Toxicity models in life cycle impact assessment (LCIA) currently only characterize a small fraction of marketed substances, mostly because of limitations in the underlying ecotoxicity data. One approach to improve the current data situation in LCIA is to identify new data sources, such as the European Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) database. The present study explored REACH as a potential data source for LCIA based on matching reported ecotoxicity data for substances that are currently also included in the United Nations Environment Programme/Society for Environmental Toxicology and Chemistry (UNEP/SETAC) scientific consensus model USEtox for characterizing toxicity impacts. Data are evaluated with respect to number of data points, reported reliability, and test duration, and are compared with data listed in USEtox at the level of hazardous concentration for 50% of the covered species per substance. The results emphasize differences between data available via REACH and in USEtox. The comparison of ecotoxicity data from REACH and USEtox shows potential for using REACH ecotoxicity data in LCIA toxicity characterization, but also highlights issues related to compliance of submitted data with REACH requirements as well as different assumptions underlying regulatory risk assessment under REACH versus data needed for LCIA. Thus, further research is required to address data quality, pre-processing, and applicability, before considering data submitted under REACH as a data source for use in LCIA, and also to explore additionally available data sources, published studies, and reports. Environ Toxicol Chem 2017;36:492-500. © 2016 SETAC. © 2016 SETAC.

A Network Centric Warfare (NCW) Compliance Process for Australian Defence

DTIC Science & Technology

2006-08-01

discovery and access by a wide range of authorised Defence users. The information could be used to simplify future NCW Compliance Assessments by re-using...Security standards 1. General Security Services - General Table 5.1 2. General Security services - Authentication Table 5.2 3. General Security...Personnel Positions in an authorised establishment must be filled by individuals who satisfy the necessary individual readiness requirements

Mapping regulatory models for medicinal cannabis: a matrix of options.

PubMed

Belackova, Vendula; Shanahan, Marian; Ritter, Alison

2017-05-30

Objective The aim of the present study was to develop a framework for assessing regulatory options for medicinal cannabis in Australia. Methods International regulatory regimes for medicinal cannabis were reviewed with a qualitative policy analysis approach and key policy features were synthesised, leading to a conceptual framework that facilitates decision making across multiple dimensions. Results Two central organising dimensions of medicinal cannabis regulation were identified: cannabis supply and patient authorisation (including patient access). A number of the different supply options can be matched with a number of different patient authorisation options, leading to a matrix of possible regulatory regimes. Conclusions The regulatory options, as used internationally, involve different forms of cannabis (synthetic and plant-based pharmaceutical preparations or herbal cannabis) and the varying extent to which patient authorisation policies and procedures are stringently or more loosely defined. The optimal combination of supply and patient authorisation options in any jurisdiction that chooses to make medicinal cannabis accessible will depend on policy goals. What is known about the topic? Internationally, regulation of medicinal cannabis has developed idiosyncratically, depending on formulations that were made available and local context. There has been no attempt to date in the scientific literature to systematically document the variety of regulatory possibilities for medicinal cannabis. What does this paper add? This paper presents a new conceptual schema for considering options for the regulation of medicinal cannabis, across both supply and patient authorisation aspects. What are the implications for practitioners? The design of regulatory systems in Australia, whether for pharmaceutical or herbal products, is a vital issue for policy makers right now as federal and state and territory governments grapple with the complexities of medicinal cannabis regulation. The conceptual schema presented herein provides a tool for more systematic thinking about the options.

Overview of the Regulatory Oversight Implemented by the French Regulatory Authorities for the Clinical Investigation of Gene Therapy and Cell Therapy Products.

PubMed

Lucas-Samuel, Sophie; Ferry, Nicolas; Trouvin, Jean-Hugues

2015-01-01

Advanced therapy medicinal products, a new class of products with promising therapeutic effects, have been classified as medicinal products and as such should be developed according to a well-structured development plan, to establish their quality, safety and efficacy profile and conclude, at the time of the marketing authorisation evaluation, on a positive risk/benefit balance for patients. An important part of this development plan is achieved through clinical trials, which have also to be approved according to a well-established regulatory process, prior any initiation. This chapter is dedicated to describe the regulatory pathway to be followed in France, before initiating any clinical trial with those investigational advanced therapy medicinal products. In France, to get the final authorisation to initiate a clinical trial, the legislation imposes to run in parallel two independent but complementary authorisation procedures. The first procedure is aimed at assessing the ethical aspect of the biomedical research, while the second has to review the safety and regulatory aspects. A third procedure has to be envisaged where in case the investigational product consists or contains a genetically modified organism. The French system herein described is in line with the EU regulation on clinical trial and follows the respective deadlines for granting the final approval. The complexity of the procedure is in fact more due to the complexity of the products and protocols to be assessed than to the procedure itself which is now very close to the well-known procedure applied routinely for more conventional chemical or biological candidate medicinal products.

Administrative complexities for a European observational study despite directives harmonising requirements.

PubMed

Gülmez, Sinem Ezgi; Lignot-Maleyran, Séverine; de Vries, Corinne S; Sturkenboom, Miriam; Micon, Sophie; Hamoud, Fatima; Blin, Patrick; Moore, Nicholas

2012-08-01

For pharmacoepidemiological studies in Europe, accessing data should require only authorisation by the relevant data protections committees, as expected from the 1995 Data Protection Directive (95/46/EC). Our experience from a multinational observational study across seven European countries shows that this is certainly not the case. The study was a multicentre, multinational, case-population study in European liver transplant centres in seven countries, retrospectively evaluating a 3-year period. Before data collection started, the procedures to obtain the necessary authorisations for the participating countries were defined. In France, a single opinion from a single data protection committee was enough to start the study. In Italy, Portugal, Greece and the UK, there was a national authority, but the hospitals requested the approval by their local committees/bodies irrespective of whether the authorisation of the national committee came after or before that of local ones. In Ireland, only one hospital participated, and the opinion of its ethics committee was sufficient. In the Netherlands, the opinion of the institutional review board of the local coordinating centre was necessary to obtain the opinions from the institutional review boards of the other hospitals. The information requested by the different committees and the time to obtain the approvals varied, even within the same country. This degree of complexity and disharmony, and resulting cost, was observed in a simple retrospective study. Regulators will need to be aware that these time-consuming, expensive and useless complexities must be factored in when estimating the time and cost of a study. Copyright © 2012 John Wiley & Sons, Ltd.

Secure FAST: Security Enhancement in the NATO Time Sensitive Targeting Tool

DTIC Science & Technology

2010-11-01

designed to aid in the tracking and prosecuting of Time Sensitive Targets. The FAST tool provides user level authentication and authorisation in terms...level authentication and authorisation in terms of security. It uses operating system level security but does not provide application level security for...and collaboration tool, designed to aid in the tracking and prosecuting of Time Sensitive Targets. The FAST tool provides user level authentication and

Strategies for monitoring the emerging polar organic contaminants in water with emphasis on integrative passive sampling.

PubMed

Söderström, Hanna; Lindberg, Richard H; Fick, Jerker

2009-01-16

Although polar organic contaminants (POCs) such as pharmaceuticals are considered as some of today's most emerging contaminants few of them are regulated or included in on-going monitoring programs. However, the growing concern among the public and researchers together with the new legislature within the European Union, the registration, evaluation and authorisation of chemicals (REACH) system will increase the future need of simple, low cost strategies for monitoring and risk assessment of POCs in aquatic environments. In this article, we overview the advantages and shortcomings of traditional and novel sampling techniques available for monitoring the emerging POCs in water. The benefits and drawbacks of using active and biological sampling were discussed and the principles of organic passive samplers (PS) presented. A detailed overview of type of polar organic PS available, and their classes of target compounds and field of applications were given, and the considerations involved in using them such as environmental effects and quality control were discussed. The usefulness of biological sampling of POCs in water was found to be limited. Polar organic PS was considered to be the only available, but nevertheless, an efficient alternative to active water sampling due to its simplicity, low cost, no need of power supply or maintenance, and the ability of collecting time-integrative samples with one sample collection. However, the polar organic PS need to be further developed before they can be used as standard in water quality monitoring programs.

Towards a more effective and efficient governance and regulation of nanomaterials.

PubMed

Teunenbroek, Tom Van; Baker, James; Dijkzeul, Aart

2017-12-19

The uncertainty regarding the effects and risks of nanomaterials on human health and the environment, and how they should be tested and assessed in the context of current regulations, is clearly holding back the full exploitation of the innovative potential of nanomaterials. To reduce this uncertainty, the European Union funded NANoREG and ProSafe projects (jointly referred to as N1P) have made a critical evaluation of methods to test and assess these risks in the context of the current registration, evaluation, authorisation and restriction of chemicals (REACH) regulation. Where essential methods were lacking, new ones have been developed. For several existing methods, adjustments have been proposed. Possible improvements to the REACH regulation have also been identified in these projects. The results of N1P have been translated into recommendations for (European) policy makers and regulators. Part of them have a "no regret" character, meaning that the proposed actions can be considered as necessary, feasible, effective and cost efficient. The recommended measures proposed for data quality and data management will create a more solid information basis for risk assessment of nanomaterials. When implemented, the recommendations regarding REACH will improve the application of REACH in both a legal and scientific sense. In practical terms however, the application of REACH will remain complex, time-consuming and costly. Besides that, adapting and specifying the information requirements and test methods in REACH for nanomaterials that are now on the market, will not solve the regulatory hurdles for next generation (nano) materials. To better align the dynamic character of developing new materials and the static character of regulations, it is recommended to explore possibilities of a more future proof approach for securing the safety of new (nano) materials.

Deriving site-specific clean-up criteria to protect ecological receptors (plants and soil invertebrates) exposed to metal or metalloid soil contaminants via the direct contact exposure pathway

PubMed Central

Checkai, Ron; Van Genderen, Eric; Sousa, José Paulo; Stephenson, Gladys; Smolders, Erik

2014-01-01

Soil contaminant concentration limits for the protection of terrestrial plants and soil invertebrates are commonly based on thresholds derived using data from laboratory ecotoxicity tests. A comprehensive assessment has been made for the derivation of ecological soil screening levels (Eco-SSL) in the United States; however, these limits are conservative because of their focus on high bioavailability scenarios. Here, we explain and evaluate approaches to soil limit derivation taken by 4 jurisdictions, 2 of which allow for correction of data for factors affecting bioavailability among soils, and between spiked and field-contaminated soils (Registration Evaluation Authorisation and Restriction of Chemicals [REACH] Regulation, European Union [EU], and the National Environment Protection Council [NEPC], Australia). Scientifically advanced features from these methods have been integrated into a newly developed method for deriving soil clean-up values (SCVs) within the context of site-specific baseline ecological risk assessment. Resulting site-specific SCVs that account for bioavailability may permit a greater residual concentration in soil when compared to generic screening limit concentrations (e.g., Eco-SSL), while still affording acceptable protection. Two choices for selecting the level of protection are compared (i.e., allowing higher effect levels per species, or allowing a higher percentile of species that are potentially unprotected). Implementation of this new method is presented for the jurisdiction of the United States, with a focus on metal and metalloid contaminants; however, the new method can be used in any jurisdiction. A case study for molybdate shows the large effect of bioavailability corrections and smaller effects of protection level choices when deriving SCVs. Integr Environ Assess Manag 2014;10:346–357. PMID:24470189

Between-User Reliability of Tier 1 Exposure Assessment Tools Used Under REACH.

PubMed

Lamb, Judith; Galea, Karen S; Miller, Brian G; Hesse, Susanne; Van Tongeren, Martie

2017-10-01

When applying simple screening (Tier 1) tools to estimate exposure to chemicals in a given exposure situation under the Registration, Evaluation, Authorisation and restriction of CHemicals Regulation 2006 (REACH), users must select from several possible input parameters. Previous studies have suggested that results from exposure assessments using expert judgement and from the use of modelling tools can vary considerably between assessors. This study aimed to investigate the between-user reliability of Tier 1 tools. A remote-completion exercise and in person workshop were used to identify and evaluate tool parameters and factors such as user demographics that may be potentially associated with between-user variability. Participants (N = 146) generated dermal and inhalation exposure estimates (N = 4066) from specified workplace descriptions ('exposure situations') and Tier 1 tool combinations (N = 20). Interactions between users, tools, and situations were investigated and described. Systematic variation associated with individual users was minor compared with random between-user variation. Although variation was observed between choices made for the majority of input parameters, differing choices of Process Category ('PROC') code/activity descriptor and dustiness level impacted most on the resultant exposure estimates. Exposure estimates ranging over several orders of magnitude were generated for the same exposure situation by different tool users. Such unpredictable between-user variation will reduce consistency within REACH processes and could result in under-estimation or overestimation of exposure, risking worker ill-health or the implementation of unnecessary risk controls, respectively. Implementation of additional support and quality control systems for all tool users is needed to reduce between-assessor variation and so ensure both the protection of worker health and avoidance of unnecessary business risk management expenditure. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

[Discussion on Technical Evaluation for Medical Device Registration Material].

PubMed

Chu, Yungao; Qian, Hong; Zhu, Yingfeng

2017-07-30

This article first introduces the main contents of the requirements for medical device registration. Secondly, this article chooses the vertebral forming surgery system as an example to discuss the technical evaluation for the registration research material. The article hopes to provide a reference for the applicant who prepare the registration material and the technical evaluator who make the evaluation for the medical device registration.

Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

PubMed Central

2009-01-01

Background Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees. Methods Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed. Discussion Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism. After an effect- and process evaluation the guideline will be adjusted and, after authorisation, published. Together with several implementation aids, the published guideline will be disseminated broadly by the Netherlands Society of Occupational Medicine. Trial Registration ISRCTN73545254/NTR1190 PMID:20003405

Improving alignment in Tract-based spatial statistics: evaluation and optimization of image registration.

PubMed

de Groot, Marius; Vernooij, Meike W; Klein, Stefan; Ikram, M Arfan; Vos, Frans M; Smith, Stephen M; Niessen, Wiro J; Andersson, Jesper L R

2013-08-01

Anatomical alignment in neuroimaging studies is of such importance that considerable effort is put into improving the registration used to establish spatial correspondence. Tract-based spatial statistics (TBSS) is a popular method for comparing diffusion characteristics across subjects. TBSS establishes spatial correspondence using a combination of nonlinear registration and a "skeleton projection" that may break topological consistency of the transformed brain images. We therefore investigated feasibility of replacing the two-stage registration-projection procedure in TBSS with a single, regularized, high-dimensional registration. To optimize registration parameters and to evaluate registration performance in diffusion MRI, we designed an evaluation framework that uses native space probabilistic tractography for 23 white matter tracts, and quantifies tract similarity across subjects in standard space. We optimized parameters for two registration algorithms on two diffusion datasets of different quality. We investigated reproducibility of the evaluation framework, and of the optimized registration algorithms. Next, we compared registration performance of the regularized registration methods and TBSS. Finally, feasibility and effect of incorporating the improved registration in TBSS were evaluated in an example study. The evaluation framework was highly reproducible for both algorithms (R(2) 0.993; 0.931). The optimal registration parameters depended on the quality of the dataset in a graded and predictable manner. At optimal parameters, both algorithms outperformed the registration of TBSS, showing feasibility of adopting such approaches in TBSS. This was further confirmed in the example experiment. Copyright © 2013 Elsevier Inc. All rights reserved.

Unstaffed trail registration compliance in a backcountry recreation area.

Treesearch

Earl C. Leatherberry; David W. Lime

1981-01-01

Presents findings from a study in Michigan's Upper Peninsula to evaluate the effectiveness of unstaffed trail registration stations to obtain recreation use information. Two registration approaches were evaluated: (1) self-issued voluntary registration form, and (2) self-issued mandatory registration form. The paper also cites factors influencing registration...

Error estimation of deformable image registration of pulmonary CT scans using convolutional neural networks.

PubMed

Eppenhof, Koen A J; Pluim, Josien P W

2018-04-01

Error estimation in nonlinear medical image registration is a nontrivial problem that is important for validation of registration methods. We propose a supervised method for estimation of registration errors in nonlinear registration of three-dimensional (3-D) images. The method is based on a 3-D convolutional neural network that learns to estimate registration errors from a pair of image patches. By applying the network to patches centered around every voxel, we construct registration error maps. The network is trained using a set of representative images that have been synthetically transformed to construct a set of image pairs with known deformations. The method is evaluated on deformable registrations of inhale-exhale pairs of thoracic CT scans. Using ground truth target registration errors on manually annotated landmarks, we evaluate the method's ability to estimate local registration errors. Estimation of full domain error maps is evaluated using a gold standard approach. The two evaluation approaches show that we can train the network to robustly estimate registration errors in a predetermined range, with subvoxel accuracy. We achieved a root-mean-square deviation of 0.51 mm from gold standard registration errors and of 0.66 mm from ground truth landmark registration errors.

The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children

PubMed Central

2014-01-01

Background Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment of Paediatric Investigation Plans (PIPs). The effect of the EU Paediatric Drug Regulation on the marketing authorisation (MA) of drugs for children with rare diseases was studied. Methods Data on all designated orphan drugs, their indication, MA, PIPs and indication group (adult or child) were obtained from the European Medicines Agency (EMA). The outcome and duration of the process from orphan drug designation (ODD) to MA, was compared, per indication, by age group. The effect of the Paediatric Drug Regulation, implemented in 2007, on the application process was assessed with survival analysis. Results Eighty-one orphan drugs obtained MA since 2000 and half are authorised for (a subgroup of) children; another 34 are currently undergoing further investigations in children through agreed PIPs. The Paediatric Drug Regulation did not significantly increase the number of ODDs with potential paediatric indications (58% before vs 64% after 2007 of ODDs, p = 0.1) and did not lead to more MAs for ODs with paediatric indications (60% vs 43%, p = 0.22). ODs authorised after 2007 had a longer time to MA than those authorised before 2007 (Hazard ratio (95% CI) 2.80 (1.84-4.28), p < 0.001); potential paediatric use did not influence the time to MA (Hazard ratio (95% CI) 1.14 (0.77-1.70), p = 0.52). Conclusions The EU Paediatric Drug Regulation had a minor impact on development and availability of ODs for children, was associated with a longer time to MA, but ensured the further paediatric development of drugs still off-label to children. The impact of the Paediatric Drug Regulation on research quantity and quality in children through PIPs is not yet clear. PMID:25091201

The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children.

PubMed

Kreeftmeijer-Vegter, Annemarie Rosan; de Boer, Anthonius; van der Vlugt-Meijer, Roselinda H; de Vries, Peter J

2014-08-05

Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment of Paediatric Investigation Plans (PIPs). The effect of the EU Paediatric Drug Regulation on the marketing authorisation (MA) of drugs for children with rare diseases was studied. Data on all designated orphan drugs, their indication, MA, PIPs and indication group (adult or child) were obtained from the European Medicines Agency (EMA). The outcome and duration of the process from orphan drug designation (ODD) to MA, was compared, per indication, by age group. The effect of the Paediatric Drug Regulation, implemented in 2007, on the application process was assessed with survival analysis. Eighty-one orphan drugs obtained MA since 2000 and half are authorised for (a subgroup of) children; another 34 are currently undergoing further investigations in children through agreed PIPs. The Paediatric Drug Regulation did not significantly increase the number of ODDs with potential paediatric indications (58% before vs 64% after 2007 of ODDs, p = 0.1) and did not lead to more MAs for ODs with paediatric indications (60% vs 43%, p = 0.22). ODs authorised after 2007 had a longer time to MA than those authorised before 2007 (Hazard ratio (95% CI) 2.80 (1.84-4.28), p < 0.001); potential paediatric use did not influence the time to MA (Hazard ratio (95% CI) 1.14 (0.77-1.70), p = 0.52). The EU Paediatric Drug Regulation had a minor impact on development and availability of ODs for children, was associated with a longer time to MA, but ensured the further paediatric development of drugs still off-label to children. The impact of the Paediatric Drug Regulation on research quantity and quality in children through PIPs is not yet clear.

[Strategies of medical self-authorization in early modern medicine: the example of Volcher Coiter (1534-1576)].

PubMed

Gross, Dominik; Steinmetzer, Jan

2005-01-01

Based on the example of Volcher Coiter--a town physician at Nuremberg and one of the leading anatomists in early modern medicine--, this essay points out that the authoritative status of contemporary physicians mainly was predicated on an interplay of self-fashioning and outside perception. It provides ample evidence that Coiter made use of several characteristic rhetorical and discourse-related strategies of self-authorisation such as the participation in social networks, a highly convincing technique of self-fashioning by emphasizing particular erudition, the presentation of academic medicine as a science authorised by god and the concurrent devaluation of non-academic healers. Furthermore, graphic and visual strategies of self-authorisation could be ascertained: Coiter took care for a premium typography of his books. He also used his talent as a graphic artist in his books to visualise his medical concepts. Moreover, the so-called 'Nuremberg Portrait' of Coiter served to illustrate his outstanding authority.

Comparators (medicinal and non medicinal) for marketing authorization, for public health, for payers and at the European level.

PubMed

Berdaï, Driss; Hotton, Jean-Michel; Lechat, Philippe

2010-01-01

Drug evaluation is based on comparison. Thus, the choice of the comparator for any new treatment becomes a key issue, especially when there are great differences in medical practice and of use conditions of the comparators depending on the geographical zones and their evolution with time. The choice of the comparators must satisfy sometimes different expectations from the registration authorities and for insurance coverage. The universal comparator that allows answering all the clinical assessment questions does not exist. Placebo, when it can be used, remains a reference for the MA (marketing authorisation) application, but does not exclude the use of the reference drug available on the market and prescribed under optimal efficacy conditions. The reference treatment is sometimes a difficult choice due to the absence of validated therapeutic recommendations or if the recommendations vary depending on the countries. The expansion and international harmonization of prescription guidelines (clinical practice guidelines) would reinforce the robustness and efficiency of clinical research efforts with respect to the relevance of the comparison to reference treatments. This principle also applies to the use of a non-drug comparator when it has been recognized as the reference comparator in the treatment of the pathology in question. In as much as possible, the search for a consensus must also aim at defining in the clinical development recommendations significant thresholds for the size of evaluated effects. Optimization of the information made available after clinical trials could also be helped by the development of use of methodologies that allow assessing superiority on secondary criteria during a non-inferiority study on the main criterion. Finally, the development of early scientific consultations by the Haute Autorité de Santé (HAS, French Health Authority) would contribute to adapt phase III clinical trials better to questions concerning the assessment of the clinical added value of the medicinal products evaluated. © 2010 Société Française de Pharmacologie et de Thérapeutique.

[Harmonisation of the Marketing Authorisation Application dossier: perspectives due to harmonised requirements. Assessing Rules and the Common Technical Document].

PubMed

Menges, Klaus

2008-07-01

Assessing Rules for Marketing Authorisation Applications and the Common Technical Document provide the framework regarding data-related requirements and regarding the structural requirements of marketing authorisation application dossiers, similar to the structural levels and rooms of buildings on the one hand and their interior equipment on the other hand. Since the 1970s requirements about how to submit application dossiers and how to assess them have become increasingly harmonised, aiming for the use of a single format and identical rules for assessment. In regard of the format, harmonisation has been achieved beyond Europe by implementing the mandatory use of CTD in the three main regions of interests of the pharmaceutical industry, Japan, the United States of America and Europe. The assessment rules have been extensively harmonised throughout Europe in a way that the same rules apply to the marketing authorisation applications submitted in Germany as well as in other Member States. Different interpretations of the guidance documents, different understanding of the provided data or divergent conclusions drawn up may still occur. All stakeholders within the European network of Drug Regulatory Affairs will act on the level floor of the European and--apart from some exceptions--also nationally implemented legislation. This will not only serve the internationally acting pharmaceutical companies' interests but also consumer interests in obtaining consistent information on drug products based on transparent rules safeguarding the necessary pharmaceutical quality, efficacy and safety with respect to an adequate risk-benefit relationship.

Changes in European legislation make it timely to introduce a transparent market surveillance system for cosmetics.

PubMed

Lodén, Marie; Ungerth, Louise; Serup, Jørgen

2007-01-01

Marketing of cosmetics often makes strong claims linked to active ingredients. This is especially so for anti-ageing products, where the presentation and content of "active" ingredients may create new difficulties in their classification as cosmetics or medicinal products. A recent change in European legislation classifies a product as medicinal by virtue of its "function", in addition to the previous definition of "presentation" (i.e. marketing linked to diseases). Thus, formulations that also restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action should henceforth be covered by the Medicinal Products Directive. A cosmetic product must be suitable for its purpose and should not lead to adverse reactions that are disproportional in relation to its intended effect. However, the forthcoming ban on animal testing of cosmetic ingredients and the new European regulation, REACH (Registration, Evaluation and Authorisation of Chemicals), which aims to ensure a high level of chemical safety to protect human health and the environment, will probably have limited impact on the safety assessment of cosmetics. In order to enable consumers to make informed purchasing decisions, greater transparency in the process of assessing the performance of cosmetics is needed. Introduction of a more transparent system, enabling consumers and professionals to examine the scientific evidence for the claimed effect and the safety assessment of cosmetics, is therefore timely. Lack of transparency increases the risk of consumers wasting money on cosmetics that do not deliver the desired effects. This may jeopardize public trust in the cosmetic industry.

The comparative toxicity to soil invertebrates of natural chemicals and their synthetic analogues.

PubMed

Whitaker, J; Chaplow, J S; Potter, E; Scott, W A; Hopkin, S; Harman, M; Sims, I; Sorokin, N

2009-07-01

The introduction of Registration, Evaluation and Authorisation of Chemicals (REACH), requires companies to register and risk assess all substances produced or imported in volumes of >1 tonne per year. Extrapolation methods which use existing data for estimating the effects of chemicals are attractive to industry, and comparative data are therefore increasingly in demand. Data on natural toxic chemicals could be used for extrapolation methods such as read-across. To test this hypothesis, the toxicity of natural chemicals and their synthetic analogues were compared using standardised toxicity tests. Two chemical pairs: the napthoquinones, juglone (natural) and 1,4-naphthoquinone (synthetic); and anthraquinones, emodin (natural) and quinizarin (synthetic) were chosen, and their comparative effects on the survival and reproduction of collembolans, earthworms, enchytraeids and predatory mites were assessed. Differences in sensitivity between the species were observed with the predatory mite (Hypoaspis aculeifer) showing the least sensitivity. Within the chemical pairs, toxicity to lethal and sub-lethal endpoints was very similar for the four invertebrate species. The exception was earthworm reproduction, which showed differential sensitivity to the chemicals in both naphthoquinone and anthraquinone pairs. Differences in toxicity identified in the present study may be related to degree of exposure and/or subtle differences in the mode of toxic action for the chemicals and species tested. It may be possible to predict differences by identifying functional groups which infer increased or decreased toxicity in one or other chemical. The development of such techniques would enable the use of read-across from natural to synthetic chemicals for a wider group of compounds.

Ecotoxicity testing of chemicals with particular reference to pesticides.

PubMed

Walker, Colin H

2006-07-01

Ecotoxicity tests are performed on vertebrates and invertebrates for the environmental risk assessment of pesticides and other chemicals and for a variety of ecotoxicological studies in the laboratory and in the field. Existing practices and strategies in ecotoxicity testing are reviewed, including an account of current requirements of the European Commission for the testing of pesticides and the recent REACH (Registration, Evaluation, Authorisation and Restrictions of Chemicals) proposals for industrial chemicals. Criticisms of existing practices have been made on both scientific and ethical grounds, and these are considered before dealing with the question of possible alternative methods and strategies both for environmental risk assessment and for ecotoxicological studies more generally. New approaches from an ecological point of view are compared with recent developments in laboratory-based methods such as toxicity tests, biomarker assays and bioassays. With regard to the development of new strategies for risk assessment, it is suggested that full consideration should be given to the findings of earlier long-term studies of pollution, which identified mechanisms of action by which environmental chemicals can cause natural populations to decline. Neurotoxicity and endocrine disruption are two cases in point, and biomarker assays for them could have an important role in testing new chemicals suspected of having these properties. In a concluding discussion, possible ways of improving testing protocols are discussed, having regard for current issues in the field of environmental risk assessment as exemplified by the debate over the REACH proposals. The importance of flexibility and the roles of ecologists and ecotoxicologists are stressed in the context of environmental risk assessment.

Toxicogenomics in Environmental Science.

PubMed

Brinke, Alexandra; Buchinger, Sebastian

This chapter reviews the current knowledge and recent progress in the field of environmental, aquatic ecotoxicogenomics with a focus on transcriptomic methods. In ecotoxicogenomics the omics technologies are applied for the detection and assessment of adverse effects in the environment, and thus are to be distinguished from omics used in human toxicology [Snape et al., Aquat Toxicol 67:143-154, 2004]. Transcriptomic methods in ecotoxicology are applied to gain a mechanistic understanding of toxic effects on organisms or populations, and thus aim to bridge the gap between cause and effect. A worthwhile effect-based interpretation of stressor induced changes on the transcriptome is based on the principle of phenotypic-anchoring [Paules, Environ Health Perspect 111:A338-A339, 2003]. Thereby, changes on the transcriptomic level can only be identified as effects if they are clearly linked to a specific stressor-induced effect on the macroscopic level. By integrating those macroscopic and transcriptomic effects, conclusions on the effect-inducing type of the stressor can be drawn. Stressor-specific effects on the transcriptomic level can be identified as stressor-specific induced pathways, transcriptomic patterns, or stressors-specific genetic biomarkers. In this chapter, examples of the combined application of macroscopic and transcriptional effects for the identification of environmental stressors, such as aquatic pollutants, are given and discussed. By means of these examples, challenges on the way to a standardized application of transcriptomics in ecotoxicology are discussed. This is also done against the background of the application of transcriptomic methods in environmental regulation such as the EU regulation Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

TREXMO: A Translation Tool to Support the Use of Regulatory Occupational Exposure Models.

PubMed

Savic, Nenad; Racordon, Dimitri; Buchs, Didier; Gasic, Bojan; Vernez, David

2016-10-01

Occupational exposure models vary significantly in their complexity, purpose, and the level of expertise required from the user. Different parameters in the same model may lead to different exposure estimates for the same exposure situation. This paper presents a tool developed to deal with this concern-TREXMO or TRanslation of EXposure MOdels. TREXMO integrates six commonly used occupational exposure models, namely, ART v.1.5, STOFFENMANAGER(®) v.5.1, ECETOC TRA v.3, MEASE v.1.02.01, EMKG-EXPO-TOOL, and EASE v.2.0. By enabling a semi-automatic translation between the parameters of these six models, TREXMO facilitates their simultaneous use. For a given exposure situation, defined by a set of parameters in one of the models, TREXMO provides the user with the most appropriate parameters to use in the other exposure models. Results showed that, once an exposure situation and parameters were set in ART, TREXMO reduced the number of possible outcomes in the other models by 1-4 orders of magnitude. The tool should manage to reduce the uncertain entry or selection of parameters in the six models, improve between-user reliability, and reduce the time required for running several models for a given exposure situation. In addition to these advantages, registrants of chemicals and authorities should benefit from more reliable exposure estimates for the risk characterization of dangerous chemicals under Regulation, Evaluation, Authorisation and restriction of CHemicals (REACH). © The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Regulatory requirements for clinical trial and marketing authorisation application for cell-based medicinal products.

PubMed

Salmikangas, P; Flory, E; Reinhardt, J; Hinz, T; Maciulaitis, R

2010-01-01

The new era of regenerative medicine has led to rapid development of new innovative therapies especially for diseases and tissue/organ defects for which traditional therapies and medicinal products have not provided satisfactory outcome. Although the clinical use and developments of cell-based medicinal products (CBMPs) could be witnessed already for a decade, robust scientific and regulatory provisions for these products have only recently been enacted. The new Regulation for Advanced Therapies (EC) 1394/2007 together with the revised Annex I, Part IV of Directive 2001/83/EC provides the new legal framework for CBMPs. The wide variety of cell-based products and the foreseen limitations (small sample sizes, short shelf life) vs. particular risks (microbiological purity, variability, immunogenicity, tumourigenicity) associated with CBMPs have called for a flexible, case-by-case regulatory approach for these products. Consequently, a risk-based approach has been developed to allow definition of the amount of scientific data needed for a Marketing Authorisation Application (MAA) of each CBMP. The article provides further insight into the initial risk evaluation, as well as to the quality, non-clinical, and clinical requirements of CBMPs. Special somatic cell therapies designed for active immunotherapy are also addressed.

Failures to further developing orphan medicinal products after designation granted in Europe: an analysis of marketing authorisation failures and abandoned drugs.

PubMed

Giannuzzi, Viviana; Landi, Annalisa; Bosone, Enrico; Giannuzzi, Floriana; Nicotri, Stefano; Torrent-Farnell, Josep; Bonifazi, Fedele; Felisi, Mariagrazia; Bonifazi, Donato; Ceci, Adriana

2017-09-11

The research and development process in the field of rare diseases is characterised by many well-known difficulties, and a large percentage of orphan medicinal products do not reach the marketing approval.This work aims at identifying orphan medicinal products that failed the developmental process and investigating reasons for and possible factors influencing failures. Drugs designated in Europe under Regulation (European Commission) 141/2000 in the period 2000-2012 were investigated in terms of the following failures: (1) marketing authorisation failures (refused or withdrawn) and (2) drugs abandoned by sponsors during development.Possible risk factors for failure were analysed using statistically validated methods. This study points out that 437 out of 788 designations are still under development, while 219 failed the developmental process. Among the latter, 34 failed the marketing authorisation process and 185 were abandoned during the developmental process. In the first group of drugs (marketing authorisation failures), 50% reached phase II, 47% reached phase III and 3% reached phase I, while in the second group (abandoned drugs), the majority of orphan medicinal products apparently never started the development process, since no data on 48.1% of them were published and the 3.2% did not progress beyond the non-clinical stage.The reasons for failures of marketing authorisation were: efficacy/safety issues (26), insufficient data (12), quality issues (7), regulatory issues on trials (4) and commercial reasons (1). The main causes for abandoned drugs were efficacy/safety issues (reported in 54 cases), inactive companies (25.4%), change of company strategy (8.1%) and drug competition (10.8%). No information concerning reasons for failure was available for 23.2% of the analysed products. This analysis shows that failures occurred in 27.8% of all designations granted in Europe, the main reasons being safety and efficacy issues. Moreover, the stage of development reached by drugs represents a specific risk factor for failures. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[New drugs in oncology--features of clinical trials for market authorisation and arguments for the rapid implementation of independent clinical trials following approval].

PubMed

Ludwig, Wolf-Dieter; Schott, Gisela

2013-01-01

The market authorisation or extension of indication for all oncology drugs in Europe is now based on Regulation (EC) No. 726/2004, a centralised procedure of the European Medicines Agency (EMA). Studies in recent years have highlighted deficiencies in pivotal studies. For example, the requirements of the EMA are not always consistently followed and studies are stopped prematurely after only interim analysis that at this time point shows improved efficacy with regard to the comparator arm. Our current analysis of the European Assessment Reports (reporting period: 01/01/2009 to 08/13/2012) on 29 drugs for 39 oncology indications shows that the quality of the trials for market authorisation has improved in several respects. Primary endpoints recommended by the EMA and the Food and Drug Administration (FDA) such as overall survival and progression-free survival are used, and only one study was conducted as a phase II trial with no comparator arm. In contrast, oncology drugs that are approved for the treatment of rare diseases (orphan drugs) are based on small studies which are often carried out without blinding, are not randomised and investigate surrogate endpoints. To answer patient-relevant issues following market authorisation, it is necessary to conduct independent clinical studies. Increased public funding needs to be provided and bureaucratic hurdles have to be reduced. Only this will permit a more efficient use of limited health care resources and allow to improve the quality of care for cancer patients. Copyright © 2013 S. Karger AG, Basel.

Treatment for gender dysphoria in children: the new legal, ethical and clinical landscape.

PubMed

Smith, Malcolm K; Mathews, Ben

2015-02-02

Gender dysphoria is a condition in which a child's subjectively felt identity and gender are not congruent with her or his biological sex. Because of this, the child suffers clinically significant distress or impairment in social functioning. The Family Court of Australia has recently received an increasing number of applications seeking authorisation for the provision of hormones to treat gender dysphoria in children. Some medical procedures and interventions performed on children are of such a grave nature that court authorisation must be obtained to render them lawful. These procedures are referred to as special medical procedures. Hormonal therapy for the treatment of gender dysphoria in children is provided in two stages occurring years apart. Until recently, both stages of treatment were regarded by courts as special medical treatments, meaning court authorisation had to be provided for both stages. In a significant recent development, courts have drawn a distinction between the two stages of treatment, permitting parents to consent to the first stage. In addition, it has been held that a child who is determined by a court to be Gillick competent can consent to stage 2 treatment. The new legal developments concerning treatment for gender dysphoria are of ethical, clinical and practical importance to children and their families, and to medical practitioners treating children with gender dysphoria. Medical practitioners should benefit from an understanding of the recent developments in legal principles. This will ensure that they have up-to-date information about the circumstances under which treatment may be conducted with parental consent, and those in which they must seek court authorisation.

St John's wort (Hypericum perforatum) products - an assessment of their authenticity and quality.

PubMed

Booker, Anthony; Agapouda, Anastasia; Frommenwiler, Débora A; Scotti, Francesca; Reich, Eike; Heinrich, Michael

2018-02-01

St John's wort products (Hypericum perforatum L.) are widely available for sale in many countries including the UK via the internet. In the UK, these products are required to hold either a marketing authorisation or Traditional herbal registration (THR) to be sold legally. The THR and other regulatory schemes help to ensure product safety and quality providing an example of best practice but there is a risk if both regulated and un-regulated products continue to be available to consumers. The project is embedded in a larger study aiming to investigate the quality of different herbal medicinal products along diverse value chains. Here we focus on a comparison of the quality of the finished products and assess phytochemical variation between registered products (THRs) and products obtained from the market without any registration. 47 commercial products (granulated powders and extracts) were sourced from different suppliers. We analysed these samples using high performance thin layer chromatography (HPTLC) and 1 H NMR spectroscopy coupled with multi-variate analysis software following a method previously developed by our group. The consistency of the products varies significantly. Adulteration of the products (36%), possibly with other Hypericum species obtained from China or use of chemically distinct H. perforatum cultivars or chemotypes, and adulteration of the products (19%) with food dyes (tartrazine, amaranth, brilliant blue, sunset yellow) were the principle findings of this study. There is significant compositional variation among commercial finished products and two main causative quality problems were identified as adulteration by incorrect species or adulteration with food dyes. Generally, food supplements and unlicensed products were found to be of poorer quality than the regulated ones including THRs. Copyright © 2017 Elsevier GmbH. All rights reserved.

Regulation of medicinal plants for public health--European community monographs on herbal substances.

PubMed

Knöss, Werner; Chinou, Ioanna

2012-08-01

The European legislation on medicinal products also addresses the medicinal use of products originating from plants. The objective of the legislation is to ensure the future existence of such products and to consider particular characteristics when assessing quality, efficacy, and safety. Two categories are defined: i) herbal medicinal products can be granted a marketing authorisation; and ii) traditional herbal medicinal products can be granted a registration based on their longstanding use if they are complying with a set of provisions ensuring their safe use. The Committee on Herbal Medicinal Products (HMPC) was established at the European Medicines Agency (EMA) to provide monographs and list entries on herbal substances and preparations thereof. Meanwhile, approx. 100 monographs have been published, which define a current scientific and regulatory standard for efficacy and safety of herbal substances and herbal preparations used in medicinal products. This harmonised European standard will facilitate the availability and adequate use of traditional herbal medicinal products and herbal medicinal products within the European Union. Consequent labelling shall also enable patients and health care professionals to differentiate medicinal products from other product categories like cosmetics, food supplements, and medical devices. Georg Thieme Verlag KG Stuttgart · New York.

Feasibility of Multimodal Deformable Registration for Head and Neck Tumor Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortunati, Valerio, E-mail: v.fortunati@erasmusmc.nl; Verhaart, René F.; Angeloni, Francesco

2014-09-01

Purpose: To investigate the feasibility of using deformable registration in clinical practice to fuse MR and CT images of the head and neck for treatment planning. Method and Materials: A state-of-the-art deformable registration algorithm was optimized, evaluated, and compared with rigid registration. The evaluation was based on manually annotated anatomic landmarks and regions of interest in both modalities. We also developed a multiparametric registration approach, which simultaneously aligns T1- and T2-weighted MR sequences to CT. This was evaluated and compared with single-parametric approaches. Results: Our results show that deformable registration yielded a better accuracy than rigid registration, without introducing unrealisticmore » deformations. For deformable registration, an average landmark alignment of approximatively 1.7 mm was obtained. For all the regions of interest excluding the cerebellum and the parotids, deformable registration provided a median modified Hausdorff distance of approximatively 1 mm. Similar accuracies were obtained for the single-parameter and multiparameter approaches. Conclusions: This study demonstrates that deformable registration of head-and-neck CT and MR images is feasible, with overall a significanlty higher accuracy than for rigid registration.« less

Conflict of interest in biomedical research: a view from Europe.

PubMed

Salvi, Maurizio

2003-01-01

In this paper I address the conflict of interest (CoI) issue from a legal point of view at a European level. We will see that the regulatory framework that exists in Europe does state the need for the independence of ethics committee involved in authorisation of research and clinical trials. We will see that CoI is an element that has to be closely monitored at National and International level. Therefore, Member States and Newly Associated States do have to address CoI in the authorisation process of research and clinical protocols of biomedicine.

How to improve the clinical development paradigm and its division into phases I, II and III.

PubMed

Bamberger, Marion; Moore, Nicholas; Lechat, Philippe

2011-01-01

Based on the observation that over the last 30 years the cost of development has risen regularly as the number of new chemical entities reaching the market has fallen, how can "savings" be made in terms of clinical development, the objective being more rapid access to a drug for medical needs that are not covered? Several instruments exist to enable innovative products to be made available more quickly: temporary use authorisations, which are not concerned by this work (ATUs), conditional marketing authorisations (MAs) and MAs under exceptional circumstances. These aspects have been taken up in the European medicines agency (EMA)'s "Road Map", which states "A key issue for Regulators will be if a more "staggered" approval should be envisaged, characterised by a better defined/more restricted population of good responders, followed by a broadening of the population post-authorisation when more "real life" data are available. In addition, maximising the value of information generated in the post-authorisation phase should be developed through the use of cohorts and other prospectively collected use data, especially in the case of conditional marketing authorisations." The rules of procedure of the Transparency Commission for their part provide for the notion of preliminary examination: in order to prepare as best as possible the examination of dossiers of products assumed to be innovative and to limit delays, the office can undertake a preliminary study as soon as the dossier has been filed at the Committee for medicinal products for human use (CHMP). It may, at this time, request the firm to provide further information and may call on external experts. The implementation of this preliminary study does not exonerate the firm of the obligation of filing a complete dossier. The post inscription studies requested by the Transparency Commission (ISPEP - public health benefit and post-marketing studies) are usually requested in the case of hesitations regarding the level of improvement of the medical benefit (ASMR) [level II/III or IV/V]. Such requests mainly concern uncertainties regarding the transposability, the patient profile or correct usage in real life. Among the studies whose results were provided, in 15 cases the results were in line with expectations, in 6 cases they resulted in downward re-evaluations and the final 3 cases were inconclusive. The final recommendations of the round table were: Defining the medical need that is not covered by working in consultation (Industry and Health Authorities); Providing a Complementary Investigations Plan (PIC) after the MA at a very early stage to reinforce the early MA, and/or HTA (health technology assessment) preparation and monitoring (possible constraining actions); Enhanced use of modelling techniques and their transposability; "Intussusception" of phases to optimise the development of a complete dossier; Early "scientific opinions" (EMA, French Health Products Safety Agency [Afssaps], French Health Authority [HAS]); Raising the awareness of the authorities, industry, doctors and patients with regard to controlled observational studies; Developing the use of public data bases. © 2011 Société Française de Pharmacologie et de Thérapeutique.

78 FR 33447 - Draft Applications for Sealed Source and Device Evaluation and Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0104] Draft Applications for Sealed Source and Device... for sealed source and device evaluation and registration. The NRC is requesting public comment on... for Sealed Source and Device Evaluation and Registration.'' The document has been updated from the...

Evaluation of the use of registration stickers.

DOT National Transportation Integrated Search

2011-04-01

This research evaluated the potential costs and benefits of doing away with license plate registration stickers as part : of the registration renewal process for Pennsylvania. The research consisted of a comprehensive literature review, a : survey of...

SU-C-207B-06: Comparison of Registration Methods for Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riyahi, S; Choi, W; Bhooshan, N

2016-06-15

Purpose: To compare linear and deformable registration methods for evaluation of tumor response to Chemoradiation therapy (CRT) in patients with esophageal cancer. Methods: Linear and multi-resolution BSpline deformable registration were performed on Pre-Post-CRT CT/PET images of 20 patients with esophageal cancer. For both registration methods, we registered CT using Mean Square Error (MSE) metric, however to register PET we used transformation obtained using Mutual Information (MI) from the same CT due to being multi-modality. Similarity of Warped-CT/PET was quantitatively evaluated using Normalized Mutual Information and plausibility of DF was assessed using inverse consistency Error. To evaluate tumor response four groupsmore » of tumor features were examined: (1) Conventional PET/CT e.g. SUV, diameter (2) Clinical parameters e.g. TNM stage, histology (3)spatial-temporal PET features that describe intensity, texture and geometry of tumor (4)all features combined. Dominant features were identified using 10-fold cross-validation and Support Vector Machine (SVM) was deployed for tumor response prediction while the accuracy was evaluated by ROC Area Under Curve (AUC). Results: Average and standard deviation of Normalized mutual information for deformable registration using MSE was 0.2±0.054 and for linear registration was 0.1±0.026, showing higher NMI for deformable registration. Likewise for MI metric, deformable registration had 0.13±0.035 comparing to linear counterpart with 0.12±0.037. Inverse consistency error for deformable registration for MSE metric was 4.65±2.49 and for linear was 1.32±2.3 showing smaller value for linear registration. The same conclusion was obtained for MI in terms of inverse consistency error. AUC for both linear and deformable registration was 1 showing no absolute difference in terms of response evaluation. Conclusion: Deformable registration showed better NMI comparing to linear registration, however inverse consistency of transformation was lower in linear registration. We do not expect to see significant difference when warping PET images using deformable or linear registration. This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

Mammogram registration: a phantom-based evaluation of compressed breast thickness variation effects.

PubMed

Richard, Frédéric J P; Bakić, Predrag R; Maidment, Andrew D A

2006-02-01

The temporal comparison of mammograms is complex; a wide variety of factors can cause changes in image appearance. Mammogram registration is proposed as a method to reduce the effects of these changes and potentially to emphasize genuine alterations in breast tissue. Evaluation of such registration techniques is difficult since ground truth regarding breast deformations is not available in clinical mammograms. In this paper, we propose a systematic approach to evaluate sensitivity of registration methods to various types of changes in mammograms using synthetic breast images with known deformations. As a first step, images of the same simulated breasts with various amounts of simulated physical compression have been used to evaluate a previously described nonrigid mammogram registration technique. Registration performance is measured by calculating the average displacement error over a set of evaluation points identified in mammogram pairs. Applying appropriate thickness compensation and using a preferred order of the registered images, we obtained an average displacement error of 1.6 mm for mammograms with compression differences of 1-3 cm. The proposed methodology is applicable to analysis of other sources of mammogram differences and can be extended to the registration of multimodality breast data.

Petition for Rulemaking to Evaluate Synergestic Effects of Pesticides during Registration and Registration Review

EPA Pesticide Factsheets

This petition from the Center for Biological Diversity asks that the Agency require all applicants and registrants to provide data on the potential synergistic effects of pesticides during the registration and registration review processes.

RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial

PubMed Central

Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

2015-01-01

Introduction Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. Methods and analysis RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. Ethics and dissemination The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals. Trial registration number ISRCTN03978701. PMID:26297361

Serial Scanning and Registration of High Resolution Quantitative Computed Tomography Volume Scans for the Determination of Local Bone Density Changes

NASA Technical Reports Server (NTRS)

Whalen, Robert T.; Napel, Sandy; Yan, Chye H.

1996-01-01

Progress in development of the methods required to study bone remodeling as a function of time is reported. The following topics are presented: 'A New Methodology for Registration Accuracy Evaluation', 'Registration of Serial Skeletal Images for Accurately Measuring Changes in Bone Density', and 'Precise and Accurate Gold Standard for Multimodality and Serial Registration Method Evaluations.'

Experimental study of digital image processing techniques for LANDSAT data

NASA Technical Reports Server (NTRS)

Rifman, S. S. (Principal Investigator); Allendoerfer, W. B.; Caron, R. H.; Pemberton, L. J.; Mckinnon, D. M.; Polanski, G.; Simon, K. W.

1976-01-01

The author has identified the following significant results. Results are reported for: (1) subscene registration, (2) full scene rectification and registration, (3) resampling techniques, (4) and ground control point (GCP) extraction. Subscenes (354 pixels x 234 lines) were registered to approximately 1/4 pixel accuracy and evaluated by change detection imagery for three cases: (1) bulk data registration, (2) precision correction of a reference subscene using GCP data, and (3) independently precision processed subscenes. Full scene rectification and registration results were evaluated by using a correlation technique to measure registration errors of 0.3 pixel rms thoughout the full scene. Resampling evaluations of nearest neighbor and TRW cubic convolution processed data included change detection imagery and feature classification. Resampled data were also evaluated for an MSS scene containing specular solar reflections.

Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures

PubMed Central

Rettmann, Maryam E.; Holmes, David R.; Kwartowitz, David M.; Gunawan, Mia; Johnson, Susan B.; Camp, Jon J.; Cameron, Bruce M.; Dalegrave, Charles; Kolasa, Mark W.; Packer, Douglas L.; Robb, Richard A.

2014-01-01

Purpose: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. Methods: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamic in vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. Results: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved landmark-only registration provided the noise in the surface points is not excessively high. Increased variability on the landmark fiducials resulted in increased registration errors; however, refinement of the initial landmark registration by the surface-based algorithm can compensate for small initial misalignments. The surface-based registration algorithm is quite robust to noise on the surface points and continues to improve landmark registration even at high levels of noise on the surface points. Both the canine and patient studies also demonstrate that combined landmark and surface registration has lower errors than landmark registration alone. Conclusions: In this work, we describe a model for evaluating the impact of noise variability on the input parameters of a registration algorithm in the context of cardiac ablation therapy. The model can be used to predict both registration error as well as assess which inputs have the largest effect on registration accuracy. PMID:24506630

Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rettmann, Maryam E., E-mail: rettmann.maryam@mayo.edu; Holmes, David R.; Camp, Jon J.

2014-02-15

Purpose: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. Methods: Datamore » from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamicin vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. Results: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved landmark-only registration provided the noise in the surface points is not excessively high. Increased variability on the landmark fiducials resulted in increased registration errors; however, refinement of the initial landmark registration by the surface-based algorithm can compensate for small initial misalignments. The surface-based registration algorithm is quite robust to noise on the surface points and continues to improve landmark registration even at high levels of noise on the surface points. Both the canine and patient studies also demonstrate that combined landmark and surface registration has lower errors than landmark registration alone. Conclusions: In this work, we describe a model for evaluating the impact of noise variability on the input parameters of a registration algorithm in the context of cardiac ablation therapy. The model can be used to predict both registration error as well as assess which inputs have the largest effect on registration accuracy.« less

Threshold Things That Think: Authorisation for Resharing

NASA Astrophysics Data System (ADS)

Peeters, Roel; Kohlweiss, Markulf; Preneel, Bart

As we are evolving towards ubiquitous computing, users carry an increasing number of mobile devices with sensitive information. The security of this information can be protected using threshold cryptography, in which secret computations are shared between multiple devices. Threshold cryptography can be made more robust by resharing protocols, which allow recovery from partial compromises. This paper introduces user-friendly and secure protocols for the authorisation of resharing protocols. We present both automatic and manual protocols, utilising a group manual authentication protocol to add a new device. We analyse the security of these protocols: our analysis considers permanent and temporary compromises, denial of service attacks and manual authentications errors of the user.

Spectroscopy applied to feed additives of the European Union Reference Laboratory: a valuable tool for traceability.

PubMed

Omar, Jone; Slowikowski, Boleslaw; Boix, Ana; von Holst, Christoph

2017-08-01

Feed additives need to be authorised to be placed on the market according to Regulation (EU) No. 1831/2003. Next to laying down the procedural requirements, the regulation creates the European Union Reference Laboratory for Feed Additives (EURL-FA) and requires that applicants send samples to the EURL-FA. Once authorised, the characteristics of the marketed feed additives should correspond to those deposited in the sample bank of the EURL-FA. For this purpose, the submitted samples were subjected to near-infrared (NIR) and Raman spectroscopy for spectral characterisation. These techniques have the valuable potential of characterising the feed additives in a non-destructive manner without any complicated sample preparation. This paper describes the capability of spectroscopy for a rapid characterisation of products to establish whether specific authorisation criteria are met. This study is based on the analysis of feed additive samples from different categories and functional groups, namely products containing (1) selenium, (2) zinc and manganese, (3) vitamins and (4) essential oils such as oregano and thyme oil. The use of chemometrics turned out to be crucial, especially in cases where the differentiation of spectra by visual inspection was very difficult.

Access and authorisation in a Glocal e-Health Policy context.

PubMed

Scott, Richard E; Jennett, Penny; Yeo, Maryann

2004-03-31

Challenges to the development of appropriate yet adaptable policy and tools for security of the individual patient electronic health record (EHR) are proving to be significant. Compounding this is the unique capability of e-health to transgress all existing geo-political and other barriers. Initiatives to develop and advance policy, standards, and tools in relation to EHR access control and authorisation management must address this capability. Currently policy development initiatives take place largely in an isolated manner. This jeopardises the potential of e-health because decisions made in one jurisdiction might hamper, even prevent, an e-health opportunity in another. This paper places access and authorisation issues in an overall policy context through describing current Canadian initiatives. The National Initiative for Telehealth (NIFTE) Guidelines project is developing a framework of national guidelines for telehealth. The Policy and Peer Permission (PPP) project is developing a unique tool that provides persistent protection of data. The new corporate body 'Infoway' is developing a pan-Canadian electronic health record solution. Finally, the Glocal e-Health Policy initiative is developing a tool with which to identify and describe the inter-relationships of e-health issues amongst policy levels, themes, and actors.

The contribution of neighbouring countries to pesticide levels in Dutch surface waters.

PubMed

Van 'T Zelfde, M; Tamis, W L M; Vijver, M G; De Snoo, G R

2011-01-01

Compared with other European countries, Dutch consumption of pesticides is high, particularly in agriculture, with many of the compounds found in surface waters in high concentrations and various standards being exceeded. Surface water quality is routinely monitored and the data obtained are published in the Dutch Pesticides Atlas. One important mechanism for reducing pesticide levels in surface waters is authorisation policy, which proceeds on the assumption that the pollution concerned has taken place in the Netherlands. The country straddles the delta of several major European rivers, however, and as river basins do not respect national borders some of the water quality problems will derive from neighbouring countries. Against this background the general question addressed in this article is the following: To what extent do countries neighbouring on the Netherlands contribute to pesticide pollution of Dutch surface waters? To answer this question, data from the Pesticides Atlas for the period 2005-2009 were used. Border zones with Belgium and Germany were defined and the data for these zones compared with Dutch data. In the analyses, due allowance was also made for authorised and non-authorised compounds and for differences between flowing and stagnant waters. Monitoring efforts in the border zones and in the Netherlands were also characterised, showing that efforts in the former are similar to those in the rest of the country. In the border zone with Belgium the relative number of non-authorised pesticides exceeding the standards is clearly higher than in the rest of the Netherlands. These exceedances are observed mainly in flowing waters. In contrast, there is no difference in the relative number of standard-exceeding measurements between the border zones and the rest of the Netherlands. In the boundary zones the array of standard-exceeding compounds clearly deviates from that in the rest of the Netherlands, with compounds authorised in the neighbouring countries but not in the Netherlands, such as flufenacet, featuring prominently. The share of the neighbouring countries in the total number of exceedances in the Netherlands is roughly proportional to the relative area of the border zones. Although there is a certain influx of pesticides from across national borders, the magnitude of the problem appears to be limited.

Risk management measures for chemicals: the "COSHH essentials" approach.

PubMed

Garrod, A N I; Evans, P G; Davy, C W

2007-12-01

"COSHH essentials" was developed in Great Britain to help duty holders comply with the Control of Substances Hazardous to Health (COSHH) Regulations. It uses a similar approach to that described in the new European "REACH" Regulation (Registration, Evaluation, Authorisation and Restriction of Chemicals; EC No. 1907/2006 of the European Parliament), insofar as it identifies measures for managing the risk for specified exposure scenarios. It can therefore assist REACH duty holders with the identification and communication of appropriate risk-management measures. The technical basis for COSHH essentials is explained in the original papers published in the Annals of Occupational Hygiene. Its details will, therefore, not be described here; rather, its ability to provide a suitable means for communicating risk-management measures will be explored. COSHH essentials is a simple tool based on an empirical approach to risk assessment and risk management. The output is a "Control Guidance Sheet" that lists the "dos" and "don'ts" for control in a specific task scenario. The guidance in COSHH essentials recognises that exposure in the workplace will depend not just on mechanical controls, but also on a number of other factors, including administrative and behavioural controls, such as systems of work, supervision and training. In 2002, COSHH essentials was made freely available via the internet (http://www.coshh-essentials.org.uk/). This electronic delivery enabled links to be made between product series that share tasks, such as drum filling, and with ancillary guidance, such as setting up health surveillance for work with a respiratory sensitiser. COSHH essentials has proved to be a popular tool for communicating good control practice. It has attracted over 1 million visits to its site since its launch. It offers a common benchmark of good practice for chemical users, manufacturers, suppliers and importers, as well as regulators and health professionals.

Patient safety in nursing education: contexts, tensions and feeling safe to learn.

PubMed

Steven, Alison; Magnusson, Carin; Smith, Pam; Pearson, Pauline H

2014-02-01

Education is crucial to how nurses practice, talk and write about keeping patients safe. The aim of this multisite study was to explore the formal and informal ways the pre-registration medical, nursing, pharmacy and physiotherapy students learn about patient safety. This paper focuses on findings from nursing. A multi-method design underpinned by the concept of knowledge contexts and illuminative evaluation was employed. Scoping of nursing curricula from four UK university programmes was followed by in-depth case studies of two programmes. Scoping involved analysing curriculum documents and interviews with 8 programme leaders. Case-study data collection included focus groups (24 students, 12 qualified nurses, 6 service users); practice placement observation (4 episodes=19 hrs) and interviews (4 Health Service managers). Within academic contexts patient safety was not visible as a curricular theme: programme leaders struggled to define it and some felt labelling to be problematic. Litigation and the risk of losing authorisation to practise were drivers to update safety in the programmes. Students reported being taught idealised skills in university with an emphasis on 'what not to do'. In organisational contexts patient safety was conceptualised as a complicated problem, addressed via strategies, systems and procedures. A tension emerged between creating a 'no blame' culture and performance management. Few formal mechanisms appeared to exist for students to learn about organisational systems and procedures. In practice, students learnt by observing staff who acted as variable role models; challenging practice was problematic, since they needed to 'fit in' and mentors were viewed as deciding whether they passed or failed their placements. The study highlights tensions both between and across contexts, which link to formal and informal patient safety education and impact negatively on students' feelings of emotional safety in their learning. Copyright © 2014 Elsevier Ltd. All rights reserved.

Xenobiotic metabolism in human skin and 3D human skin reconstructs: a review.

PubMed

Gibbs, Sue; van de Sandt, Johannes J M; Merk, Hans F; Lockley, David J; Pendlington, Ruth U; Pease, Camilla K

2007-12-01

In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential target organ for adverse health effects. Occupational, accidental or intended-use exposure to toxic chemicals could result in acute or delayed injury to the skin (e.g. inflammation, allergy, cancer). Skin metabolism may play a role in the manifestation or amelioration of adverse effects via the topical route. Today, we have robust testing strategies to assess the potential for local skin toxicity of chemical exposure. Such methods (e.g. the local lymph node assay for assessing skin sensitisation; skin painting carcinogenicity studies) incorporate skin metabolism implicitly in the in vivo model system used. In light of recent European legislation (i.e. 7(th) Amendment to the Cosmetics Directive and Registration Evaluation and Authorisation of existing Chemicals (REACH)), non-animal approaches will be required to reduce and replace animal experiments for chemical risk assessment. It is expected that new models and approaches will need to account for skin metabolism explicitly, as the mechanisms of adverse effects in the skin are deconvoluted. 3D skin models have been proposed as a tool to use in new in vitro alternative approaches. In order to be able to use 3D skin models in this context, we need to understand their metabolic competency in relation to xenobiotic biotransformation and whether functional activity is representative of that seen in human skin.

Development and validation of clinical prediction models for mortality, functional outcome and cognitive impairment after stroke: a study protocol

PubMed Central

Fahey, Marion; Rudd, Anthony; Béjot, Yannick; Wolfe, Charles; Douiri, Abdel

2017-01-01

Introduction Stroke is a leading cause of adult disability and death worldwide. The neurological impairments associated with stroke prevent patients from performing basic daily activities and have enormous impact on families and caregivers. Practical and accurate tools to assist in predicting outcome after stroke at patient level can provide significant aid for patient management. Furthermore, prediction models of this kind can be useful for clinical research, health economics, policymaking and clinical decision support. Methods 2869 patients with first-ever stroke from South London Stroke Register (SLSR) (1995–2004) will be included in the development cohort. We will use information captured after baseline to construct multilevel models and a Cox proportional hazard model to predict cognitive impairment, functional outcome and mortality up to 5 years after stroke. Repeated random subsampling validation (Monte Carlo cross-validation) will be evaluated in model development. Data from participants recruited to the stroke register (2005–2014) will be used for temporal validation of the models. Data from participants recruited to the Dijon Stroke Register (1985–2015) will be used for external validation. Discrimination, calibration and clinical utility of the models will be presented. Ethics Patients, or for patients who cannot consent their relatives, gave written informed consent to participate in stroke-related studies within the SLSR. The SLSR design was approved by the ethics committees of Guy’s and St Thomas’ NHS Foundation Trust, Kings College Hospital, Queens Square and Westminster Hospitals (London). The Dijon Stroke Registry was approved by the Comité National des Registres and the InVS and has authorisation of the Commission Nationale de l’Informatique et des Libertés. PMID:28821511

Evaluation of Tier 5 Medical Training Initiative opportunities in dentistry.

PubMed

Wilson, M A; Burke, M

2012-03-09

This paper reviews the first two years of overseas postgraduate dental placements in the UK under the Medical Training Initiative (MTI), which is part of Tier 5 government authorised exchange. Details of the objectives of the programme, the trainees appointed, specialty areas studied and length of training are described. The methods used for assessing the training are reported. It is concluded that the objectives of the MTI have been met in dentistry and that Tier 5 provides a valuable opportunity for establishing international links in postgraduate clinical dentistry.

Development and validation of rapid multiresidue and multi-class analysis for antibiotics and anthelmintics in feed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry.

PubMed

Robert, Christelle; Brasseur, Pierre-Yves; Dubois, Michel; Delahaut, Philippe; Gillard, Nathalie

2016-08-01

A new multi-residue method for the analysis of veterinary drugs, namely amoxicillin, chlortetracycline, colistins A and B, doxycycline, fenbendazole, flubendazole, ivermectin, lincomycin, oxytetracycline, sulfadiazine, tiamulin, tilmicosin and trimethoprim, was developed and validated for feed. After acidic extraction, the samples were centrifuged, purified by SPE and analysed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Quantitative validation was done in accordance with the guidelines laid down in European Commission Decision 2002/657/CE. Matrix-matched calibration with internal standards was used to reduce matrix effects. The target level was set at the authorised carryover level (1%) and validation levels were set at 0.5%, 1% and 1.5%. Method performances were evaluated by the following parameters: linearity (0.986 < R(2) < 0.999), precision (repeatability < 12.4% and reproducibility < 14.0%), accuracy (89% < recovery < 107%), sensitivity, decision limit (CCα), detection capability (CCβ), selectivity and expanded measurement uncertainty (k = 2).This method has been used successfully for three years for routine monitoring of antibiotic residues in feeds during which period 20% of samples were found to exceed the 1% authorised carryover limit and were deemed non-compliant.

Development and evaluation of an articulated registration algorithm for human skeleton registration

NASA Astrophysics Data System (ADS)

Yip, Stephen; Perk, Timothy; Jeraj, Robert

2014-03-01

Accurate registration over multiple scans is necessary to assess treatment response of bone diseases (e.g. metastatic bone lesions). This study aimed to develop and evaluate an articulated registration algorithm for the whole-body skeleton registration in human patients. In articulated registration, whole-body skeletons are registered by auto-segmenting into individual bones using atlas-based segmentation, and then rigidly aligning them. Sixteen patients (weight = 80-117 kg, height = 168-191 cm) with advanced prostate cancer underwent the pre- and mid-treatment PET/CT scans over a course of cancer therapy. Skeletons were extracted from the CT images by thresholding (HU>150). Skeletons were registered using the articulated, rigid, and deformable registration algorithms to account for position and postural variability between scans. The inter-observers agreement in the atlas creation, the agreement between the manually and atlas-based segmented bones, and the registration performances of all three registration algorithms were all assessed using the Dice similarity index—DSIobserved, DSIatlas, and DSIregister. Hausdorff distance (dHausdorff) of the registered skeletons was also used for registration evaluation. Nearly negligible inter-observers variability was found in the bone atlases creation as the DSIobserver was 96 ± 2%. Atlas-based and manual segmented bones were in excellent agreement with DSIatlas of 90 ± 3%. Articulated (DSIregsiter = 75 ± 2%, dHausdorff = 0.37 ± 0.08 cm) and deformable registration algorithms (DSIregister = 77 ± 3%, dHausdorff = 0.34 ± 0.08 cm) considerably outperformed the rigid registration algorithm (DSIregsiter = 59 ± 9%, dHausdorff = 0.69 ± 0.20 cm) in the skeleton registration as the rigid registration algorithm failed to capture the skeleton flexibility in the joints. Despite superior skeleton registration performance, deformable registration algorithm failed to preserve the local rigidity of bones as over 60% of the skeletons were deformed. Articulated registration is superior to rigid and deformable registrations by capturing global flexibility while preserving local rigidity inherent in skeleton registration. Therefore, articulated registration can be employed to accurately register the whole-body human skeletons, and it enables the treatment response assessment of various bone diseases.

Evaluation of 4D-CT lung registration.

PubMed

Kabus, Sven; Klinder, Tobias; Murphy, Keelin; van Ginneken, Bram; van Lorenz, Cristian; Pluim, Josien P W

2009-01-01

Non-rigid registration accuracy assessment is typically performed by evaluating the target registration error at manually placed landmarks. For 4D-CT lung data, we compare two sets of landmark distributions: a smaller set primarily defined on vessel bifurcations as commonly described in the literature and a larger set being well-distributed throughout the lung volume. For six different registration schemes (three in-house schemes and three schemes frequently used by the community) the landmark error is evaluated and found to depend significantly on the distribution of the landmarks. In particular, lung regions near to the pleura show a target registration error three times larger than near-mediastinal regions. While the inter-method variability on the landmark positions is rather small, the methods show discriminating differences with respect to consistency and local volume change. In conclusion, both a well-distributed set of landmarks and a deformation vector field analysis are necessary for reliable non-rigid registration accuracy assessment.

Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective.

PubMed

Salmikangas, Paula; Schuessler-Lenz, Martina; Ruiz, Sol; Celis, Patrick; Reischl, Ilona; Menezes-Ferreira, Margarida; Flory, Egbert; Renner, Matthias; Ferry, Nicolas

2015-01-01

With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk-based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs.

Unauthorised absences from leave from an Australian security hospital.

PubMed

Scott, Russ; Goel, Vikram; Neillie, Darren; Stedman, Terry; Meehan, Tom

2014-04-01

To consider incidents relating to absences without permission from authorised leave from a security hospital. A retrospective audit over a 10-year period of all critical incidents relating to leave from the High Security Inpatient Services, Brisbane, Australia. There has been a low incidence of patients absenting themselves without permission from leave. Of the 12 patients who went absent without permission over the 10-year study period, only one patient was reported to have committed an offence and no patient seriously self-harmed. Attention to patient selection and risk management strategies have been effective in minimising the risk to patients and to the community as a direct result of absences without permission from authorised leave.

Determinants for successful marketing authorisation of orphan medicinal products in the EU.

PubMed

Putzeist, Michelle; Heemstra, Harald E; Garcia, Jordi Llinares; Mantel-Teeuwisse, Aukje K; Gispen-De Wied, Christine C; Hoes, Arno W; Leufkens, Hubert G M

2012-04-01

In 2010, the European Regulation for Orphan Medicinal Products (OMPs) was in force for ten years. In this study we assessed possible determinants of applications for OMPs in the EU since 2000 that are associated with a successful marketing authorisation. Our analysis shows that clinical trial characteristics such as demonstrating convincing evidence of a beneficial effect on the primary endpoint, the selection of a clinically relevant endpoint, providing RCT data as pivotal study evidence and the submission of sound dose finding data are critical success factors. In addition, high medical need seems to counterweigh uncertainties about the scientific evidence in the benefit-risk assessment of OMPs. Copyright © 2011 Elsevier Ltd. All rights reserved.

Drug evaluation in children 10years after the European pediatric regulation current challenges and perspectives.

PubMed

Élie, Valery; Leroux, Stéphanie; Kaguelidou, Florentia; Jacqz-Aigrain, Evelyne

2018-04-01

The European pediatric regulation, that entered into force in June 2007 with the objectives to improve the health of children in Europe, dramatically changed the regulatory environment of paediatric drug evaluation in Europe. The recent 10years European medicines agency (EMA) report showed that the number of paediatric trials increased and that 238 new medicines and indications for use in children were authorised in the EU. However, results remain constrated and futur developments require european collaborations beween all experts in developmental pharmacology, drug evaluation and trial conduct, training, all aspects already considered in different EU paediatric programs. Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Comparative Evaluation of Registration Algorithms in Different Brain Databases With Varying Difficulty: Results and Insights

PubMed Central

Akbari, Hamed; Bilello, Michel; Da, Xiao; Davatzikos, Christos

2015-01-01

Evaluating various algorithms for the inter-subject registration of brain magnetic resonance images (MRI) is a necessary topic receiving growing attention. Existing studies evaluated image registration algorithms in specific tasks or using specific databases (e.g., only for skull-stripped images, only for single-site images, etc.). Consequently, the choice of registration algorithms seems task- and usage/parameter-dependent. Nevertheless, recent large-scale, often multi-institutional imaging-related studies create the need and raise the question whether some registration algorithms can 1) generally apply to various tasks/databases posing various challenges; 2) perform consistently well, and while doing so, 3) require minimal or ideally no parameter tuning. In seeking answers to this question, we evaluated 12 general-purpose registration algorithms, for their generality, accuracy and robustness. We fixed their parameters at values suggested by algorithm developers as reported in the literature. We tested them in 7 databases/tasks, which present one or more of 4 commonly-encountered challenges: 1) inter-subject anatomical variability in skull-stripped images; 2) intensity homogeneity, noise and large structural differences in raw images; 3) imaging protocol and field-of-view (FOV) differences in multi-site data; and 4) missing correspondences in pathology-bearing images. Totally 7,562 registrations were performed. Registration accuracies were measured by (multi-)expert-annotated landmarks or regions of interest (ROIs). To ensure reproducibility, we used public software tools, public databases (whenever possible), and we fully disclose the parameter settings. We show evaluation results, and discuss the performances in light of algorithms’ similarity metrics, transformation models and optimization strategies. We also discuss future directions for the algorithm development and evaluations. PMID:24951685

Pharmaceutical issues during the review of European Marketing Authorisation Applications in Malta.

PubMed

Chetcuti, Michael; Serracino-Inglott, Anthony; Flores, Gavril; Borg, John J

2018-07-01

The aim of this study was to identify pharmaceutical issues encountered during regulatory review in European Procedures. A database of issues from Day 70 assessment reports of 150 EU procedures was compiled; most procedures were for generics (108). Frequencies of common deficiencies have been calculated and summarised for use of all stakeholders. Out of the 150 procedures reviewed, covering 309 products, a total of 4796 concerns were identified. Of these concerns, 167 were Potential Serious Risks to Public Health, 67 were raised on drug substance and 100 on the drug product. The distribution of total concerns was as follows: 2168 concerns on drug substance and 2584 on drug product. Most concerns raised were on control of drug substance and drug product (834 & 626 for 3.2.S.4 and 3.2.P.5, respectively), followed by concerns on the manufacturing (482 & 564 for 3.2.S.2 and 3.2.P.3, respectively) and stability 147 & 398 for 3.2.S.7 and 3.2.P.8, respectively). In conclusion, the frequencies and trends of identified deficiencies together with their impact were discussed from a regulatory point of view. The main findings indicate that applicants would benefit from following published guidelines so that delays in the registration of medicines could be avoided.

From wastewater to fertilisers--Technical overview and critical review of European legislation governing phosphorus recycling.

PubMed

Hukari, Sirja; Hermann, Ludwig; Nättorp, Anders

2016-01-15

The present paper is based on an analysis of the EU legislation regulating phosphorus recovery and recycling from wastewater stream, in particular as fertiliser. To recover phosphorus, operators need to deal with market regulations, health and environment protection laws. Often, several permits and lengthy authorisation processes for both installation (e.g. environmental impact assessment) and the recovered phosphorus (e.g. End-of-Waste, REACH) are required. Exemptions to certain registration processes for recoverers are in place but rarely applied. National solutions are often needed. Emerging recovery and recycling sectors are affected by legislation in different ways: Wastewater treatment plants are obliged to remove phosphorus but may also recover it in low quantities for operational reasons. Permit processes allowing recovery and recycling operations next to water purification should thus be rationalised. In contrast, the fertiliser industry relies on legal quality requirements, ensuring their market reputation. For start-ups, raw-material sourcing and related legislation will be the key. Phosphorus recycling is governed by fragmented decision-making in regional administrations. Active regulatory support, such as recycling obligation or subsidies, is lacking. Legislation harmonisation, inclusion of recycled phosphorus in existing fertiliser regulations and support of new operators would speed up market penetration of novel technologies, reduce phosphorus losses and safeguard European quality standards.

Acceptance test of a commercially available software for automatic image registration of computed tomography (CT), magnetic resonance imaging (MRI) and 99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography (SPECT) brain images.

PubMed

Loi, Gianfranco; Dominietto, Marco; Manfredda, Irene; Mones, Eleonora; Carriero, Alessandro; Inglese, Eugenio; Krengli, Marco; Brambilla, Marco

2008-09-01

This note describes a method to characterize the performances of image fusion software (Syntegra) with respect to accuracy and robustness. Computed tomography (CT), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) studies were acquired from two phantoms and 10 patients. Image registration was performed independently by two couples composed of one radiotherapist and one physicist by means of superposition of anatomic landmarks. Each couple performed jointly and saved the registration. The two solutions were averaged to obtain the gold standard registration. A new set of estimators was defined to identify translation and rotation errors in the coordinate axes, independently from point position in image field of view (FOV). Algorithms evaluated were local correlation (LC) for CT-MRI, normalized mutual information (MI) for CT-MRI, and CT-SPECT registrations. To evaluate accuracy, estimator values were compared to limiting values for the algorithms employed, both in phantoms and in patients. To evaluate robustness, different alignments between images taken from a sample patient were produced and registration errors determined. LC algorithm resulted accurate in CT-MRI registrations in phantoms, but exceeded limiting values in 3 of 10 patients. MI algorithm resulted accurate in CT-MRI and CT-SPECT registrations in phantoms; limiting values were exceeded in one case in CT-MRI and never reached in CT-SPECT registrations. Thus, the evaluation of robustness was restricted to the algorithm of MI both for CT-MRI and CT-SPECT registrations. The algorithm of MI proved to be robust: limiting values were not exceeded with translation perturbations up to 2.5 cm, rotation perturbations up to 10 degrees and roto-translational perturbation up to 3 cm and 5 degrees.

Realistic simulated MRI and SPECT databases. Application to SPECT/MRI registration evaluation.

PubMed

Aubert-Broche, Berengere; Grova, Christophe; Reilhac, Anthonin; Evans, Alan C; Collins, D Louis

2006-01-01

This paper describes the construction of simulated SPECT and MRI databases that account for realistic anatomical and functional variability. The data is used as a gold-standard to evaluate four SPECT/MRI similarity-based registration methods. Simulation realism was accounted for using accurate physical models of data generation and acquisition. MRI and SPECT simulations were generated from three subjects to take into account inter-subject anatomical variability. Functional SPECT data were computed from six functional models of brain perfusion. Previous models of normal perfusion and ictal perfusion observed in Mesial Temporal Lobe Epilepsy (MTLE) were considered to generate functional variability. We studied the impact noise and intensity non-uniformity in MRI simulations and SPECT scatter correction may have on registration accuracy. We quantified the amount of registration error caused by anatomical and functional variability. Registration involving ictal data was less accurate than registration involving normal data. MR intensity nonuniformity was the main factor decreasing registration accuracy. The proposed simulated database is promising to evaluate many functional neuroimaging methods, involving MRI and SPECT data.

Image Registration for Stability Testing of MEMS

NASA Technical Reports Server (NTRS)

Memarsadeghi, Nargess; LeMoigne, Jacqueline; Blake, Peter N.; Morey, Peter A.; Landsman, Wayne B.; Chambers, Victor J.; Moseley, Samuel H.

2011-01-01

Image registration, or alignment of two or more images covering the same scenes or objects, is of great interest in many disciplines such as remote sensing, medical imaging. astronomy, and computer vision. In this paper, we introduce a new application of image registration algorithms. We demonstrate how through a wavelet based image registration algorithm, engineers can evaluate stability of Micro-Electro-Mechanical Systems (MEMS). In particular, we applied image registration algorithms to assess alignment stability of the MicroShutters Subsystem (MSS) of the Near Infrared Spectrograph (NIRSpec) instrument of the James Webb Space Telescope (JWST). This work introduces a new methodology for evaluating stability of MEMS devices to engineers as well as a new application of image registration algorithms to computer scientists.

Development and inter-laboratory assessment of droplet digital PCR assays for multiplex quantification of 15 genetically modified soybean lines.

PubMed

Košir, Alexandra Bogožalec; Spilsberg, Bjørn; Holst-Jensen, Arne; Žel, Jana; Dobnik, David

2017-08-17

Quantification of genetically modified organisms (GMOs) in food and feed products is often required for their labelling or for tolerance thresholds. Standard-curve-based simplex quantitative polymerase chain reaction (qPCR) is the prevailing technology, which is often combined with screening analysis. With the rapidly growing number of GMOs on the world market, qPCR analysis becomes laborious and expensive. Innovative cost-effective approaches are therefore urgently needed. Here, we report the development and inter-laboratory assessment of multiplex assays to quantify GMO soybean using droplet digital PCR (ddPCR). The assays were developed to facilitate testing of foods and feed for compliance with current GMO regulations in the European Union (EU). Within the EU, the threshold for labelling is 0.9% for authorised GMOs per ingredient. Furthermore, the EU has set a technical zero tolerance limit of 0.1% for certain unauthorised GMOs. The novel multiplex ddPCR assays developed target 11 GMO soybean lines that are currently authorised, and four that are tolerated, pending authorisation in the EU. Potential significant improvements in cost efficiency are demonstrated. Performance was assessed for the critical parameters, including limits of detection and quantification, and trueness, repeatability, and robustness. Inter-laboratory performance was also determined on a number of proficiency programme and real-life samples.

Investigation assessing the publicly available evidence supporting postmarketing withdrawals, revocations and suspensions of marketing authorisations in the EU since 2012

PubMed Central

Lynn, Elizabeth; Shakir, Saad

2018-01-01

Objectives To assess the sources of publicly available evidence supporting withdrawal, revocation or suspension of marketing authorisations (‘regulatory actions’) due to safety reasons in the EU since 2012 and to investigate the time taken since initial marketing authorisation to reach these regulatory decisions. Setting This investigation examined the sources of evidence supporting 18 identified prescription medicinal products which underwent regulatory action due to safety reasons within the EU in the period 1 July 2012 to 31 December 2016. Results Eighteen single or combined active substances (‘medicinal products’) withdrawn, revoked or suspended within the EU for safety reasons between 2012 and 2016 met the inclusion criteria. Case reports were most commonly cited, supporting 94.4% of regulatory actions (n=17), followed by randomised controlled trial, meta-analyses, animal and in vitro, ex vivo or in silico study designs, each cited in 72.2% of regulatory actions (n=13). Epidemiological study designs were least commonly cited (n=8, 44.4%). Multiple sources of evidence contributed to 94.4% of regulatory decisions (n=17). Death was the most common adverse drug reaction leading to regulatory action (n=5; 27.8%), with four of these related to medication error or overdose. Median (IQR) time taken to reach a decision from the start of regulatory review was found to be 204.5 days (143, 535 days) and decreased across the study period. Duration of marketing prior to regulatory action, from the medicinal product’s authorisation date, increased across the period 2012–2016. Conclusions The sources of evidence supporting pharmacovigilance regulatory activities appear to have changed since implementation of Directive 2010/84/EU and Regulation (EU) No. 1235/2010. This, together with a small improvement in regulatory efficiency, suggests progress towards more rapid regulatory decisions based on more robust evidence. Future research should continue to monitor sources of evidence supporting regulatory decisions and the time taken to reach these decisions over time. PMID:29362275

Dual-projection 3D-2D registration for surgical guidance: preclinical evaluation of performance and minimum angular separation

NASA Astrophysics Data System (ADS)

Uneri, A.; Otake, Y.; Wang, A. S.; Kleinszig, G.; Vogt, S.; Gallia, G. L.; Rigamonti, D.; Wolinsky, J.-P.; Gokaslan, Ziya L.; Khanna, A. J.; Siewerdsen, J. H.

2014-03-01

An algorithm for 3D-2D registration of CT and x-ray projections has been developed using dual projection views to provide 3D localization with accuracy exceeding that of conventional tracking systems. The registration framework employs a normalized gradient information (NGI) similarity metric and covariance matrix adaptation evolution strategy (CMAES) to solve for the patient pose in 6 degrees of freedom. Registration performance was evaluated in anthropomorphic head and chest phantoms, as well as a human torso cadaver, using C-arm projection views acquired at angular separations (Δ𝜃) ranging 0-178°. Registration accuracy was assessed in terms target registration error (TRE) and compared to that of an electromagnetic tracker. Studies evaluated the influence of C-arm magnification, x-ray dose, and preoperative CT slice thickness on registration accuracy and the minimum angular separation required to achieve TRE ~2 mm. The results indicate that Δ𝜃 as small as 10-20° is adequate to achieve TRE <2 mm with 95% confidence, comparable or superior to that of commercial trackers. The method allows direct registration of preoperative CT and planning data to intraoperative fluoroscopy, providing 3D localization free from conventional limitations associated with external fiducial markers, stereotactic frames, trackers, and manual registration. The studies support potential application to percutaneous spine procedures and intracranial neurosurgery.

3D-2D registration for surgical guidance: effect of projection view angles on registration accuracy

NASA Astrophysics Data System (ADS)

Uneri, A.; Otake, Y.; Wang, A. S.; Kleinszig, G.; Vogt, S.; Khanna, A. J.; Siewerdsen, J. H.

2014-01-01

An algorithm for intensity-based 3D-2D registration of CT and x-ray projections is evaluated, specifically using single- or dual-projection views to provide 3D localization. The registration framework employs the gradient information similarity metric and covariance matrix adaptation evolution strategy to solve for the patient pose in six degrees of freedom. Registration performance was evaluated in an anthropomorphic phantom and cadaver, using C-arm projection views acquired at angular separation, Δθ, ranging from ˜0°-180° at variable C-arm magnification. Registration accuracy was assessed in terms of 2D projection distance error and 3D target registration error (TRE) and compared to that of an electromagnetic (EM) tracker. The results indicate that angular separation as small as Δθ ˜10°-20° achieved TRE <2 mm with 95% confidence, comparable or superior to that of the EM tracker. The method allows direct registration of preoperative CT and planning data to intraoperative fluoroscopy, providing 3D localization free from conventional limitations associated with external fiducial markers, stereotactic frames, trackers and manual registration.

Responsibilities of regulatory agencies in the marketing of antimicrobials.

PubMed

Grein, K

2012-04-01

The regulatory agencies' main responsibility regarding the marketing of veterinary medicinal products is to ensure that the products have a marketing authorisation with specific conditions of use adequate to ensure the quality, safety and efficacy of the product under consideration. In addition, control and surveillance systems are necessary to allow monitoring of the product after it has been authorised. In respectto antimicrobials, specific consideration must be given to minimising resistance development and retaining the effectiveness of these drugs for the treatment of humans and animals. Surveillance programmes should be in place to follow trends in resistance development, as well as in the consumption of veterinary antimicrobials, in order to provide for science-based policy recommendations regarding public and animal health.

Open-source image registration for MRI-TRUS fusion-guided prostate interventions.

PubMed

Fedorov, Andriy; Khallaghi, Siavash; Sánchez, C Antonio; Lasso, Andras; Fels, Sidney; Tuncali, Kemal; Sugar, Emily Neubauer; Kapur, Tina; Zhang, Chenxi; Wells, William; Nguyen, Paul L; Abolmaesumi, Purang; Tempany, Clare

2015-06-01

We propose two software tools for non-rigid registration of MRI and transrectal ultrasound (TRUS) images of the prostate. Our ultimate goal is to develop an open-source solution to support MRI-TRUS fusion image guidance of prostate interventions, such as targeted biopsy for prostate cancer detection and focal therapy. It is widely hypothesized that image registration is an essential component in such systems. The two non-rigid registration methods are: (1) a deformable registration of the prostate segmentation distance maps with B-spline regularization and (2) a finite element-based deformable registration of the segmentation surfaces in the presence of partial data. We evaluate the methods retrospectively using clinical patient image data collected during standard clinical procedures. Computation time and Target Registration Error (TRE) calculated at the expert-identified anatomical landmarks were used as quantitative measures for the evaluation. The presented image registration tools were capable of completing deformable registration computation within 5 min. Average TRE was approximately 3 mm for both methods, which is comparable with the slice thickness in our MRI data. Both tools are available under nonrestrictive open-source license. We release open-source tools that may be used for registration during MRI-TRUS-guided prostate interventions. Our tools implement novel registration approaches and produce acceptable registration results. We believe these tools will lower the barriers in development and deployment of interventional research solutions and facilitate comparison with similar tools.

Evaluation of 4-dimensional Computed Tomography to 4-dimensional Cone-Beam Computed Tomography Deformable Image Registration for Lung Cancer Adaptive Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balik, Salim; Weiss, Elisabeth; Jan, Nuzhat

2013-06-01

Purpose: To evaluate 2 deformable image registration (DIR) algorithms for the purpose of contour mapping to support image-guided adaptive radiation therapy with 4-dimensional cone-beam CT (4DCBCT). Methods and Materials: One planning 4D fan-beam CT (4DFBCT) and 7 weekly 4DCBCT scans were acquired for 10 locally advanced non-small cell lung cancer patients. The gross tumor volume was delineated by a physician in all 4D images. End-of-inspiration phase planning 4DFBCT was registered to the corresponding phase in weekly 4DCBCT images for day-to-day registrations. For phase-to-phase registration, the end-of-inspiration phase from each 4D image was registered to the end-of-expiration phase. Two DIR algorithms—smallmore » deformation inverse consistent linear elastic (SICLE) and Insight Toolkit diffeomorphic demons (DEMONS)—were evaluated. Physician-delineated contours were compared with the warped contours by using the Dice similarity coefficient (DSC), average symmetric distance, and false-positive and false-negative indices. The DIR results are compared with rigid registration of tumor. Results: For day-to-day registrations, the mean DSC was 0.75 ± 0.09 with SICLE, 0.70 ± 0.12 with DEMONS, 0.66 ± 0.12 with rigid-tumor registration, and 0.60 ± 0.14 with rigid-bone registration. Results were comparable to intraobserver variability calculated from phase-to-phase registrations as well as measured interobserver variation for 1 patient. SICLE and DEMONS, when compared with rigid-bone (4.1 mm) and rigid-tumor (3.6 mm) registration, respectively reduced the average symmetric distance to 2.6 and 3.3 mm. On average, SICLE and DEMONS increased the DSC to 0.80 and 0.79, respectively, compared with rigid-tumor (0.78) registrations for 4DCBCT phase-to-phase registrations. Conclusions: Deformable image registration achieved comparable accuracy to reported interobserver delineation variability and higher accuracy than rigid-tumor registration. Deformable image registration performance varied with the algorithm and the patient.« less

3D-2D registration in endovascular image-guided surgery: evaluation of state-of-the-art methods on cerebral angiograms.

PubMed

Mitrović, Uroš; Likar, Boštjan; Pernuš, Franjo; Špiclin, Žiga

2018-02-01

Image guidance for minimally invasive surgery is based on spatial co-registration and fusion of 3D pre-interventional images and treatment plans with the 2D live intra-interventional images. The spatial co-registration or 3D-2D registration is the key enabling technology; however, the performance of state-of-the-art automated methods is rather unclear as they have not been assessed under the same test conditions. Herein we perform a quantitative and comparative evaluation of ten state-of-the-art methods for 3D-2D registration on a public dataset of clinical angiograms. Image database consisted of 3D and 2D angiograms of 25 patients undergoing treatment for cerebral aneurysms or arteriovenous malformations. On each of the datasets, highly accurate "gold-standard" registrations of 3D and 2D images were established based on patient-attached fiducial markers. The database was used to rigorously evaluate ten state-of-the-art 3D-2D registration methods, namely two intensity-, two gradient-, three feature-based and three hybrid methods, both for registration of 3D pre-interventional image to monoplane or biplane 2D images. Intensity-based methods were most accurate in all tests (0.3 mm). One of the hybrid methods was most robust with 98.75% of successful registrations (SR) and capture range of 18 mm for registrations of 3D to biplane 2D angiograms. In general, registration accuracy was similar whether registration of 3D image was performed onto mono- or biplanar 2D images; however, the SR was substantially lower in case of 3D to monoplane 2D registration. Two feature-based and two hybrid methods had clinically feasible execution times in the order of a second. Performance of methods seems to fall below expectations in terms of robustness in case of registration of 3D to monoplane 2D images, while translation into clinical image guidance systems seems readily feasible for methods that perform registration of the 3D pre-interventional image onto biplanar intra-interventional 2D images.

Policies and availability of orphan medicines in outpatient care in 24 European countries.

PubMed

Sarnola, Kati; Ahonen, Riitta; Martikainen, Jaana E; Timonen, Johanna

2018-04-09

To assess pricing and reimbursement policies specific to orphan medicines and the availability and distribution settings of ten recently authorised medicinal products suitable for outpatient care with orphan status and centralised marketing authorisation in Europe, and whether patients receive these products free of charge or have to pay some or all of the costs themselves. Web survey to authorities and representatives of third party payers in the Pharmaceutical Pricing and Reimbursement Information (PPRI) network in April 2016. In most of the 24 countries, special policies were not implemented in the assessment of reimbursement status (22 countries) or in the pricing (20 countries) of orphan medicines. An average of five of the ten recently authorised products per country were available for outpatient care. Products were dispensed from community pharmacies in eight countries and from health care units in five countries. In four countries, both distribution settings were used. When products were dispensed from community pharmacies, patients typically paid some of the price themselves. Products dispensed from health care units were often free of charge for patients. Most European countries had not implemented pricing and reimbursement policies specific to orphan medicines. The availability of orphan products varied between countries. It is important to discuss whether orphan medicines should be considered as a separate group in the reimbursement regulations in order to secure patient access to these medicines.

Keeping mum about dad: "contracts" to protect gamete donor anonymity.

PubMed

Rees, Anne

2012-06-01

This article considers the legal status of so-called contracts for anonymity between fertility clinics and donors of gametes that were made in the period before legislation authorising disclosure. It notes that while clinics frequently cite the existence of these "contracts" to argue against retrospective legislation authorising disclosure of the donor's identity, they may be nothing more than one-sided statements of informed consent. However, the article notes that even if an agreement between a donor and a clinic is not contractual, it does not follow that a person conceived through assisted reproductive technology has any right of access to the identity of the donor. The writer has not been able to locate examples of written promises by the clinics promising anonymity. There are written promises by the donors not to seek the identity of the recipients. These promises do not bind the resulting offspring nor do they appear to be supported by consideration. The article suggests that the basis for any individual donor to restrain a clinic from revealing their identity may be found in promissory estoppel. Nevertheless, there is no real issue in Australia concerning clinics revealing these details absent legislative authority. The issue is whether parliaments will legislate to authorise the disclosure. The article notes that it would be rare for parliaments to legislate to overturn existing legal contracts but suggests that the contract argument may not be as strong as has been thought.

Multimodality Non-Rigid Image Registration for Planning, Targeting and Monitoring during CT-guided Percutaneous Liver Tumor Cryoablation

PubMed Central

Elhawary, Haytham; Oguro, Sota; Tuncali, Kemal; Morrison, Paul R.; Tatli, Servet; Shyn, Paul B.; Silverman, Stuart G.; Hata, Nobuhiko

2010-01-01

Rationale and Objectives To develop non-rigid image registration between pre-procedure contrast enhanced MR images and intra-procedure unenhanced CT images, to enhance tumor visualization and localization during CT-guided liver tumor cryoablation procedures. Materials and Methods After IRB approval, a non-rigid registration (NRR) technique was evaluated with different pre-processing steps and algorithm parameters and compared to a standard rigid registration (RR) approach. The Dice Similarity Coefficient (DSC), Target Registration Error (TRE), 95% Hausdorff distance (HD) and total registration time (minutes) were compared using a two-sided Student’s t-test. The entire registration method was then applied during five CT-guided liver cryoablation cases with the intra-procedural CT data transmitted directly from the CT scanner, with both accuracy and registration time evaluated. Results Selected optimal parameters for registration were section thickness of 5mm, cropping the field of view to 66% of its original size, manual segmentation of the liver, B-spline control grid of 5×5×5 and spatial sampling of 50,000 pixels. Mean 95% HD of 3.3mm (2.5x improvement compared to RR, p<0.05); mean DSC metric of 0.97 (13% increase); and mean TRE of 4.1mm (2.7x reduction) were measured. During the cryoablation procedure registration between the pre-procedure MR and the planning intra-procedure CT took a mean time of 10.6 minutes, the MR to targeting CT image took 4 minutes and MR to monitoring CT took 4.3 minutes. Mean registration accuracy was under 3.4mm. Conclusion Non-rigid registration allowed improved visualization of the tumor during interventional planning, targeting and evaluation of tumor coverage by the ice ball. Future work is focused on reducing segmentation time to make the method more clinically acceptable. PMID:20817574

Evaluating a community-based dental registration program for preschool children living in areas of high social deprivation.

PubMed

Yuan, S; Kerr, G; Salmon, K; Speedy, P; Freeman, R

2007-03-01

This was to evaluate the effectiveness of a community-based program to promote dental registration and access to dental services for preschool children residing in areas of high social deprivation using monthly registration data provided by the Central Services Agency (CSA). A quasi-experimental non-equivalent two group comparison. Areas of high social deprivation in the greater Belfast area. The dental registration program was conducted by community-based nurses (health visitors). The health visitors provided oral health education and distributed registration vouchers to mothers of new babies during home visits. The mothers exchanged the vouchers for motivational materials from the participating dental practices. Preschool child registration data were obtained from the CSA to evaluate the effectiveness of the program. The registration rates were significantly greater 5 months after the program for 0-2-year old children residing in the intervention wards compared with control wards. During the program the rate of change in registration for the 0-2-year-old group residing in the intervention wards was significantly greater compared with those residing in the control wards (t [DF:21]=4.26: p<0.001). There was a significant increase in registration rate 5 months after the program compared with 6 months before the study started for the 0-2 year old group residing in the intervention wards compared with those residing in the control wards (t [df: 21]=3.33: P=0.003). There were no equivalent effects for the 3-5-year old group. The adoption of a community-based approach assisted in promoting dental registration and access to dental services for preschool children residing in areas of high social deprivation.

Effect of iris registration on outcomes of FEMTOLASIK for myopia and myopic astigmatism.

PubMed

Ghoreishi, Mohammad; Beni, Zahra Naderi; Beni, Afsaneh Naderi; Kianersi, Farzan

2017-09-05

To compare the visual and refractive outcomes after FEMTOLASIK with and without iris registration. In this randomized, prospective, comparative, contralateral eye study, 118 eyes of 59 patients with myopia and myopic astigmatism underwent LASIK using the Femto LDV femtosecond laser (160 µm) and the MEL80 with or without iris registration. For each patient, iris registration FEMTOLASIK was performed on one eye and non-iris registration FEMTOLASIK was performed on the other eye, assigned at random. Patients were evaluated before and 12 months. Uncorrected visual acuity, best-corrected visual acuity, manifest refraction, contrast sensitivity, and higher-order aberrations (HOAs) were evaluated. At 12 months, the mean UDVA was 0.002 ± 0.07 logMAR (20/19) in iris registration eyes and 0.00 ± 0.06 logMAR (20/24) in non-iris registration eyes (P = 0.9). 61% of iris registration eyes and 71.2% of non-iris registration eyes achieved a UDVA of 20/20 or better (P = 0.31); 98.3% of eyes with the iris registration FEMTOLASIK and 94.9% with the non-iris registration FEMTOLASIK were within ±0.50 D from emmetropia (P = 0.71). No statistically significant difference was found in postoperative contrast sensitivity between groups at 3, 6, 12, or 18 cycles/degree (P > 0.05). There was significant increase in total HOA root mean square in two groups. The mean error magnitude of surgically induced astigmatism 12 months postoperatively was -0.33 in iris registration eyes and -0.24 in the non-iris registration eyes (P = 0.36). FEMTOLASIK with and without iris registration provides similar results in myopic and myopic astigmatism patients.

Non-invasive breast biopsy method using GD-DTPA contrast enhanced MRI series and F-18-FDG PET/CT dynamic image series

NASA Astrophysics Data System (ADS)

Magri, Alphonso William

This study was undertaken to develop a nonsurgical breast biopsy from Gd-DTPA Contrast Enhanced Magnetic Resonance (CE-MR) images and F-18-FDG PET/CT dynamic image series. A five-step process was developed to accomplish this. (1) Dynamic PET series were nonrigidly registered to the initial frame using a finite element method (FEM) based registration that requires fiducial skin markers to sample the displacement field between image frames. A commercial FEM package (ANSYS) was used for meshing and FEM calculations. Dynamic PET image series registrations were evaluated using similarity measurements SAVD and NCC. (2) Dynamic CE-MR series were nonrigidly registered to the initial frame using two registration methods: a multi-resolution free-form deformation (FFD) registration driven by normalized mutual information, and a FEM-based registration method. Dynamic CE-MR image series registrations were evaluated using similarity measurements, localization measurements, and qualitative comparison of motion artifacts. FFD registration was found to be superior to FEM-based registration. (3) Nonlinear curve fitting was performed for each voxel of the PET/CT volume of activity versus time, based on a realistic two-compartmental Patlak model. Three parameters for this model were fitted; two of them describe the activity levels in the blood and in the cellular compartment, while the third characterizes the washout rate of F-18-FDG from the cellular compartment. (4) Nonlinear curve fitting was performed for each voxel of the MR volume of signal intensity versus time, based on a realistic two-compartment Brix model. Three parameters for this model were fitted: rate of Gd exiting the compartment, representing the extracellular space of a lesion; rate of Gd exiting a blood compartment; and a parameter that characterizes the strength of signal intensities. Curve fitting used for PET/CT and MR series was accomplished by application of the Levenburg-Marquardt nonlinear regression algorithm. The best-fit parameters were used to create 3D parametric images. Compartmental modeling evaluation was based on the ability of parameter values to differentiate between tissue types. This evaluation was used on registered and unregistered image series and found that registration improved results. (5) PET and MR parametric images were registered through FEM- and FFD-based registration. Parametric image registration was evaluated using similarity measurements, target registration error, and qualitative comparison. Comparing FFD and FEM-based registration results showed that the FEM method is superior. This five-step process constitutes a novel multifaceted approach to a nonsurgical breast biopsy that successfully executes each step. Comparison of this method to biopsy still needs to be done with a larger set of subject data.

Student Evaluation of Summer Orientation, Learning, Advising, and Registration.

ERIC Educational Resources Information Center

Allen, David F.

Incoming freshmen at the University of North Carolina at Wilmington completed evaluations of their two-day orientation. The Orientation Evaluation is administered to freshmen who have chosen to participate in one of three sessions: Summer Orientation, Learning, Advising, and Registration sessions (SOLAR). A total of 166 students completed the…

Multimodal Image Registration through Simultaneous Segmentation.

PubMed

Aganj, Iman; Fischl, Bruce

2017-11-01

Multimodal image registration facilitates the combination of complementary information from images acquired with different modalities. Most existing methods require computation of the joint histogram of the images, while some perform joint segmentation and registration in alternate iterations. In this work, we introduce a new non-information-theoretical method for pairwise multimodal image registration, in which the error of segmentation - using both images - is considered as the registration cost function. We empirically evaluate our method via rigid registration of multi-contrast brain magnetic resonance images, and demonstrate an often higher registration accuracy in the results produced by the proposed technique, compared to those by several existing methods.

CAT--the new committee for advanced therapies at the European Medicines Agency.

PubMed

Celis, P

2010-01-01

The Regulation on Advanced Therapies (Regulation (EC) 1394/2007) establishes a new scientific committee, the Committee for Advanced Therapies (CAT), at the European Medicines Agency. The CAT is composed of experts in the field of Advanced Therapy Medicinal Products (ATMPs)--gene and cell therapy and tissue engineered products--and is responsible for the evaluation of the marketing authorisation applications for this novel class of products. The CAT is also involved in all scientific advice on ATMPs and in two new regulatory procedures for ATMPs, the classification and the certification procedures. The CAT will also play a key role in early contacts with developers of ATMPs.

Adaptive Diffeomorphic Multiresolution Demons and Their Application to Same Modality Medical Image Registration with Large Deformation

PubMed Central

Wang, Chang; Ren, Qiongqiong; Qin, Xin

2018-01-01

Diffeomorphic demons can guarantee smooth and reversible deformation and avoid unreasonable deformation. However, the number of iterations needs to be set manually, and this greatly influences the registration result. In order to solve this problem, we proposed adaptive diffeomorphic multiresolution demons in this paper. We used an optimized framework with nonrigid registration and diffeomorphism strategy, designed a similarity energy function based on grey value, and stopped iterations adaptively. This method was tested by synthetic image and same modality medical image. Large deformation was simulated by rotational distortion and extrusion transform, medical image registration with large deformation was performed, and quantitative analyses were conducted using the registration evaluation indexes, and the influence of different driving forces and parameters on the registration result was analyzed. The registration results of same modality medical images were compared with those obtained using active demons, additive demons, and diffeomorphic demons. Quantitative analyses showed that the proposed method's normalized cross-correlation coefficient and structural similarity were the highest and mean square error was the lowest. Medical image registration with large deformation could be performed successfully; evaluation indexes remained stable with an increase in deformation strength. The proposed method is effective and robust, and it can be applied to nonrigid registration of same modality medical images with large deformation.

Adaptive Diffeomorphic Multiresolution Demons and Their Application to Same Modality Medical Image Registration with Large Deformation.

PubMed

Wang, Chang; Ren, Qiongqiong; Qin, Xin; Yu, Yi

2018-01-01

Diffeomorphic demons can guarantee smooth and reversible deformation and avoid unreasonable deformation. However, the number of iterations needs to be set manually, and this greatly influences the registration result. In order to solve this problem, we proposed adaptive diffeomorphic multiresolution demons in this paper. We used an optimized framework with nonrigid registration and diffeomorphism strategy, designed a similarity energy function based on grey value, and stopped iterations adaptively. This method was tested by synthetic image and same modality medical image. Large deformation was simulated by rotational distortion and extrusion transform, medical image registration with large deformation was performed, and quantitative analyses were conducted using the registration evaluation indexes, and the influence of different driving forces and parameters on the registration result was analyzed. The registration results of same modality medical images were compared with those obtained using active demons, additive demons, and diffeomorphic demons. Quantitative analyses showed that the proposed method's normalized cross-correlation coefficient and structural similarity were the highest and mean square error was the lowest. Medical image registration with large deformation could be performed successfully; evaluation indexes remained stable with an increase in deformation strength. The proposed method is effective and robust, and it can be applied to nonrigid registration of same modality medical images with large deformation.

Three-Dimensional Registration for Handheld Profiling Systems Based on Multiple Shot Structured Light

PubMed Central

Ayaz, Shirazi Muhammad; Kim, Min Young

2018-01-01

In this article, a multi-view registration approach for the 3D handheld profiling system based on the multiple shot structured light technique is proposed. The multi-view registration approach is categorized into coarse registration and point cloud refinement using the iterative closest point (ICP) algorithm. Coarse registration of multiple point clouds was performed using relative orientation and translation parameters estimated via homography-based visual navigation. The proposed system was evaluated using an artificial human skull and a paper box object. For the quantitative evaluation of the accuracy of a single 3D scan, a paper box was reconstructed, and the mean errors in its height and breadth were found to be 9.4 μm and 23 μm, respectively. A comprehensive quantitative evaluation and comparison of proposed algorithm was performed with other variants of ICP. The root mean square error for the ICP algorithm to register a pair of point clouds of the skull object was also found to be less than 1 mm. PMID:29642552

Guidelines, Criteria and Regulations for the Registration of Units and Qualifications for National Certificates and National Diplomas. Quality Assurance in Education and Training.

ERIC Educational Resources Information Center

New Zealand Qualifications Authority, Wellington.

This booklet contains guidelines for the registration of units and qualifications in New Zealand's National Qualifications Framework, a system of education and employment qualifications. An introduction provides an overview of registration, including endorsement, evaluation, and reregistration. Section 2 focuses on registration of unit standards.…

α-Information Based Registration of Dynamic Scans for Magnetic Resonance Cystography

PubMed Central

Han, Hao; Lin, Qin; Li, Lihong; Duan, Chaijie; Lu, Hongbing; Li, Haifang; Yan, Zengmin; Fitzgerald, John

2015-01-01

To continue our effort on developing magnetic resonance (MR) cystography, we introduce a novel non–rigid 3D registration method to compensate for bladder wall motion and deformation in dynamic MR scans, which are impaired by relatively low signal–to–noise ratio in each time frame. The registration method is developed on the similarity measure of α–information, which has the potential of achieving higher registration accuracy than the commonly-used mutual information (MI) measure for either mono-modality or multi-modality image registration. The α–information metric was also demonstrated to be superior to both the mean squares and the cross-correlation metrics in multi-modality scenarios. The proposed α–registration method was applied for bladder motion compensation via real patient studies, and its effect to the automatic and accurate segmentation of bladder wall was also evaluated. Compared with the prevailing MI-based image registration approach, the presented α–information based registration was more effective to capture the bladder wall motion and deformation, which ensured the success of the following bladder wall segmentation to achieve the goal of evaluating the entire bladder wall for detection and diagnosis of abnormality. PMID:26087506

The scope of the conscience-based exemption in Section 4(1) of the Abortion Act 1967: Doogan and Wood v NHS Greater Glasgow Health Board [2013] CSIH 36.

PubMed

Neal, Mary

2014-01-01

Doogan is a judgment of the Inner House of the Scottish Court of Session in an action brought by two midwives ('petitioners' at first instance and 'reclaimers' on appeal) for judicial review of a decision by Greater Glasgow and Clyde Health Board ('respondents'). At issue in the litigation was the scope of the conscience-based exemption contained in section 4(1) of the Abortion Act 1967, which included consideration of where the burden of managing the exemption should fall. The court of first instance (Outer House) had held that section 4(1), which exempts people with a conscientious objection from having to 'participate in any treatment authorised by this Act', ought to be read in light of section 1, which was the authorising provision. On the analysis adopted by the Outer House, any activity which was not unlawful before the 1967 Act came into force, and which therefore did not require to be authorised by section 1, was not covered by section 4(1). Roles which consisted of 'supervision, delegation, and support' were held not to fall within the scope of section 4(1) for this reason. The Inner House rejected the argument that the scope of the exemption in section 4(1) must be coextensive with the scope of the authorisation in section 1, and held that section 4(1) covered the 'whole process of treatment' given for the purpose of terminating a pregnancy. For the Inner House, therefore, 'supervision, delegation, and support' of staff directly involved in the abortion process did constitute the kind of 'participation' that a person could be exempted from under section 4(1). Moreover, the court took the view that the reclaimers' interpretation of section 4(1) was also to be preferred in terms of its likely management consequences. The appeal succeeded, and the Health Board has begun the process of appealing to the UK Supreme Court. © The Author [2014]. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of an in vitro test battery for assessing chemical effects on bovine germ cells under the ReProTect umbrella

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lazzari, Giovanna; Tessaro, Irene; Crotti, Gabriella

2008-12-15

Current European legislation for the registration and authorisation of chemicals (REACH) will require a dramatic increase in the use of animals for reproductive toxicity testing. Since one objective of REACH is to use vertebrates only as last resort, the development and validation of alternative methods is urgently needed. For this purpose ReProTect, an integrated research project funded by the European Union, joining together 33 partners with complementary expertise in reproductive toxicology, was designed. The study presented here describes a battery of two tests developed within ReProTect. The objective of these tests is the detection of chemical effects during the processesmore » of oocyte maturation and fertilisation in a bovine model. The corresponding toxicological endpoints are the reaching of metaphase II and the formation of the pronuclei respectively. Fifteen chemicals have been tested (Benzo[a]pyrene, Busulfan, Butylparaben, Cadmium Chloride, Carbendazim, Cycloheximide, Diethylstilbestrol, Genistein, Ionomycin, Ketoconazole, Lindane, Methylacetoacetate, Mifepristone, Nocodazole and DMSO as solvent) demonstrating high intra-laboratory reproducibility of the tests. Furthermore, the responses obtained in both tests, for several substances, had a good correlation with the available in vivo and in vitro data. These tests therefore, could predictably become part of an integrated testing strategy that combines the bovine models with additional in vitro tests, in order to predict chemical hazards on mammalian fertility.« less

Health risk assessment of exposures to a high molecular weight plasticizer present in automobile interiors.

PubMed

Perez, Angela L; Liong, Monty; Plotkin, Kevin; Rickabaugh, Keith P; Paustenbach, Dennis J

2017-01-01

This study provides an exposure and risk assessment of diundecyl phthalate (DUP), a high molecular weight phthalate plasticizer present in automobile interiors. Total daily intake of DUP was calculated from DUP measured in wipe samples from vehicle seats from six automobiles. Four of the vehicles exhibited atypical visible surface residue on the seats. Two vehicles with no visible surface residue were sampled as a comparison. DUP was the predominant organic compound identified in each of the wipes from all seats. A risk assessment of DUP via oral, dermal, and inhalation routes resulting from contact with automobile seats was conducted. The mean, standard deviation, and maximum DUP concentrations on the seats with visible surface residue were 6983 ± 7823 μg/100 cm 2 and 38300 μg/100 cm 2 , respectively. The mean and 95th percentile of the mean for daily cumulative dose of DUP for all exposure routes for the seats with no visible surface residue ranged from 7 × 10 -4 to 4 × 10 -3  mg/kg-day and from 8 × 10 -4 to 5 × 10 -3  mg/kg-day, respectively. For seats with visible surface residue, cumulative doses ranged from 2 × 10 -3 to 2 × 10 -2  mg/kg-day and from 4 × 10 -3 to 2 × 10 -2  mg/kg-day, respectively. The estimated daily intake (contact or absorbed dose) of DUP from automobile seats were far lower than the NOAELs reported in and derived from animal studies, and are well below the reported Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Derived No Effect Levels (DNELs) for the general population. Based on this analysis, using virtually any benchmark for evaluating safety, exposure to DUP via automobile seat covers did not pose a measureable increased health-risk in any population under any reasonably plausible exposure scenario. Copyright © 2016 Elsevier Ltd. All rights reserved.

EVALUATION OF REGISTRATION, COMPRESSION AND CLASSIFICATION ALGORITHMS

NASA Technical Reports Server (NTRS)

Jayroe, R. R.

1994-01-01

Several types of algorithms are generally used to process digital imagery such as Landsat data. The most commonly used algorithms perform the task of registration, compression, and classification. Because there are different techniques available for performing registration, compression, and classification, imagery data users need a rationale for selecting a particular approach to meet their particular needs. This collection of registration, compression, and classification algorithms was developed so that different approaches could be evaluated and the best approach for a particular application determined. Routines are included for six registration algorithms, six compression algorithms, and two classification algorithms. The package also includes routines for evaluating the effects of processing on the image data. This collection of routines should be useful to anyone using or developing image processing software. Registration of image data involves the geometrical alteration of the imagery. Registration routines available in the evaluation package include image magnification, mapping functions, partitioning, map overlay, and data interpolation. The compression of image data involves reducing the volume of data needed for a given image. Compression routines available in the package include adaptive differential pulse code modulation, two-dimensional transforms, clustering, vector reduction, and picture segmentation. Classification of image data involves analyzing the uncompressed or compressed image data to produce inventories and maps of areas of similar spectral properties within a scene. The classification routines available include a sequential linear technique and a maximum likelihood technique. The choice of the appropriate evaluation criteria is quite important in evaluating the image processing functions. The user is therefore given a choice of evaluation criteria with which to investigate the available image processing functions. All of the available evaluation criteria basically compare the observed results with the expected results. For the image reconstruction processes of registration and compression, the expected results are usually the original data or some selected characteristics of the original data. For classification processes the expected result is the ground truth of the scene. Thus, the comparison process consists of determining what changes occur in processing, where the changes occur, how much change occurs, and the amplitude of the change. The package includes evaluation routines for performing such comparisons as average uncertainty, average information transfer, chi-square statistics, multidimensional histograms, and computation of contingency matrices. This collection of routines is written in FORTRAN IV for batch execution and has been implemented on an IBM 360 computer with a central memory requirement of approximately 662K of 8 bit bytes. This collection of image processing and evaluation routines was developed in 1979.

SU-F-J-96: Comparison of Frame-Based and Mutual Information Registration Techniques for CT and MR Image Sets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popple, R; Bredel, M; Brezovich, I

Purpose: To compare the accuracy of CT-MR registration using a mutual information method with registration using a frame-based localizer box. Methods: Ten patients having the Leksell head frame and scanned with a modality specific localizer box were imported into the treatment planning system. The fiducial rods of the localizer box were contoured on both the MR and CT scans. The skull was contoured on the CT images. The MR and CT images were registered by two methods. The frame-based method used the transformation that minimized the mean square distance of the centroids of the contours of the fiducial rods frommore » a mathematical model of the localizer. The mutual information method used automated image registration tools in the TPS and was restricted to a volume-of-interest defined by the skull contours with a 5 mm margin. For each case, the two registrations were adjusted by two evaluation teams, each comprised of an experienced radiation oncologist and neurosurgeon, to optimize alignment in the region of the brainstem. The teams were blinded to the registration method. Results: The mean adjustment was 0.4 mm (range 0 to 2 mm) and 0.2 mm (range 0 to 1 mm) for the frame and mutual information methods, respectively. The median difference between the frame and mutual information registrations was 0.3 mm, but was not statistically significant using the Wilcoxon signed rank test (p=0.37). Conclusion: The difference between frame and mutual information registration techniques was neither statistically significant nor, for most applications, clinically important. These results suggest that mutual information is equivalent to frame-based image registration for radiosurgery. Work is ongoing to add additional evaluators and to assess the differences between evaluators.« less

Catumaxomab: malignant ascites: unjustified marketing authorisation.

PubMed

2010-10-01

The only treatment for malignant ascites in patients with refractory cancer is paracentesis, a procedure to relieve symptoms. Catumaxomab, a monoclonal antibody, is now authorised in the European Union for intraperitoneal administration to patients with epithelial cancers that overexpress epithelial cellular adhesion molecule (EpCAM) and provoke ascites unresponsive to chemotherapy. Clinical evaluation of catumaxomab in this setting is based on a comparative, randomised but unblinded trial including 258 patients. Patients in the catumaxomab group had four paracenteses over a 10-day period, followed by a 6-hour intraperitoneal catumaxomab infusion, while patients in the control group had a single paracentesis. Catumaxomab did not extend median survival time, which was about two months. Methodological biases rule out any conclusions as to whether catumaxomab reduced the number of paracenteses needed during this short survival period. In this trial, 80% of patients treated with catumaxomab experienced serious adverse events, versus 29% of controls, resulting in hospitalisation in respectively about 29% versus 16% of patients. Two-thirds of patients had reactions linked to intraperitoneal catumaxomab infusion. Gastrointestinal disorders were frequent, and included abdominal pain, nausea and vomiting. Catumaxomab is hepatotoxic. In addition, most patients develop anti-catumaxomab antibodies, although the clinical consequences are unclear. Catumaxomab therapy is inconvenient: it lasts 10 days and requires 4 intraperitoneal infusions that last 6 hours each and require 24-hour monitoring. In practice, catumaxomab has more harms than benefits. It is better to focus on individually tailored palliative care for these terminally ill patients.

Risk Management Plans: are they a tool for improving drug safety?

PubMed

Frau, Serena; Font Pous, Maria; Luppino, Maria Rosa; Conforti, Anita

2010-08-01

In 2005, new European legislation authorised Regulatory Agencies to require drug companies to submit a risk management plan (RMP) comprising detailed commitments for post-marketing pharmacovigilance. The aim of the study is to describe the characteristics of RMP for 15 drugs approved by the European Medicines Agency (EMA) and their impact on post-marketing safety issues. Of the 90 new Chemical Entities approved through a centralised procedure by the EMA during 2006 and 2007, 15 of them were selected and their safety aspects and relative RMPs analysed. All post-marketing communications released for safety reasons related to these drugs were also considered. A total of 157 safety specifications were established for the drugs assessed. Risk minimisation activities were foreseen for 5 drugs as training activities. Post-marketing safety issues emerged for 12 of them, leading to 39 type II variations in Summary of Product Characteristics (SPC). Nearly half of such variations, 19 (49%), concerned safety aspects not envisaged by the RMPs. Besides this, 9 Safety Communications were published for 6 out of 15 drugs assessed. The present study reveals several critical points on the way RMPs have been implemented. Several activities proposed by the RMPs do not appear to be adequate in dealing with the potential risks of drugs. Poor communication of risk to practitioners and to the public, and above all limited transparency for the total assessment of risk, seem to transform RMPs into a tool to reassure the public when inadequately evaluated drugs are granted premature marketing authorisation.

[Improving drug licensing for children and adolescents : Position paper from the More Medicines for Minors Symposion 8 June 2015 in Bonn].

PubMed

Riedel, Claudia; Lehmann, Birka; Broich, Karl; Sudhop, Thomas

2016-12-01

In Germany and throughout Europe, medicinal products for adults have been developed and evaluated systematically for decades. Medicinal products for children and adolescents, however, have only been researched for the past ten years. As a result, many medicinal products have been administered to children without systematic clinical trials, for example regarding dosage or pharmaceutical form.EU Regulation 1901/2006 aimes to close the gaps in the medical treatment of children and adolescents. In order to do so, the regulation provides for paediatric use marketing authorisations (PUMA) for previously authorised products no longer covered by intellectual property rights and also grants holders of such PUMA licenses further property rights. However, only two PUMA licenses have been applied for. Thus, the PUMA license instrument is hardly being used despite the fact that many medicinal products have a great potential for closing medical gaps for children and adolescents.In order to improve the situation regarding medicinal products for children and adolescents, this scientific symposium "More Medicines for Minors" intended to promote dialogue among the parties involved and to provide an opportunity to discuss reasons for the reluctance to apply for PUMA licenses. Speakers specialised in paediatric and adolescent medicine as well as those from licensing authorities, the Federal Joint Committee (Gemeinsamer Bundesausschuss, G‑BA), the pharmaceutical industry and the federal ministries presented problems and possible solutions from their point of view with the aim of making the PUMA license instrument more attractive.

Mass preserving registration for lung CT

NASA Astrophysics Data System (ADS)

Gorbunova, Vladlena; Lo, Pechin; Loeve, Martine; Tiddens, Harm A.; Sporring, Jon; Nielsen, Mads; de Bruijne, Marleen

2009-02-01

In this paper, we evaluate a novel image registration method on a set of expiratory-inspiratory pairs of computed tomography (CT) lung scans. A free-form multi resolution image registration technique is used to match two scans of the same subject. To account for the differences in the lung intensities due to differences in inspiration level, we propose to adjust the intensity of lung tissue according to the local expansion or compression. An image registration method without intensity adjustment is compared to the proposed method. Both approaches are evaluated on a set of 10 pairs of expiration and inspiration CT scans of children with cystic fibrosis lung disease. The proposed method with mass preserving adjustment results in significantly better alignment of the vessel trees. Analysis of local volume change for regions with trapped air compared to normally ventilated regions revealed larger differences between these regions in the case of mass preserving image registration, indicating that mass preserving registration is better at capturing localized differences in lung deformation.

OUTSOURCING ETHICAL DILEMMAS: REGULATING INTERNATIONAL SURROGACY ARRANGEMENTS.

PubMed

Fenton-Glynn, Claire

2016-01-01

This article argues that the English legislative regime is ineffective in regulating international surrogacy, particularly with regard to commercial payments. It suggests that if English law views surrogacy as exploitative, we have a responsibility to protect women both in England and abroad, and the only way to do so effectively is to create a domestic system of regulation that caters adequately for the demand in this country. This requires a system of authorisation for surrogacy before it is undertaken; ex-post facto examinations of agreements completed in other jurisdictions, after the child is already living with the commissioning parents, cannot be seen as an acceptable compromise, as authorisation will inevitably be granted in the child's best interests. © The Author 2016. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

Regulating medicines in Europe: the European Medicines Agency, marketing authorisation, transparency and pharmacovigilance.

PubMed

Permanand, Govin; Mossialos, Elias; McKee, Martin

2006-01-01

Following a review process lasting almost four years, and culminating in several pieces of new European legislation, adjustments have been made to the European Union's (EU) regulatory framework for pharmaceuticals. The European Commission laid out its priorities for the review as: simplifying the authorisation system, ensuring a high quality of public health, completing the internal market in medicines, and preparing for the enlargement of the Union. Amongst the most important changes brought about by the new rules are those relating to the European drug approval procedures, the functions and operational transparency of the European Medicines Agency (EMEA), and the EU's pharmacovigilance system. This article provides a brief examination of key elements of these changes, and considers the extent to which they serve the goal of improved public health protection within the EU.

US Army Corps of Engineers Section 404: permitting of valley fills - red flag or red tape?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas R. Johnston, Jr.

2009-03-15

Since 2001 the US Army Corps of Engineers has been permitting most surface coal mines as Individual Permits rather than Nationwide Permits under the Section 404 program. This was shown in a survey by Skelly & Loy of permits published by Huntingdon Crops District and the state of Kentucky. Nationwide Permit 21 (NWP21) authorises the filling of waters of the United States associated with surface coal mining and reclamation operations already authorised or currently being processed as part of the integrated permit processing procedure. NWP21 has received much opposition and two noticeable court cases involving it, in West Virginia andmore » Kentucy, are briefly reported. The article first appeared in Skelly & Loy's newsletter, Portal to the mining industry, Vol II, Issue 1. 4 photos.« less

[Marketing approval and market surveillance of medical devices in Germany: Where does policy integration take place?].

PubMed

Lang, Achim

2014-01-01

Since 2011 new regulatory measures regarding medical devices have been set up with the aim to eliminate obstacles to innovations and to find more coordinated ways to marketing authorisation and market surveillance. This essay investigates whether these new and existing coordination mechanisms build up to a Joined-up Government approach. The analysis shows that the regulatory process should be adjusted along several dimensions. First, many organisations lack awareness regarding their stakeholders and focus solely on their immediate organisational activities. Second, the regulatory process (marketing authorisation and market surveillance) is too fragmented for an effective communication to take place. Finally, the underlying strategy process is an ad-hoc approach lacking continuity and continued involvement of, in particular, the responsible federal ministries. Copyright © 2013. Published by Elsevier GmbH.

Requirements for authorisation of internal dosimetry services.

PubMed

Melo, D R; Cunha, P G; Torres, M M C; Lourenço, M C

2003-01-01

In order to ensure that a facility is in compliance with the occupational exposure requirements established by regulatory authorities, the measurements and dose assessments specified in the individual monitoring programme need to be reliable. There are two important questions that shall be addressed here: one is how the licensed facilities can demonstrate to their workers and regulatory bodies compliance with the regulatory limits and the reliability of the results of the individual monitoring programmes; the other concerns the mechanisms used to demonstrate to a facility in another country the reliability of the measurement results of an individual monitoring bioassay programme. The accreditation of the bioassay laboratory, according to ISO/IEC 17025, shall be the basic requirement for obtaining the authorisation granted by the national regulatory authority. For the second question, such confidence can be achieved through International Laboratory Accreditation Cooperation (ILAC).

Estimation of motion fields by non-linear registration for local lung motion analysis in 4D CT image data.

PubMed

Werner, René; Ehrhardt, Jan; Schmidt-Richberg, Alexander; Heiss, Anabell; Handels, Heinz

2010-11-01

Motivated by radiotherapy of lung cancer non- linear registration is applied to estimate 3D motion fields for local lung motion analysis in thoracic 4D CT images. Reliability of analysis results depends on the registration accuracy. Therefore, our study consists of two parts: optimization and evaluation of a non-linear registration scheme for motion field estimation, followed by a registration-based analysis of lung motion patterns. The study is based on 4D CT data of 17 patients. Different distance measures and force terms for thoracic CT registration are implemented and compared: sum of squared differences versus a force term related to Thirion's demons registration; masked versus unmasked force computation. The most accurate approach is applied to local lung motion analysis. Masked Thirion forces outperform the other force terms. The mean target registration error is 1.3 ± 0.2 mm, which is in the order of voxel size. Based on resulting motion fields and inter-patient normalization of inner lung coordinates and breathing depths a non-linear dependency between inner lung position and corresponding strength of motion is identified. The dependency is observed for all patients without or with only small tumors. Quantitative evaluation of the estimated motion fields indicates high spatial registration accuracy. It allows for reliable registration-based local lung motion analysis. The large amount of information encoded in the motion fields makes it possible to draw detailed conclusions, e.g., to identify the dependency of inner lung localization and motion. Our examinations illustrate the potential of registration-based motion analysis.

Propagation of registration uncertainty during multi-fraction cervical cancer brachytherapy

NASA Astrophysics Data System (ADS)

Amir-Khalili, A.; Hamarneh, G.; Zakariaee, R.; Spadinger, I.; Abugharbieh, R.

2017-10-01

Multi-fraction cervical cancer brachytherapy is a form of image-guided radiotherapy that heavily relies on 3D imaging during treatment planning, delivery, and quality control. In this context, deformable image registration can increase the accuracy of dosimetric evaluations, provided that one can account for the uncertainties associated with the registration process. To enable such capability, we propose a mathematical framework that first estimates the registration uncertainty and subsequently propagates the effects of the computed uncertainties from the registration stage through to the visualizations, organ segmentations, and dosimetric evaluations. To ensure the practicality of our proposed framework in real world image-guided radiotherapy contexts, we implemented our technique via a computationally efficient and generalizable algorithm that is compatible with existing deformable image registration software. In our clinical context of fractionated cervical cancer brachytherapy, we perform a retrospective analysis on 37 patients and present evidence that our proposed methodology for computing and propagating registration uncertainties may be beneficial during therapy planning and quality control. Specifically, we quantify and visualize the influence of registration uncertainty on dosimetric analysis during the computation of the total accumulated radiation dose on the bladder wall. We further show how registration uncertainty may be leveraged into enhanced visualizations that depict the quality of the registration and highlight potential deviations from the treatment plan prior to the delivery of radiation treatment. Finally, we show that we can improve the transfer of delineated volumetric organ segmentation labels from one fraction to the next by encoding the computed registration uncertainties into the segmentation labels.

3D point cloud analysis of structured light registration in computer-assisted navigation in spinal surgeries

NASA Astrophysics Data System (ADS)

Gupta, Shaurya; Guha, Daipayan; Jakubovic, Raphael; Yang, Victor X. D.

2017-02-01

Computer-assisted navigation is used by surgeons in spine procedures to guide pedicle screws to improve placement accuracy and in some cases, to better visualize patient's underlying anatomy. Intraoperative registration is performed to establish a correlation between patient's anatomy and the pre/intra-operative image. Current algorithms rely on seeding points obtained directly from the exposed spinal surface to achieve clinically acceptable registration accuracy. Registration of these three dimensional surface point-clouds are prone to various systematic errors. The goal of this study was to evaluate the robustness of surgical navigation systems by looking at the relationship between the optical density of an acquired 3D point-cloud and the corresponding surgical navigation error. A retrospective review of a total of 48 registrations performed using an experimental structured light navigation system developed within our lab was conducted. For each registration, the number of points in the acquired point cloud was evaluated relative to whether the registration was acceptable, the corresponding system reported error and target registration error. It was demonstrated that the number of points in the point cloud neither correlates with the acceptance/rejection of a registration or the system reported error. However, a negative correlation was observed between the number of the points in the point-cloud and the corresponding sagittal angular error. Thus, system reported total registration points and accuracy are insufficient to gauge the accuracy of a navigation system and the operating surgeon must verify and validate registration based on anatomical landmarks prior to commencing surgery.

[Population-based cancer registration in Germany. Essentials and perspectives].

PubMed

Katalinic, A

2004-05-01

Although cancer registration has a long tradition in Germany, wide areas remained blank spaces on the map concerning population-based cancer registration. The situation changed completely when a federal law on cancer registration (KRG, 1995-1999) took effect. Now all federal states have established population-based cancer registries on a legal basis. In spite of the uniform model of cancer registration anchored in the KRG, 16 different models have developed in Germany. Completeness of cancer registration was constantly improved over the last several years. In addition to the Saarland cancer registry, further registries can now provide a high grade of registration for all cancer sites. Essential tasks, such as public reporting and support of cancer research, can now be better fulfilled. Even taking the great developments in cancer registration in Germany into consideration, some deficits still continue to exist. These deficits are mostly caused by heterogeneity and missing compatibility of the cancer registry laws of the federal states. After the focus of cancer registration was on developing valid registries,now the focus has to be changed to the usability of cancer registry data. These data can be used e. g. for research on etiology and evaluation of programs on early cancer detection. Scientists in the field of cancer epidemiology, public health, and cancer care are invited to use data of cancer registries for research and evaluation projects intensively.

An atlas-based multimodal registration method for 2D images with discrepancy structures.

PubMed

Lv, Wenchao; Chen, Houjin; Peng, Yahui; Li, Yanfeng; Li, Jupeng

2018-06-04

An atlas-based multimodal registration method for 2-dimension images with discrepancy structures was proposed in this paper. Atlas was utilized for complementing the discrepancy structure information in multimodal medical images. The scheme includes three steps: floating image to atlas registration, atlas to reference image registration, and field-based deformation. To evaluate the performance, a frame model, a brain model, and clinical images were employed in registration experiments. We measured the registration performance by the squared sum of intensity differences. Results indicate that this method is robust and performs better than the direct registration for multimodal images with discrepancy structures. We conclude that the proposed method is suitable for multimodal images with discrepancy structures. Graphical Abstract An Atlas-based multimodal registration method schematic diagram.

Validation of motion correction techniques for liver CT perfusion studies

PubMed Central

Chandler, A; Wei, W; Anderson, E F; Herron, D H; Ye, Z; Ng, C S

2012-01-01

Objectives Motion in images potentially compromises the evaluation of temporally acquired CT perfusion (CTp) data; image registration should mitigate this, but first requires validation. Our objective was to compare the relative performance of manual, rigid and non-rigid registration techniques to correct anatomical misalignment in acquired liver CTp data sets. Methods 17 data sets in patients with liver tumours who had undergone a CTp protocol were evaluated. Each data set consisted of a cine acquisition during a breath-hold (Phase 1), followed by six further sets of cine scans (each containing 11 images) acquired during free breathing (Phase 2). Phase 2 images were registered to a reference image from Phase 1 cine using two semi-automated intensity-based registration techniques (rigid and non-rigid) and a manual technique (the only option available in the relevant vendor CTp software). The performance of each technique to align liver anatomy was assessed by four observers, independently and blindly, on two separate occasions, using a semi-quantitative visual validation study (employing a six-point score). The registration techniques were statistically compared using an ordinal probit regression model. Results 306 registrations (2448 observer scores) were evaluated. The three registration techniques were significantly different from each other (p=0.03). On pairwise comparison, the semi-automated techniques were significantly superior to the manual technique, with non-rigid significantly superior to rigid (p<0.0001), which in turn was significantly superior to manual registration (p=0.04). Conclusion Semi-automated registration techniques achieved superior alignment of liver anatomy compared with the manual technique. We hope this will translate into more reliable CTp analyses. PMID:22374283

The influence of the image registration method on the adaptive radiotherapy. A proof of the principle in a selected case of prostate IMRT.

PubMed

Berenguer, Roberto; de la Vara, Victoria; Lopez-Honrubia, Veronica; Nuñez, Ana Teresa; Rivera, Miguel; Villas, Maria Victoria; Sabater, Sebastia

2018-01-01

To analyse the influence of the image registration method on the adaptive radiotherapy of an IMRT prostate treatment, and to compare the dose accumulation according to 3 different image registration methods with the planned dose. The IMRT prostate patient was CT imaged 3 times throughout his treatment. The prostate, PTV, rectum and bladder were segmented on each CT. A Rigid, a deformable (DIR) B-spline and a DIR with landmarks registration algorithms were employed. The difference between the accumulated doses and planned doses were evaluated by the gamma index. The Dice coefficient and Hausdorff distance was used to evaluate the overlap between volumes, to quantify the quality of the registration. When comparing adaptive vs no adaptive RT, the gamma index calculation showed large differences depending on the image registration method (as much as 87.6% in the case of DIR B-spline). The quality of the registration was evaluated using an index such as the Dice coefficient. This showed that the best result was obtained with DIR with landmarks compared with the rest and it was always above 0.77, reported as a recommended minimum value for prostate studies in a multi-centre review. Apart from showing the importance of the application of an adaptive RT protocol in a particular treatment, this work shows that the election of the registration method is decisive in the result of the adaptive radiotherapy and dose accumulation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Comparison of time-series registration methods in breast dynamic infrared imaging

NASA Astrophysics Data System (ADS)

Riyahi-Alam, S.; Agostini, V.; Molinari, F.; Knaflitz, M.

2015-03-01

Automated motion reduction in dynamic infrared imaging is on demand in clinical applications, since movement disarranges time-temperature series of each pixel, thus originating thermal artifacts that might bias the clinical decision. All previously proposed registration methods are feature based algorithms requiring manual intervention. The aim of this work is to optimize the registration strategy specifically for Breast Dynamic Infrared Imaging and to make it user-independent. We implemented and evaluated 3 different 3D time-series registration methods: 1. Linear affine, 2. Non-linear Bspline, 3. Demons applied to 12 datasets of healthy breast thermal images. The results are evaluated through normalized mutual information with average values of 0.70 ±0.03, 0.74 ±0.03 and 0.81 ±0.09 (out of 1) for Affine, Bspline and Demons registration, respectively, as well as breast boundary overlap and Jacobian determinant of the deformation field. The statistical analysis of the results showed that symmetric diffeomorphic Demons' registration method outperforms also with the best breast alignment and non-negative Jacobian values which guarantee image similarity and anatomical consistency of the transformation, due to homologous forces enforcing the pixel geometric disparities to be shortened on all the frames. We propose Demons' registration as an effective technique for time-series dynamic infrared registration, to stabilize the local temperature oscillation.

Integrated in silico strategy for PBT assessment and prioritization under REACH.

PubMed

Pizzo, Fabiola; Lombardo, Anna; Manganaro, Alberto; Cappelli, Claudia I; Petoumenou, Maria I; Albanese, Federica; Roncaglioni, Alessandra; Brandt, Marc; Benfenati, Emilio

2016-11-01

Chemicals may persist in the environment, bioaccumulate and be toxic for humans and wildlife, posing great concern. These three properties, persistence (P), bioaccumulation (B), and toxicity (T) are the key targets of the PBT-hazard assessment. The European regulation for the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) requires assessment of PBT-properties for all chemicals that are produced or imported in Europe in amounts exceeding 10 tonnes per year, checking whether the criteria set out in REACH Annex XIII are met, so the substance should therefore be considered to have properties of very high concern. Considering how many substances can fall under the REACH regulation, there is a pressing need for new strategies to identify and screen large numbers fast and inexpensively. An efficient non-testing screening approach to identify PBT candidates is necessary, as a valuable alternative to money- and time-consuming laboratory tests and a good start for prioritization since few tools exist (e.g. the PBT profiler developed by US EPA). The aim of this work was to offer a conceptual scheme for identifying and prioritizing chemicals for further assessment and if appropriate further testing, based on their PBT-potential, using a non-testing screening approach. We integrated in silico models (using existing and developing new ones) in a final algorithm for screening and ranking PBT-potential, which uses experimental and predicted values as well as associated uncertainties. The Multi-Criteria Decision-Making (MCDM) theory was used to integrate the different values. Then we compiled a new set of data containing known PBT and non-PBT substances, in order to check how well our approach clearly differentiated compounds labeled as PBT from those labeled as non-PBT. This indicated that the integrated model distinguished between PBT from non-PBT compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Toward a New U.S. Chemicals Policy: Rebuilding the Foundation to Advance New Science, Green Chemistry, and Environmental Health

PubMed Central

Wilson, Michael P.; Schwarzman, Megan R.

2009-01-01

Objective We describe fundamental weaknesses in U.S. chemicals policy, present principles of chemicals policy reform, and articulate interdisciplinary research questions that should be addressed. With global chemical production projected to double over the next 24 years, federal policies that shape the priorities of the U.S. chemical enterprise will be a cornerstone of sustainability. To date, these policies have largely failed to adequately protect public health or the environment or motivate investment in or scientific exploration of cleaner chemical technologies, known collectively as green chemistry. On this trajectory, the United States will face growing health, environmental, and economic problems related to chemical exposures and pollution. Conclusions Existing policies have produced a U.S. chemicals market in which the safety of chemicals for human health and the environment is undervalued relative to chemical function, price, and performance. This market barrier to green chemistry is primarily a consequence of weaknesses in the Toxic Substances Control Act. These weaknesses have produced a chemical data gap, because producers are not required to investigate and disclose sufficient information on chemicals’ hazard traits to government, businesses that use chemicals, or the public; a safety gap, because government lacks the legal tools it needs to efficiently identify, prioritize, and take action to mitigate the potential health and environmental effects of hazardous chemicals; and a technology gap, because industry and government have invested only marginally in green chemistry research, development, and education. Policy reforms that close the three gaps—creating transparency and accountability in the market—are crucial for improving public and environmental health and reducing the barriers to green chemistry. The European Union’s REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation has opened an opportunity for the United States to take this step; doing so will present the nation with new research questions in science, policy, law, and technology. PMID:19672398

Toward a new U.S. chemicals policy: rebuilding the foundation to advance new science, green chemistry, and environmental health.

PubMed

Wilson, Michael P; Schwarzman, Megan R

2009-08-01

We describe fundamental weaknesses in U.S. chemicals policy, present principles of chemicals policy reform, and articulate interdisciplinary research questions that should be addressed. With global chemical production projected to double over the next 24 years, federal policies that shape the priorities of the U.S. chemical enterprise will be a cornerstone of sustainability. To date, these policies have largely failed to adequately protect public health or the environment or motivate investment in or scientific exploration of cleaner chemical technologies, known collectively as green chemistry. On this trajectory, the United States will face growing health, environmental, and economic problems related to chemical exposures and pollution. Existing policies have produced a U.S. chemicals market in which the safety of chemicals for human health and the environment is undervalued relative to chemical function, price, and performance. This market barrier to green chemistry is primarily a consequence of weaknesses in the Toxic Substances Control Act. These weaknesses have produced a chemical data gap, because producers are not required to investigate and disclose sufficient information on chemicals' hazard traits to government, businesses that use chemicals, or the public; a safety gap, because government lacks the legal tools it needs to efficiently identify, prioritize, and take action to mitigate the potential health and environmental effects of hazardous chemicals; and a technology gap, because industry and government have invested only marginally in green chemistry research, development, and education. Policy reforms that close the three gaps-creating transparency and accountability in the market-are crucial for improving public and environmental health and reducing the barriers to green chemistry. The European Union's REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation has opened an opportunity for the United States to take this step; doing so will present the nation with new research questions in science, policy, law, and technology.

Deriving Biomonitoring Equivalents for selected E- and P-series glycol ethers for public health risk assessment.

PubMed

Poet, Torka; Ball, Nicholas; Hays, Sean M

2016-01-01

Glycol ethers are a widely used class of solvents that may lead to both workplace and general population exposures. Biomonitoring studies are available that have quantified glycol ethers or their metabolites in blood and/or urine amongst exposed populations. These biomonitoring levels indicate exposures to the glycol ethers, but do not by themselves indicate a health hazard risk. Biomonitoring Equivalents (BEs) have been created to provide the ability to interpret human biomonitoring data in a public health risk context. The BE is defined as the concentration of a chemical or metabolite in a biological fluid (blood or urine) that is consistent with exposures at a regulatory derived safe exposure limit, such as a tolerable daily intake (TDI). In this exercise, we derived BEs for general population exposures for selected E- and P-series glycol ethers based on their respective derived no effect levels (DNELs). Selected DNELs have been derived as part of respective Registration, Evaluation, Authorisation and Regulation of Chemicals (REACh) regulation dossiers in the EU. The BEs derived here are unique in the sense that they are the first BEs derived for urinary excretion of compounds following inhalation exposures. The urinary mass excretion fractions (Fue) of the acetic acid metabolites for the E-series GEs range from approximately 0.2 to 0.7. The Fues for the excretion of the parent P-series GEs range from approximately 0.1 to 0.2, with the exception of propylene glycol methyl ether and its acetate (Fue = 0.004). Despite the narrow range of Fues, the BEs exhibit a larger range, resulting from the larger range in DNELs across GEs. The BEs derived here can be used to interpret human biomonitoring data for inhalation exposures to GEs amongst the general population. Copyright © 2015 Elsevier GmbH. All rights reserved.

Development and validation of clinical prediction models for mortality, functional outcome and cognitive impairment after stroke: a study protocol.

PubMed

Fahey, Marion; Rudd, Anthony; Béjot, Yannick; Wolfe, Charles; Douiri, Abdel

2017-08-18

Stroke is a leading cause of adult disability and death worldwide. The neurological impairments associated with stroke prevent patients from performing basic daily activities and have enormous impact on families and caregivers. Practical and accurate tools to assist in predicting outcome after stroke at patient level can provide significant aid for patient management. Furthermore, prediction models of this kind can be useful for clinical research, health economics, policymaking and clinical decision support. 2869 patients with first-ever stroke from South London Stroke Register (SLSR) (1995-2004) will be included in the development cohort. We will use information captured after baseline to construct multilevel models and a Cox proportional hazard model to predict cognitive impairment, functional outcome and mortality up to 5 years after stroke. Repeated random subsampling validation (Monte Carlo cross-validation) will be evaluated in model development. Data from participants recruited to the stroke register (2005-2014) will be used for temporal validation of the models. Data from participants recruited to the Dijon Stroke Register (1985-2015) will be used for external validation. Discrimination, calibration and clinical utility of the models will be presented. Patients, or for patients who cannot consent their relatives, gave written informed consent to participate in stroke-related studies within the SLSR. The SLSR design was approved by the ethics committees of Guy's and St Thomas' NHS Foundation Trust, Kings College Hospital, Queens Square and Westminster Hospitals (London). The Dijon Stroke Registry was approved by the Comité National des Registres and the InVS and has authorisation of the Commission Nationale de l'Informatique et des Libertés. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Improving substance information in USEtox® , part 2: Data for estimating fate and ecosystem exposure factors.

PubMed

Saouter, Erwan; Aschberger, Karin; Fantke, Peter; Hauschild, Michael Z; Kienzler, Aude; Paini, Alicia; Pant, Rana; Radovnikovic, Anita; Secchi, Michela; Sala, Serenella

2017-12-01

The scientific consensus model USEtox ® has been developed since 2003 under the auspices of the United Nations Environment Programme-Society of Environmental Toxicology and Chemistry Life Cycle Initiative as a harmonized approach for characterizing human and freshwater toxicity in life cycle assessment and other comparative assessment frameworks. Using physicochemical substance properties, USEtox quantifies potential human toxicity and freshwater ecotoxicity impacts by combining environmental fate, exposure, and toxicity effects information, considering multimedia fate and multipathway exposure processes. The main source to obtain substance properties for USEtox 1.01 and 2.0 is the Estimation Program Interface (EPI Suite™) from the US Environmental Protection Agency. However, since the development of the original USEtox substance databases, new chemical regulations have been enforced in Europe, such as the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and the Plant Protection Products regulations. These regulations require that a chemical risk assessment for humans and the environment is performed before a chemical is placed on the European market. Consequently, additional physicochemical property data and new toxicological endpoints are now available for thousands of chemical substances. The aim of the present study was to explore the extent to which the new available data can be used as input for USEtox-especially for application in environmental footprint studies-and to discuss how this would influence the quantification of fate and exposure factors. Initial results show that the choice of data source and the parameters selected can greatly influence fate and exposure factors, leading to potentially different rankings and relative contributions of substances to overall human toxicity and ecotoxicity impacts. Moreover, it is crucial to discuss the relevance of the exposure factor for freshwater ecotoxicity impacts, particularly for persistent highly adsorbing and bioaccumulating substances. Environ Toxicol Chem 2017;36:3463-3470. © 2017 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

A survey of stakeholder organisations on the proposed new European chemical policy.

PubMed

Dandrea, Jennifer; Combes, Robert

2006-03-01

In February 2001, the European Commission published a White Paper proposing that a single new system of chemical regulation should be applied throughout the Member States of the European Union. The proposed Registration, Evaluation and Authorisation of Chemicals (REACH) system was to include both new and existing chemicals, with the aim of ensuring that sufficient pertinent data were made available to enable human health and the environment to be protected. The policy was founded on the principle of sustainable industrial development, and ambitiously attempted to incorporate the needs and views of key stakeholder organisations, such as industry, trade associations, consumer groups, environmentalists, animal welfarists and Member State governments. During the period between the publication of the White Paper and the on-line publication of consultation documents, as part of a public consultation exercise, in May 2003, many of these key stakeholder organisations produced material in support of or critical of the White Paper, either in part or as a whole. In this paper, we have attempted to review this extensive material and to present it in the context of the current chemical regulatory system that the REACH system will replace. Emphasis is placed on the impact of the new policy on the number of animals used in the testing regimes within the REACH system and the inclusion of alternative methods into the legislation. Although supportive of the overriding aims of the new policy, FRAME believes that the fundamental concept of a risk-free environment is flawed, and that the new REACH system will involve the unjustifiable use of millions of laboratory animals. The new policy does include alternative methods, particularly for base set substances. Nevertheless, alternative testing methods that are already available have been excluded and replaced with outdated in vivo versions. There is also insufficient detail with regard to the further development and validation of alternative methods, particularly for substances of high concern, such as endocrine disrupters or reproductive toxins, for which no alternative testing methods currently exist.

A survey of stakeholder organisations on the proposed new European chemicals policy.

PubMed

Dandrea, Jennifer; Combes, Robert D

2003-11-01

In February 2001, the European Commission published a White Paper proposing that a single new system of chemical regulation should be applied throughout the Member States of the European Union. The proposed Registration, Evaluation and Authorisation of Chemicals (REACH) system was to include both new and existing chemicals, with the aim of ensuring that sufficient pertinent data were made available to enable human health and the environment to be protected. The policy was founded on the principle of sustainable industrial development, and ambitiously attempted to incorporate the needs and views of key stakeholder organisations, such as industry, trade associations, consumer groups, environmentalists, animal welfarists and Member State governments. During the period between the publication of the White Paper and the on-line publication of consultation documents, as part of a public consultation exercise, in May 2003, many of these key stakeholder organisations produced material in support of or critical of the White Paper, either in part or as a whole. In this paper, we have attempted to review this extensive material and to present it in the context of the current chemical regulatory system that the REACH system will replace. Emphasis is placed on the impact of the new policy on the number of animals used in the testing regimes within the REACH system and the inclusion of alternative methods into the legislation. Although supportive of the overriding aims of the new policy, FRAME believes that the fundamental concept of a risk-free environment is flawed, and that the new REACH system will involve the unjustifiable use of millions of laboratory animals. The new policy does include alternative methods, particularly for base-set substances. Nevertheless, alternative testing methods that are already available have been excluded and replaced with outdated in vivo versions. There is also insufficient detail with regard to the further development and validation of alternative methods, particularly for substances of high concern, such as endocrine disrupters or reproductive toxins, for which no alternative testing methods currently exist.

Consumer exposure scenarios: development, challenges and possible solutions.

PubMed

Van Engelen, J G M; Heinemeyer, G; Rodriguez, C

2007-12-01

Exposure scenarios (ES) under REACH (Registration, Evaluation, and Authorisation of Chemicals; new EU legislation) aim to describe safe conditions of product and substance use. Both operational conditions and risk management measures (RMMs) are part of the ES. For consumer use of chemicals, one of the challenges will be to identify all of the consumer uses of a given chemical and then quantify the exposure derived from each of them. Product use categories can be established to identify in a systematic fashion how products are used. These product categories comprise products that are used similarly (e.g. paints, adhesives). They deliver information about product use characteristics, and provide an easy-to-handle tool for exchanging standardised information. For practical reasons, broad ES will have to be developed, which cover a wide range of products and use. The challenge will be to define them broadly, but not in a way that they provide such an overestimation of exposure that a next iteration or a more complex model is always needed. Tiered and targeted approaches for estimation of exposure at the right level of detail may offer the best solution. RMMs relevant for consumers include those inherent to product design (controllable) and those that are communicated to consumers as directions for use (non-controllable). Quantification of the effect of non-controllable RMMs on consumer exposure can prove to be difficult. REACH requires aggregation of exposure from all relevant identified sources. Development of appropriate methodology for realistic aggregation of exposure will be no small challenge and will likely require probabilistic approaches and comprehensive databases on populations' habits, practices and behaviours. REACH regulation aims at controlling the use of chemicals so that exposure to every chemical can be demonstrated to be safe for consumers, workers, and the environment when considered separately, but also when considered in an integrated way. This integration will be another substantial challenge for the future.

[Correlation of noises in the channels of digital X-ray receiver-transformer and the evaluation of registration's quant efficiency].

PubMed

Porosev, V V; Shekhtman, L I; Zelikman, M I; Blinov, N N

2004-01-01

Theoretical and experimental research results related with the influence of correlation of signals in neighboring elements of digital X-ray receiver-transformer produced on the evaluation of the output ratio noise/signal and, as a consequence, on the evaluation of quantum registration efficiency are described in the paper.

76 FR 72404 - Pesticides: Availability of Pesticide Registration Notice Regarding the Non-Dietary Exposure Task...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

... Pesticide Registration Notice Regarding the Non-Dietary Exposure Task Force AGENCY: Environmental Protection... Registration Notice (PR Notice) regarding the data development efforts of the Non-Dietary Exposure Task Force... participate. FOR FURTHER INFORMATION CONTACT: Richard P. Dumas, Pesticide Re- evaluation Division (7508P...

Cross contrast multi-channel image registration using image synthesis for MR brain images.

PubMed

Chen, Min; Carass, Aaron; Jog, Amod; Lee, Junghoon; Roy, Snehashis; Prince, Jerry L

2017-02-01

Multi-modal deformable registration is important for many medical image analysis tasks such as atlas alignment, image fusion, and distortion correction. Whereas a conventional method would register images with different modalities using modality independent features or information theoretic metrics such as mutual information, this paper presents a new framework that addresses the problem using a two-channel registration algorithm capable of using mono-modal similarity measures such as sum of squared differences or cross-correlation. To make it possible to use these same-modality measures, image synthesis is used to create proxy images for the opposite modality as well as intensity-normalized images from each of the two available images. The new deformable registration framework was evaluated by performing intra-subject deformation recovery, intra-subject boundary alignment, and inter-subject label transfer experiments using multi-contrast magnetic resonance brain imaging data. Three different multi-channel registration algorithms were evaluated, revealing that the framework is robust to the multi-channel deformable registration algorithm that is used. With a single exception, all results demonstrated improvements when compared against single channel registrations using the same algorithm with mutual information. Copyright © 2016 Elsevier B.V. All rights reserved.

SU-E-J-90: 2D/3D Registration Using KV-MV Image Pairs for Higher Accuracy Image Guided Radiotherapy.

PubMed

Furtado, H; Figl, M; Stock, M; Georg, D; Birkfellner, W

2012-06-01

In this work, we investigate the impact of using paired portal mega-voltage (MV) and kilo-voltage (kV) images, on 2D/3D registration accuracy with the purpose of improving tumor motion tracking during radiotherapy. Tumor motion tracking is important as motion remains one of the biggest sources of uncertainty in dose application. 2D/3D registration is successfully used in online tumor motion tracking, nevertheless, one limitation of this technique is the inability to resolve movement along the imaging beam axis using only one projection image. Our evaluation consisted in comparing the accuracy of registration using different 2D image combinations: only one 2D image (1-kV), one kV and one MV image (1kV-1MV) and two kV images (2-kV). For each of the image combinations we evaluated the registration results using 250 starting points as initial displacements from the gold standard. We measured the final mean target registration error (mTRE) and the success rate for each registration. Each of the combinations was evaluated using four different merit functions. When using the MI merit function (a popular choice for this application) the RMS mTRE drops from 6.4 mm when using only one image to 2.1 mm when using image pairs. The success rate increases from 62% to 99.6%. A similar trend was observed for all four merit functions. Typically, the results are slightly better with 2-kV images than with 1kV-1MV. We evaluated the impact of using different image combinations on accuracy of 2D/3D registration for tumor motion monitoring. Our results show that using a kV-MV image pair, leads to improved results as motion can be accurately resolved in six degrees of freedom. Given the possibility to acquire these two images simultaneously, this is not only very workflow efficient but is also shown to be a good approach to improve registration accuracy. © 2012 American Association of Physicists in Medicine.

Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations.

PubMed

Meyer, C R; Boes, J L; Kim, B; Bland, P H; Zasadny, K R; Kison, P V; Koral, K; Frey, K A; Wahl, R L

1997-04-01

This paper applies and evaluates an automatic mutual information-based registration algorithm across a broad spectrum of multimodal volume data sets. The algorithm requires little or no pre-processing, minimal user input and easily implements either affine, i.e. linear or thin-plate spline (TPS) warped registrations. We have evaluated the algorithm in phantom studies as well as in selected cases where few other algorithms could perform as well, if at all, to demonstrate the value of this new method. Pairs of multimodal gray-scale volume data sets were registered by iteratively changing registration parameters to maximize mutual information. Quantitative registration errors were assessed in registrations of a thorax phantom using PET/CT and in the National Library of Medicine's Visible Male using MRI T2-/T1-weighted acquisitions. Registrations of diverse clinical data sets were demonstrated including rotate-translate mapping of PET/MRI brain scans with significant missing data, full affine mapping of thoracic PET/CT and rotate-translate mapping of abdominal SPECT/CT. A five-point thin-plate spline (TPS) warped registration of thoracic PET/CT is also demonstrated. The registration algorithm converged in times ranging between 3.5 and 31 min for affine clinical registrations and 57 min for TPS warping. Mean error vector lengths for rotate-translate registrations were measured to be subvoxel in phantoms. More importantly the rotate-translate algorithm performs well even with missing data. The demonstrated clinical fusions are qualitatively excellent at all levels. We conclude that such automatic, rapid, robust algorithms significantly increase the likelihood that multimodality registrations will be routinely used to aid clinical diagnoses and post-therapeutic assessment in the near future.

Fundamental limits of image registration performance: Effects of image noise and resolution in CT-guided interventions.

PubMed

Ketcha, M D; de Silva, T; Han, R; Uneri, A; Goerres, J; Jacobson, M; Vogt, S; Kleinszig, G; Siewerdsen, J H

2017-02-11

In image-guided procedures, image acquisition is often performed primarily for the task of geometrically registering information from another image dataset, rather than detection / visualization of a particular feature. While the ability to detect a particular feature in an image has been studied extensively with respect to image quality characteristics (noise, resolution) and is an ongoing, active area of research, comparatively little has been accomplished to relate such image quality characteristics to registration performance. To establish such a framework, we derived Cramer-Rao lower bounds (CRLB) for registration accuracy, revealing the underlying dependencies on image variance and gradient strength. The CRLB was analyzed as a function of image quality factors (in particular, dose) for various similarity metrics and compared to registration accuracy using CT images of an anthropomorphic head phantom at various simulated dose levels. Performance was evaluated in terms of root mean square error (RMSE) of the registration parameters. Analysis of the CRLB shows two primary dependencies: 1) noise variance (related to dose); and 2) sum of squared image gradients (related to spatial resolution and image content). Comparison of the measured RMSE to the CRLB showed that the best registration method, RMSE achieved the CRLB to within an efficiency factor of 0.21, and optimal estimators followed the predicted inverse proportionality between registration performance and radiation dose. Analysis of the CRLB for image registration is an important step toward understanding and evaluating an intraoperative imaging system with respect to a registration task. While the CRLB is optimistic in absolute performance, it reveals a basis for relating the performance of registration estimators as a function of noise content and may be used to guide acquisition parameter selection (e.g., dose) for purposes of intraoperative registration.

TU-B-19A-01: Image Registration II: TG132-Quality Assurance for Image Registration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brock, K; Mutic, S

2014-06-15

AAPM Task Group 132 was charged with a review of the current approaches and solutions for image registration in radiotherapy and to provide recommendations for quality assurance and quality control of these clinical processes. As the results of image registration are always used as the input of another process for planning or delivery, it is important for the user to understand and document the uncertainty associate with the algorithm in general and the Result of a specific registration. The recommendations of this task group, which at the time of abstract submission are currently being reviewed by the AAPM, include themore » following components. The user should understand the basic image registration techniques and methods of visualizing image fusion. The disclosure of basic components of the image registration by commercial vendors is critical in this respect. The physicists should perform end-to-end tests of imaging, registration, and planning/treatment systems if image registration is performed on a stand-alone system. A comprehensive commissioning process should be performed and documented by the physicist prior to clinical use of the system. As documentation is important to the safe implementation of this process, a request and report system should be integrated into the clinical workflow. Finally, a patient specific QA practice should be established for efficient evaluation of image registration results. The implementation of these recommendations will be described and illustrated during this educational session. Learning Objectives: Highlight the importance of understanding the image registration techniques used in their clinic. Describe the end-to-end tests needed for stand-alone registration systems. Illustrate a comprehensive commissioning program using both phantom data and clinical images. Describe a request and report system to ensure communication and documentation. Demonstrate an clinically-efficient patient QA practice for efficient evaluation of image registration.« less

A 4D biomechanical lung phantom for joint segmentation/registration evaluation

NASA Astrophysics Data System (ADS)

Markel, Daniel; Levesque, Ives; Larkin, Joe; Léger, Pierre; El Naqa, Issam

2016-10-01

At present, there exists few openly available methods for evaluation of simultaneous segmentation and registration algorithms. These methods allow for a combination of both techniques to track the tumor in complex settings such as adaptive radiotherapy. We have produced a quality assurance platform for evaluating this specific subset of algorithms using a preserved porcine lung in such that it is multi-modality compatible: positron emission tomography (PET), computer tomography (CT) and magnetic resonance imaging (MRI). A computer controlled respirator was constructed to pneumatically manipulate the lungs in order to replicate human breathing traces. A registration ground truth was provided using an in-house bifurcation tracking pipeline. Segmentation ground truth was provided by synthetic multi-compartment lesions to simulate biologically active tumor, background tissue and a necrotic core. The bifurcation tracking pipeline results were compared to digital deformations and used to evaluate three registration algorithms, Diffeomorphic demons, fast-symmetric forces demons and MiMVista’s deformable registration tool. Three segmentation algorithms the Chan Vese level sets method, a Hybrid technique and the multi-valued level sets algorithm. The respirator was able to replicate three seperate breathing traces with a mean accuracy of 2-2.2%. Bifurcation tracking error was found to be sub-voxel when using human CT data for displacements up to 6.5 cm and approximately 1.5 voxel widths for displacements up to 3.5 cm for the porcine lungs. For the fast-symmetric, diffeomorphic and MiMvista registration algorithms, mean geometric errors were found to be 0.430+/- 0.001 , 0.416+/- 0.001 and 0.605+/- 0.002 voxels widths respectively using the vector field differences and 0.4+/- 0.2 , 0.4+/- 0.2 and 0.6+/- 0.2 voxel widths using the bifurcation tracking pipeline. The proposed phantom was found sufficient for accurate evaluation of registration and segmentation algorithms. The use of automatically generated anatomical landmarks proposed can eliminate the time and potential innacuracy of manual landmark selection using expert observers.

ICH: an exclusive club of drug regulatory agencies and drug companies imposing its rules on the rest of the world.

PubMed

2010-08-01

Under the pretext of harmonising regulatory requirements for marketing authorisation of new drugs, the drug regulatory agencies of the world's wealthiest countries and three pharmaceutical industry trade associations, joined together since 1990 in the ICH, are promoting their own interests by imposing their criteria for evaluating drugs on the whole world. The toxicity standards advocated by ICH sometimes promote faster, cheaper drug development over patient protection. The drug quality standards advocated by ICH sometimes increase manufacturing costs without providing any public health benefit. It would be preferable if the World Health Organization were in charge of setting standards for drug development, focusing on patients' interests.

Fast interactive registration tool for reproducible multi-spectral imaging for wound healing and treatment evaluation

NASA Astrophysics Data System (ADS)

Noordmans, Herke J.; de Roode, Rowland; Verdaasdonk, Rudolf

2007-02-01

Multi-spectral images of human tissue taken in-vivo often contain image alignment problems as patients have difficulty in retaining their posture during the acquisition time of 20 seconds. Previously, it has been attempted to correct motion errors with image registration software developed for MR or CT data but these algorithms have been proven to be too slow and erroneous for practical use with multi-spectral images. A new software package has been developed which allows the user to play a decisive role in the registration process as the user can monitor the progress of the registration continuously and force it in the right direction when it starts to fail. The software efficiently exploits videocard hardware to gain speed and to provide a perfect subvoxel correspondence between registration field and display. An 8 bit graphic card was used to efficiently register and resample 12 bit images using the hardware interpolation modes present on the graphic card. To show the feasibility of this new registration process, the software was applied in clinical practice evaluating the dosimetry for psoriasis and KTP laser treatment. The microscopic differences between images of normal skin and skin exposed to UV light proved that an affine registration step including zooming and slanting is critical for a subsequent elastic match to have success. The combination of user interactive registration software with optimal addressing the potentials of PC video card hardware greatly improves the speed of multi spectral image registration.

Authority, autonomy, responsibility and authorisation: with specific reference to adolescent mental health practice.

PubMed Central

Sutton, A

1997-01-01

Standards for professional training and practice are defined by accrediting organisations or statutory bodies. These describe the arena in which the practitioner may speak with authority. The sphere of authorised practice is further delineated by the external resources available. Within this explicit framework, unconscious mental processes can affect the professional response in potentially adverse ways. This is particularly important in mental health practice. Professionals must be prepared to examine their own responses on this basis in order to enhance their knowledge of the patient and minimise the possibilities of the patient becoming the victim of the professional's own psychopathology. The maintenance of such a position in an institution or organisation requires a similar process within its structure in order to provide the necessary setting and define the limits of good practice. In this paper, the field of adolescent mental health is specifically examined. PMID:9055159

Best practicable means (BPM) and as low as reasonably practicable (ALARP) in action at Sellafield.

PubMed

Morley, Bob

2004-03-01

Operators within the UK nuclear industry are required to employ 'best practicable means' (BPM) to control and minimise radioactive discharges. The requirement for the use of BPM is in order to ensure that doses from discharges are as low as reasonably practicable (ALARP). This facet is increasingly becoming the principal feature of discharge authorisations issued by the Environment Agencies under the Radioactive Substances Act, 1993 (RSA 93), which are enforceable by law. It is important to state at the outset, however, that scientific assessments to date indicate that there are no expectations of environmental harm from authorised discharges, even where those discharges have historically been up to two orders of magnitude higher than current levels. There is also no evidence to indicate that foreseeable future discharges from the Sellafield site will make any contribution to environmental harm.

[Food, health claims and drugs. Conclusions - recommendations. The National Academy of Pharmacy].

PubMed

Bourlioux, P

2008-01-01

Even if the activity of health claim foods is not relevant to the activity of drugs, we are just at the frontier of two fields which needs the greatest attention. Since foods and drugs are present in the same domain of prevention, the French Academy of Pharmacy draws attention on the necessary relevant and scientifically proven demonstration of the health claims using the same quality standard than those used for drugs (good clinical practises, methodologies correspondent to the current requirement, etc.). It is why the Academy wishes to express five recommendations fearing that the risks of confusion and abuse prevail on the possibilities of information and control. Make sure that foods are not mistaken with drugs; largely spread the lists of authorised claims; introduce the new notion of "nutrivigilance"; make sure that the only authorised health claims use advertising; reject the terms "alicaments" and "nutraceuticals" which are confusing with drugs.

4D co-registration of X-ray and MR-mammograms: initial clinical results and potential incremental diagnostic value.

PubMed

Dietzel, Matthias; Hopp, Torsten; Ruiter, Nicole V; Kaiser, Clemens G; Kaiser, Werner A; Baltzer, Pascal A

2015-01-01

4D co-registration of X-ray- and MR-mammograms (XM and MM) is a new method of image fusion. The present study aims to evaluate its clinical feasibility, radiological accuracy, and potential clinical value. XM and MM of 25 patients were co-registered. Results were evaluated by a blinded reader. Precision of the 4D co-registration was "very good" (mean-score [ms]=7), and lesions were "easier to delineate" (ms=5). In 88.8%, "relevant additional diagnostic information" was present, accounting for a more "confident diagnosis" in 76% (ms=5). 4D co-registration is feasible, accurate, and of potential clinical value. Copyright © 2015 Elsevier Inc. All rights reserved.

Automatic bone detection and soft tissue aware ultrasound-CT registration for computer-aided orthopedic surgery.

PubMed

Wein, Wolfgang; Karamalis, Athanasios; Baumgartner, Adrian; Navab, Nassir

2015-06-01

The transfer of preoperative CT data into the tracking system coordinates within an operating room is of high interest for computer-aided orthopedic surgery. In this work, we introduce a solution for intra-operative ultrasound-CT registration of bones. We have developed methods for fully automatic real-time bone detection in ultrasound images and global automatic registration to CT. The bone detection algorithm uses a novel bone-specific feature descriptor and was thoroughly evaluated on both in-vivo and ex-vivo data. A global optimization strategy aligns the bone surface, followed by a soft tissue aware intensity-based registration to provide higher local registration accuracy. We evaluated the system on femur, tibia and fibula anatomy in a cadaver study with human legs, where magnetically tracked bone markers were implanted to yield ground truth information. An overall median system error of 3.7 mm was achieved on 11 datasets. Global and fully automatic registration of bones aquired with ultrasound to CT is feasible, with bone detection and tracking operating in real time for immediate feedback to the surgeon.

Landsat image registration for agricultural applications

NASA Technical Reports Server (NTRS)

Wolfe, R. H., Jr.; Juday, R. D.; Wacker, A. G.; Kaneko, T.

1982-01-01

An image registration system has been developed at the NASA Johnson Space Center (JSC) to spatially align multi-temporal Landsat acquisitions for use in agriculture and forestry research. Working in conjunction with the Master Data Processor (MDP) at the Goddard Space Flight Center, it functionally replaces the long-standing LACIE Registration Processor as JSC's data supplier. The system represents an expansion of the techniques developed for the MDP and LACIE Registration Processor, and it utilizes the experience gained in an IBM/JSC effort evaluating the performance of the latter. These techniques are discussed in detail. Several tests were developed to evaluate the registration performance of the system. The results indicate that 1/15-pixel accuracy (about 4m for Landsat MSS) is achievable in ideal circumstances, sub-pixel accuracy (often to 0.2 pixel or better) was attained on a representative set of U.S. acquisitions, and a success rate commensurate with the LACIE Registration Processor was realized. The system has been employed in a production mode on U.S. and foreign data, and a performance similar to the earlier tests has been noted.

Evaluation of similarity measures for use in the intensity-based rigid 2D-3D registration for patient positioning in radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu Jian; Kim, Minho; Peters, Jorg

2009-12-15

Purpose: Rigid 2D-3D registration is an alternative to 3D-3D registration for cases where largely bony anatomy can be used for patient positioning in external beam radiation therapy. In this article, the authors evaluated seven similarity measures for use in the intensity-based rigid 2D-3D registration using a variation in Skerl's similarity measure evaluation protocol. Methods: The seven similarity measures are partitioned intensity uniformity, normalized mutual information (NMI), normalized cross correlation (NCC), entropy of the difference image, pattern intensity (PI), gradient correlation (GC), and gradient difference (GD). In contrast to traditional evaluation methods that rely on visual inspection or registration outcomes, themore » similarity measure evaluation protocol probes the transform parameter space and computes a number of similarity measure properties, which is objective and optimization method independent. The variation in protocol offers an improved property in the quantification of the capture range. The authors used this protocol to investigate the effects of the downsampling ratio, the region of interest, and the method of the digitally reconstructed radiograph (DRR) calculation [i.e., the incremental ray-tracing method implemented on a central processing unit (CPU) or the 3D texture rendering method implemented on a graphics processing unit (GPU)] on the performance of the similarity measures. The studies were carried out using both the kilovoltage (kV) and the megavoltage (MV) images of an anthropomorphic cranial phantom and the MV images of a head-and-neck cancer patient. Results: Both the phantom and the patient studies showed the 2D-3D registration using the GPU-based DRR calculation yielded better robustness, while providing similar accuracy compared to the CPU-based calculation. The phantom study using kV imaging suggested that NCC has the best accuracy and robustness, but its slow function value change near the global maximum requires a stricter termination condition for an optimization method. The phantom study using MV imaging indicated that PI, GD, and GC have the best accuracy, while NCC and NMI have the best robustness. The clinical study using MV imaging showed that NCC and NMI have the best robustness. Conclusions: The authors evaluated the performance of seven similarity measures for use in 2D-3D image registration using the variation in Skerl's similarity measure evaluation protocol. The generalized methodology can be used to select the best similarity measures, determine the optimal or near optimal choice of parameter, and choose the appropriate registration strategy for the end user in his specific registration applications in medical imaging.« less

76 FR 37822 - General Meeting Registration and Evaluation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

...), National Protection and Programs Directorate (NPPD, Office of Cybersecurity and Communications (CS&C... Cybersecurity and Communications, Office of Emergency Communications. Title: General Meeting Registration and...

Registration factors that limit international mobility of people holding physiotherapy qualifications: A systematic review.

PubMed

Foo, Jonathan S; Storr, Michael; Maloney, Stephen

2016-06-01

There is no enforced international standardisation of the physiotherapy profession. Thus, registration is used in many countries to maintain standards of care and to protect the public. However, registration may also limit international workforce mobility. What is known about the professional registration factors that may limit the international mobility of people holding physiotherapy qualifications? Systematic review using an electronic database search and hand searching of the World Confederation for Physical Therapy and International Network of Physiotherapy Regulatory Authorities websites. Analysis was conducted using thematic analysis. 10 articles and eight websites were included from the search strategy. Data is representative of high-income English speaking countries. Four themes emerged regarding limitations to professional mobility: practice context, qualification recognition, verification of fitness to practice, and incidental limitations arising from the registration process. Professional mobility is limited by differences in physiotherapy education programmes, resulting in varying standards of competency. Thus, it is often necessary to verify clinical competencies through assessments, as well as determining professional attributes and ability to apply competencies in a different practice context, as part of the registration process. There has been little evaluation of registration practices, and at present, there is a need to re-evaluate current registration processes to ensure they are efficient and effective, thereby enhancing workforce mobility. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Improving oncoplastic breast tumor bed localization for radiotherapy planning using image registration algorithms

NASA Astrophysics Data System (ADS)

Wodzinski, Marek; Skalski, Andrzej; Ciepiela, Izabela; Kuszewski, Tomasz; Kedzierawski, Piotr; Gajda, Janusz

2018-02-01

Knowledge about tumor bed localization and its shape analysis is a crucial factor for preventing irradiation of healthy tissues during supportive radiotherapy and as a result, cancer recurrence. The localization process is especially hard for tumors placed nearby soft tissues, which undergo complex, nonrigid deformations. Among them, breast cancer can be considered as the most representative example. A natural approach to improving tumor bed localization is the use of image registration algorithms. However, this involves two unusual aspects which are not common in typical medical image registration: the real deformation field is discontinuous, and there is no direct correspondence between the cancer and its bed in the source and the target 3D images respectively. The tumor no longer exists during radiotherapy planning. Therefore, a traditional evaluation approach based on known, smooth deformations and target registration error are not directly applicable. In this work, we propose alternative artificial deformations which model the tumor bed creation process. We perform a comprehensive evaluation of the most commonly used deformable registration algorithms: B-Splines free form deformations (B-Splines FFD), different variants of the Demons and TV-L1 optical flow. The evaluation procedure includes quantitative assessment of the dedicated artificial deformations, target registration error calculation, 3D contour propagation and medical experts visual judgment. The results demonstrate that the currently, practically applied image registration (rigid registration and B-Splines FFD) are not able to correctly reconstruct discontinuous deformation fields. We show that the symmetric Demons provide the most accurate soft tissues alignment in terms of the ability to reconstruct the deformation field, target registration error and relative tumor volume change, while B-Splines FFD and TV-L1 optical flow are not an appropriate choice for the breast tumor bed localization problem, even though the visual alignment seems to be better than for the Demons algorithm. However, no algorithm could recover the deformation field with sufficient accuracy in terms of vector length and rotation angle differences.

Victoria's review of registration for health practitioners.

PubMed

Scotts, H; Carter, M

1988-01-01

This article discusses some of the issues raised in the Interim Report of the current Review of Registration of Health Practitioners being conducted for the Victorian Health Department. The Report attempts to develop the framework in which the registration Boards will operate as part of a cohesive registration system. It proposed a mechanism and criteria for the registration of new groups as well as principles which can be applied to the ongoing review of each existing Board. The Review takes the perspective that registration of health practitioners carries with it both advantages and disadvantages for the general community. Under the proposed new system the controls exercised over health care providers by Registration Boards would be evaluated on the basis of to what extent the benefits to the public outweighed the potential costs. It is in this context that the Report addresses issues such as consumer complaints handling, registration of individual practitioners and controls over professional advertising and other business practices.

Pesticide exposure assessment for surface waters in the EU. Part 2: Determination of statistically based run-off and drainage scenarios for Germany.

PubMed

Bach, Martin; Diesner, Mirjam; Großmann, Dietlinde; Guerniche, Djamal; Hommen, Udo; Klein, Michael; Kubiak, Roland; Müller, Alexandra; Preuss, Thomas G; Priegnitz, Jan; Reichenberger, Stefan; Thomas, Kai; Trapp, Matthias

2017-05-01

In order to assess surface water exposure to active substances of plant protection products (PPPs) in the European Union (EU), the FOCUS (FOrum for the Co-ordination of pesticide fate models and their USe) surface water workgroup introduced four run-off and six drainage scenarios for Step 3 of the tiered FOCUSsw approach. These scenarios may not necessarily represent realistic worst-case situations for the different Member States of the EU. Hence, the suitability of the scenarios for risk assessment in the national authorisation procedures is not known. Using Germany as an example, the paper illustrates how national soil-climate scenarios can be developed to model entries of active substances into surface waters from run-off and erosion (using the model PRZM) and from drainage (using the model MACRO). In the authorisation procedure for PPPs on Member State level, such soil-climate scenarios can be used to determine exposure endpoints with a defined overall percentile. The approach allows the development of national specific soil-climate scenarios and to calculate percentile-based exposure endpoints. The scenarios have been integrated into a software tool analogous to FOCUS-SWASH which can be used in the future to assess surface water exposure in authorisation procedures of PPPs in Germany. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Data Requirements for Pesticide Registration

EPA Pesticide Factsheets

In evaluating a pesticide registration application, we assess a wide variety of potential human health and environmental effects associated with use of the product. Learn about these data requirements.

76 FR 14677 - General Meeting Registration and Evaluation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-17

... (capital/startup): $0. Total Burden Cost (operating/maintaining): $20,757. Post-Meeting/Workshop/Training..., including conferences, meetings, workshops, etc. The general registration form, general pre-meeting form...

Validation of a deformable MRI to CT registration algorithm employing same day planning MRI for surrogate analysis.

PubMed

Padgett, Kyle R; Stoyanova, Radka; Pirozzi, Sara; Johnson, Perry; Piper, Jon; Dogan, Nesrin; Pollack, Alan

2018-03-01

Validating deformable multimodality image registrations is challenging due to intrinsic differences in signal characteristics and their spatial intensity distributions. Evaluating multimodality registrations using these spatial intensity distributions is also complicated by the fact that these metrics are often employed in the registration optimization process. This work evaluates rigid and deformable image registrations of the prostate in between diagnostic-MRI and radiation treatment planning-CT by utilizing a planning-MRI after fiducial marker placement as a surrogate. The surrogate allows for the direct quantitative analysis that can be difficult in the multimodality domain. For thirteen prostate patients, T2 images were acquired at two different time points, the first several weeks prior to planning (diagnostic-MRI) and the second on the same day as the planning-CT (planning-MRI). The diagnostic-MRI was deformed to the planning-CT utilizing a commercially available algorithm which synthesizes a deformable image registration (DIR) algorithm from local rigid registrations. The planning-MRI provided an independent surrogate for the planning-CT for assessing registration accuracy using image similarity metrics, including Pearson correlation and normalized mutual information (NMI). A local analysis was performed by looking only within the prostate, proximal seminal vesicles, penile bulb, and combined areas. The planning-MRI provided an excellent surrogate for the planning-CT with residual error in fiducial alignment between the two datasets being submillimeter, 0.78 mm. DIR was superior to the rigid registration in 11 of 13 cases demonstrating a 27.37% improvement in NMI (P < 0.009) within a regional area surrounding the prostate and associated critical organs. Pearson correlations showed similar results, demonstrating a 13.02% improvement (P < 0.013). By utilizing the planning-MRI as a surrogate for the planning-CT, an independent evaluation of registration accuracy is possible. This population provides an ideal testing ground for MRI to CT DIR by obviating the need for multimodality comparisons which are inherently more challenging. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Registration verification of SEA/AR fields. [Oregon, Texas, Montana, Nebraska, Washington, Colorado, Kansas, Oklahoma, and North Dakota

NASA Technical Reports Server (NTRS)

Austin, W. W.; Lautenschlager, L. (Principal Investigator)

1981-01-01

A method of field registration verification for 20 SEA/AR sites for the 1979 crop year is evaluated. Field delineations for the sites were entered into the data base, and their registration verified using single channel gray scale computer printout maps of LANDSAT data taken over the site.

[A standardised German translation of the STAndards for Reporting of Diagnostic accuracy studies (STARD statement)*: Methodological aspects].

PubMed

Breuer, Jan-Philipp; Seeling, Matthes; Barz, Michael; Baldini, Timo; Scholtz, Kathrin; Spies, Claudia

2012-01-01

In order to be comprehensible and comparable scientific data should be reported according to a certain standard. One example is the 'STAndards for Reporting of Diagnostic Accuracy (STARD) Statement', a 25-item checklist for the appropriate conduct and reporting of diagnostic studies. Usually such scientific standards are published in English. The International Society for Pharmacoeconomics and Outcome Research (ISPOR) has developed guidelines for the translation and cultural adaptation of written medical instruments. The aim was to apply these ISPOR criteria to the German translation of the STARD Statement in order to allow for authorisation to be conferred by the original authors. In cooperation with the original authors the STARD statement was translated according to the ISPOR steps: (1) Preparation, (2) Forward Translation, (3) Reconciliation, (4) Back Translation, (5) Back Translation Review, (6) Harmonisation, (7) Cognitive Debriefing, which evaluated comprehensiveness and linguistic style with marks from 1 (very good) to 6 (insufficient), and (8) Review of Cognitive Debriefing Results and Finalisation. Die ISPOR criteria applied reasonably to the translation process, which required the work input and energy of four scientists and one professional translator and 177 accumulated working hours. The cognitive debriefing resulted in average grades 1.62±0.33 and 1.72±0.39 for comprehensiveness and linguistic style, respectively. Finally, the German STARD version was authorised by the original authors. Die ISPOR guidelines seem to be a suitable means to facilitate the structured adaptation of defined criteria for the reporting of studies, such as the STARD statement, to other languages. Copyright © 2012. Published by Elsevier GmbH.

An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register

PubMed Central

Carroll, Robert; Ramagopalan, Sreeram V.; Cid-Ruzafa, Javier; Lambrelli, Dimitra; McDonald, Laura

2017-01-01

Background: The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS) requested by the European Medicines Agency which were recorded on the European Union (EU) PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Methods: We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18 th October 2016. Results: We identified a total of 314 studies on the EU PAS Register, including 81 (26%) finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified, 205 (65%) included risk assessment in their scope, 133 (42%) included drug utilisation and 94 (30%) included effectiveness evaluation. Just over half of the studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4 (1%) used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary). The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs) whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs). Conclusions: Results of this analysis show that PAS design varies according to study objectives and therapeutic area. PMID:29188016

Compassionate use of orphan drugs.

PubMed

Hyry, Hanna I; Manuel, Jeremy; Cox, Timothy M; Roos, Jonathan C P

2015-08-21

EU regulation 726/2004 authorises manufacturers to provide drugs to patients on a temporary basis when marketing authorisation sought centrally for the entire EU is still pending. Individual Member States retain the right to approve and implement such 'compassionate use' programmes which companies will usually provide for free. Nevertheless some companies have opted not to partake in such programmes, in effect restricting access to drugs for patients in need. Here we survey the state of compassionate use programmes in the EU with particular reference to the rare disease field, and provide legal and ethical arguments to encourage their increased compassionate use in the EU and beyond. We contend that if enacted, these recommendations will be mutually beneficial to companies as well as patients. Requests for information from the European Medicines Agency were made under the UK Freedom of Information Act 2000. Legal, ethical and economic/pragmatic analysis identified means by which provision of therapy in compassionate use programmes might be increased. More than 50 notifications of compassionate use programmes have been submitted to the EMA by Member States since 2006. About 40 % relate to orphan drugs. As there is a compulsory register of programmes but not of outcomes, their success is difficult to evaluate but, for example, the French programme expedited treatment for more than 20,000 (orphan and non-orphan) patients over a period of three years. Compelling self-interested, legal and ethical arguments can be mounted to encourage manufacturers to offer therapies on a compassionate use basis and these are often equally applicable to provision on a humanitarian aid basis. The EU's compassionate use programmes are instrumental in ensuring continuity of access to drugs until approval and reimbursement decisions are finalised. We propose the creation of a registry of drugs offered on a compassionate use basis; further transparency would allow such programmes to be evaluated and direct patients to sources of treatment.

Accurate CT-MR image registration for deep brain stimulation: a multi-observer evaluation study

NASA Astrophysics Data System (ADS)

Rühaak, Jan; Derksen, Alexander; Heldmann, Stefan; Hallmann, Marc; Meine, Hans

2015-03-01

Since the first clinical interventions in the late 1980s, Deep Brain Stimulation (DBS) of the subthalamic nucleus has evolved into a very effective treatment option for patients with severe Parkinson's disease. DBS entails the implantation of an electrode that performs high frequency stimulations to a target area deep inside the brain. A very accurate placement of the electrode is a prerequisite for positive therapy outcome. The assessment of the intervention result is of central importance in DBS treatment and involves the registration of pre- and postinterventional scans. In this paper, we present an image processing pipeline for highly accurate registration of postoperative CT to preoperative MR. Our method consists of two steps: a fully automatic pre-alignment using a detection of the skull tip in the CT based on fuzzy connectedness, and an intensity-based rigid registration. The registration uses the Normalized Gradient Fields distance measure in a multilevel Gauss-Newton optimization framework and focuses on a region around the subthalamic nucleus in the MR. The accuracy of our method was extensively evaluated on 20 DBS datasets from clinical routine and compared with manual expert registrations. For each dataset, three independent registrations were available, thus allowing to relate algorithmic with expert performance. Our method achieved an average registration error of 0.95mm in the target region around the subthalamic nucleus as compared to an inter-observer variability of 1.12 mm. Together with the short registration time of about five seconds on average, our method forms a very attractive package that can be considered ready for clinical use.

Registration of Laser Scanning Point Clouds: A Review.

PubMed

Cheng, Liang; Chen, Song; Liu, Xiaoqiang; Xu, Hao; Wu, Yang; Li, Manchun; Chen, Yanming

2018-05-21

The integration of multi-platform, multi-angle, and multi-temporal LiDAR data has become important for geospatial data applications. This paper presents a comprehensive review of LiDAR data registration in the fields of photogrammetry and remote sensing. At present, a coarse-to-fine registration strategy is commonly used for LiDAR point clouds registration. The coarse registration method is first used to achieve a good initial position, based on which registration is then refined utilizing the fine registration method. According to the coarse-to-fine framework, this paper reviews current registration methods and their methodologies, and identifies important differences between them. The lack of standard data and unified evaluation systems is identified as a factor limiting objective comparison of different methods. The paper also describes the most commonly-used point cloud registration error analysis methods. Finally, avenues for future work on LiDAR data registration in terms of applications, data, and technology are discussed. In particular, there is a need to address registration of multi-angle and multi-scale data from various newly available types of LiDAR hardware, which will play an important role in diverse applications such as forest resource surveys, urban energy use, cultural heritage protection, and unmanned vehicles.

Registration of Laser Scanning Point Clouds: A Review

PubMed Central

Cheng, Liang; Chen, Song; Xu, Hao; Wu, Yang; Li, Manchun

2018-01-01

The integration of multi-platform, multi-angle, and multi-temporal LiDAR data has become important for geospatial data applications. This paper presents a comprehensive review of LiDAR data registration in the fields of photogrammetry and remote sensing. At present, a coarse-to-fine registration strategy is commonly used for LiDAR point clouds registration. The coarse registration method is first used to achieve a good initial position, based on which registration is then refined utilizing the fine registration method. According to the coarse-to-fine framework, this paper reviews current registration methods and their methodologies, and identifies important differences between them. The lack of standard data and unified evaluation systems is identified as a factor limiting objective comparison of different methods. The paper also describes the most commonly-used point cloud registration error analysis methods. Finally, avenues for future work on LiDAR data registration in terms of applications, data, and technology are discussed. In particular, there is a need to address registration of multi-angle and multi-scale data from various newly available types of LiDAR hardware, which will play an important role in diverse applications such as forest resource surveys, urban energy use, cultural heritage protection, and unmanned vehicles. PMID:29883397

2D-3D registration for cranial radiation therapy using a 3D kV CBCT and a single limited field-of-view 2D kV radiograph.

PubMed

Munbodh, Reshma; Knisely, Jonathan Ps; Jaffray, David A; Moseley, Douglas J

2018-05-01

We present and evaluate a fully automated 2D-3D intensity-based registration framework using a single limited field-of-view (FOV) 2D kV radiograph and a 3D kV CBCT for 3D estimation of patient setup errors during brain radiotherapy. We evaluated two similarity measures, the Pearson correlation coefficient on image intensity values (ICC) and maximum likelihood measure with Gaussian noise (MLG), derived from the statistics of transmission images. Pose determination experiments were conducted on 2D kV radiographs in the anterior-posterior (AP) and left lateral (LL) views and 3D kV CBCTs of an anthropomorphic head phantom. In order to minimize radiation exposure and exclude nonrigid structures from the registration, limited FOV 2D kV radiographs were employed. A spatial frequency band useful for the 2D-3D registration was identified from the bone-to-no-bone spectral ratio (BNBSR) of digitally reconstructed radiographs (DRRs) computed from the 3D kV planning CT of the phantom. The images being registered were filtered accordingly prior to computation of the similarity measures. We evaluated the registration accuracy achievable with a single 2D kV radiograph and with the registration results from the AP and LL views combined. We also compared the performance of the 2D-3D registration solutions proposed to that of a commercial 3D-3D registration algorithm, which used the entire skull for the registration. The ground truth was determined from markers affixed to the phantom and visible in the CBCT images. The accuracy of the 2D-3D registration solutions, as quantified by the root mean squared value of the target registration error (TRE) calculated over a radius of 3 cm for all poses tested, was ICC AP : 0.56 mm, MLG AP : 0.74 mm, ICC LL : 0.57 mm, MLG LL : 0.54 mm, ICC (AP and LL combined): 0.19 mm, and MLG (AP and LL combined): 0.21 mm. The accuracy of the 3D-3D registration algorithm was 0.27 mm. There was no significant difference in mean TRE for the 2D-3D registration algorithms using a single 2D kV radiograph with similarity measure and image view point. There was no significant difference in mean TRE between ICC LL , MLG LL , ICC (AP and LL combined), MLG (AP and LL combined), and the 3D-3D registration algorithm despite the smaller FOV used for the 2D-3D registration. While submillimeter registration accuracy was obtained with both ICC and MLG using a single 2D kV radiograph, combining the results from the two projection views resulted in a significantly smaller (P≤0.05) mean TRE. Our results indicate that it is possible to achieve submillimeter registration accuracy with both ICC and MLG using either single or dual limited FOV 2D kV radiographs of the head in the AP and LL views. The registration accuracy suggests that the 2D-3D registration solutions presented are suitable for the estimation of patient setup errors not only during conventional brain radiation therapy, but also during stereotactic procedures and proton radiation therapy where tighter setup margins are required. © 2018 American Association of Physicists in Medicine.

Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial

PubMed Central

López-Cortés, Luis Eduardo; Rosso-Fernández, Clara; Núñez-Núñez, María; Lavín-Alconero, Lucía; Bravo-Ferrer, José; Barriga, Ángel; Delgado, Mercedes; Lupión, Carmen; Retamar, Pilar; Rodríguez-Baño, Jesús

2017-01-01

Introduction Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. Methods and analysis The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic ‘real-practice’ trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Ethics and dissemination Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Discussion Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. Trial registration number The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry. PMID:28601833

Self-correcting multi-atlas segmentation

NASA Astrophysics Data System (ADS)

Gao, Yi; Wilford, Andrew; Guo, Liang

2016-03-01

In multi-atlas segmentation, one typically registers several atlases to the new image, and their respective segmented label images are transformed and fused to form the final segmentation. After each registration, the quality of the registration is reflected by the single global value: the final registration cost. Ideally, if the quality of the registration can be evaluated at each point, independent of the registration process, which also provides a direction in which the deformation can further be improved, the overall segmentation performance can be improved. We propose such a self-correcting multi-atlas segmentation method. The method is applied on hippocampus segmentation from brain images and statistically significantly improvement is observed.

A concept for holistic whole body MRI data analysis, Imiomics

PubMed Central

Malmberg, Filip; Johansson, Lars; Lind, Lars; Sundbom, Magnus; Ahlström, Håkan; Kullberg, Joel

2017-01-01

Purpose To present and evaluate a whole-body image analysis concept, Imiomics (imaging–omics) and an image registration method that enables Imiomics analyses by deforming all image data to a common coordinate system, so that the information in each voxel can be compared between persons or within a person over time and integrated with non-imaging data. Methods The presented image registration method utilizes relative elasticity constraints of different tissue obtained from whole-body water-fat MRI. The registration method is evaluated by inverse consistency and Dice coefficients and the Imiomics concept is evaluated by example analyses of importance for metabolic research using non-imaging parameters where we know what to expect. The example analyses include whole body imaging atlas creation, anomaly detection, and cross-sectional and longitudinal analysis. Results The image registration method evaluation on 128 subjects shows low inverse consistency errors and high Dice coefficients. Also, the statistical atlas with fat content intensity values shows low standard deviation values, indicating successful deformations to the common coordinate system. The example analyses show expected associations and correlations which agree with explicit measurements, and thereby illustrate the usefulness of the proposed Imiomics concept. Conclusions The registration method is well-suited for Imiomics analyses, which enable analyses of relationships to non-imaging data, e.g. clinical data, in new types of holistic targeted and untargeted big-data analysis. PMID:28241015

Termite testing continues

Treesearch

Terence L. Wagner; Joe Mulrooney; Chris Petereson

2002-01-01

The United States Department of Agriculture Forest Service's termiticide testing program provides unbiased efficacy data for product registration using standardized tests, sites and evaluation procedures. Virtually all termiticides undergo Forest Service tests prior to registration.

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1 trial): study protocol for a pragmatic, stepped-wedge, cluster randomized controlled registry.

PubMed

Li, Alvin H; Garg, Amit X; Prakash, Versha; Grimshaw, Jeremy M; Taljaard, Monica; Mitchell, Joanna; Matti, Danny; Linklater, Stefanie; Naylor, Kyla L; Dixon, Stephanie; Faulds, Cathy; Bevan, Rachel; Getchell, Leah; Knoll, Greg; Kim, S Joseph; Sontrop, Jessica; Bjerre, Lise M; Tong, Allison; Presseau, Justin

2017-12-21

There is a worldwide shortage of organs available for transplant, leading to preventable mortality associated with end-stage organ disease. While most citizens in many countries with an intent-to-donate "opt-in" system support organ donation, registration rates remain low. In Canada, most Canadians support organ donation but less than 25% in most provinces have registered their desire to donate their organs when they die. The family physician office is a promising yet underused setting in which to promote organ donor registration and address known barriers and enablers to registering for deceased organ and tissue donation. We developed a protocol to evaluate an intervention to promote registration for organ and tissue donation in family physician waiting rooms. This protocol describes a planned, stepped-wedge, cluster randomized registry trial in six family physician offices in Ontario, Canada to evaluate the effectiveness of reception staff providing patients with a pamphlet that addresses barriers and enablers to registration including a description of how to register for organ donation. An Internet-enabled tablet will also be provided in waiting rooms so that interested patients can register while waiting for their appointments. Family physicians and reception staff will be provided with training and/or materials to support any conversations about organ donation with their patients. Following a 2-week control period, the six offices will cross sequentially into the intervention arm in randomized sequence at 2-week intervals until all offices deliver the intervention. The primary outcome will be the proportion of patients visiting the office who are registered organ donors 7 days following their office visit. We will evaluate this outcome using routinely collected registry data from provincial administrative databases. A post-trial qualitative evaluation process will assess the experiences of reception staff and family physicians with the intervention and the stepped-wedge trial design. Promoting registration for organ donation in family physician offices is a potentially useful strategy for increasing registration for organ donation. Increased registration may ultimately help to increase the number of organs available for transplant. The results of this trial will provide important preliminary data on the effectiveness of using family physician offices to promote registration for organ donation. ClinicalTrials.gov, ID: NCT03213171 . Registered on 11 July 2017.

Automatic Intensity-based 3D-to-2D Registration of CT Volume and Dual-energy Digital Radiography for the Detection of Cardiac Calcification

PubMed Central

Chen, Xiang; Gilkeson, Robert; Fei, Baowei

2013-01-01

We are investigating three-dimensional (3D) to two-dimensional (2D) registration methods for computed tomography (CT) and dual-energy digital radiography (DR) for the detection of coronary artery calcification. CT is an established tool for the diagnosis of coronary artery diseases (CADs). Dual-energy digital radiography could be a cost-effective alternative for screening coronary artery calcification. In order to utilize CT as the “gold standard” to evaluate the ability of DR images for the detection and localization of calcium, we developed an automatic intensity-based 3D-to-2D registration method for 3D CT volumes and 2D DR images. To generate digital rendering radiographs (DRR) from the CT volumes, we developed three projection methods, i.e. Gaussian-weighted projection, threshold-based projection, and average-based projection. We tested normalized cross correlation (NCC) and normalized mutual information (NMI) as similarity measurement. We used the Downhill Simplex method as the search strategy. Simulated projection images from CT were fused with the corresponding DR images to evaluate the localization of cardiac calcification. The registration method was evaluated by digital phantoms, physical phantoms, and clinical data sets. The results from the digital phantoms show that the success rate is 100% with mean errors of less 0.8 mm and 0.2 degree for both NCC and NMI. The registration accuracy of the physical phantoms is 0.34 ± 0.27 mm. Color overlay and 3D visualization of the clinical data show that the two images are registered well. This is consistent with the improvement of the NMI values from 0.20 ± 0.03 to 0.25 ± 0.03 after registration. The automatic 3D-to-2D registration method is accurate and robust and may provide a useful tool to evaluate the dual-energy DR images for the detection of coronary artery calcification. PMID:24386527

Automatic Intensity-based 3D-to-2D Registration of CT Volume and Dual-energy Digital Radiography for the Detection of Cardiac Calcification.

PubMed

Chen, Xiang; Gilkeson, Robert; Fei, Baowei

2007-03-03

We are investigating three-dimensional (3D) to two-dimensional (2D) registration methods for computed tomography (CT) and dual-energy digital radiography (DR) for the detection of coronary artery calcification. CT is an established tool for the diagnosis of coronary artery diseases (CADs). Dual-energy digital radiography could be a cost-effective alternative for screening coronary artery calcification. In order to utilize CT as the "gold standard" to evaluate the ability of DR images for the detection and localization of calcium, we developed an automatic intensity-based 3D-to-2D registration method for 3D CT volumes and 2D DR images. To generate digital rendering radiographs (DRR) from the CT volumes, we developed three projection methods, i.e. Gaussian-weighted projection, threshold-based projection, and average-based projection. We tested normalized cross correlation (NCC) and normalized mutual information (NMI) as similarity measurement. We used the Downhill Simplex method as the search strategy. Simulated projection images from CT were fused with the corresponding DR images to evaluate the localization of cardiac calcification. The registration method was evaluated by digital phantoms, physical phantoms, and clinical data sets. The results from the digital phantoms show that the success rate is 100% with mean errors of less 0.8 mm and 0.2 degree for both NCC and NMI. The registration accuracy of the physical phantoms is 0.34 ± 0.27 mm. Color overlay and 3D visualization of the clinical data show that the two images are registered well. This is consistent with the improvement of the NMI values from 0.20 ± 0.03 to 0.25 ± 0.03 after registration. The automatic 3D-to-2D registration method is accurate and robust and may provide a useful tool to evaluate the dual-energy DR images for the detection of coronary artery calcification.

Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration

PubMed Central

Klein, Arno; Andersson, Jesper; Ardekani, Babak A.; Ashburner, John; Avants, Brian; Chiang, Ming-Chang; Christensen, Gary E.; Collins, D. Louis; Gee, James; Hellier, Pierre; Song, Joo Hyun; Jenkinson, Mark; Lepage, Claude; Rueckert, Daniel; Thompson, Paul; Vercauteren, Tom; Woods, Roger P.; Mann, J. John; Parsey, Ramin V.

2009-01-01

All fields of neuroscience that employ brain imaging need to communicate their results with reference to anatomical regions. In particular, comparative morphometry and group analysis of functional and physiological data require coregistration of brains to establish correspondences across brain structures. It is well established that linear registration of one brain to another is inadequate for aligning brain structures, so numerous algorithms have emerged to nonlinearly register brains to one another. This study is the largest evaluation of nonlinear deformation algorithms applied to brain image registration ever conducted. Fourteen algorithms from laboratories around the world are evaluated using 8 different error measures. More than 45,000 registrations between 80 manually labeled brains were performed by algorithms including: AIR, ANIMAL, ART, Diffeomorphic Demons, FNIRT, IRTK, JRD-fluid, ROMEO, SICLE, SyN, and four different SPM5 algorithms (“SPM2-type” and regular Normalization, Unified Segmentation, and the DARTEL Toolbox). All of these registrations were preceded by linear registration between the same image pairs using FLIRT. One of the most significant findings of this study is that the relative performances of the registration methods under comparison appear to be little affected by the choice of subject population, labeling protocol, and type of overlap measure. This is important because it suggests that the findings are generalizable to new subject populations that are labeled or evaluated using different labeling protocols. Furthermore, we ranked the 14 methods according to three completely independent analyses (permutation tests, one-way ANOVA tests, and indifference-zone ranking) and derived three almost identical top rankings of the methods. ART, SyN, IRTK, and SPM's DARTEL Toolbox gave the best results according to overlap and distance measures, with ART and SyN delivering the most consistently high accuracy across subjects and label sets. Updates will be published on the http://www.mindboggle.info/papers/ website. PMID:19195496

Technical Note: Development of a combined molecular breast imaging/ultrasound system for diagnostic evaluation of MBI-detected lesions.

PubMed

O'Connor, Michael K; Morrow, Melissa M; Tran, Thuy; Hruska, Carrie B; Conners, Amy L; Hunt, Katie N

2017-02-01

The purpose of this study was to perform a pilot evaluation of an integrated molecular breast imaging/ultrasound (MBI/US) system designed to enable, in real-time, the registration of US to MBI and diagnostic evaluation of breast lesions detected on MBI. The MBI/US system was constructed by modifying an existing dual-head cadmium zinc telluride (CZT)-based MBI gamma camera. The upper MBI detector head was replaced with a mesh panel, which allowed an ultrasound probe to access the breast. An optical tracking system was used to monitor the location of the ultrasound transducer, referenced to the MBI detector. The lesion depth at which ultrasound was targeted was estimated from analysis of previously acquired dual-head MBI datasets. A software tool was developed to project the US field of view onto the current MBI image. Correlation of lesion location between both modalities with real-time MBI/US scanning was confirmed in a breast phantom model and assessed in 12 patients with a breast lesion detected on MBI. Combined MBI/US scanning allowed for registration of lesions detected on US and MBI as validated in phantom experiments. In patient studies, successful registration was achieved in 8 of 12 (67%) patients, with complete registration achieved in seven and partial registration achieved in one patient. In 4 of 12 (37%) patients, lesion registration was not achieved, partially attributed to uncertainty in lesion depth estimates from MBI. The MBI/US system enabled successful registration of US to MBI in over half of patients studied in this pilot evaluation. Future studies are needed to determine if real-time, registered US imaging of MBI-detected lesions may obviate the need to proceed to more expensive procedures such as contrast-enhanced breast MRI for diagnostic workup or biopsy of MBI findings. © 2016 American Association of Physicists in Medicine.

Automatic intensity-based 3D-to-2D registration of CT volume and dual-energy digital radiography for the detection of cardiac calcification

NASA Astrophysics Data System (ADS)

Chen, Xiang; Gilkeson, Robert; Fei, Baowei

2007-03-01

We are investigating three-dimensional (3D) to two-dimensional (2D) registration methods for computed tomography (CT) and dual-energy digital radiography (DR) for the detection of coronary artery calcification. CT is an established tool for the diagnosis of coronary artery diseases (CADs). Dual-energy digital radiography could be a cost-effective alternative for screening coronary artery calcification. In order to utilize CT as the "gold standard" to evaluate the ability of DR images for the detection and localization of calcium, we developed an automatic intensity-based 3D-to-2D registration method for 3D CT volumes and 2D DR images. To generate digital rendering radiographs (DRR) from the CT volumes, we developed three projection methods, i.e. Gaussian-weighted projection, threshold-based projection, and average-based projection. We tested normalized cross correlation (NCC) and normalized mutual information (NMI) as similarity measurement. We used the Downhill Simplex method as the search strategy. Simulated projection images from CT were fused with the corresponding DR images to evaluate the localization of cardiac calcification. The registration method was evaluated by digital phantoms, physical phantoms, and clinical data sets. The results from the digital phantoms show that the success rate is 100% with mean errors of less 0.8 mm and 0.2 degree for both NCC and NMI. The registration accuracy of the physical phantoms is 0.34 +/- 0.27 mm. Color overlay and 3D visualization of the clinical data show that the two images are registered well. This is consistent with the improvement of the NMI values from 0.20 +/- 0.03 to 0.25 +/- 0.03 after registration. The automatic 3D-to-2D registration method is accurate and robust and may provide a useful tool to evaluate the dual-energy DR images for the detection of coronary artery calcification.

Study on networking issues of medium earth orbit satellite communications systems

NASA Technical Reports Server (NTRS)

Araki, Noriyuki; Shinonaga, Hideyuki; Ito, Yasuhiko

1993-01-01

Two networking issues of communications systems with medium earth orbit (MEO) satellites, namely network architectures and location determination and registration methods for hand-held terminals, are investigated in this paper. For network architecture, five candidate architectures are considered and evaluated in terms of signaling traffic. For location determination and registration, two methods are discussed and evaluated.

Selecting registration schemes in case of interstitial lung disease follow-up in CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vlachopoulos, Georgios; Korfiatis, Panayiotis; Skiadopoulos, Spyros

Purpose: Primary goal of this study is to select optimal registration schemes in the framework of interstitial lung disease (ILD) follow-up analysis in CT. Methods: A set of 128 multiresolution schemes composed of multiresolution nonrigid and combinations of rigid and nonrigid registration schemes are evaluated, utilizing ten artificially warped ILD follow-up volumes, originating from ten clinical volumetric CT scans of ILD affected patients, to select candidate optimal schemes. Specifically, all combinations of four transformation models (three rigid: rigid, similarity, affine and one nonrigid: third order B-spline), four cost functions (sum-of-square distances, normalized correlation coefficient, mutual information, and normalized mutual information),more » four gradient descent optimizers (standard, regular step, adaptive stochastic, and finite difference), and two types of pyramids (recursive and Gaussian-smoothing) were considered. The selection process involves two stages. The first stage involves identification of schemes with deformation field singularities, according to the determinant of the Jacobian matrix. In the second stage, evaluation methodology is based on distance between corresponding landmark points in both normal lung parenchyma (NLP) and ILD affected regions. Statistical analysis was performed in order to select near optimal registration schemes per evaluation metric. Performance of the candidate registration schemes was verified on a case sample of ten clinical follow-up CT scans to obtain the selected registration schemes. Results: By considering near optimal schemes common to all ranking lists, 16 out of 128 registration schemes were initially selected. These schemes obtained submillimeter registration accuracies in terms of average distance errors 0.18 ± 0.01 mm for NLP and 0.20 ± 0.01 mm for ILD, in case of artificially generated follow-up data. Registration accuracy in terms of average distance error in clinical follow-up data was in the range of 1.985–2.156 mm and 1.966–2.234 mm, for NLP and ILD affected regions, respectively, excluding schemes with statistically significant lower performance (Wilcoxon signed-ranks test, p < 0.05), resulting in 13 finally selected registration schemes. Conclusions: Selected registration schemes in case of ILD CT follow-up analysis indicate the significance of adaptive stochastic gradient descent optimizer, as well as the importance of combined rigid and nonrigid schemes providing high accuracy and time efficiency. The selected optimal deformable registration schemes are equivalent in terms of their accuracy and thus compatible in terms of their clinical outcome.« less

Safe use of vaccines and vaccine compliance with food safety requirements.

PubMed

Grein, K; Papadopoulos, O; Tollis, M

2007-08-01

Advanced technologies and regulatory regimes have contributed to the availability of veterinary vaccines that have high quality and favourable safety profiles in terms of potential risks posed to the target animals, the persons who come into contact with the vaccine, the consumers of food derived from vaccinated animals and the environment. The authorisation process requires that a range of safety studies are provided to evaluate the products. The design and production of vaccines, and their safe use, are primarily assessed by using data gathered from extensive pre-marketing studies performed on target animals and specific quality tests. The current post-marketing safeguards include good manufacturing practices, batch safety testing, inspections and pharmacovigilance. In addition to hazard identification, a full benefit/risk evaluation needs to be undertaken. The outcome of that evaluation will determine options for risk management and affect regulatory decisions on the safety of the vaccine; options might, for example, include special warnings on package inserts and labels.

Using patient-specific phantoms to evaluate deformable image registration algorithms for adaptive radiation therapy

PubMed Central

Stanley, Nick; Glide-Hurst, Carri; Kim, Jinkoo; Adams, Jeffrey; Li, Shunshan; Wen, Ning; Chetty, Indrin J.; Zhong, Hualiang

2014-01-01

The quality of adaptive treatment planning depends on the accuracy of its underlying deformable image registration (DIR). The purpose of this study is to evaluate the performance of two DIR algorithms, B-spline–based deformable multipass (DMP) and deformable demons (Demons), implemented in a commercial software package. Evaluations were conducted using both computational and physical deformable phantoms. Based on a finite element method (FEM), a total of 11 computational models were developed from a set of CT images acquired from four lung and one prostate cancer patients. FEM generated displacement vector fields (DVF) were used to construct the lung and prostate image phantoms. Based on a fast-Fourier transform technique, image noise power spectrum was incorporated into the prostate image phantoms to create simulated CBCT images. The FEM-DVF served as a gold standard for verification of the two registration algorithms performed on these phantoms. The registration algorithms were also evaluated at the homologous points quantified in the CT images of a physical lung phantom. The results indicated that the mean errors of the DMP algorithm were in the range of 1.0 ~ 3.1 mm for the computational phantoms and 1.9 mm for the physical lung phantom. For the computational prostate phantoms, the corresponding mean error was 1.0–1.9 mm in the prostate, 1.9–2.4 mm in the rectum, and 1.8–2.1 mm over the entire patient body. Sinusoidal errors induced by B-spline interpolations were observed in all the displacement profiles of the DMP registrations. Regions of large displacements were observed to have more registration errors. Patient-specific FEM models have been developed to evaluate the DIR algorithms implemented in the commercial software package. It has been found that the accuracy of these algorithms is patient-dependent and related to various factors including tissue deformation magnitudes and image intensity gradients across the regions of interest. This may suggest that DIR algorithms need to be verified for each registration instance when implementing adaptive radiation therapy. PMID:24257278

Using patient‐specific phantoms to evaluate deformable image registration algorithms for adaptive radiation therapy

PubMed Central

Stanley, Nick; Glide‐Hurst, Carri; Kim, Jinkoo; Adams, Jeffrey; Li, Shunshan; Wen, Ning; Chetty, Indrin J

2013-01-01

The quality of adaptive treatment planning depends on the accuracy of its underlying deformable image registration (DIR). The purpose of this study is to evaluate the performance of two DIR algorithms, B‐spline‐based deformable multipass (DMP) and deformable demons (Demons), implemented in a commercial software package. Evaluations were conducted using both computational and physical deformable phantoms. Based on a finite element method (FEM), a total of 11 computational models were developed from a set of CT images acquired from four lung and one prostate cancer patients. FEM generated displacement vector fields (DVF) were used to construct the lung and prostate image phantoms. Based on a fast‐Fourier transform technique, image noise power spectrum was incorporated into the prostate image phantoms to create simulated CBCT images. The FEM‐DVF served as a gold standard for verification of the two registration algorithms performed on these phantoms. The registration algorithms were also evaluated at the homologous points quantified in the CT images of a physical lung phantom. The results indicated that the mean errors of the DMP algorithm were in the range of 1.0~3.1mm for the computational phantoms and 1.9 mm for the physical lung phantom. For the computational prostate phantoms, the corresponding mean error was 1.0–1.9 mm in the prostate, 1.9–2.4 mm in the rectum, and 1.8–2.1 mm over the entire patient body. Sinusoidal errors induced by B‐spline interpolations were observed in all the displacement profiles of the DMP registrations. Regions of large displacements were observed to have more registration errors. Patient‐specific FEM models have been developed to evaluate the DIR algorithms implemented in the commercial software package. It has been found that the accuracy of these algorithms is patient‐dependent and related to various factors including tissue deformation magnitudes and image intensity gradients across the regions of interest. This may suggest that DIR algorithms need to be verified for each registration instance when implementing adaptive radiation therapy. PACS numbers: 87.10.Kn, 87.55.km, 87.55.Qr, 87.57.nj

Evaluation of image registration in PET/CT of the liver and recommendations for optimized imaging.

PubMed

Vogel, Wouter V; van Dalen, Jorn A; Wiering, Bas; Huisman, Henkjan; Corstens, Frans H M; Ruers, Theo J M; Oyen, Wim J G

2007-06-01

Multimodality PET/CT of the liver can be performed with an integrated (hybrid) PET/CT scanner or with software fusion of dedicated PET and CT. Accurate anatomic correlation and good image quality of both modalities are important prerequisites, regardless of the applied method. Registration accuracy is influenced by breathing motion differences on PET and CT, which may also have impact on (attenuation correction-related) artifacts, especially in the upper abdomen. The impact of these issues was evaluated for both hybrid PET/CT and software fusion, focused on imaging of the liver. Thirty patients underwent hybrid PET/CT, 20 with CT during expiration breath-hold (EB) and 10 with CT during free breathing (FB). Ten additional patients underwent software fusion of dedicated PET and dedicated expiration breath-hold CT (SF). The image registration accuracy was evaluated at the location of liver borders on CT and uncorrected PET images and at the location of liver lesions. Attenuation-correction artifacts were evaluated by comparison of liver borders on uncorrected and attenuation-corrected PET images. CT images were evaluated for the presence of breathing artifacts. In EB, 40% of patients had an absolute registration error of the diaphragm in the craniocaudal direction of >1 cm (range, -16 to 44 mm), and 45% of lesions were mispositioned >1 cm. In 50% of cases, attenuation-correction artifacts caused a deformation of the liver dome on PET of >1 cm. Poor compliance to breath-hold instructions caused CT artifacts in 55% of cases. In FB, 30% had registration errors of >1 cm (range, -4 to 16 mm) and PET artifacts were less extensive, but all CT images had breathing artifacts. As SF allows independent alignment of PET and CT, no registration errors or artifacts of >1 cm of the diaphragm occurred. Hybrid PET/CT of the liver may have significant registration errors and artifacts related to breathing motion. The extent of these issues depends on the selected breathing protocol and the speed of the CT scanner. No protocol or scanner can guarantee perfect image fusion. On the basis of these findings, recommendations were formulated with regard to scanner requirements, breathing protocols, and reporting.

Registration of central paths and colonic polyps between supine and prone scans in computed tomography colonography: Pilot study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Ping; Napel, Sandy; Acar, Burak

2004-10-01

Computed tomography colonography (CTC) is a minimally invasive method that allows the evaluation of the colon wall from CT sections of the abdomen/pelvis. The primary goal of CTC is to detect colonic polyps, precursors to colorectal cancer. Because imperfect cleansing and distension can cause portions of the colon wall to be collapsed, covered with water, and/or covered with retained stool, patients are scanned in both prone and supine positions. We believe that both reading efficiency and computer aided detection (CAD) of CTC images can be improved by accurate registration of data from the supine and prone positions. We developed amore » two-stage approach that first registers the colonic central paths using a heuristic and automated algorithm and then matches polyps or polyp candidates (CAD hits) by a statistical approach. We evaluated the registration algorithm on 24 patient cases. After path registration, the mean misalignment distance between prone and supine identical anatomic landmarks was reduced from 47.08 to 12.66 mm, a 73% improvement. The polyp registration algorithm was specifically evaluated using eight patient cases for which radiologists identified polyps separately for both supine and prone data sets, and then manually registered corresponding pairs. The algorithm correctly matched 78% of these pairs without user input. The algorithm was also applied to the 30 highest-scoring CAD hits in the prone and supine scans and showed a success rate of 50% in automatically registering corresponding polyp pairs. Finally, we computed the average number of CAD hits that need to be manually compared in order to find the correct matches among the top 30 CAD hits. With polyp registration, the average number of comparisons was 1.78 per polyp, as opposed to 4.28 comparisons without polyp registration.« less

Quantitative Analysis of Geometry and Lateral Symmetry of Proximal Middle Cerebral Artery.

PubMed

Peter, Roman; Emmer, Bart J; van Es, Adriaan C G M; van Walsum, Theo

2017-10-01

The purpose of our work is to quantitatively assess clinically relevant geometric properties of proximal middle cerebral arteries (pMCA), to investigate the degree of their lateral symmetry, and to evaluate whether the pMCA can be modeled by using state-of-the-art deformable image registration of the ipsi- and contralateral hemispheres. Individual pMCA segments were identified, quantified, and statistically evaluated on a set of 55 publicly available magnetic resonance angiography time-of-flight images. Rigid and deformable image registrations were used for geometric alignment of the ipsi- and contralateral hemispheres. Lateral symmetry of relevant geometric properties was evaluated before and after the image registration. No significant lateral differences regarding tortuosity and diameters of contralateral M1 segments of pMCA were identified. Regarding the length of M1 segment, 44% of all subjects could be considered laterally symmetrical. Dominant M2 segment was identified in 30% of men and 9% of women in both brain hemispheres. Deformable image registration performed significantly better (P < .01) than rigid registration with regard to distances between the ipsi- and the contralateral centerlines of M1 segments (1.5 ± 1.1 mm versus 2.8 ± 1.2 mm respectively) and between the M1 and the anterior cerebral artery (ACA) branching points (1.6 ± 1.4 mm after deformable registration). Although natural lateral variation of the length of M1 may not allow for sufficient modeling of the complete pMCA, deformable image registration of the contralateral brain hemisphere to the ipsilateral hemisphere is feasible for localization of ACA-M1 branching point and for modeling 71 ± 23% of M1 segment. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Evaluating the utility of 3D TRUS image information in guiding intra-procedure registration for motion compensation

NASA Astrophysics Data System (ADS)

De Silva, Tharindu; Cool, Derek W.; Romagnoli, Cesare; Fenster, Aaron; Ward, Aaron D.

2014-03-01

In targeted 3D transrectal ultrasound (TRUS)-guided biopsy, patient and prostate movement during the procedure can cause target misalignments that hinder accurate sampling of pre-planned suspicious tissue locations. Multiple solutions have been proposed for motion compensation via registration of intra-procedural TRUS images to a baseline 3D TRUS image acquired at the beginning of the biopsy procedure. While 2D TRUS images are widely used for intra-procedural guidance, some solutions utilize richer intra-procedural images such as bi- or multi-planar TRUS or 3D TRUS, acquired by specialized probes. In this work, we measured the impact of such richer intra-procedural imaging on motion compensation accuracy, to evaluate the tradeoff between cost and complexity of intra-procedural imaging versus improved motion compensation. We acquired baseline and intra-procedural 3D TRUS images from 29 patients at standard sextant-template biopsy locations. We used the planes extracted from the 3D intra-procedural scans to simulate 2D and 3D information available in different clinically relevant scenarios for registration. The registration accuracy was evaluated by calculating the target registration error (TRE) using manually identified homologous fiducial markers (micro-calcifications). Our results indicate that TRE improves gradually when the number of intra-procedural imaging planes used in registration is increased. Full 3D TRUS information helps the registration algorithm to robustly converge to more accurate solutions. These results can also inform the design of a fail-safe workflow during motion compensation in a system using a tracked 2D TRUS probe, by prescribing rotational acquisitions that can be performed quickly and easily by the physician immediately prior to needle targeting.

Evaluation of low-dose limits in 3D-2D rigid registration for surgical guidance

NASA Astrophysics Data System (ADS)

Uneri, A.; Wang, A. S.; Otake, Y.; Kleinszig, G.; Vogt, S.; Khanna, A. J.; Gallia, G. L.; Gokaslan, Z. L.; Siewerdsen, J. H.

2014-09-01

An algorithm for intensity-based 3D-2D registration of CT and C-arm fluoroscopy is evaluated for use in surgical guidance, specifically considering the low-dose limits of the fluoroscopic x-ray projections. The registration method is based on a framework using the covariance matrix adaptation evolution strategy (CMA-ES) to identify the 3D patient pose that maximizes the gradient information similarity metric. Registration performance was evaluated in an anthropomorphic head phantom emulating intracranial neurosurgery, using target registration error (TRE) to characterize accuracy and robustness in terms of 95% confidence upper bound in comparison to that of an infrared surgical tracking system. Three clinical scenarios were considered: (1) single-view image + guidance, wherein a single x-ray projection is used for visualization and 3D-2D guidance; (2) dual-view image + guidance, wherein one projection is acquired for visualization, combined with a second (lower-dose) projection acquired at a different C-arm angle for 3D-2D guidance; and (3) dual-view guidance, wherein both projections are acquired at low dose for the purpose of 3D-2D guidance alone (not visualization). In each case, registration accuracy was evaluated as a function of the entrance surface dose associated with the projection view(s). Results indicate that images acquired at a dose as low as 4 μGy (approximately one-tenth the dose of a typical fluoroscopic frame) were sufficient to provide TRE comparable or superior to that of conventional surgical tracking, allowing 3D-2D guidance at a level of dose that is at most 10% greater than conventional fluoroscopy (scenario #2) and potentially reducing the dose to approximately 20% of the level in a conventional fluoroscopically guided procedure (scenario #3).

Performance evaluations of demons and free form deformation algorithms for the liver region.

PubMed

Wang, Hui; Gong, Guanzhong; Wang, Hongjun; Li, Dengwang; Yin, Yong; Lu, Jie

2014-04-01

We investigated the influence of breathing motion on radiation therapy according to four- dimensional computed tomography (4D-CT) technology and indicated the registration of 4D-CT images was significant. The demons algorithm in two interpolation modes was compared to the FFD model algorithm to register the different phase images of 4D-CT in tumor tracking, using iodipin as verification. Linear interpolation was used in both mode 1 and mode 2. Mode 1 set outside pixels to nearest pixel, while mode 2 set outside pixels to zero. We used normalized mutual information (NMI), sum of squared differences, modified Hausdorff-distance, and registration speed to evaluate the performance of each algorithm. The average NMI after demons registration method in mode 1 improved 1.76% and 4.75% when compared to mode 2 and FFD model algorithm, respectively. Further, the modified Hausdorff-distance was no different between demons modes 1 and 2, but mode 1 was 15.2% lower than FFD. Finally, demons algorithm has the absolute advantage in registration speed. The demons algorithm in mode 1 was therefore found to be much more suitable for the registration of 4D-CT images. The subtractions of floating images and reference image before and after registration by demons further verified that influence of breathing motion cannot be ignored and the demons registration method is feasible.

Groupwise registration of MR brain images with tumors.

PubMed

Tang, Zhenyu; Wu, Yihong; Fan, Yong

2017-08-04

A novel groupwise image registration framework is developed for registering MR brain images with tumors. Our method iteratively estimates a normal-appearance counterpart for each tumor image to be registered and constructs a directed graph (digraph) of normal-appearance images to guide the groupwise image registration. Particularly, our method maps each tumor image to its normal appearance counterpart by identifying and inpainting brain tumor regions with intensity information estimated using a low-rank plus sparse matrix decomposition based image representation technique. The estimated normal-appearance images are groupwisely registered to a group center image guided by a digraph of images so that the total length of 'image registration paths' to be the minimum, and then the original tumor images are warped to the group center image using the resulting deformation fields. We have evaluated our method based on both simulated and real MR brain tumor images. The registration results were evaluated with overlap measures of corresponding brain regions and average entropy of image intensity information, and Wilcoxon signed rank tests were adopted to compare different methods with respect to their regional overlap measures. Compared with a groupwise image registration method that is applied to normal-appearance images estimated using the traditional low-rank plus sparse matrix decomposition based image inpainting, our method achieved higher image registration accuracy with statistical significance (p  =  7.02  ×  10 -9 ).

Application of tolerance limits to the characterization of image registration performance.

PubMed

Fedorov, Andriy; Wells, William M; Kikinis, Ron; Tempany, Clare M; Vangel, Mark G

2014-07-01

Deformable image registration is used increasingly in image-guided interventions and other applications. However, validation and characterization of registration performance remain areas that require further study. We propose an analysis methodology for deriving tolerance limits on the initial conditions for deformable registration that reliably lead to a successful registration. This approach results in a concise summary of the probability of registration failure, while accounting for the variability in the test data. The (β, γ) tolerance limit can be interpreted as a value of the input parameter that leads to successful registration outcome in at least 100β% of cases with the 100γ% confidence. The utility of the methodology is illustrated by summarizing the performance of a deformable registration algorithm evaluated in three different experimental setups of increasing complexity. Our examples are based on clinical data collected during MRI-guided prostate biopsy registered using publicly available deformable registration tool. The results indicate that the proposed methodology can be used to generate concise graphical summaries of the experiments, as well as a probabilistic estimate of the registration outcome for a future sample. Its use may facilitate improved objective assessment, comparison and retrospective stress-testing of deformable.

Contrasting clinical evidence for market authorisation of cardio-vascular devices in Europe and the USA: a systematic analysis of 10 devices based on Austrian pre-reimbursement assessments.

PubMed

Wild, Claudia; Erdös, Judit; Zechmeister, Ingrid

2014-11-04

European medical device regulation is under scrutiny and will be re-regulated with stricter rules concerning requirements for clinical evidence for high-risk medical devices. It is the aim of this study to analyse the differences between Europe and USA in dealing with risks and benefits of new cardio-vascular devices. Since no information is available on clinical data used by the Notified Body for CE-marking, data from Austrian pre-reimbursement assessments close to European market approval were used as proxy and compared with clinical data available at time of market approval by FDA in the USA. 10 cardio-vascular interventions with 27 newly CE approved medical devices were analysed. The time lag between market authorisation in Europe and in the USA is 3 to 7 years. Only 7 CE-marked devices also hold a FDA market approval, 7 further devices are in FDA approved ongoing efficacy trials. For 4 of the CE-marked devices the FDA market application or the approval-trial was either suspended due to efficacy or safety concerns or the approval was denied. Evidence available at time of CE-marking are most often case-series or small feasibility RCTs, while large RCTs and only in rare cases prospective cohort studies are the basis of FDA approvals. Additionally, the FDA often requires post-approval studies for high-risk devices. Market authorisation based on mature clinical data deriving from larger RCTs and longer follow-ups do not only change the perspective on the risk-benefit ratio, but also secures real patient benefit and safety and assures payers of investing only in truly innovative devices.

Authorising bortezomib treatment prior to reviewing haematology results: a step toward home administration.

PubMed

Waight, Clinton C; Cain, Rebecca

2014-10-01

Bortezomib treatment requires four visits to a chemotherapy unit in each 21-day cycle. Analysis of the Day 1 full blood count could allow clinicians to predict the risk of Grade 4 thrombocytopenia, thus negating the need to review the full blood count prior to each dose. The freedom to administer bortezomib without reviewing full blood count results on each treatment day could minimise appointment times and be a step toward home administration. A prospective study of treatment authorisation following a full toxicity assessment and full blood count results from the previous treatment day was undertaken. The full blood count results from 27 patients, receiving 381 doses revealed 12 treatment episodes where bortezomib was administered in the presence of Grade 4 thrombocytopenia. One instance of bleeding and two episodes of neutropenic sepsis were detected during toxicity assessments and treatment was not administered. Only one instance of Grade 4 thrombocytopenia was reported on any other treatment day when the Day 1 platelet count was greater than 75 × 10(9) units/l. From this data, Day 1 full blood count parameters were derived, which minimise the risk of Grade 4 haematological toxicity on subsequent treatment days, allowing clinicians to identify suitable patients for administration of bortezomib prior to reviewing full blood count results. When platelet counts on Day 1 are greater than 75 × 10(9) units/l and neutrophil counts are greater than 1.0 × 10(9) units/l, the administration of bortezomib can be authorised without the need for review of the full blood count on subsequent days of that cycle. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Determinants of utilisation differences for cancer medicines in Belgium, Scotland and Sweden.

PubMed

Ferrario, Alessandra

2017-12-01

Little comparative evidence is available on utilisation of cancer medicines in different countries and its determinants. The aim of this study was to develop a statistical model to test the correlation between utilisation and possible determinants in selected European countries. A sample of 31 medicines for cancer treatment that obtained EU-wide marketing authorisation between 2000 and 2012 was selected. Annual data on medicines' utilisation covering the in- and out-patient public sectors were obtained from national authorities between 2008 and 2013. Possible determinants of utilisation were extracted from HTA reports and complemented by contacts with key informants. A longitudinal mixed effect model was fitted to test possible determinants of medicines utilisation in Belgium, Scotland and Sweden. In the all-country model, the number of indications reimbursed positively correlated with increased consumption of medicines [one indication 2.6, 95% CI (1.8-3.6); two indications 2.4, 95% CI (1.4-4.3); three indications 4.9, 95% CI (2.2-10.9); all P < 0.01], years since EU-wide marketing authorisation [1.2, 95% CI (1.02-1.4); p < 0.05], price per DDD [0.9, 95% CI (0.998-0.999), P < 0.01], and Prescrire rating [0.5, 95% CI (0.3-0.9), P < 0.05] after adjusting for time and other covariates. In this study, the most important correlates of increased utilisation in a sample of cancer medicines introduced in the past 15 years were: medicines coverage and time since marketing authorisation. Prices had a negative effect on consumption in Belgium and Sweden. The positive impact of financial MEAs in Scotland suggests that the latter may remove the regressive effect of list prices on consumption.

Optimised padlock probe ligation and microarray detection of multiple (non-authorised) GMOs in a single reaction

PubMed Central

Prins, Theo W; van Dijk, Jeroen P; Beenen, Henriek G; Van Hoef, AM Angeline; Voorhuijzen, Marleen M; Schoen, Cor D; Aarts, Henk JM; Kok, Esther J

2008-01-01

Background To maintain EU GMO regulations, producers of new GM crop varieties need to supply an event-specific method for the new variety. As a result methods are nowadays available for EU-authorised genetically modified organisms (GMOs), but only to a limited extent for EU-non-authorised GMOs (NAGs). In the last decade the diversity of genetically modified (GM) ingredients in food and feed has increased significantly. As a result of this increase GMO laboratories currently need to apply many different methods to establish to potential presence of NAGs in raw materials and complex derived products. Results In this paper we present an innovative method for detecting (approved) GMOs as well as the potential presence of NAGs in complex DNA samples containing different crop species. An optimised protocol has been developed for padlock probe ligation in combination with microarray detection (PPLMD) that can easily be scaled up. Linear padlock probes targeted against GMO-events, -elements and -species have been developed that can hybridise to their genomic target DNA and are visualised using microarray hybridisation. In a tenplex PPLMD experiment, different genomic targets in Roundup-Ready soya, MON1445 cotton and Bt176 maize were detected down to at least 1%. In single experiments, the targets were detected down to 0.1%, i.e. comparable to standard qPCR. Conclusion Compared to currently available methods this is a significant step forward towards multiplex detection in complex raw materials and derived products. It is shown that the PPLMD approach is suitable for large-scale detection of GMOs in real-life samples and provides the possibility to detect and/or identify NAGs that would otherwise remain undetected. PMID:19055784

Optimised padlock probe ligation and microarray detection of multiple (non-authorised) GMOs in a single reaction.

PubMed

Prins, Theo W; van Dijk, Jeroen P; Beenen, Henriek G; Van Hoef, Am Angeline; Voorhuijzen, Marleen M; Schoen, Cor D; Aarts, Henk J M; Kok, Esther J

2008-12-04

To maintain EU GMO regulations, producers of new GM crop varieties need to supply an event-specific method for the new variety. As a result methods are nowadays available for EU-authorised genetically modified organisms (GMOs), but only to a limited extent for EU-non-authorised GMOs (NAGs). In the last decade the diversity of genetically modified (GM) ingredients in food and feed has increased significantly. As a result of this increase GMO laboratories currently need to apply many different methods to establish to potential presence of NAGs in raw materials and complex derived products. In this paper we present an innovative method for detecting (approved) GMOs as well as the potential presence of NAGs in complex DNA samples containing different crop species. An optimised protocol has been developed for padlock probe ligation in combination with microarray detection (PPLMD) that can easily be scaled up. Linear padlock probes targeted against GMO-events, -elements and -species have been developed that can hybridise to their genomic target DNA and are visualised using microarray hybridisation.In a tenplex PPLMD experiment, different genomic targets in Roundup-Ready soya, MON1445 cotton and Bt176 maize were detected down to at least 1%. In single experiments, the targets were detected down to 0.1%, i.e. comparable to standard qPCR. Compared to currently available methods this is a significant step forward towards multiplex detection in complex raw materials and derived products. It is shown that the PPLMD approach is suitable for large-scale detection of GMOs in real-life samples and provides the possibility to detect and/or identify NAGs that would otherwise remain undetected.

Evaluation of a Hockey Deceased Organ Donation Awareness Campaign: A Population-Based Cohort Study

PubMed Central

Naylor, Kyla L.; McKenzie, Susan; Cherry, Cindy; McArthur, Eric; Li, Alvin H.; McCallum, Megan K.; Kim, S. Joseph; Prakash, Versha; Knoll, Gregory A.; Garg, Amit X.

2017-01-01

Background: The Kidney Foundation of Canada developed a pilot campaign to educate persons attending junior hockey league games in London, Ontario, Canada, on deceased organ donation. Objective: To evaluate the impact of a hockey campaign on the number of new organ and tissue donor registrants. Design: Population-based retrospective cohort study. Setting: Residents of London, Ontario. Patients: We included 255 476 individuals eligible to register for organ donation with a London, Ontario postal code. Measurements: We compared the number of new deceased organ donor registrants in London, Ontario, during the campaign period (March 12 to April 16, 2015) with 3 different time periods (December 30, 2014 to February 3, 2015; February 4 to March 11, 2015; April 17 to May 22, 2015). We also compared registration rates in London with 2 Ontario cities (Kitchener-Waterloo and Hamilton) matching in a 1:1 ratio on age, sex, and income quintile. Methods: To compare registrations across time periods, we used binomial regression with an identity link function and generalized estimating equations with an independence correlation structure. We used modified Poisson regression to compare registration rates between cities. Results: During the campaign period, there were slightly more registrations (1218 registered of 252 832 unregistered individuals [0.48%]) compared with an earlier time period (risk difference: 0.09%; 95% confidence interval [CI]: 0.05%-0.12%). However, there was no significant difference compared with 2 time periods immediately before and after the campaign. London had slightly more registrations during the campaign period compared with the matched city of Hamilton (1180 registered of 236 582 unregistered individuals [0.50%] vs 490 registered of 236 582 unregistered individuals [0.21%]; risk ratio: 2.41; 95% CI: 2.17-2.68). The registration rate in London did not significantly differ from Kitchener-Waterloo. Limitations: Unable to conclude whether the minor increase in deceased organ donor registration was the result of the campaign or other factors (e.g., simultaneous organ registration events, seasonality). Conclusions: Overall, a minor increase in deceased organ donor registration was observed during the hockey organ donation awareness campaign; however, the specific impact of the campaign on organ donor registration could not be determined. PMID:28748101

Process Evaluation of a School-Based Education Program about Organ Donation and Registration, and the Intention for Continuance

ERIC Educational Resources Information Center

Reubsaet, A.; Reinaerts, E. B. M.; Brug, J.; van Hooff, J. P.; van den Borne, H. W.

2004-01-01

This paper describes the process evaluation of an organ donation education program for high school students aged 15-18 years of which the effectiveness was established. The program consisted of three components: a video with group discussion, an interactive computer-tailored program and a registration training session. A cross-sectional survey was…

Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

PubMed

Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

2015-01-01

In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

Legal and organisational innovation in the Italian pharmacy system: commercial vs public interest.

PubMed

Santuari, Alceste

2017-10-01

Pharmacy services are undoubtedly an important part of primary care. Pharmacists are entrepreneurs and simultaneously they are entrusted with a public mission in the health care sector. Pharmacies then reflect a contrast between a commercial/economic objective and public interest, which is to be identified with citizens' universal right to health care services. This is the reason why in Italy, as in many other EU countries, pharmacies supply their services according to a prior authorisation granted by public authorities. In common with many EU countries, this authorisation is secured according to a demographic criterion. It is only by means of these licensed pharmacies that citizens can buy drugs under medical prescription. Accordingly, the health system is to be driven by public interest, which has yet to prove how competing interests may be regulated in serving health needs. In the light of EU law, the article advocates for an innovative legal and organisational tool whereby to organise the Italian pharmacy system in order to combine economic consideration and public benefit.

Managing ethically questionable parental requests: growth suppression and manipulation of puberty.

PubMed

Isaacs, David; Tobin, Bernadette; Hamblin, Julie; Slaytor, Emma; Donaghue, Kim C; Munns, Craig; Kilham, Henry A

2011-09-01

Doctors sometimes struggle with ethically challenging requests for treatment from children's parents. For instance, we have recently had two requests by parents of children, a girl and a boy, each with a severe developmental disability, for hormonal therapy to suppress growth and puberty: the girl's parents requested, in addition, hysterectomy and mastectomy. We propose a reliable approach to assessing the ethical and legal aspects of these and other requests for 'non-therapeutic' treatment of a minor who lacks the capacity to give informed consent. We argue that a doctor should first assess whether the request is one that he or she can, in conscience, accede to, and then, if it is, seek the authorisation of a court. We outline considerations relevant to the doctor's assessment of both the ethical issues and to the need for court authorisation. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Technical and Regulatory Considerations in Using Freight Containers as Industrial Packages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hawk, Mark B; Opperman, Erich; Natali, Ronald

2008-01-01

The US Department of Energy (DOE), Office of Environmental Management (EM), is actively pursuing activities to reduce the radiological risk and clean up the environmental legacy of the nation's nuclear weapons programmes. The EM has made significant progress in recent years in the clean-up and closure of sites and is also focusing on longer term activities necessary for the completion of the clean-up programme. The packaging and transportation of contaminated demolition debris and low level waste materials in a safe and cost effective manner are essential in completing this mission. Toward this end, the US Department of Transportation's Final Rulemore » on Hazardous Materials Regulation issued on 26 January 2004, included a new provision authorising the use of freight containers (e.g. 20 and 40 ft ISO containers) as industrial packages type 2 or 3. This paper will discuss the technical and regulatory considerations in using these newly authorised and large packages for the packaging and transportation of low level waste materials.« less

Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project.

PubMed

Hanning, Sara M; Orlu Gul, Mine; Winslade, Jackie; Baarslag, Manuel A; Neubert, Antje; Tuleu, Catherine

2016-09-25

A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project. Copyright © 2016 Elsevier B.V. All rights reserved.

Image Navigation and Registration Performance Assessment Evaluation Tools for GOES-R ABI and GLM

NASA Technical Reports Server (NTRS)

Houchin, Scott; Porter, Brian; Graybill, Justin; Slingerland, Philip

2017-01-01

The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24 hour evaluation period. This paper describes the software design and implementation of IPATS and provides preliminary test results.

Multi-modality image registration for effective thermographic fever screening

NASA Astrophysics Data System (ADS)

Dwith, C. Y. N.; Ghassemi, Pejhman; Pfefer, Joshua; Casamento, Jon; Wang, Quanzeng

2017-02-01

Fever screening based on infrared thermographs (IRTs) is a viable mass screening approach during infectious disease pandemics, such as Ebola and Severe Acute Respiratory Syndrome (SARS), for temperature monitoring in public places like hospitals and airports. IRTs have been found to be powerful, quick and non-invasive methods for detecting elevated temperatures. Moreover, regions medially adjacent to the inner canthi (called the canthi regions in this paper) are preferred sites for fever screening. Accurate localization of the canthi regions can be achieved through multi-modality registration of infrared (IR) and white-light images. Here we propose a registration method through a coarse-fine registration strategy using different registration models based on landmarks and edge detection on eye contours. We have evaluated the registration accuracy to be within +/- 2.7 mm, which enables accurate localization of the canthi regions.

Closed-Form Jensen-Renyi Divergence for Mixture of Gaussians and Applications to Group-Wise Shape Registration*

PubMed Central

Wang, Fei; Syeda-Mahmood, Tanveer; Vemuri, Baba C.; Beymer, David; Rangarajan, Anand

2010-01-01

In this paper, we propose a generalized group-wise non-rigid registration strategy for multiple unlabeled point-sets of unequal cardinality, with no bias toward any of the given point-sets. To quantify the divergence between the probability distributions – specifically Mixture of Gaussians – estimated from the given point sets, we use a recently developed information-theoretic measure called Jensen-Renyi (JR) divergence. We evaluate a closed-form JR divergence between multiple probabilistic representations for the general case where the mixture models differ in variance and the number of components. We derive the analytic gradient of the divergence measure with respect to the non-rigid registration parameters, and apply it to numerical optimization of the group-wise registration, leading to a computationally efficient and accurate algorithm. We validate our approach on synthetic data, and evaluate it on 3D cardiac shapes. PMID:20426043

Closed-form Jensen-Renyi divergence for mixture of Gaussians and applications to group-wise shape registration.

PubMed

Wang, Fei; Syeda-Mahmood, Tanveer; Vemuri, Baba C; Beymer, David; Rangarajan, Anand

2009-01-01

In this paper, we propose a generalized group-wise non-rigid registration strategy for multiple unlabeled point-sets of unequal cardinality, with no bias toward any of the given point-sets. To quantify the divergence between the probability distributions--specifically Mixture of Gaussians--estimated from the given point sets, we use a recently developed information-theoretic measure called Jensen-Renyi (JR) divergence. We evaluate a closed-form JR divergence between multiple probabilistic representations for the general case where the mixture models differ in variance and the number of components. We derive the analytic gradient of the divergence measure with respect to the non-rigid registration parameters, and apply it to numerical optimization of the group-wise registration, leading to a computationally efficient and accurate algorithm. We validate our approach on synthetic data, and evaluate it on 3D cardiac shapes.

Automatic lung nodule matching for the follow-up in temporal chest CT scans

NASA Astrophysics Data System (ADS)

Hong, Helen; Lee, Jeongjin; Shin, Yeong Gil

2006-03-01

We propose a fast and robust registration method for matching lung nodules of temporal chest CT scans. Our method is composed of four stages. First, the lungs are extracted from chest CT scans by the automatic segmentation method. Second, the gross translational mismatch is corrected by the optimal cube registration. This initial registration does not require extracting any anatomical landmarks. Third, initial alignment is step by step refined by the iterative surface registration. To evaluate the distance measure between surface boundary points, a 3D distance map is generated by the narrow-band distance propagation, which drives fast and robust convergence to the optimal location. Fourth, nodule correspondences are established by the pairs with the smallest Euclidean distances. The results of pulmonary nodule alignment of twenty patients are reported on a per-center-of mass point basis using the average Euclidean distance (AED) error between corresponding nodules of initial and follow-up scans. The average AED error of twenty patients is significantly reduced to 4.7mm from 30.0mm by our registration. Experimental results show that our registration method aligns the lung nodules much faster than the conventional ones using a distance measure. Accurate and fast result of our method would be more useful for the radiologist's evaluation of pulmonary nodules on chest CT scans.

Robust registration of sparsely sectioned histology to ex-vivo MRI of temporal lobe resections

NASA Astrophysics Data System (ADS)

Goubran, Maged; Khan, Ali R.; Crukley, Cathie; Buchanan, Susan; Santyr, Brendan; deRibaupierre, Sandrine; Peters, Terry M.

2012-02-01

Surgical resection of epileptic foci is a typical treatment for drug-resistant epilepsy, however, accurate preoperative localization is challenging and often requires invasive sub-dural or intra-cranial electrode placement. The presence of cellular abnormalities in the resected tissue can be used to validate the effectiveness of multispectralMagnetic Resonance Imaging (MRI) in pre-operative foci localization and surgical planning. If successful, these techniques can lead to improved surgical outcomes and less invasive procedures. Towards this goal, a novel pipeline is presented here for post-operative imaging of temporal lobe specimens involving MRI and digital histology, and present and evaluate methods for bringing these images into spatial correspondence. The sparsely-sectioned histology images of resected tissue represents a challenge for 3D reconstruction which we address with a combined 3D and 2D rigid registration algorithm that alternates between slice-based and volume-based registration with the ex-vivo MRI. We also evaluate four methods for non-rigid within-plane registration using both images and fiducials, with the top performing method resulting in a target registration error of 0.87 mm. This work allows for the spatially-local comparison of histology with post-operative MRI and paves the way for eventual registration with pre-operative MRI images.

Few candidate termiticides are left in the pipeline, according to the 2011 USDA-FS termiticide report

Treesearch

Terry Wagner; Thomas Shelton; Chris Peterson

2012-01-01

Candidate termiticides typically undergo a five-year evaluation at four field sites before the U.S. Environmental Protection Agency (EPA) considers them for registration. The tests are conducted by the U.S. Department of Agriculture Forest Service (USDA-FS), which has a long history of evaluating termiticides for federal and state registration. In 2011, the USDA-FS...

Cost-effective surgical registration using consumer depth cameras

NASA Astrophysics Data System (ADS)

Potter, Michael; Yaniv, Ziv

2016-03-01

The high costs associated with technological innovation have been previously identified as both a major contributor to the rise of health care expenses, and as a limitation for widespread adoption of new technologies. In this work we evaluate the use of two consumer grade depth cameras, the Microsoft Kinect v1 and 3DSystems Sense, as a means for acquiring point clouds for registration. These devices have the potential to replace professional grade laser range scanning devices in medical interventions that do not require sub-millimetric registration accuracy, and may do so at a significantly reduced cost. To facilitate the use of these devices we have developed a near real-time (1-4 sec/frame) rigid registration framework combining several alignment heuristics with the Iterative Closest Point (ICP) algorithm. Using nearest neighbor registration error as our evaluation criterion we found the optimal scanning distances for the Sense and Kinect to be 50-60cm and 70-80cm respectively. When imaging a skull phantom at these distances, RMS error values of 1.35mm and 1.14mm were obtained. The registration framework was then evaluated using cranial MR scans of two subjects. For the first subject, the RMS error using the Sense was 1.28 +/- 0.01 mm. Using the Kinect this error was 1.24 +/- 0.03 mm. For the second subject, whose MR scan was significantly corrupted by metal implants, the errors increased to 1.44 +/- 0.03 mm and 1.74 +/- 0.06 mm but the system nonetheless performed within acceptable bounds.

Evaluation of non-rigid registration parameters for atlas-based segmentation of CT images of human cochlea

NASA Astrophysics Data System (ADS)

Elfarnawany, Mai; Alam, S. Riyahi; Agrawal, Sumit K.; Ladak, Hanif M.

2017-02-01

Cochlear implant surgery is a hearing restoration procedure for patients with profound hearing loss. In this surgery, an electrode is inserted into the cochlea to stimulate the auditory nerve and restore the patient's hearing. Clinical computed tomography (CT) images are used for planning and evaluation of electrode placement, but their low resolution limits the visualization of internal cochlear structures. Therefore, high resolution micro-CT images are used to develop atlas-based segmentation methods to extract these nonvisible anatomical features in clinical CT images. Accurate registration of the high and low resolution CT images is a prerequisite for reliable atlas-based segmentation. In this study, we evaluate and compare different non-rigid B-spline registration parameters using micro-CT and clinical CT images of five cadaveric human cochleae. The varying registration parameters are cost function (normalized correlation (NC), mutual information and mean square error), interpolation method (linear, windowed-sinc and B-spline) and sampling percentage (1%, 10% and 100%). We compare the registration results visually and quantitatively using the Dice similarity coefficient (DSC), Hausdorff distance (HD) and absolute percentage error in cochlear volume. Using MI or MSE cost functions and linear or windowed-sinc interpolation resulted in visually undesirable deformation of internal cochlear structures. Quantitatively, the transforms using 100% sampling percentage yielded the highest DSC and smallest HD (0.828+/-0.021 and 0.25+/-0.09mm respectively). Therefore, B-spline registration with cost function: NC, interpolation: B-spline and sampling percentage: moments 100% can be the foundation of developing an optimized atlas-based segmentation algorithm of intracochlear structures in clinical CT images.

Validation of non-rigid point-set registration methods using a porcine bladder pelvic phantom

NASA Astrophysics Data System (ADS)

Zakariaee, Roja; Hamarneh, Ghassan; Brown, Colin J.; Spadinger, Ingrid

2016-01-01

The problem of accurate dose accumulation in fractionated radiotherapy treatment for highly deformable organs, such as bladder, has garnered increasing interest over the past few years. However, more research is required in order to find a robust and efficient solution and to increase the accuracy over the current methods. The purpose of this study was to evaluate the feasibility and accuracy of utilizing non-rigid (affine or deformable) point-set registration in accumulating dose in bladder of different sizes and shapes. A pelvic phantom was built to house an ex vivo porcine bladder with fiducial landmarks adhered onto its surface. Four different volume fillings of the bladder were used (90, 180, 360 and 480 cc). The performance of MATLAB implementations of five different methods were compared, in aligning the bladder contour point-sets. The approaches evaluated were coherent point drift (CPD), gaussian mixture model, shape context, thin-plate spline robust point matching (TPS-RPM) and finite iterative closest point (ICP-finite). The evaluation metrics included registration runtime, target registration error (TRE), root-mean-square error (RMS) and Hausdorff distance (HD). The reference (source) dataset was alternated through all four points-sets, in order to study the effect of reference volume on the registration outcomes. While all deformable algorithms provided reasonable registration results, CPD provided the best TRE values (6.4 mm), and TPS-RPM yielded the best mean RMS and HD values (1.4 and 6.8 mm, respectively). ICP-finite was the fastest technique and TPS-RPM, the slowest.

TH-EF-BRA-03: Assessment of Data-Driven Respiratory Motion-Compensation Methods for 4D-CBCT Image Registration and Reconstruction Using Clinical Datasets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riblett, MJ; Weiss, E; Hugo, GD

Purpose: To evaluate the performance of a 4D-CBCT registration and reconstruction method that corrects for respiratory motion and enhances image quality under clinically relevant conditions. Methods: Building on previous work, which tested feasibility of a motion-compensation workflow using image datasets superior to clinical acquisitions, this study assesses workflow performance under clinical conditions in terms of image quality improvement. Evaluated workflows utilized a combination of groupwise deformable image registration (DIR) and image reconstruction. Four-dimensional cone beam CT (4D-CBCT) FDK reconstructions were registered to either mean or respiratory phase reference frame images to model respiratory motion. The resulting 4D transformation was usedmore » to deform projection data during the FDK backprojection operation to create a motion-compensated reconstruction. To simulate clinically realistic conditions, superior quality projection datasets were sampled using a phase-binned striding method. Tissue interface sharpness (TIS) was defined as the slope of a sigmoid curve fit to the lung-diaphragm boundary or to the carina tissue-airway boundary when no diaphragm was discernable. Image quality improvement was assessed in 19 clinical cases by evaluating mitigation of view-aliasing artifacts, tissue interface sharpness recovery, and noise reduction. Results: For clinical datasets, evaluated average TIS recovery relative to base 4D-CBCT reconstructions was observed to be 87% using fixed-frame registration alone; 87% using fixed-frame with motion-compensated reconstruction; 92% using mean-frame registration alone; and 90% using mean-frame with motion-compensated reconstruction. Soft tissue noise was reduced on average by 43% and 44% for the fixed-frame registration and registration with motion-compensation methods, respectively, and by 40% and 42% for the corresponding mean-frame methods. Considerable reductions in view aliasing artifacts were observed for each method. Conclusion: Data-driven groupwise registration and motion-compensated reconstruction have the potential to improve the quality of 4D-CBCT images acquired under clinical conditions. For clinical image datasets, the addition of motion compensation after groupwise registration visibly reduced artifact impact. This work was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA166119. Hugo and Weiss hold a research agreement with Philips Healthcare and license agreement with Varian Medical Systems. Weiss receives royalties from UpToDate. Christensen receives funds from Roger Koch to support research.« less

Oral surgery in the European Union: challenges of diversity in training and practice.

PubMed

Nasseripour, M N; Hervé, C; Meningaud, J-P

2017-02-01

At the crossroads of medicine and dentistry, oral surgery with orthodontics are the only recognised dental specialties by the European Union. The goal of our study is to evaluate the current state of oral surgery in Europe from its teaching to its practice, the hypothesis being that a notable diversity persists despite European Union harmonisation process. To understand the impact of this diversity applied to European Union freedom of movement and its ethical implications for the practice of oral surgery, English and French questionnaires were sent by email to universities and organisations delivering authorisation to practise in France, Germany, Spain, Sweden and United Kingdom chosen based upon inclusion and exclusion criteria. An analysis of documents on these organisations' official websites was also conducted. Demographic information was obtained from the aforementioned organisations. The profile of practising oral surgeons is different dependent on the country. The university and hospital trainings conform to European recommendations and span 3-4 years. European Board certification is not required. Continuing education is mandatory only in France, Germany and United Kingdom. As for curricula and scope of practice, no consensus can be derived. There is potential conflict of interest between European Union principles of freedom of movement and protection of all citizens, as member countries do not uniformly apply Directives and recommendations. A new survey of all European Union oral surgery programmes as well as organisations delivering authorisation to practise is necessary to implement across the board harmonisation of training and practice to insure patient safety in light of the migration of European Union practitioners. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Challenges in conducting post-authorisation safety studies (PASS): A vaccine manufacturer's view.

PubMed

Cohet, Catherine; Rosillon, Dominique; Willame, Corinne; Haguinet, Francois; Marenne, Marie-Noëlle; Fontaine, Sandrine; Buyse, Hubert; Bauchau, Vincent; Baril, Laurence

2017-05-25

Post-authorisation safety studies (PASS) of vaccines assess or quantify the risk of adverse events following immunisation that were not identified or could not be estimated pre-licensure. The aim of this perspective paper is to describe the authors' experience in the design and conduct of twelve PASS that contributed to the evaluation of the benefit-risk of vaccines in real-world settings. We describe challenges and learnings from selected PASS of rotavirus, malaria, influenza, human papillomavirus and measles-mumps-rubella-varicella vaccines that assessed or identified potential or theoretical risks, which may lead to changes to risk management plans and/or to label updates. Study settings include the use of large healthcare databases and de novo data collection. PASS methodology is influenced by the background incidence of the outcome of interest, vaccine uptake, availability and quality of data sources, identification of the at-risk population and of suitable comparators, availability of validated case definitions, and the frequent need for case ascertainment in large databases. Challenges include the requirement for valid exposure and outcome data, identification of, and access to, adequate data sources, and mitigating limitations including bias and confounding. Assessing feasibility is becoming a key step to confirm that study objectives can be met in a timely manner. PASS provide critical information for regulators, public health agencies, vaccine manufacturers and ultimately, individuals. Collaborative approaches and synergistic efforts between vaccine manufacturers and key stakeholders, such as regulatory and public health agencies, are needed to facilitate access to data, and to drive optimal study design and implementation, with the aim of generating robust evidence. Copyright © 2017 GSK Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

Comparison of not for resuscitation (NFR) forms across five Victorian health services.

PubMed

Levinson, M; Mills, A; Hutchinson, A M; Heriot, G; Stephenson, G; Gellie, A

2014-07-01

Within Australian hospitals, cardiac and respiratory arrests result in a resuscitation attempt unless the patient is documented as not for resuscitation. To examine the consistency of policies and documentation for withholding in-hospital resuscitation across health services. An observational, qualitative review of hospital policy and documentation was conducted in June 2013 in three public and two private sector hospitals in metropolitan Melbourne. Not for resuscitation (NFR) forms were evaluated for physical characteristics, content, authorisation and decision-making. Hospital policies were coded for alerts, definition of futility and burden of treatment and management of discussions and dissent. There was a lack of standardisation, with each site using its own unique NFR form and accompanying site-specific policies. Differences were found in who could authorise the decision, what was included on the form, the role of patients and families, and how discussions were managed and dissent resolved. Futility and burden of treatment were not defined independently. These inconsistencies across sites contribute to a lack of clarity regarding the decision to withhold resuscitation, and have implications for staff employed across multiple hospitals. NFR forms should be reviewed and standardised so as to be clear, uniform and consistent with the legislative framework. We propose a two-stage process of documentation. Stage 1 facilitates discussion of patient-specific goals of care and consideration of limitations of treatment. Stage 2 serves to communicate a NFR order. Decisions to withhold resuscitation are inherently complex but could be aided by separating the decision-making process from the communication of the decision, resulting in improved end-of-life care. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Influence of image registration on apparent diffusion coefficient images computed from free-breathing diffusion MR images of the abdomen.

PubMed

Guyader, Jean-Marie; Bernardin, Livia; Douglas, Naomi H M; Poot, Dirk H J; Niessen, Wiro J; Klein, Stefan

2015-08-01

To evaluate the influence of image registration on apparent diffusion coefficient (ADC) images obtained from abdominal free-breathing diffusion-weighted MR images (DW-MRIs). A comprehensive pipeline based on automatic three-dimensional nonrigid image registrations is developed to compensate for misalignments in DW-MRI datasets obtained from five healthy subjects scanned twice. Motion is corrected both within each image and between images in a time series. ADC distributions are compared with and without registration in two abdominal volumes of interest (VOIs). The effects of interpolations and Gaussian blurring as alternative strategies to reduce motion artifacts are also investigated. Among the four considered scenarios (no processing, interpolation, blurring and registration), registration yields the best alignment scores. Median ADCs vary according to the chosen scenario: for the considered datasets, ADCs obtained without processing are 30% higher than with registration. Registration improves voxelwise reproducibility at least by a factor of 2 and decreases uncertainty (Fréchet-Cramér-Rao lower bound). Registration provides similar improvements in reproducibility and uncertainty as acquiring four times more data. Patient motion during image acquisition leads to misaligned DW-MRIs and inaccurate ADCs, which can be addressed using automatic registration. © 2014 Wiley Periodicals, Inc.

Gaussian Process Interpolation for Uncertainty Estimation in Image Registration

PubMed Central

Wachinger, Christian; Golland, Polina; Reuter, Martin; Wells, William

2014-01-01

Intensity-based image registration requires resampling images on a common grid to evaluate the similarity function. The uncertainty of interpolation varies across the image, depending on the location of resampled points relative to the base grid. We propose to perform Bayesian inference with Gaussian processes, where the covariance matrix of the Gaussian process posterior distribution estimates the uncertainty in interpolation. The Gaussian process replaces a single image with a distribution over images that we integrate into a generative model for registration. Marginalization over resampled images leads to a new similarity measure that includes the uncertainty of the interpolation. We demonstrate that our approach increases the registration accuracy and propose an efficient approximation scheme that enables seamless integration with existing registration methods. PMID:25333127

A prospective comparison between auto-registration and manual registration of real-time ultrasound with MR images for percutaneous ablation or biopsy of hepatic lesions.

PubMed

Cha, Dong Ik; Lee, Min Woo; Song, Kyoung Doo; Oh, Young-Taek; Jeong, Ja-Yeon; Chang, Jung-Woo; Ryu, Jiwon; Lee, Kyong Joon; Kim, Jaeil; Bang, Won-Chul; Shin, Dong Kuk; Choi, Sung Jin; Koh, Dalkwon; Seo, Bong Koo; Kim, Kyunga

2017-06-01

To compare the accuracy and required time for image fusion of real-time ultrasound (US) with pre-procedural magnetic resonance (MR) images between positioning auto-registration and manual registration for percutaneous radiofrequency ablation or biopsy of hepatic lesions. This prospective study was approved by the institutional review board, and all patients gave written informed consent. Twenty-two patients (male/female, n = 18/n = 4; age, 61.0 ± 7.7 years) who were referred for planning US to assess the feasibility of radiofrequency ablation (n = 21) or biopsy (n = 1) for focal hepatic lesions were included. One experienced radiologist performed the two types of image fusion methods in each patient. The performance of auto-registration and manual registration was evaluated. The accuracy of the two methods, based on measuring registration error, and the time required for image fusion for both methods were recorded using in-house software and respectively compared using the Wilcoxon signed rank test. Image fusion was successful in all patients. The registration error was not significantly different between the two methods (auto-registration: median, 3.75 mm; range, 1.0-15.8 mm vs. manual registration: median, 2.95 mm; range, 1.2-12.5 mm, p = 0.242). The time required for image fusion was significantly shorter with auto-registration than with manual registration (median, 28.5 s; range, 18-47 s, vs. median, 36.5 s; range, 14-105 s, p = 0.026). Positioning auto-registration showed promising results compared with manual registration, with similar accuracy and even shorter registration time.

"Unwalling" the Classroom: Teacher Reaction and Adaptation

ERIC Educational Resources Information Center

Deed, Craig; Lesko, Thomas

2015-01-01

Modern open school architecture abstractly expresses ideas about choice, flexibility and autonomy. While open spaces express and authorise different teaching practice, these versions of school and classrooms present challenges to teaching routines and practice. This paper examines how teachers adapt as they move into new school buildings designed…

New Protocol for Skin Landmark Registration in Image-Guided Neurosurgery: Technical Note.

PubMed

Gerard, Ian J; Hall, Jeffery A; Mok, Kelvin; Collins, D Louis

2015-09-01

Newer versions of the commercial Medtronic StealthStation allow the use of only 8 landmark pairs for patient-to-image registration as opposed to 9 landmarks in older systems. The choice of which landmark pair to drop in these newer systems can have an effect on the quality of the patient-to-image registration. To investigate 4 landmark registration protocols based on 8 landmark pairs and compare the resulting registration accuracy with a 9-landmark protocol. Four different protocols were tested on both phantoms and patients. Two of the protocols involved using 4 ear landmarks and 4 facial landmarks and the other 2 involved using 3 ear landmarks and 5 facial landmarks. Both the fiducial registration error and target registration error were evaluated for each of the different protocols to determine any difference between them and the 9-landmark protocol. No difference in fiducial registration error was found between any of the 8-landmark protocols and the 9-landmark protocol. A significant decrease (P < .05) in target registration error was found when using a protocol based on 4 ear landmarks and 4 facial landmarks compared with the other protocols based on 3 ear landmarks. When using 8 landmarks to perform the patient-to-image registration, the protocol using 4 ear landmarks and 4 facial landmarks greatly outperformed the other 8-landmark protocols and 9-landmark protocol, resulting in the lowest target registration error.

SmartPill® as an objective parameter for determination of severity and duration of postoperative ileus: study protocol of a prospective, two-arm, open-label trial (the PIDuSA study)

PubMed Central

Vilz, Tim O; Pantelis, Dimitrios; Lingohr, Philipp; Fimmers, Rolf; Esmann, Anke; Randau, Thomas; Kalff, Jörg C; Coenen, Martin; Wehner, Sven

2016-01-01

Introduction Postoperative ileus (POI) is a frequent complication after abdominal surgery (AS). Until today, neither a prophylaxis nor an evidence-based therapy exists. This originates from the absence of objective parameters evaluating the severity and duration of POI resulting in clinical trials of modest quality. The SmartPill®, a capsule which frequently measures pH value, temperature and intraluminal pressure after swallowing, offers an elegant option for analysing gastrointestinal (GI) transit times and smooth muscle activity in vivo. As the use in patients in the first months after AS is not covered by the marketing authorisation, we aim to investigate the safety and feasibility of the SmartPill® immediately after surgery. Additionally, we analyse the influence of prokinetics and laxatives as well as standardised physiotherapy on postoperative bowel contractility, as scientific evidence of its effects is still lacking. Methods and analysis The PIDuSA study is a prospective, single-centre, two-arm, open-label trial. The SmartPill® will be applied to 55 patients undergoing AS having a high risk for POI and 10 patients undergoing extra-abdominal surgery rarely developing POI. The primary objective is the safety of the SmartPill® in patients after surgery on the basis of adverse device effects/serious adverse device effects (ADE/SADE). The sample size suggests that events with a probability of 3% could be seen with a certainty of 80% for at least once in the sample. Secondary objective is the analysis of postoperative intestinal activity in the GI tract in both groups. Furthermore, clinical signs of bowel motility disorders will be correlated to the data measured by the SmartPill® to evaluate its significance as an objective parameter for assessing POI severity. Additionally, effects of prokinetics, laxatives and physiotherapy on postoperative peristaltic activity recorded by the SmartPill® will be analysed. Ethics and dissemination The protocol was approved by the federal authority (94.1.05-5660-8976) and the local ethics committee (092/14-MPG). Findings will be disseminated through publications and conference presentations. Trial registration number NCT02329912; Pre-results. PMID:27401360

[On the work of Austrian authorised experts on procedures in custodial and visiting rights--a survey of current practice from the parents and children view].

PubMed

Vöelkl-Kernstock, Sabine; Bein, Nicolas; Gutschner, Daniel; Klicpera, Christian; Ponocny-Seliger, Elisabeth; Friedrich, Max H

2008-01-01

Children who are involved in their parents' contentious separations, and about whom custody or visiting rights have become a matter of legal dispute, often demonstrate changes in behaviour, sometimes to the extent that these changes develop into noticeable psychological problems. Where custody and visiting rights are in dispute the expert child psychological/psychiatric evaluator appraises the family and recognises the suffering of the children involved, but is unable to intervene to treat the child for they have only been authorised to provide an appraisal. The goal of this study is to determine the extent to which an expert's evaluation provides the opportunity to intervene with the child's parents, and to what extent it offers a greater insight and understanding of the child's behaviour. The study also aims to record the children's own attitude to the expert evaluation. With the support of each Austrian district court, 1200 parents involved in custodial proceedings were contacted by post. Likewise, 27 children aged between 6 and 14 years old who were referred to a forensic psychology outpatient's clinic as a result of their parent's highly contentious separations, were recruited as test persons. Parents as well as children were asked to complete an especially designed questionnaire in order to assess the work of the expert evaluator; this took place before the study began and was conducted by an expert who didn;t work at the forensic outpatient clinic of the department of child and adolescent psychiatry. Overall, the parents displayed a high level of dissatisfaction with the expert evaluation procedure. More than a third of those questioned highlighted the lack of information about the psychological and educational contents of the appraisal, and about the way the child is treated in terms of the provisions for custody and visiting rights. A key point of criticism turned out to be the brevity of the discussion with the expert evaluator, whilst the opportunity to hold a sympathetic and understanding discussion with the expert evaluator was commonly regarded as desirable. The children evaluate the appraisal experience and the evaluator more positively, but they believe themselves to be responsible for the outcome of the court decision and feel insecure about the statements they make regarding their father and mother. In order to provide greater relief for the affected children, and because of the demonstrable and overwhelming parental dissatisfaction with the evaluation process, a modification of the current form of evaluation to create a solution-oriented process approach should be considered in Austria. The feasibility of this proposal, and its adherence to methodological-theoretical and normative framework conditions, should be discussed amongst expert evaluators. This requires relevant legal input to ensure that a modified form of the expert evaluator's work is implemented in a manner which is legally compliant.

The Insight ToolKit image registration framework

PubMed Central

Avants, Brian B.; Tustison, Nicholas J.; Stauffer, Michael; Song, Gang; Wu, Baohua; Gee, James C.

2014-01-01

Publicly available scientific resources help establish evaluation standards, provide a platform for teaching and improve reproducibility. Version 4 of the Insight ToolKit (ITK4) seeks to establish new standards in publicly available image registration methodology. ITK4 makes several advances in comparison to previous versions of ITK. ITK4 supports both multivariate images and objective functions; it also unifies high-dimensional (deformation field) and low-dimensional (affine) transformations with metrics that are reusable across transform types and with composite transforms that allow arbitrary series of geometric mappings to be chained together seamlessly. Metrics and optimizers take advantage of multi-core resources, when available. Furthermore, ITK4 reduces the parameter optimization burden via principled heuristics that automatically set scaling across disparate parameter types (rotations vs. translations). A related approach also constrains steps sizes for gradient-based optimizers. The result is that tuning for different metrics and/or image pairs is rarely necessary allowing the researcher to more easily focus on design/comparison of registration strategies. In total, the ITK4 contribution is intended as a structure to support reproducible research practices, will provide a more extensive foundation against which to evaluate new work in image registration and also enable application level programmers a broad suite of tools on which to build. Finally, we contextualize this work with a reference registration evaluation study with application to pediatric brain labeling.1 PMID:24817849

Reproducibility measurements of three methods for calculating in vivo MR-based knee kinematics.

PubMed

Lansdown, Drew A; Zaid, Musa; Pedoia, Valentina; Subburaj, Karupppasamy; Souza, Richard; Benjamin, C; Li, Xiaojuan

2015-08-01

To describe three quantification methods for magnetic resonance imaging (MRI)-based knee kinematic evaluation and to report on the reproducibility of these algorithms. T2 -weighted, fast-spin echo images were obtained of the bilateral knees in six healthy volunteers. Scans were repeated for each knee after repositioning to evaluate protocol reproducibility. Semiautomatic segmentation defined regions of interest for the tibia and femur. The posterior femoral condyles and diaphyseal axes were defined using the previously defined tibia and femur. All segmentation was performed twice to evaluate segmentation reliability. Anterior tibial translation (ATT) and internal tibial rotation (ITR) were calculated using three methods: a tibial-based registration system, a combined tibiofemoral-based registration method with all manual segmentation, and a combined tibiofemoral-based registration method with automatic definition of condyles and axes. Intraclass correlation coefficients and standard deviations across multiple measures were determined. Reproducibility of segmentation was excellent (ATT = 0.98; ITR = 0.99) for both combined methods. ATT and ITR measurements were also reproducible across multiple scans in the combined registration measurements with manual (ATT = 0.94; ITR = 0.94) or automatic (ATT = 0.95; ITR = 0.94) condyles and axes. The combined tibiofemoral registration with automatic definition of the posterior femoral condyle and diaphyseal axes allows for improved knee kinematics quantification with excellent in vivo reproducibility. © 2014 Wiley Periodicals, Inc.

Real-time three dimensional CT and MRI to guide interventions for congenital heart disease and acquired pulmonary vein stenosis.

PubMed

Suntharos, Patcharapong; Setser, Randolph M; Bradley-Skelton, Sharon; Prieto, Lourdes R

2017-10-01

To validate the feasibility and spatial accuracy of pre-procedural 3D images to 3D rotational fluoroscopy registration to guide interventional procedures in patients with congenital heart disease and acquired pulmonary vein stenosis. Cardiac interventions in patients with congenital and structural heart disease require complex catheter manipulation. Current technology allows registration of the anatomy obtained from 3D CT and/or MRI to be overlaid onto fluoroscopy. Thirty patients scheduled for interventional procedures from 12/2012 to 8/2015 were prospectively recruited. A C-arm CT using a biplane C-arm system (Artis zee, VC14H, Siemens Healthcare) was acquired to enable 3D3D registration with pre-procedural images. Following successful image fusion, the anatomic landmarks marked in pre-procedural images were overlaid on live fluoroscopy. The accuracy of image registration was determined by measuring the distance between overlay markers and a reference point in the image. The clinical utility of the registration was evaluated as either "High", "Medium" or "None". Seventeen patients with congenital heart disease and 13 with acquired pulmonary vein stenosis were enrolled. Accuracy and benefit of registration were not evaluated in two patients due to suboptimal images. The distance between the marker and the actual anatomical location was 0-2 mm in 18 (64%), 2-4 mm in 3 (11%) and >4 mm in 7 (25%) patients. 3D3D registration was highly beneficial in 18 (64%), intermediate in 3 (11%), and not beneficial in 7 (25%) patients. 3D3D registration can facilitate complex congenital and structural interventions. It may reduce procedure time, radiation and contrast dose.

A fast rigid-registration method of inferior limb X-ray image and 3D CT images for TKA surgery

NASA Astrophysics Data System (ADS)

Ito, Fumihito; O. D. A, Prima; Uwano, Ikuko; Ito, Kenzo

2010-03-01

In this paper, we propose a fast rigid-registration method of inferior limb X-ray films (two-dimensional Computed Radiography (CR) images) and three-dimensional Computed Tomography (CT) images for Total Knee Arthroplasty (TKA) surgery planning. The position of the each bone, such as femur and tibia (shin bone), in X-ray film and 3D CT images is slightly different, and we must pay attention how to use the two different images, since X-ray film image is captured in the standing position, and 3D CT is captured in decubitus (face up) position, respectively. Though the conventional registration mainly uses cross-correlation function between two images,and utilizes optimization techniques, it takes enormous calculation time and it is difficult to use it in interactive operations. In order to solve these problems, we calculate the center line (bone axis) of femur and tibia (shin bone) automatically, and we use them as initial positions for the registration. We evaluate our registration method by using three patient's image data, and we compare our proposed method and a conventional registration, which uses down-hill simplex algorithm. The down-hill simplex method is an optimization algorithm that requires only function evaluations, and doesn't need the calculation of derivatives. Our registration method is more effective than the downhill simplex method in computational time and the stable convergence. We have developed the implant simulation system on a personal computer, in order to support the surgeon in a preoperative planning of TKA. Our registration method is implemented in the simulation system, and user can manipulate 2D/3D translucent templates of implant components on X-ray film and 3D CT images.

Performance Evaluation of MIND Demons Deformable Registration of MR and CT Images in Spinal Interventions

PubMed Central

Reaungamornrat, S.; De Silva, T.; Uneri, A.; Goerres, J.; Jacobson, M.; Ketcha, M.; Vogt, S.; Kleinszig, G.; Khanna, A. J.; Wolinsky, J.-P.; Prince, J. L.; Siewerdsen, J. H.

2016-01-01

Accurate intraoperative localization of target anatomy and adjacent nervous and vascular tissue is essential to safe, effective surgery, and multimodality deformable registration can be used to identify such anatomy by fusing preoperative CT or MR images with intraoperative images. A deformable image registration method has been developed to estimate viscoelastic diffeomorphisms between preoperative MR and intraoperative CT using modality-independent neighborhood descriptors (MIND) and a Huber metric for robust registration. The method, called MIND Demons, optimizes a constrained symmetric energy functional incorporating priors on smoothness, geodesics, and invertibility by alternating between Gauss-Newton optimization and Tikhonov regularization in a multiresolution scheme. Registration performance was evaluated for the MIND Demons method with a symmetric energy formulation in comparison to an asymmetric form, and sensitivity to anisotropic MR voxel-size was analyzed in phantom experiments emulating image-guided spine-surgery in comparison to a free-form deformation (FFD) method using local mutual information (LMI). Performance was validated in a clinical study involving 15 patients undergoing intervention of the cervical, thoracic, and lumbar spine. The target registration error (TRE) for the symmetric MIND Demons formulation [1.3 ± 0.8 mm (median ± interquartile)] outperformed the asymmetric form [3.6 ± 4.4 mm]. The method demonstrated fairly minor sensitivity to anisotropic MR voxel size, with median TRE ranging 1.3 – 2.9 mm for MR slice thickness ranging 0.9 – 9.9 mm, compared to TRE = 3.2 – 4.1 mm for LMI FFD over the same range. Evaluation in clinical data demonstrated sub-voxel TRE (< 2 mm) in all fifteen cases with realistic deformations that preserved topology with sub-voxel invertibility (0.001 mm) and positive-determinant spatial Jacobians. The approach therefore appears robust against realistic anisotropic resolution characteristics in MR and yields registration accuracy suitable to application in image-guided spine-surgery. PMID:27811396

Performance evaluation of MIND demons deformable registration of MR and CT images in spinal interventions.

PubMed

Reaungamornrat, S; De Silva, T; Uneri, A; Goerres, J; Jacobson, M; Ketcha, M; Vogt, S; Kleinszig, G; Khanna, A J; Wolinsky, J-P; Prince, J L; Siewerdsen, J H

2016-12-07

Accurate intraoperative localization of target anatomy and adjacent nervous and vascular tissue is essential to safe, effective surgery, and multimodality deformable registration can be used to identify such anatomy by fusing preoperative CT or MR images with intraoperative images. A deformable image registration method has been developed to estimate viscoelastic diffeomorphisms between preoperative MR and intraoperative CT using modality-independent neighborhood descriptors (MIND) and a Huber metric for robust registration. The method, called MIND Demons, optimizes a constrained symmetric energy functional incorporating priors on smoothness, geodesics, and invertibility by alternating between Gauss-Newton optimization and Tikhonov regularization in a multiresolution scheme. Registration performance was evaluated for the MIND Demons method with a symmetric energy formulation in comparison to an asymmetric form, and sensitivity to anisotropic MR voxel-size was analyzed in phantom experiments emulating image-guided spine-surgery in comparison to a free-form deformation (FFD) method using local mutual information (LMI). Performance was validated in a clinical study involving 15 patients undergoing intervention of the cervical, thoracic, and lumbar spine. The target registration error (TRE) for the symmetric MIND Demons formulation (1.3  ±  0.8 mm (median  ±  interquartile)) outperformed the asymmetric form (3.6  ±  4.4 mm). The method demonstrated fairly minor sensitivity to anisotropic MR voxel size, with median TRE ranging 1.3-2.9 mm for MR slice thickness ranging 0.9-9.9 mm, compared to TRE  =  3.2-4.1 mm for LMI FFD over the same range. Evaluation in clinical data demonstrated sub-voxel TRE (<2 mm) in all fifteen cases with realistic deformations that preserved topology with sub-voxel invertibility (0.001 mm) and positive-determinant spatial Jacobians. The approach therefore appears robust against realistic anisotropic resolution characteristics in MR and yields registration accuracy suitable to application in image-guided spine-surgery.

Performance evaluation of MIND demons deformable registration of MR and CT images in spinal interventions

NASA Astrophysics Data System (ADS)

Reaungamornrat, S.; De Silva, T.; Uneri, A.; Goerres, J.; Jacobson, M.; Ketcha, M.; Vogt, S.; Kleinszig, G.; Khanna, A. J.; Wolinsky, J.-P.; Prince, J. L.; Siewerdsen, J. H.

2016-12-01

Accurate intraoperative localization of target anatomy and adjacent nervous and vascular tissue is essential to safe, effective surgery, and multimodality deformable registration can be used to identify such anatomy by fusing preoperative CT or MR images with intraoperative images. A deformable image registration method has been developed to estimate viscoelastic diffeomorphisms between preoperative MR and intraoperative CT using modality-independent neighborhood descriptors (MIND) and a Huber metric for robust registration. The method, called MIND Demons, optimizes a constrained symmetric energy functional incorporating priors on smoothness, geodesics, and invertibility by alternating between Gauss-Newton optimization and Tikhonov regularization in a multiresolution scheme. Registration performance was evaluated for the MIND Demons method with a symmetric energy formulation in comparison to an asymmetric form, and sensitivity to anisotropic MR voxel-size was analyzed in phantom experiments emulating image-guided spine-surgery in comparison to a free-form deformation (FFD) method using local mutual information (LMI). Performance was validated in a clinical study involving 15 patients undergoing intervention of the cervical, thoracic, and lumbar spine. The target registration error (TRE) for the symmetric MIND Demons formulation (1.3  ±  0.8 mm (median  ±  interquartile)) outperformed the asymmetric form (3.6  ±  4.4 mm). The method demonstrated fairly minor sensitivity to anisotropic MR voxel size, with median TRE ranging 1.3-2.9 mm for MR slice thickness ranging 0.9-9.9 mm, compared to TRE  =  3.2-4.1 mm for LMI FFD over the same range. Evaluation in clinical data demonstrated sub-voxel TRE (<2 mm) in all fifteen cases with realistic deformations that preserved topology with sub-voxel invertibility (0.001 mm) and positive-determinant spatial Jacobians. The approach therefore appears robust against realistic anisotropic resolution characteristics in MR and yields registration accuracy suitable to application in image-guided spine-surgery.

Non-rigid registration of serial dedicated breast CT, longitudinal dedicated breast CT and PET/CT images using the diffeomorphic demons method.

PubMed

Santos, Jonathan; Chaudhari, Abhijit J; Joshi, Anand A; Ferrero, Andrea; Yang, Kai; Boone, John M; Badawi, Ramsey D

2014-09-01

Dedicated breast CT and PET/CT scanners provide detailed 3D anatomical and functional imaging data sets and are currently being investigated for applications in breast cancer management such as diagnosis, monitoring response to therapy and radiation therapy planning. Our objective was to evaluate the performance of the diffeomorphic demons (DD) non-rigid image registration method to spatially align 3D serial (pre- and post-contrast) dedicated breast computed tomography (CT), and longitudinally-acquired dedicated 3D breast CT and positron emission tomography (PET)/CT images. The algorithmic parameters of the DD method were optimized for the alignment of dedicated breast CT images using training data and fixed. The performance of the method for image alignment was quantitatively evaluated using three separate data sets; (1) serial breast CT pre- and post-contrast images of 20 women, (2) breast CT images of 20 women acquired before and after repositioning the subject on the scanner, and (3) dedicated breast PET/CT images of 7 women undergoing neo-adjuvant chemotherapy acquired pre-treatment and after 1 cycle of therapy. The DD registration method outperformed no registration (p < 0.001) and conventional affine registration (p ≤ 0.002) for serial and longitudinal breast CT and PET/CT image alignment. In spite of the large size of the imaging data, the computational cost of the DD method was found to be reasonable (3-5 min). Co-registration of dedicated breast CT and PET/CT images can be performed rapidly and reliably using the DD method. This is the first study evaluating the DD registration method for the alignment of dedicated breast CT and PET/CT images. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Deformable planning CT to cone-beam CT image registration in head-and-neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou Jidong; Guerrero, Mariana; Chen, Wenjuan

2011-04-15

Purpose: The purpose of this work was to implement and validate a deformable CT to cone-beam computed tomography (CBCT) image registration method in head-and-neck cancer to eventually facilitate automatic target delineation on CBCT. Methods: Twelve head-and-neck cancer patients underwent a planning CT and weekly CBCT during the 5-7 week treatment period. The 12 planning CT images (moving images) of these patients were registered to their weekly CBCT images (fixed images) via the symmetric force Demons algorithm and using a multiresolution scheme. Histogram matching was used to compensate for the intensity difference between the two types of images. Using nine knownmore » anatomic points as registration targets, the accuracy of the registration was evaluated using the target registration error (TRE). In addition, region-of-interest (ROI) contours drawn on the planning CT were morphed to the CBCT images and the volume overlap index (VOI) between registered contours and manually delineated contours was evaluated. Results: The mean TRE value of the nine target points was less than 3.0 mm, the slice thickness of the planning CT. Of the 369 target points evaluated for registration accuracy, the average TRE value was 2.6{+-}0.6 mm. The mean TRE for bony tissue targets was 2.4{+-}0.2 mm, while the mean TRE for soft tissue targets was 2.8{+-}0.2 mm. The average VOI between the registered and manually delineated ROI contours was 76.2{+-}4.6%, which is consistent with that reported in previous studies. Conclusions: The authors have implemented and validated a deformable image registration method to register planning CT images to weekly CBCT images in head-and-neck cancer cases. The accuracy of the TRE values suggests that they can be used as a promising tool for automatic target delineation on CBCT.« less

Orthogonal Rings, Fiducial Markers, and Overlay Accuracy When Image Fusion is Used for EVAR Guidance.

PubMed

Koutouzi, G; Sandström, C; Roos, H; Henrikson, O; Leonhardt, H; Falkenberg, M

2016-11-01

Evaluation of orthogonal rings, fiducial markers, and overlay accuracy when image fusion is used for endovascular aortic repair (EVAR). This was a prospective single centre study. In 19 patients undergoing standard EVAR, 3D image fusion was used for intra-operative guidance. Renal arteries and targeted stent graft positions were marked with rings orthogonal to the respective centre lines from pre-operative computed tomography (CT). Radiopaque reference objects attached to the back of the patient were used as fiducial markers to detect patient movement intra-operatively. Automatic 3D-3D registration of the pre-operative CT with an intra-operative cone beam computed tomography (CBCT) as well as 3D-3D registration after manual alignment of nearby vertebrae were evaluated. Registration was defined as being sufficient for EVAR guidance if the deviation of the origin of the lower renal artery was less than 3 mm. For final overlay registration, the renal arteries were manually aligned using aortic calcification and vessel outlines. The accuracy of the overlay before stent graft deployment was evaluated using digital subtraction angiography (DSA) as direct comparison. Fiducial markers helped in detecting misalignment caused by patient movement during the procedure. Use of automatic intensity based registration alone was insufficient for EVAR guidance. Manual registration based on vertebrae L1-L2 was sufficient in 7/19 patients (37%). Using the final adjusted registration as overlay, the median alignment error of the lower renal artery marking at pre-deployment DSA was 2 mm (0-5) sideways and 2 mm (0-9) longitudinally, mostly in a caudal direction. 3D image fusion can facilitate intra-operative guidance during EVAR. Orthogonal rings and fiducial markers are useful for visualization and overlay correction. However, the accuracy of the overlaid 3D image is not always ideal and further technical development is needed. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kronfeld, Andrea; Müller-Forell, Wibke; Buchholz, Hans-Georg

Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods: Five male Sprague Dawleymore » rats were investigated for template construction using MRI and [{sup 18}F]MK-9470 PET for CB1 receptor representation. PET images were reconstructed using the algorithms filtered back-projection, ordered subset expectation maximization in 2D, and maximum a posteriori in 3D. Landmarks were defined on each MR image, and templates were constructed under different settings, i.e., based on different tissue class images [gray matter (GM), white matter (WM), and GM + WM] and regularization forms (“linear elastic energy,” “membrane energy,” and “bending energy”). Registration accuracy for MRI and PET templates was evaluated by means of the distance between landmark coordinates. Results: The best MRI template was constructed based on gray and white matter images and the regularization form linear elastic energy. In this case, most distances between landmark coordinates were <1 mm. Accordingly, MRI-based spatial normalization was most accurate, but results of the PET-based spatial normalization were quite comparable. Conclusions: Image registration using DARTEL provides a standardized and automatic framework for small animal brain data analysis. The authors were able to show that this method works with high reliability and validity. Using DARTEL templates together with nonlinear registration algorithms allows for accurate spatial normalization of combined MRI/PET or PET-only studies.« less

A Bayesian nonrigid registration method to enhance intraoperative target definition in image-guided prostate procedures through uncertainty characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pursley, Jennifer; Risholm, Petter; Fedorov, Andriy

2012-11-15

Purpose: This study introduces a probabilistic nonrigid registration method for use in image-guided prostate brachytherapy. Intraoperative imaging for prostate procedures, usually transrectal ultrasound (TRUS), is typically inferior to diagnostic-quality imaging of the pelvis such as endorectal magnetic resonance imaging (MRI). MR images contain superior detail of the prostate boundaries and provide substructure features not otherwise visible. Previous efforts to register diagnostic prostate images with the intraoperative coordinate system have been deterministic and did not offer a measure of the registration uncertainty. The authors developed a Bayesian registration method to estimate the posterior distribution on deformations and provide a case-specific measuremore » of the associated registration uncertainty. Methods: The authors adapted a biomechanical-based probabilistic nonrigid method to register diagnostic to intraoperative images by aligning a physician's segmentations of the prostate in the two images. The posterior distribution was characterized with a Markov Chain Monte Carlo method; the maximum a posteriori deformation and the associated uncertainty were estimated from the collection of deformation samples drawn from the posterior distribution. The authors validated the registration method using a dataset created from ten patients with MRI-guided prostate biopsies who had both diagnostic and intraprocedural 3 Tesla MRI scans. The accuracy and precision of the estimated posterior distribution on deformations were evaluated from two predictive distance distributions: between the deformed central zone-peripheral zone (CZ-PZ) interface and the physician-labeled interface, and based on physician-defined landmarks. Geometric margins on the registration of the prostate's peripheral zone were determined from the posterior predictive distance to the CZ-PZ interface separately for the base, mid-gland, and apical regions of the prostate. Results: The authors observed variation in the shape and volume of the segmented prostate in diagnostic and intraprocedural images. The probabilistic method allowed us to convey registration results in terms of posterior distributions, with the dispersion providing a patient-specific estimate of the registration uncertainty. The median of the predictive distance distribution between the deformed prostate boundary and the segmented boundary was Less-Than-Or-Slanted-Equal-To 3 mm (95th percentiles within {+-}4 mm) for all ten patients. The accuracy and precision of the internal deformation was evaluated by comparing the posterior predictive distance distribution for the CZ-PZ interface for each patient, with the median distance ranging from -0.6 to 2.4 mm. Posterior predictive distances between naturally occurring landmarks showed registration errors of Less-Than-Or-Slanted-Equal-To 5 mm in any direction. The uncertainty was not a global measure, but instead was local and varied throughout the registration region. Registration uncertainties were largest in the apical region of the prostate. Conclusions: Using a Bayesian nonrigid registration method, the authors determined the posterior distribution on deformations between diagnostic and intraprocedural MR images and quantified the uncertainty in the registration results. The feasibility of this approach was tested and results were positive. The probabilistic framework allows us to evaluate both patient-specific and location-specific estimates of the uncertainty in the registration result. Although the framework was tested on MR-guided procedures, the preliminary results suggest that it may be applied to TRUS-guided procedures as well, where the addition of diagnostic MR information may have a larger impact on target definition and clinical guidance.« less

A Bayesian nonrigid registration method to enhance intraoperative target definition in image-guided prostate procedures through uncertainty characterization

PubMed Central

Pursley, Jennifer; Risholm, Petter; Fedorov, Andriy; Tuncali, Kemal; Fennessy, Fiona M.; Wells, William M.; Tempany, Clare M.; Cormack, Robert A.

2012-01-01

Purpose: This study introduces a probabilistic nonrigid registration method for use in image-guided prostate brachytherapy. Intraoperative imaging for prostate procedures, usually transrectal ultrasound (TRUS), is typically inferior to diagnostic-quality imaging of the pelvis such as endorectal magnetic resonance imaging (MRI). MR images contain superior detail of the prostate boundaries and provide substructure features not otherwise visible. Previous efforts to register diagnostic prostate images with the intraoperative coordinate system have been deterministic and did not offer a measure of the registration uncertainty. The authors developed a Bayesian registration method to estimate the posterior distribution on deformations and provide a case-specific measure of the associated registration uncertainty. Methods: The authors adapted a biomechanical-based probabilistic nonrigid method to register diagnostic to intraoperative images by aligning a physician's segmentations of the prostate in the two images. The posterior distribution was characterized with a Markov Chain Monte Carlo method; the maximum a posteriori deformation and the associated uncertainty were estimated from the collection of deformation samples drawn from the posterior distribution. The authors validated the registration method using a dataset created from ten patients with MRI-guided prostate biopsies who had both diagnostic and intraprocedural 3 Tesla MRI scans. The accuracy and precision of the estimated posterior distribution on deformations were evaluated from two predictive distance distributions: between the deformed central zone-peripheral zone (CZ-PZ) interface and the physician-labeled interface, and based on physician-defined landmarks. Geometric margins on the registration of the prostate's peripheral zone were determined from the posterior predictive distance to the CZ-PZ interface separately for the base, mid-gland, and apical regions of the prostate. Results: The authors observed variation in the shape and volume of the segmented prostate in diagnostic and intraprocedural images. The probabilistic method allowed us to convey registration results in terms of posterior distributions, with the dispersion providing a patient-specific estimate of the registration uncertainty. The median of the predictive distance distribution between the deformed prostate boundary and the segmented boundary was ⩽3 mm (95th percentiles within ±4 mm) for all ten patients. The accuracy and precision of the internal deformation was evaluated by comparing the posterior predictive distance distribution for the CZ-PZ interface for each patient, with the median distance ranging from −0.6 to 2.4 mm. Posterior predictive distances between naturally occurring landmarks showed registration errors of ⩽5 mm in any direction. The uncertainty was not a global measure, but instead was local and varied throughout the registration region. Registration uncertainties were largest in the apical region of the prostate. Conclusions: Using a Bayesian nonrigid registration method, the authors determined the posterior distribution on deformations between diagnostic and intraprocedural MR images and quantified the uncertainty in the registration results. The feasibility of this approach was tested and results were positive. The probabilistic framework allows us to evaluate both patient-specific and location-specific estimates of the uncertainty in the registration result. Although the framework was tested on MR-guided procedures, the preliminary results suggest that it may be applied to TRUS-guided procedures as well, where the addition of diagnostic MR information may have a larger impact on target definition and clinical guidance. PMID:23127078

Mechanistic modeling of insecticide risks to breeding birds in North American agroecosystems

EPA Science Inventory

Insecticide usage in the United States is ubiquitous in urban, suburban, and rural environments. In evaluating data for an insecticide registration application and for registration review, scientists at the United States Environmental Protection Agency (USEPA) assess the fate of ...

10 CFR 32.210 - Registration of product information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... sent to the Office of Federal and State Materials and Environmental Management Programs, by an... device must include sufficient information about the design, manufacture, prototype testing, quality... the evaluation, the Commission issues a certificate of registration to the person making the request...

Research Issues in Image Registration for Remote Sensing

NASA Technical Reports Server (NTRS)

Eastman, Roger D.; LeMoigne, Jacqueline; Netanyahu, Nathan S.

2007-01-01

Image registration is an important element in data processing for remote sensing with many applications and a wide range of solutions. Despite considerable investigation the field has not settled on a definitive solution for most applications and a number of questions remain open. This article looks at selected research issues by surveying the experience of operational satellite teams, application-specific requirements for Earth science, and our experiments in the evaluation of image registration algorithms with emphasis on the comparison of algorithms for subpixel accuracy. We conclude that remote sensing applications put particular demands on image registration algorithms to take into account domain-specific knowledge of geometric transformations and image content.

Homographic Patch Feature Transform: A Robustness Registration for Gastroscopic Surgery.

PubMed

Hu, Weiling; Zhang, Xu; Wang, Bin; Liu, Jiquan; Duan, Huilong; Dai, Ning; Si, Jianmin

2016-01-01

Image registration is a key component of computer assistance in image guided surgery, and it is a challenging topic in endoscopic environments. In this study, we present a method for image registration named Homographic Patch Feature Transform (HPFT) to match gastroscopic images. HPFT can be used for tracking lesions and augmenting reality applications during gastroscopy. Furthermore, an overall evaluation scheme is proposed to validate the precision, robustness and uniformity of the registration results, which provides a standard for rejection of false matching pairs from corresponding results. Finally, HPFT is applied for processing in vivo gastroscopic data. The experimental results show that HPFT has stable performance in gastroscopic applications.

Prospective registration trends, reasons for retrospective registration and mechanisms to increase prospective registration compliance: descriptive analysis and survey

PubMed Central

Seidler, Anna Lene; Askie, Lisa M

2018-01-01

Objectives To analyse prospective versus retrospective trial registration trends on the Australian New Zealand Clinical Trials Registry (ANZCTR) and to evaluate the reasons for non-compliance with prospective registration. Design Part 1: Descriptive analysis of trial registration trends from 2006 to 2015. Part 2: Online registrant survey. Participants Part 1: All interventional trials registered on ANZCTR from 2006 to 2015. Part 2: Random sample of those who had retrospectively registered a trial on ANZCTR between 2010 and 2015. Main outcome measures Part 1: Proportion of prospective versus retrospective clinical trial registrations (ie, registration before versus after enrolment of the first participant) on the ANZCTR overall and by various key metrics, such as sponsor, funder, recruitment country and sample size. Part 2: Reasons for non-compliance with prospective registration and perceived usefulness of various proposed mechanisms to improve prospective registration compliance. Results Part 1: Analysis of the complete dataset of 9450 trials revealed that compliance with prospective registration increased from 48% (216 out of 446 trials) in 2006 to 63% (723/1148) in 2012 and has since plateaued at around 64%. Patterns of compliance were relatively consistent across sponsor and funder types (industry vs non-industry), type of intervention (drug vs non-drug) and size of trial (n<100, 100–500, >500). However, primary sponsors from Australia/New Zealand were almost twice as likely to register prospectively (62%; 4613/7452) compared with sponsors from other countries with a WHO Network Registry (35%; 377/1084) or sponsors from countries without a WHO Registry (29%; 230/781). Part 2: The majority (56%; 84/149) of survey respondents cited lack of awareness as a reason for not registering their study prospectively. Seventy-four per cent (111/149) stated that linking registration to ethics approval would facilitate prospective registration. Conclusions Despite some progress, compliance with prospective registration remains suboptimal. Linking registration to ethics approval was the favoured strategy among those sampled for improving compliance. PMID:29496896

An evaluation of vital registers as sources of data for infant mortality rates in Cameroon.

PubMed

Ndong, I; Gloyd, S; Gale, J

1994-06-01

Infant mortality rates have been widely used as indicators of health status and the availability, utilization and effectiveness of health services. Two principal sources of data for infant mortality rates are vital registers and censuses. This study was designed to evaluate the accuracy of vital registers as sources of data for infant mortality rates in Cameroon. A household census of births and infant deaths that occurred in Buea Subdivision between 1 November 1991 and 31 October 1992 was conducted to determine the proportion that were registered and the reasons why the remainder were not registered. The registration coverage was found to be 62% for births and 4% for infant deaths. The most frequently reported reasons for not registering births were lack of money, lack of time and a complicated registration procedure. For infant deaths the reasons were lack of knowledge and no perceived benefits. Vital registers of birth and death are not an accurate source of data for infant mortality rates in Cameroon. Motivation for birth and death registration appear to be dependent on the perceived benefits. A mechanism of registration that uses medical institutions may substantially increase registration coverage for births and infant deaths.

Experimental Evaluation of a Deformable Registration Algorithm for Motion Correction in PET-CT Guided Biopsy.

PubMed

Khare, Rahul; Sala, Guillaume; Kinahan, Paul; Esposito, Giuseppe; Banovac, Filip; Cleary, Kevin; Enquobahrie, Andinet

2013-01-01

Positron emission tomography computed tomography (PET-CT) images are increasingly being used for guidance during percutaneous biopsy. However, due to the physics of image acquisition, PET-CT images are susceptible to problems due to respiratory and cardiac motion, leading to inaccurate tumor localization, shape distortion, and attenuation correction. To address these problems, we present a method for motion correction that relies on respiratory gated CT images aligned using a deformable registration algorithm. In this work, we use two deformable registration algorithms and two optimization approaches for registering the CT images obtained over the respiratory cycle. The two algorithms are the BSpline and the symmetric forces Demons registration. In the first optmization approach, CT images at each time point are registered to a single reference time point. In the second approach, deformation maps are obtained to align each CT time point with its adjacent time point. These deformations are then composed to find the deformation with respect to a reference time point. We evaluate these two algorithms and optimization approaches using respiratory gated CT images obtained from 7 patients. Our results show that overall the BSpline registration algorithm with the reference optimization approach gives the best results.

PET guidance for liver radiofrequency ablation: an evaluation

NASA Astrophysics Data System (ADS)

Lei, Peng; Dandekar, Omkar; Mahmoud, Faaiza; Widlus, David; Malloy, Patrick; Shekhar, Raj

2007-03-01

Radiofrequency ablation (RFA) is emerging as the primary mode of treatment of unresectable malignant liver tumors. With current intraoperative imaging modalities, quick, precise, and complete localization of lesions remains a challenge for liver RFA. Fusion of intraoperative CT and preoperative PET images, which relies on PET and CT registration, can produce a new image with complementary metabolic and anatomic data and thus greatly improve the targeting accuracy. Unlike neurological images, alignment of abdominal images by combined PET/CT scanner is prone to errors as a result of large nonrigid misalignment in abdominal images. Our use of a normalized mutual information-based 3D nonrigid registration technique has proven powerful for whole-body PET and CT registration. We demonstrate here that this technique is capable of acceptable abdominal PET and CT registration as well. In five clinical cases, both qualitative and quantitative validation showed that the registration is robust and accurate. Quantitative accuracy was evaluated by comparison between the result from the algorithm and clinical experts. The accuracy of registration is much less than the allowable margin in liver RFA. Study findings show the technique's potential to enable the augmentation of intraoperative CT with preoperative PET to reduce procedure time, avoid repeating procedures, provide clinicians with complementary functional/anatomic maps, avoid omitting dispersed small lesions, and improve the accuracy of tumor targeting in liver RFA.

LCC-Demons: a robust and accurate symmetric diffeomorphic registration algorithm.

PubMed

Lorenzi, M; Ayache, N; Frisoni, G B; Pennec, X

2013-11-01

Non-linear registration is a key instrument for computational anatomy to study the morphology of organs and tissues. However, in order to be an effective instrument for the clinical practice, registration algorithms must be computationally efficient, accurate and most importantly robust to the multiple biases affecting medical images. In this work we propose a fast and robust registration framework based on the log-Demons diffeomorphic registration algorithm. The transformation is parameterized by stationary velocity fields (SVFs), and the similarity metric implements a symmetric local correlation coefficient (LCC). Moreover, we show how the SVF setting provides a stable and consistent numerical scheme for the computation of the Jacobian determinant and the flux of the deformation across the boundaries of a given region. Thus, it provides a robust evaluation of spatial changes. We tested the LCC-Demons in the inter-subject registration setting, by comparing with state-of-the-art registration algorithms on public available datasets, and in the intra-subject longitudinal registration problem, for the statistically powered measurements of the longitudinal atrophy in Alzheimer's disease. Experimental results show that LCC-Demons is a generic, flexible, efficient and robust algorithm for the accurate non-linear registration of images, which can find several applications in the field of medical imaging. Without any additional optimization, it solves equally well intra & inter-subject registration problems, and compares favorably to state-of-the-art methods. Copyright © 2013 Elsevier Inc. All rights reserved.

Surface-based prostate registration with biomechanical regularization

NASA Astrophysics Data System (ADS)

van de Ven, Wendy J. M.; Hu, Yipeng; Barentsz, Jelle O.; Karssemeijer, Nico; Barratt, Dean; Huisman, Henkjan J.

2013-03-01

Adding MR-derived information to standard transrectal ultrasound (TRUS) images for guiding prostate biopsy is of substantial clinical interest. A tumor visible on MR images can be projected on ultrasound by using MRUS registration. A common approach is to use surface-based registration. We hypothesize that biomechanical modeling will better control deformation inside the prostate than a regular surface-based registration method. We developed a novel method by extending a surface-based registration with finite element (FE) simulation to better predict internal deformation of the prostate. For each of six patients, a tetrahedral mesh was constructed from the manual prostate segmentation. Next, the internal prostate deformation was simulated using the derived radial surface displacement as boundary condition. The deformation field within the gland was calculated using the predicted FE node displacements and thin-plate spline interpolation. We tested our method on MR guided MR biopsy imaging data, as landmarks can easily be identified on MR images. For evaluation of the registration accuracy we used 45 anatomical landmarks located in all regions of the prostate. Our results show that the median target registration error of a surface-based registration with biomechanical regularization is 1.88 mm, which is significantly different from 2.61 mm without biomechanical regularization. We can conclude that biomechanical FE modeling has the potential to improve the accuracy of multimodal prostate registration when comparing it to regular surface-based registration.

A comprehensive study on decreasing the kilovoltage cone-beam CT dose by reducing the projection number.

PubMed

Lu, Bo; Lu, Haibin; Palta, Jatinder

2010-05-12

The objective of this study was to evaluate the effect of kilovoltage cone-beam computed tomography (CBCT) on registration accuracy and image qualities with a reduced number of planar projections used in volumetric imaging reconstruction. The ultimate goal is to evaluate the possibility of reducing the patient dose while maintaining registration accuracy under different projection-number schemes for various clinical sites. An Elekta Synergy Linear accelerator with an onboard CBCT system was used in this study. The quality of the Elekta XVI cone-beam three-dimensional volumetric images reconstructed with a decreasing number of projections was quantitatively evaluated by a Catphan phantom. Subsequently, we tested the registration accuracy of imaging data sets on three rigid anthropomorphic phantoms and three real patient sites under the reduced projection-number (as low as 1/6th) reconstruction of CBCT data with different rectilinear shifts and rota-tions. CBCT scan results of the Catphan phantom indicated the CBCT images got noisier when the number of projections was reduced, but their spatial resolution and uniformity were hardly affected. The maximum registration errors under the small amount transformation of the reference CT images were found to be within 0.7 mm translation and 0.3 masculine rotation. However, when the projection number was lower than one-fourth of the full set with a large amount of transformation of reference CT images, the registration could easily be trapped into local minima solutions for a nonrigid anatomy. We concluded, by using projection-number reduction strategy under conscientious care, imaging-guided localization procedure could achieve a lower patient dose without losing the registration accuracy for various clinical sites and situations. A faster scanning time is the main advantage compared to the mA decrease-based, dose-reduction method.

Registration of retinal sequences from new video-ophthalmoscopic camera.

PubMed

Kolar, Radim; Tornow, Ralf P; Odstrcilik, Jan; Liberdova, Ivana

2016-05-20

Analysis of fast temporal changes on retinas has become an important part of diagnostic video-ophthalmology. It enables investigation of the hemodynamic processes in retinal tissue, e.g. blood-vessel diameter changes as a result of blood-pressure variation, spontaneous venous pulsation influenced by intracranial-intraocular pressure difference, blood-volume changes as a result of changes in light reflection from retinal tissue, and blood flow using laser speckle contrast imaging. For such applications, image registration of the recorded sequence must be performed. Here we use a new non-mydriatic video-ophthalmoscope for simple and fast acquisition of low SNR retinal sequences. We introduce a novel, two-step approach for fast image registration. The phase correlation in the first stage removes large eye movements. Lucas-Kanade tracking in the second stage removes small eye movements. We propose robust adaptive selection of the tracking points, which is the most important part of tracking-based approaches. We also describe a method for quantitative evaluation of the registration results, based on vascular tree intensity profiles. The achieved registration error evaluated on 23 sequences (5840 frames) is 0.78 ± 0.67 pixels inside the optic disc and 1.39 ± 0.63 pixels outside the optic disc. We compared the results with the commonly used approaches based on Lucas-Kanade tracking and scale-invariant feature transform, which achieved worse results. The proposed method can efficiently correct particular frames of retinal sequences for shift and rotation. The registration results for each frame (shift in X and Y direction and eye rotation) can also be used for eye-movement evaluation during single-spot fixation tasks.

Augmented Reality Using Transurethral Ultrasound for Laparoscopic Radical Prostatectomy: Preclinical Evaluation.

PubMed

Lanchon, Cecilia; Custillon, Guillaume; Moreau-Gaudry, Alexandre; Descotes, Jean-Luc; Long, Jean-Alexandre; Fiard, Gaelle; Voros, Sandrine

2016-07-01

To guide the surgeon during laparoscopic or robot-assisted radical prostatectomy an innovative laparoscopic/ultrasound fusion platform was developed using a motorized 3-dimensional transurethral ultrasound probe. We present what is to our knowledge the first preclinical evaluation of 3-dimensional prostate visualization using transurethral ultrasound and the preliminary results of this new augmented reality. The transurethral probe and laparoscopic/ultrasound registration were tested on realistic prostate phantoms made of standard polyvinyl chloride. The quality of transurethral ultrasound images and the detection of passive markers placed on the prostate surface were evaluated on 2-dimensional dynamic views and 3-dimensional reconstructions. The feasibility, precision and reproducibility of laparoscopic/transurethral ultrasound registration was then determined using 4, 5, 6 and 7 markers to assess the optimal amount needed. The root mean square error was calculated for each registration and the median root mean square error and IQR were calculated according to the number of markers. The transurethral ultrasound probe was easy to manipulate and the prostatic capsule was well visualized in 2 and 3 dimensions. Passive markers could precisely be localized in the volume. Laparoscopic/transurethral ultrasound registration procedures were performed on 74 phantoms of various sizes and shapes. All were successful. The median root mean square error of 1.1 mm (IQR 0.8-1.4) was significantly associated with the number of landmarks (p = 0.001). The highest accuracy was achieved using 6 markers. However, prostate volume did not affect registration precision. Transurethral ultrasound provided high quality prostate reconstruction and easy marker detection. Laparoscopic/ultrasound registration was successful with acceptable mm precision. Further investigations are necessary to achieve sub mm accuracy and assess feasibility in a human model. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinical leadership and pre-registration nursing programmes: A model for clinical leadership and a prospective curriculum implementation and evaluation research strategy.

PubMed

Brown, Angela; Dewing, Jan; Crookes, Patrick

2016-07-01

To present for wider debate a conceptual model for clinical leadership development in pre-registration nursing programmes and a proposed implementation plan. Globally, leadership in nursing has become a significant issue. Whilst there is continued support for leadership preparation in pre-registration nursing programmes, there have been very few published accounts of curriculum content and/or pedagogical approaches that foster clinical leadership development in pre-registration nursing. A doctoral research study has resulted in the creation of an overarching model for clinical leadership. A multi-method research study using theoretical and empirical literature 1974-2015, a focus group, expert opinion and a national on-line survey. A conceptual model of clinical leadership development in pre-registration nursing programme is presented, including the infinity loop of clinical leadership, an integral curriculum thread and a conceptual model: a curriculum-pedagogy nexus for clinical leadership. In order to test out usability and evaluate effectiveness, a multi method programme of research in one school of nursing in Australia is outlined. Implementation of the proposed conceptual model for clinical leadership development in pre-registration nursing programmes and a programme of (post-doctoral) research will contribute to what is known about curriculum content and pedagogy for nurse academics. Importantly, for nursing students and the profession as a whole, there is a clearer expectation of what clinical leadership might look like in the novice registered nurse. For nurse academics a model is offered for consideration in curriculum design and implementation with an evaluation strategy that could be replicated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accuracy of computer-assisted navigation: significant augmentation by facial recognition software.

PubMed

Glicksman, Jordan T; Reger, Christine; Parasher, Arjun K; Kennedy, David W

2017-09-01

Over the past 20 years, image guidance navigation has been used with increasing frequency as an adjunct during sinus and skull base surgery. These devices commonly utilize surface registration, where varying pressure of the registration probe and loss of contact with the face during the skin tracing process can lead to registration inaccuracies, and the number of registration points incorporated is necessarily limited. The aim of this study was to evaluate the use of novel facial recognition software for image guidance registration. Consecutive adults undergoing endoscopic sinus surgery (ESS) were prospectively studied. Patients underwent image guidance registration via both conventional surface registration and facial recognition software. The accuracy of both registration processes were measured at the head of the middle turbinate (MTH), middle turbinate axilla (MTA), anterior wall of sphenoid sinus (SS), and nasal tip (NT). Forty-five patients were included in this investigation. Facial recognition was accurate to within a mean of 0.47 mm at the MTH, 0.33 mm at the MTA, 0.39 mm at the SS, and 0.36 mm at the NT. Facial recognition was more accurate than surface registration at the MTH by an average of 0.43 mm (p = 0.002), at the MTA by an average of 0.44 mm (p < 0.001), and at the SS by an average of 0.40 mm (p < 0.001). The integration of facial recognition software did not adversely affect registration time. In this prospective study, automated facial recognition software significantly improved the accuracy of image guidance registration when compared to conventional surface registration. © 2017 ARS-AAOA, LLC.

Image navigation and registration performance assessment tool set for the GOES-R Advanced Baseline Imager and Geostationary Lightning Mapper

NASA Astrophysics Data System (ADS)

De Luccia, Frank J.; Houchin, Scott; Porter, Brian C.; Graybill, Justin; Haas, Evan; Johnson, Patrick D.; Isaacson, Peter J.; Reth, Alan D.

2016-05-01

The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. For ABI, these metrics are the 3-sigma errors in navigation (NAV), channel-to-channel registration (CCR), frame-to-frame registration (FFR), swath-to-swath registration (SSR), and within frame registration (WIFR) for the Level 1B image products. For GLM, the single metric of interest is the 3-sigma error in the navigation of background images (GLM NAV) used by the system to navigate lightning strikes. 3-sigma errors are estimates of the 99. 73rd percentile of the errors accumulated over a 24 hour data collection period. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24 hour evaluation period. Another aspect of the IPATS design that vastly reduces execution time is the off-line propagation of Landsat based truth images to the fixed grid coordinates system for each of the three GOES-R satellite locations, operational East and West and initial checkout locations. This paper describes the algorithmic design and implementation of IPATS and provides preliminary test results.

Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for the GOES-R Advanced Baseline Imager and Geostationary Lightning Mapper

NASA Technical Reports Server (NTRS)

DeLuccia, Frank J.; Houchin, Scott; Porter, Brian C.; Graybill, Justin; Haas, Evan; Johnson, Patrick D.; Isaacson, Peter J.; Reth, Alan D.

2016-01-01

The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. For ABI, these metrics are the 3-sigma errors in navigation (NAV), channel-to-channel registration (CCR), frame-to-frame registration (FFR), swath-to-swath registration (SSR), and within frame registration (WIFR) for the Level 1B image products. For GLM, the single metric of interest is the 3-sigma error in the navigation of background images (GLM NAV) used by the system to navigate lightning strikes. 3-sigma errors are estimates of the 99.73rd percentile of the errors accumulated over a 24 hour data collection period. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24 hour evaluation period. Another aspect of the IPATS design that vastly reduces execution time is the off-line propagation of Landsat based truth images to the fixed grid coordinates system for each of the three GOES-R satellite locations, operational East and West and initial checkout locations. This paper describes the algorithmic design and implementation of IPATS and provides preliminary test results.

SU-G-IeP2-06: Evaluation of Registration Accuracy for Cone-Beam CT Reconstruction Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, J; Wang, P; Zhang, H

2016-06-15

Purpose: Cone-beam (CB) computed tomography (CT) is used for image guidance during radiotherapy treatment delivery. Conventional Feldkamp and compressed sensing (CS) based CBCT recon-struction techniques are compared for image registration. This study is to evaluate the image registration accuracy of conventional and CS CBCT for head-and-neck (HN) patients. Methods: Ten HN patients with oropharyngeal tumors were retrospectively selected. Each HN patient had one planning CT (CTP) and three CBCTs were acquired during an adaptive radiotherapy proto-col. Each CBCT was reconstructed by both the conventional (CBCTCON) and compressed sens-ing (CBCTCS) methods. Two oncologists manually labeled 23 landmarks of normal tissue andmore » implanted gold markers on both the CTP and CBCTCON. Subsequently, landmarks on CTp were propagated to CBCTs, using a b-spline-based deformable image registration (DIR) and rigid registration (RR). The errors of these registration methods between two CBCT methods were calcu-lated. Results: For DIR, the mean distance between the propagated and the labeled landmarks was 2.8 mm ± 0.52 for CBCTCS, and 3.5 mm ± 0.75 for CBCTCON. For RR, the mean distance between the propagated and the labeled landmarks was 6.8 mm ± 0.92 for CBCTCS, and 8.7 mm ± 0.95 CBCTCON. Conclusion: This study has demonstrated that CS CBCT is more accurate than conventional CBCT in image registration by both rigid and non-rigid methods. It is potentially suggested that CS CBCT is an improved image modality for image guided adaptive applications.« less

Image Navigation and Registration Performance Assessment Tool Set for the GOES-R Advanced Baseline Imager and Geostationary Lightning Mapper

NASA Technical Reports Server (NTRS)

De Luccia, Frank J.; Houchin, Scott; Porter, Brian C.; Graybill, Justin; Haas, Evan; Johnson, Patrick D.; Isaacson, Peter J.; Reth, Alan D.

2016-01-01

The GOES-R Flight Project has developed an Image Navigation and Registration (INR) Performance Assessment Tool Set (IPATS) for measuring Advanced Baseline Imager (ABI) and Geostationary Lightning Mapper (GLM) INR performance metrics in the post-launch period for performance evaluation and long term monitoring. For ABI, these metrics are the 3-sigma errors in navigation (NAV), channel-to-channel registration (CCR), frame-to-frame registration (FFR), swath-to-swath registration (SSR), and within frame registration (WIFR) for the Level 1B image products. For GLM, the single metric of interest is the 3-sigma error in the navigation of background images (GLM NAV) used by the system to navigate lightning strikes. 3-sigma errors are estimates of the 99.73rd percentile of the errors accumulated over a 24-hour data collection period. IPATS utilizes a modular algorithmic design to allow user selection of data processing sequences optimized for generation of each INR metric. This novel modular approach minimizes duplication of common processing elements, thereby maximizing code efficiency and speed. Fast processing is essential given the large number of sub-image registrations required to generate INR metrics for the many images produced over a 24-hour evaluation period. Another aspect of the IPATS design that vastly reduces execution time is the off-line propagation of Landsat based truth images to the fixed grid coordinates system for each of the three GOES-R satellite locations, operational East and West and initial checkout locations. This paper describes the algorithmic design and implementation of IPATS and provides preliminary test results.

Semiautomatic registration of 3D transabdominal ultrasound images for patient repositioning during postprostatectomy radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Presles, Benoît, E-mail: benoit.presles@creatis.insa-lyon.fr; Rit, Simon; Sarrut, David

2014-12-15

Purpose: The aim of the present work is to propose and evaluate registration algorithms of three-dimensional (3D) transabdominal (TA) ultrasound (US) images to setup postprostatectomy patients during radiation therapy. Methods: Three registration methods have been developed and evaluated to register a reference 3D-TA-US image acquired during the planning CT session and a 3D-TA-US image acquired before each treatment session. The first method (method A) uses only gray value information, whereas the second one (method B) uses only gradient information. The third one (method C) combines both sets of information. All methods restrict the comparison to a region of interest computedmore » from the dilated reference positioning volume drawn on the reference image and use mutual information as a similarity measure. The considered geometric transformations are translations and have been optimized by using the adaptive stochastic gradient descent algorithm. Validation has been carried out using manual registration by three operators of the same set of image pairs as the algorithms. Sixty-two treatment US images of seven patients irradiated after a prostatectomy have been registered to their corresponding reference US image. The reference registration has been defined as the average of the manual registration values. Registration error has been calculated by subtracting the reference registration from the algorithm result. For each session, the method has been considered a failure if the registration error was above both the interoperator variability of the session and a global threshold of 3.0 mm. Results: All proposed registration algorithms have no systematic bias. Method B leads to the best results with mean errors of −0.6, 0.7, and −0.2 mm in left–right (LR), superior–inferior (SI), and anterior–posterior (AP) directions, respectively. With this method, the standard deviations of the mean error are of 1.7, 2.4, and 2.6 mm in LR, SI, and AP directions, respectively. The latter are inferior to the interoperator registration variabilities which are of 2.5, 2.5, and 3.5 mm in LR, SI, and AP directions, respectively. Failures occur in 5%, 18%, and 10% of cases in LR, SI, and AP directions, respectively. 69% of the sessions have no failure. Conclusions: Results of the best proposed registration algorithm of 3D-TA-US images for postprostatectomy treatment have no bias and are in the same variability range as manual registration. As the algorithm requires a short computation time, it could be used in clinical practice provided that a visual review is performed.« less

An individualized strategy to estimate the effect of deformable registration uncertainty on accumulated dose in the upper abdomen

NASA Astrophysics Data System (ADS)

Wang, Yibing; Petit, Steven F.; Vásquez Osorio, Eliana; Gupta, Vikas; Méndez Romero, Alejandra; Heijmen, Ben

2018-06-01

In the abdomen, it is challenging to assess the accuracy of deformable image registration (DIR) for individual patients, due to the lack of clear anatomical landmarks, which can hamper clinical applications that require high accuracy DIR, such as adaptive radiotherapy. In this study, we propose and evaluate a methodology for estimating the impact of uncertainties in DIR on calculated accumulated dose in the upper abdomen, in order to aid decision making in adaptive treatment approaches. Sixteen liver metastasis patients treated with SBRT were evaluated. Each patient had one planning and three daily treatment CT-scans. Each daily CT scan was deformably registered 132 times to the planning CT-scan, using a wide range of parameter settings for the registration algorithm. A subset of ‘realistic’ registrations was then objectively selected based on distances between mapped and target contours. The underlying 3D transformations of these registrations were used to assess the corresponding uncertainties in voxel positions, and delivered dose, with a focus on accumulated maximum doses in the hollow OARs, i.e. esophagus, stomach, and duodenum. The number of realistic registrations varied from 5 to 109, depending on the patient, emphasizing the need for individualized registration parameters. Considering for all patients the realistic registrations, the 99th percentile of the voxel position uncertainties was 5.6  ±  3.3 mm. This translated into a variation (difference between 1st and 99th percentile) in accumulated D max in hollow OARs of up to 3.3 Gy. For one patient a violation of the accumulated stomach dose outside the uncertainty band was detected. The observed variation in accumulated doses in the OARs related to registration uncertainty, emphasizes the need to investigate the impact of this uncertainty for any DIR algorithm prior to clinical use for dose accumulation. The proposed method for assessing on an individual patient basis the impact of uncertainties in DIR on accumulated dose is in principle applicable for all DIR algorithms allowing variation in registration parameters.

Evaluation of registration, compression and classification algorithms. Volume 1: Results

NASA Technical Reports Server (NTRS)

Jayroe, R.; Atkinson, R.; Callas, L.; Hodges, J.; Gaggini, B.; Peterson, J.

1979-01-01

The registration, compression, and classification algorithms were selected on the basis that such a group would include most of the different and commonly used approaches. The results of the investigation indicate clearcut, cost effective choices for registering, compressing, and classifying multispectral imagery.

A REGIONAL APPROACH TO ECOLOGICAL RISK ASSESSMENTS FOR PRODUCT REGISTRATION

EPA Science Inventory

Currently, most ecological risk assessments for EPA registration are evaluated at the national scale using a predetermined list of species with little regard to where the product will ultimately be used. The assumption is that the test species presently used are representative a...

Canny edge-based deformable image registration

NASA Astrophysics Data System (ADS)

Kearney, Vasant; Huang, Yihui; Mao, Weihua; Yuan, Baohong; Tang, Liping

2017-02-01

This work focuses on developing a 2D Canny edge-based deformable image registration (Canny DIR) algorithm to register in vivo white light images taken at various time points. This method uses a sparse interpolation deformation algorithm to sparsely register regions of the image with strong edge information. A stability criterion is enforced which removes regions of edges that do not deform in a smooth uniform manner. Using a synthetic mouse surface ground truth model, the accuracy of the Canny DIR algorithm was evaluated under axial rotation in the presence of deformation. The accuracy was also tested using fluorescent dye injections, which were then used for gamma analysis to establish a second ground truth. The results indicate that the Canny DIR algorithm performs better than rigid registration, intensity corrected Demons, and distinctive features for all evaluation matrices and ground truth scenarios. In conclusion Canny DIR performs well in the presence of the unique lighting and shading variations associated with white-light-based image registration.

LANDSAT-4 MSS Geometric Correction: Methods and Results

NASA Technical Reports Server (NTRS)

Brooks, J.; Kimmer, E.; Su, J.

1984-01-01

An automated image registration system such as that developed for LANDSAT-4 can produce all of the information needed to verify and calibrate the software and to evaluate system performance. The on-line MSS archive generation process which upgrades systematic correction data to geodetic correction data is described as well as the control point library build subsystem which generates control point chips and support data for on-line upgrade of correction data. The system performance was evaluated for both temporal and geodetic registration. For temporal registration, 90% errors were computed to be .36 IFOV (instantaneous field of view) = 82.7 meters) cross track, and .29 IFOV along track. Also, for actual production runs monitored, the 90% errors were .29 IFOV cross track and .25 IFOV along track. The system specification is .3 IFOV, 90% of the time, both cross and along track. For geodetic registration performance, the model bias was measured by designating control points in the geodetically corrected imagery.

Hyperbolic Harmonic Mapping for Surface Registration

PubMed Central

Shi, Rui; Zeng, Wei; Su, Zhengyu; Jiang, Jian; Damasio, Hanna; Lu, Zhonglin; Wang, Yalin; Yau, Shing-Tung; Gu, Xianfeng

2016-01-01

Automatic computation of surface correspondence via harmonic map is an active research field in computer vision, computer graphics and computational geometry. It may help document and understand physical and biological phenomena and also has broad applications in biometrics, medical imaging and motion capture inducstries. Although numerous studies have been devoted to harmonic map research, limited progress has been made to compute a diffeomorphic harmonic map on general topology surfaces with landmark constraints. This work conquers this problem by changing the Riemannian metric on the target surface to a hyperbolic metric so that the harmonic mapping is guaranteed to be a diffeomorphism under landmark constraints. The computational algorithms are based on Ricci flow and nonlinear heat diffusion methods. The approach is general and robust. We employ our algorithm to study the constrained surface registration problem which applies to both computer vision and medical imaging applications. Experimental results demonstrate that, by changing the Riemannian metric, the registrations are always diffeomorphic and achieve relatively high performance when evaluated with some popular surface registration evaluation standards. PMID:27187948

Point cloud registration from local feature correspondences-Evaluation on challenging datasets.

PubMed

Petricek, Tomas; Svoboda, Tomas

2017-01-01

Registration of laser scans, or point clouds in general, is a crucial step of localization and mapping with mobile robots or in object modeling pipelines. A coarse alignment of the point clouds is generally needed before applying local methods such as the Iterative Closest Point (ICP) algorithm. We propose a feature-based approach to point cloud registration and evaluate the proposed method and its individual components on challenging real-world datasets. For a moderate overlap between the laser scans, the method provides a superior registration accuracy compared to state-of-the-art methods including Generalized ICP, 3D Normal-Distribution Transform, Fast Point-Feature Histograms, and 4-Points Congruent Sets. Compared to the surface normals, the points as the underlying features yield higher performance in both keypoint detection and establishing local reference frames. Moreover, sign disambiguation of the basis vectors proves to be an important aspect in creating repeatable local reference frames. A novel method for sign disambiguation is proposed which yields highly repeatable reference frames.

Comparison of subpixel image registration algorithms

NASA Astrophysics Data System (ADS)

Boye, R. R.; Nelson, C. L.

2009-02-01

Research into the use of multiframe superresolution has led to the development of algorithms for providing images with enhanced resolution using several lower resolution copies. An integral component of these algorithms is the determination of the registration of each of the low resolution images to a reference image. Without this information, no resolution enhancement can be attained. We have endeavored to find a suitable method for registering severely undersampled images by comparing several approaches. To test the algorithms, an ideal image is input to a simulated image formation program, creating several undersampled images with known geometric transformations. The registration algorithms are then applied to the set of low resolution images and the estimated registration parameters compared to the actual values. This investigation is limited to monochromatic images (extension to color images is not difficult) and only considers global geometric transformations. Each registration approach will be reviewed and evaluated with respect to the accuracy of the estimated registration parameters as well as the computational complexity required. In addition, the effects of image content, specifically spatial frequency content, as well as the immunity of the registration algorithms to noise will be discussed.

Automatic Marker-free Longitudinal Infrared Image Registration by Shape Context Based Matching and Competitive Winner-guided Optimal Corresponding

PubMed Central

Lee, Chia-Yen; Wang, Hao-Jen; Lai, Jhih-Hao; Chang, Yeun-Chung; Huang, Chiun-Sheng

2017-01-01

Long-term comparisons of infrared image can facilitate the assessment of breast cancer tissue growth and early tumor detection, in which longitudinal infrared image registration is a necessary step. However, it is hard to keep markers attached on a body surface for weeks, and rather difficult to detect anatomic fiducial markers and match them in the infrared image during registration process. The proposed study, automatic longitudinal infrared registration algorithm, develops an automatic vascular intersection detection method and establishes feature descriptors by shape context to achieve robust matching, as well as to obtain control points for the deformation model. In addition, competitive winner-guided mechanism is developed for optimal corresponding. The proposed algorithm is evaluated in two ways. Results show that the algorithm can quickly lead to accurate image registration and that the effectiveness is superior to manual registration with a mean error being 0.91 pixels. These findings demonstrate that the proposed registration algorithm is reasonably accurate and provide a novel method of extracting a greater amount of useful data from infrared images. PMID:28145474

The heritability of the functional connectome is robust to common nonlinear registration methods

NASA Astrophysics Data System (ADS)

Hafzalla, George W.; Prasad, Gautam; Baboyan, Vatche G.; Faskowitz, Joshua; Jahanshad, Neda; McMahon, Katie L.; de Zubicaray, Greig I.; Wright, Margaret J.; Braskie, Meredith N.; Thompson, Paul M.

2016-03-01

Nonlinear registration algorithms are routinely used in brain imaging, to align data for inter-subject and group comparisons, and for voxelwise statistical analyses. To understand how the choice of registration method affects maps of functional brain connectivity in a sample of 611 twins, we evaluated three popular nonlinear registration methods: Advanced Normalization Tools (ANTs), Automatic Registration Toolbox (ART), and FMRIB's Nonlinear Image Registration Tool (FNIRT). Using both structural and functional MRI, we used each of the three methods to align the MNI152 brain template, and 80 regions of interest (ROIs), to each subject's T1-weighted (T1w) anatomical image. We then transformed each subject's ROIs onto the associated resting state functional MRI (rs-fMRI) scans and computed a connectivity network or functional connectome for each subject. Given the different degrees of genetic similarity between pairs of monozygotic (MZ) and same-sex dizygotic (DZ) twins, we used structural equation modeling to estimate the additive genetic influences on the elements of the function networks, or their heritability. The functional connectome and derived statistics were relatively robust to nonlinear registration effects.

Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

PubMed Central

Lindson, Nicola; Aveyard, Paul; Ingram, Jackie T; Inglis, Jennie; Beach, Jane; West, Robert; Michie, Susan

2009-01-01

Background The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy. Design/Methods We will conduct a non-inferiority randomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm, participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely. This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation. Outcomes/Follow-up The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day. Trial Registration Current Controlled Trials ISRCTN22526020 PMID:19682359

Estimating emissions from adhesives and sealants uses and manufacturing for environmental risk assessments.

PubMed

Tolls, Johannes; Gómez, Divina; Guhl, Walter; Funk, Torsten; Seger, Erich; Wind, Thorsten

2016-01-01

Regulation (EC) No 1907/2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) requires that environmental exposure assessments be performed for all uses of dangerous substances that are marketed in the European Union in quantities above 10 tons per year. The quantification of emissions to the environment is a key step in this process. This publication describes the derivation of release factors and gives guidance for estimating use rates for quantifying the emissions from the manufacturing and application of adhesives and sealants. Release factors available for coatings and paints are read across to adhesives or sealants based on similarities between these 2 product groups with regard to chemical composition and to processing during manufacturing and application. The granular emission scenarios in these documents are mapped to the broad emission scenarios for adhesives or sealants. According to the mapping, the worst-case release factors for coatings or paints are identified and assigned to the adhesives or sealants scenarios. The resulting 10 specific environmental release categories (SPERCs) for adhesives and sealants are defined by differentiating between solvent and nonsolvent ingredients and between water-borne and solvent-borne or solvent-free products. These cover the vast majority of the production processes and uses and are more realistic than the 5 relevant emission estimation defaults provided in the REACH guidance. They are accompanied with adhesive or sealant consumption rates in the EU and with guidance for estimating conservative substance use rates at a generic level. The approach of combining conservative SPERC release factors with conservative estimates of substance rates is likely to yield emission estimates that tend to overpredict actual releases. Because this qualifies the approach for use in lower-tier environmental exposure assessment, the Association of the European Adhesive & Sealant Industry (FEICA) SPERCs are available in several exposure assessment tools that are used under REACH. Given the limited regional variation in the manufacturing and use processes of adhesives and sealants, the SPERCs may be applicable for emission estimation not only in the EU but also in other regions. © 2015 SETAC.

2D and 3D registration methods for dual-energy contrast-enhanced digital breast tomosynthesis

NASA Astrophysics Data System (ADS)

Lau, Kristen C.; Roth, Susan; Maidment, Andrew D. A.

2014-03-01

Contrast-enhanced digital breast tomosynthesis (CE-DBT) uses an iodinated contrast agent to image the threedimensional breast vasculature. The University of Pennsylvania is conducting a CE-DBT clinical study in patients with known breast cancers. The breast is compressed continuously and imaged at four time points (1 pre-contrast; 3 postcontrast). A hybrid subtraction scheme is proposed. First, dual-energy (DE) images are obtained by a weighted logarithmic subtraction of the high-energy and low-energy image pairs. Then, post-contrast DE images are subtracted from the pre-contrast DE image. This hybrid temporal subtraction of DE images is performed to analyze iodine uptake, but suffers from motion artifacts. Employing image registration further helps to correct for motion, enhancing the evaluation of vascular kinetics. Registration using ANTS (Advanced Normalization Tools) is performed in an iterative manner. Mutual information optimization first corrects large-scale motions. Normalized cross-correlation optimization then iteratively corrects fine-scale misalignment. Two methods have been evaluated: a 2D method using a slice-by-slice approach, and a 3D method using a volumetric approach to account for out-of-plane breast motion. Our results demonstrate that iterative registration qualitatively improves with each iteration (five iterations total). Motion artifacts near the edge of the breast are corrected effectively and structures within the breast (e.g. blood vessels, surgical clip) are better visualized. Statistical and clinical evaluations of registration accuracy in the CE-DBT images are ongoing.

Deformable image registration using convolutional neural networks

NASA Astrophysics Data System (ADS)

Eppenhof, Koen A. J.; Lafarge, Maxime W.; Moeskops, Pim; Veta, Mitko; Pluim, Josien P. W.

2018-03-01

Deformable image registration can be time-consuming and often needs extensive parameterization to perform well on a specific application. We present a step towards a registration framework based on a three-dimensional convolutional neural network. The network directly learns transformations between pairs of three-dimensional images. The outputs of the network are three maps for the x, y, and z components of a thin plate spline transformation grid. The network is trained on synthetic random transformations, which are applied to a small set of representative images for the desired application. Training therefore does not require manually annotated ground truth deformation information. The methodology is demonstrated on public data sets of inspiration-expiration lung CT image pairs, which come with annotated corresponding landmarks for evaluation of the registration accuracy. Advantages of this methodology are its fast registration times and its minimal parameterization.

USDA registration and rectification requirements

NASA Technical Reports Server (NTRS)

Allen, R.

1982-01-01

Some of the requirements of the United States Department of Agriculture for accuracy of aerospace acquired data, and specifically, requirements for registration and rectification of remotely sensed data are discussed. Particular attention is given to foreign and domestic crop estimation and forecasting, forestry information applications, and rangeland condition evaluations.

Simulation Models Evaluation of Pest Resistance Development to Refuge in the Bag Concepts Related to Pioneer Submission

EPA Science Inventory

The USEPA, under its administration of the Federal Insecticide Fungicide and Rodenticide Act (FIFRA), requires the registration of all pesticides and pesticidal materials. The GM crops containing pesticidal traits are subject to FIFRA registration requirements. Concerns relating ...

77 FR 68123 - Privacy Act of 1974; System of Records Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

... test records, including registrant's first and last name, evaluation data, pretest and posttest scores..., pretest and posttest scores, and registration information, will be disclosed to accrediting bodies (such... educational information, training, best practices, and tools to health professionals as one initiative to help...

A Knowledge Use Perspective: Comments on a Conference.

ERIC Educational Resources Information Center

Fisher, Evelyn

The papers from the 1982 conference on Pennsylvania's Long Range Plan for School Improvement (LRPSI) assist in constructing reality about LRPSI itself. Focusing on the program's registration phase, Charles Gorman offers an alternative proposal, linking registration and evaluation, that would contribute to improving schools and increasing public…

76 FR 552 - Pesticides; Availability of Pesticide Registration Notice Regarding the Residential Exposure...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... interested persons about important policies, procedures, and registration related decisions, and serve to...: Richard P. Dumas, Pesticide Re- evaluation Division, Office of Pesticide Programs, Environmental... applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION...

My "Ill" Literacy Narrative: Growing up Black, Po and a Girl, in the Hood

ERIC Educational Resources Information Center

Richardson, Elaine

2009-01-01

Hegemonic discourses authorise certain ways of being, knowing, and doing. We internalise or appropriate images, patterns, and words from the social activities in which we have participated. Race, gender, sexuality, age, education, class are among aspects of identity (social constructions) that affect our language and literacy acquisition, the way…

Becoming an "Authorised" Postgraduate Research Writer

ERIC Educational Resources Information Center

James, Bronwyn

2012-01-01

Within the context of postgraduate research education and training in the higher education sector, drafting might be understood as "not quite the final product" produced by the student who is "not yet the final product" of the university. In this paper, I turn this assumption "off centre" to argue instead that writing and subjectivity are mutually…

Higher Education in TAFE. NCVER Monograph Series 01/2009

ERIC Educational Resources Information Center

Wheelahan, Leesa; Moodie, Gavin; Billet, Stephen; Kelly, Ann

2009-01-01

Degrees in technical and further education (TAFE) are relatively new, but are likely to grow as a consequence of government policies that both seek to increase the percentage of Australians holding a bachelor degree and create a more unified tertiary education sector. There are ten TAFE institutes authorised to offer higher education in five…

Lubiprostone for chronic constipation in adults.

PubMed

2014-04-01

Lubiprostone (Amitiza-Sucampo Pharma Europe), a chloride-channel activator is licensed for the treatment of chronic idiopathic constipation in adults. It received a marketing authorisation in the UK in September 2012. In this article, we consider the evidence for lubiprostone in the management of constipation and how the treatment fits with current management strategies for constipation.

[A strategy for institutionalisation of health impact assessment in Andalusia (Spain)].

PubMed

Vela-Ríos, José; Rodríguez-Rasero, Francisco J; Moya-Ruano, Luis A; Candau-Bejarano, Ana; Ruiz-Fernández, Josefa

2016-01-01

Health impact assessment (HIA) aims to incorporate people's health and wellbeing as a key feature in policy-making. Many authors believe that HIA might be systematically integrated into all decision-making processes as a way to achieve that goal. To that end, there is need to overcome a number of challenges, including the fact that Andalusia (Spain) has made HIA compulsory by law, the need for awareness of all public sectors whose decisions might have substantial impacts on health and for a methodology that would enable a comprehensive approach to health determinants and inequalities, and the training of both the public health staff and professional sectors responsible for its application. In Andalusia, a law provides mandatory and binding health impact reports for most authorisation procedures in different areas: from sectoral plans to urban planning schemes, and especially projects subject to environmental assessment. Implementation of this law has required its integration into authorisation procedures, the training of interdisciplinary working groups in public health, the preparation of technical guidelines, and the organisation of dissemination and training seminars for developers. Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.

A practical approach to screen for authorised and unauthorised genetically modified plants.

PubMed

Waiblinger, Hans-Ulrich; Grohmann, Lutz; Mankertz, Joachim; Engelbert, Dirk; Pietsch, Klaus

2010-03-01

In routine analysis, screening methods based on real-time PCR are most commonly used for the detection of genetically modified (GM) plant material in food and feed. In this paper, it is shown that the combination of five DNA target sequences can be used as a universal screening approach for at least 81 GM plant events authorised or unauthorised for placing on the market and described in publicly available databases. Except for maize event LY038, soybean events DP-305423 and BPS-CV127-9 and cotton event 281-24-236 x 3006-210-23, at least one of the five genetic elements has been inserted in these GM plants and is targeted by this screening approach. For the detection of these sequences, fully validated real-time PCR methods have been selected. A screening table is presented that describes the presence or absence of the target sequences for most of the listed GM plants. These data have been verified either theoretically according to available databases or experimentally using available reference materials. The screening table will be updated regularly by a network of German enforcement laboratories.

Third molar development: evaluation of nine tooth development registration techniques for age estimations.

PubMed

Thevissen, Patrick W; Fieuws, Steffen; Willems, Guy

2013-03-01

Multiple third molar development registration techniques exist. Therefore the aim of this study was to detect which third molar development registration technique was most promising to use as a tool for subadult age estimation. On a collection of 1199 panoramic radiographs the development of all present third molars was registered following nine different registration techniques [Gleiser, Hunt (GH); Haavikko (HV); Demirjian (DM); Raungpaka (RA); Gustafson, Koch (GK); Harris, Nortje (HN); Kullman (KU); Moorrees (MO); Cameriere (CA)]. Regression models with age as response and the third molar registration as predictor were developed for each registration technique separately. The MO technique disclosed highest R(2) (F 51%, M 45%) and lowest root mean squared error (F 3.42 years; M 3.67 years) values, but differences with other techniques were small in magnitude. The amount of stages utilized in the explored staging techniques slightly influenced the age predictions. © 2013 American Academy of Forensic Sciences.

Investigation of 3D histograms of oriented gradients for image-based registration of CT with interventional CBCT

NASA Astrophysics Data System (ADS)

Trimborn, Barbara; Wolf, Ivo; Abu-Sammour, Denis; Henzler, Thomas; Schad, Lothar R.; Zöllner, Frank G.

2017-03-01

Image registration of preprocedural contrast-enhanced CTs to intraprocedual cone-beam computed tomography (CBCT) can provide additional information for interventional liver oncology procedures such as transcatheter arterial chemoembolisation (TACE). In this paper, a novel similarity metric for gradient-based image registration is proposed. The metric relies on the patch-based computation of histograms of oriented gradients (HOG) building the basis for a feature descriptor. The metric was implemented in a framework for rigid 3D-3D-registration of pre-interventional CT with intra-interventional CBCT data obtained during the workflow of a TACE. To evaluate the performance of the new metric, the capture range was estimated based on the calculation of the mean target registration error and compared to the results obtained with a normalized cross correlation metric. The results show that 3D HOG feature descriptors are suitable as image-similarity metric and that the novel metric can compete with established methods in terms of registration accuracy

Lung texture in serial thoracic CT scans: Assessment of change introduced by image registration1

PubMed Central

Cunliffe, Alexandra R.; Al-Hallaq, Hania A.; Labby, Zacariah E.; Pelizzari, Charles A.; Straus, Christopher; Sensakovic, William F.; Ludwig, Michelle; Armato, Samuel G.

2012-01-01

Purpose: The aim of this study was to quantify the effect of four image registration methods on lung texture features extracted from serial computed tomography (CT) scans obtained from healthy human subjects. Methods: Two chest CT scans acquired at different time points were collected retrospectively for each of 27 patients. Following automated lung segmentation, each follow-up CT scan was registered to the baseline scan using four algorithms: (1) rigid, (2) affine, (3) B-splines deformable, and (4) demons deformable. The registration accuracy for each scan pair was evaluated by measuring the Euclidean distance between 150 identified landmarks. On average, 1432 spatially matched 32 × 32-pixel region-of-interest (ROI) pairs were automatically extracted from each scan pair. First-order, fractal, Fourier, Laws’ filter, and gray-level co-occurrence matrix texture features were calculated in each ROI, for a total of 140 features. Agreement between baseline and follow-up scan ROI feature values was assessed by Bland–Altman analysis for each feature; the range spanned by the 95% limits of agreement of feature value differences was calculated and normalized by the average feature value to obtain the normalized range of agreement (nRoA). Features with small nRoA were considered “registration-stable.” The normalized bias for each feature was calculated from the feature value differences between baseline and follow-up scans averaged across all ROIs in every patient. Because patients had “normal” chest CT scans, minimal change in texture feature values between scan pairs was anticipated, with the expectation of small bias and narrow limits of agreement. Results: Registration with demons reduced the Euclidean distance between landmarks such that only 9% of landmarks were separated by ≥1 mm, compared with rigid (98%), affine (95%), and B-splines (90%). Ninety-nine of the 140 (71%) features analyzed yielded nRoA > 50% for all registration methods, indicating that the majority of feature values were perturbed following registration. Nineteen of the features (14%) had nRoA < 15% following demons registration, indicating relative feature value stability. Student's t-tests showed that the nRoA of these 19 features was significantly larger when rigid, affine, or B-splines registration methods were used compared with demons registration. Demons registration yielded greater normalized bias in feature value change than B-splines registration, though this difference was not significant (p = 0.15). Conclusions: Demons registration provided higher spatial accuracy between matched anatomic landmarks in serial CT scans than rigid, affine, or B-splines algorithms. Texture feature changes calculated in healthy lung tissue from serial CT scans were smaller following demons registration compared with all other algorithms. Though registration altered the values of the majority of texture features, 19 features remained relatively stable after demons registration, indicating their potential for detecting pathologic change in serial CT scans. Combined use of accurate deformable registration using demons and texture analysis may allow for quantitative evaluation of local changes in lung tissue due to disease progression or treatment response. PMID:22894392

2D/3D registration using a rotation-invariant cost function based on Zernike moments

NASA Astrophysics Data System (ADS)

Birkfellner, Wolfgang; Yang, Xinhui; Burgstaller, Wolfgang; Baumann, Bernard; Jacob, Augustinus L.; Niederer, Peter F.; Regazzoni, Pietro; Messmer, Peter

2004-05-01

We present a novel in-plane rotation invariant cost function for 2D/3D registration utilizing projection-invariant transformation properties and the decomposition of the X-ray nad the DRR under comparision into orhogonal Zernike moments. As a result, only five dof have to be optimized, and the number of iteration necessary for registration can be significantly reduced. Results in a phantom study show that an accuracy of approximately 0.7° and 2 mm can be achieved using this method. We conclude that reduction of coupled dof and usage of linear independent coefficients for cost function evaluation provide intersting new perspectives for the field of 2D/3D registration.

Improvement of registration accuracy in accelerated partial breast irradiation using the point-based rigid-body registration algorithm for patients with implanted fiducial markers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Minoru; Yoshimura, Michio, E-mail: myossy@kuhp.kyoto-u.ac.jp; Sato, Sayaka

2015-04-15

Purpose: To investigate image-registration errors when using fiducial markers with a manual method and the point-based rigid-body registration (PRBR) algorithm in accelerated partial breast irradiation (APBI) patients, with accompanying fiducial deviations. Methods: Twenty-two consecutive patients were enrolled in a prospective trial examining 10-fraction APBI. Titanium clips were implanted intraoperatively around the seroma in all patients. For image-registration, the positions of the clips in daily kV x-ray images were matched to those in the planning digitally reconstructed radiographs. Fiducial and gravity registration errors (FREs and GREs, respectively), representing resulting misalignments of the edge and center of the target, respectively, were comparedmore » between the manual and algorithm-based methods. Results: In total, 218 fractions were evaluated. Although the mean FRE/GRE values for the manual and algorithm-based methods were within 3 mm (2.3/1.7 and 1.3/0.4 mm, respectively), the percentages of fractions where FRE/GRE exceeded 3 mm using the manual and algorithm-based methods were 18.8%/7.3% and 0%/0%, respectively. Manual registration resulted in 18.6% of patients with fractions of FRE/GRE exceeding 5 mm. The patients with larger clip deviation had significantly more fractions showing large FRE/GRE using manual registration. Conclusions: For image-registration using fiducial markers in APBI, the manual registration results in more fractions with considerable registration error due to loss of fiducial objectivity resulting from their deviation. The authors recommend the PRBR algorithm as a safe and effective strategy for accurate, image-guided registration and PTV margin reduction.« less

Registration of T2-weighted and diffusion-weighted MR images of the prostate: comparison between manual and landmark-based methods

NASA Astrophysics Data System (ADS)

Peng, Yahui; Jiang, Yulei; Soylu, Fatma N.; Tomek, Mark; Sensakovic, William; Oto, Aytekin

2012-02-01

Quantitative analysis of multi-parametric magnetic resonance (MR) images of the prostate, including T2-weighted (T2w) and diffusion-weighted (DW) images, requires accurate image registration. We compared two registration methods between T2w and DW images. We collected pre-operative MR images of 124 prostate cancer patients (68 patients scanned with a GE scanner and 56 with Philips scanners). A landmark-based rigid registration was done based on six prostate landmarks in both T2w and DW images identified by a radiologist. Independently, a researcher manually registered the same images. A radiologist visually evaluated the registration results by using a 5-point ordinal scale of 1 (worst) to 5 (best). The Wilcoxon signed-rank test was used to determine whether the radiologist's ratings of the results of the two registration methods were significantly different. Results demonstrated that both methods were accurate: the average ratings were 4.2, 3.3, and 3.8 for GE, Philips, and all images, respectively, for the landmark-based method; and 4.6, 3.7, and 4.2, respectively, for the manual method. The manual registration results were more accurate than the landmark-based registration results (p < 0.0001 for GE, Philips, and all images). Therefore, the manual method produces more accurate registration between T2w and DW images than the landmark-based method.

76 FR 64960 - Extension of Agency Information Collection Activity Under OMB Review: Flight Crew Self-Defense...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... Information Collection Activity Under OMB Review: Flight Crew Self-Defense Training--Registration and... self-defense training class provided by TSA, the collection process involves requesting, the name.... Information Collection Requirement Title: Flight Crew Self-Defense Training--Registration and Evaluation. Type...

A REGIONAL APPROACH TO ECOLOGICAL RISK ASSESSMENTS FOR PESTICIDE REGISTRATION

EPA Science Inventory

Currently, most ecological risk assessments for EPA pesticide registration are evaluated at the national scale using a predetermined list of test species (OPPTS 850.4225 and 8504250) as a model system with little regard to where and how the product will ultimately be used. The a...

78 FR 24195 - Product Cancellation Order for Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... Insecticide, Fungicide, and Rodenticide Act (FIFRA). This cancellation order follows a December 19, 2012... effective December 31, 2016. FOR FURTHER INFORMATION CONTACT: Molly Clayton, Pesticide Re-Evaluation... registrants of the products in Tables 1. and 2. of this unit, in sequence by EPA company number. This number...

76 FR 57058 - International Cooperation on Harmonisation of Technical Requirements for Registration of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0165] International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products; Guidance for Industry on Studies To Evaluate the Metabolism and Residue Kinetics of Veterinary...

Registries in European post-marketing surveillance: a retrospective analysis of centrally approved products, 2005-2013.

PubMed

Bouvy, Jacoline C; Blake, Kevin; Slattery, Jim; De Bruin, Marie L; Arlett, Peter; Kurz, Xavier

2017-12-01

Regulatory agencies and other stakeholders increasingly rely on data collected through registries to support their decision-making. Data from registries are a cornerstone of post-marketing surveillance for monitoring the use of medicines in clinical practice. This study was aimed at gaining further insight into the European Medicines Agency's (EMA) requests for new registries and registry studies using existing registries and to review the experience gained in their conduct. European Public Assessment Reports were consulted to identify products for which a request for a registry was made as a condition of the marketing authorisation. All centrally authorised products that received a positive opinion of the EMA Committee for Medicinal Products for Human Use between 1 January 2005 and 31 December 2013 were included. Data regarding registry design and experiences were collected from EMA electronic record keeping systems. Of 392 products that received a positive Committee for Medicinal Products for Human Use opinion during 2005-2013, 31 registries were requested for 30 products in total. Sixty-five percent were product registries whereas 35% were disease registries and 71% of the registries had a primary safety objective. Most commonly reported issues with registries were delayed time to start and low patient accrual rates. The delays found in getting new registries up and running support the need to improve the timeliness of data collection in the post-marketing setting. Methodological challenges met in conducting this study highlighted the need for a clarification of definitions and epidemiological concepts around patient registries. The results will inform the EMA Patient Registry initiative to support use of existing patient registries for the post-authorisation benefit-risk monitoring of medicinal products. © 2017 Commonwealth of Australia. Pharmacoepidemiology & Drug Safety © 2017 John Wiley & Sons, Ltd. © 2017 Commonwealth of Australia. Pharmacoepidemiology & Drug Safety © 2017 John Wiley & Sons, Ltd.

Preparation of medicines for children - a hierarchy of classification.

PubMed

Ernest, Terry B; Craig, Jo; Nunn, Anthony; Salunke, Smita; Tuleu, Catherine; Breitkreutz, Joerg; Alex, Rainer; Hempenstall, John

2012-10-05

There is some confusion about the types of paediatric pharmaceutical preparation (in a regulatory and pharmaceutical development context) that are acceptable for approval by medicines regulators. Some of the confusion relates to terminology which may mean different things to different stakeholders. It may not always be possible to provide authorised, commercially manufactured, age appropriate, ready-to-administer preparations. In terms of assurance of quality and bioavailability there is a continuum from this ideal through intermediate products through authorised compounding and manipulation of commercial dosage forms to ad hoc compounding using only the skills and experience of the individual pharmacist. Additionally, it is widely known that caregivers may manipulate medicines at home, for example by segmenting tablets and by addition to foods or liquids. The first intent of the manufacturer should be to provide for children an age appropriate, ready-to-administer preparation which is commercially manufactured and approved by the competent authorities. However, there will still be a place for providing other age appropriate preparations such as approved products that are 'intermediates' requiring reconstitution before use, or instructions for compounding or manipulation of a dosage form. If compounding or manipulation is likely to be required it is preferable that data are generated by Industry, approved by the competent authorities and provided in the Summary of Product Characteristics (SmPC). It is acknowledged however, that ad hoc compounding or manipulation may also take place in certain circumstances such as logistical difficulties or to satisfy the needs of the child who does not find the authorised product to be 'age appropriate'. This paper explores compounding and manipulation of medicines in relation to approval by medicines regulators and non-approved preparation to fulfil the needs of the individual patient. Definitions are proposed to provide a hierarchical classification based on assurances of quality and bioavailability. Copyright © 2012 Elsevier B.V. All rights reserved.

Quality of evidence considered by Health Canada in granting full market authorisation to new drugs with a conditional approval: a retrospective cohort study.

PubMed

Lexchin, Joel

2018-04-28

This study examines the characteristics of studies that Health Canada uses to grant full marketing authorisation for products given a conditional approval between 1 January 1998 and 30 June 2017. Cohort study. Journal articles listing drugs that fulfilled their conditions and received full marketing authorisation, Notice of Compliance database, Notice of Compliance with conditions website, Qualifying Notices listing required confirmatory studies, clinicaltrials.gov, PubMed, Embase, companies making products being analysed, journal articles resulting from confirmatory studies. None. Characteristics of studies-study design (randomised controlled trials, observational), primary outcome used (clinical, surrogate), blinding, number of patients in studies, patient median age, number of men and women. Eleven companies confirmed 36 publications for 19 products (21 indications). Twenty-nine out of the 36 studies were randomised controlled trials (RCTs) but only 10 stated if they were blinded. Twenty used surrogate outcomes. The median age of patients was 56 (IQR 44-61). The median number of men per study/trial was 184 (IQR 58-514) versus women 141 (IQR 46-263). Postmarket studies required by Health Canada had more rigorous methodology than those required by either the Food and Drug Administration or the European Medicines Agency. There were still deficiencies in these studies. The absence of blinding in the majority of RCTs may introduce bias in their results. The use of surrogate outcomes especially in oncology trials means that improvements in survival are not available. The relatively young age of patients, even for products for cancer, means that predicting how the elderly will respond is often unknown. The almost universal finding that men outnumbered women may make it hard to differentiate responses by sex. These results raise potential concerns about the quality of evidence that Health Canada accepts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Internet-using men who have sex with men would be interested in accessing authorised HIV self-tests available for purchase online.

PubMed

Greacen, Tim; Friboulet, David; Blachier, Audrey; Fugon, Lionel; Hefez, Serge; Lorente, Nicolas; Spire, Bruno

2013-01-01

Men who have sex with men (MSM) recruited in sex venues have been shown to be interested in accessing HIV home-tests if reliable and authorised tests were available. To what extent is this true for MSM recruited online? In an online survey in French on the use of unauthorised HIV home-tests purchased online, MSM previously unaware of the existence of these tests were asked if they would be interested in accessing them if these tests were authorised. Among 5908 non-HIV positive respondents, 86.5% expressed interest. Independent variables associated with interest included: being younger, living in smaller towns, having a job but not tertiary education and living in a conventional family with one's parents or a wife and family. Interested men were also more likely to have never done the standard HIV test or not in the last year, to have casual sex partners but on average not more than once a week, to take sexual risks with these partners, to live their sex-lives with men in absolute secrecy and yet often to try to make a date to see their sex partners again. Of the 5109 respondents interested in accessing self-tests purchasable online, 4362 (85.4%) answered an open question on their reasons for being interested. Using thematic analysis, principle themes identified proved to be similar to those found in earlier studies with MSM recruited in sex venues: convenience, rapidity accessing results and privacy. In answer to a closed question, men not interested chose as reasons: satisfaction with current method, doubts about reliability, not wanting to be alone when discovering results and fear of incorrect use. In conclusion, although the online questionnaire may have introduced selection bias over-representing men already interested, many Internet-using MSM are interested in accessing self-tests available for purchase online.

[Consideration about chemistry, manufacture and control (CMC) key problems in simplified registration of classical traditional Chinese medicine excellent prescriptions].

PubMed

Wang, Zhi-Min; Liu, Ju-Yan; Liu, Xiao-Qian; Wang, De-Qin; Yan, Li-Hua; Zhu, Jin-Jin; Gao, Hui-Min; Li, Chun; Wang, Jin-Yu; Li, Chu-Yuan; Ni, Qing-Chun; Huang, Ji-Sheng; Lin, Juan

2017-05-01

As an outstanding representative of traditional Chinese medicine(TCM) prescriptions accumulated from famous TCM doctors' clinical experiences in past dynasties, classical TCM excellent prescriptions (cTCMeP) are the most valuable part of TCM system. To support the research and development of cTCMeP, a series of regulations and measures were issued to encourage its simplified registration. There is still a long-way to go because many key problems and puzzles about technology, registration and administration in cTCMeP R&D process are not resolved. Based on the analysis of registration and management regulations of botanical drug products in FDA of USA and Japan, and EMA of Europe, the possible key problems and countermeasures in chemistry, manufacture and control (CMC) of simplified registration of cTCMeP were analyzed on the consideration of its actual situation. The method of "reference decoction extract by traditional prescription" (RDETP) was firstly proposed as standard to evaluate the quality and preparation uniformity between the new developing product under simplified registration and traditional original usages of cTCMeP, instead of Standard Decoction method in Japan. "Totality of the evidence" approach, mass balance and bioassay/biological assay of cTCMeP were emphatically suggested to introduce to the quality uniformity evaluation system in the raw drug material, drug substance and final product between the modern product and traditional decoction. Copyright© by the Chinese Pharmaceutical Association.

Registration status and outcome reporting of trials published in core headache medicine journals.

PubMed

Rayhill, Melissa L; Sharon, Roni; Burch, Rebecca; Loder, Elizabeth

2015-11-17

To evaluate randomized controlled trial (RCT) registration and outcome reporting compliance in core headache medicine journals. We identified RCTs published in core journals (Headache, Cephalalgia, and the Journal of Headache and Pain) from 2005 through 2014. We searched articles for trial registration numbers, which were verified in the corresponding trial registry. We categorized trial funding sources as industry, academic, government, or mixed. We contacted corresponding authors to assess reasons for nonregistration. We evaluated whether primary outcomes in trial registries matched those in corresponding publications. The journals published 225 RCTs over the study period. Fifty-eight of 225 (26%) reported a trial registration number in the article that could be linked to a corresponding registry entry. Trial registration rates increased over the 9 years of the study. Forty-six of 118 (39%) of industry-funded studies were registered compared with 27% of academic and 0% of government-funded studies. Only 5% of RCTs were prospectively registered, reported primary outcomes identical to those in the trial registry, and did not report unacknowledged post hoc outcomes. The most common reason for nonregistration was lack of awareness. Only about a quarter of the articles published in the core headache medicine journals are compliant with trial registration, but compliance has increased over time. Selective reporting of outcomes remains a problem, and very few trials met all 3 reporting standards assessed in this study. Efforts to improve the quality of trial reporting in the headache literature should continue. © 2015 American Academy of Neurology.

Toward magnetic resonance-guided electroanatomical voltage mapping for catheter ablation of scar-related ventricular tachycardia: a comparison of registration methods.

PubMed

Tao, Qian; Milles, Julien; VAN Huls VAN Taxis, Carine; Lamb, Hildo J; Reiber, Johan H C; Zeppenfeld, Katja; VAN DER Geest, Rob J

2012-01-01

Integration of preprocedural delayed enhanced magnetic resonance imaging (DE-MRI) with electroanatomical voltage mapping (EAVM) may provide additional high-resolution substrate information for catheter ablation of scar-related ventricular tachycardias (VT). Accurate and fast image integration of DE-MRI with EAVM is desirable for MR-guided ablation. Twenty-six VT patients with large transmural scar underwent catheter ablation and preprocedural DE-MRI. With different registration models and EAVM input, 3 image integration methods were evaluated and compared to the commercial registration module CartoMerge. The performance was evaluated both in terms of distance measure that describes surface matching, and correlation measure that describes actual scar correspondence. Compared to CartoMerge, the method that uses the translation-and-rotation model and high-density EAVM input resulted in a registration error of 4.32±0.69 mm as compared to 4.84 ± 1.07 (P <0.05); the method that uses the translation model and high-density EAVM input resulted in a registration error of 4.60 ± 0.65 mm (P = NS); and the method that uses the translation model and a single anatomical landmark input resulted in a registration error of 6.58 ± 1.63 mm (P < 0.05). No significant difference in scar correlation was observed between all 3 methods and CartoMerge (P = NS). During VT ablation procedures, accurate integration of EAVM and DE-MRI can be achieved using a translation registration model and a single anatomical landmark. This model allows for image integration in minimal mapping time and is likely to reduce fluoroscopy time and increase procedure efficacy. © 2011 Wiley Periodicals, Inc.

Automatic Masking for Robust 3D-2D Image Registration in Image-Guided Spine Surgery.

PubMed

Ketcha, M D; De Silva, T; Uneri, A; Kleinszig, G; Vogt, S; Wolinsky, J-P; Siewerdsen, J H

During spinal neurosurgery, patient-specific information, planning, and annotation such as vertebral labels can be mapped from preoperative 3D CT to intraoperative 2D radiographs via image-based 3D-2D registration. Such registration has been shown to provide a potentially valuable means of decision support in target localization as well as quality assurance of the surgical product. However, robust registration can be challenged by mismatch in image content between the preoperative CT and intraoperative radiographs, arising, for example, from anatomical deformation or the presence of surgical tools within the radiograph. In this work, we develop and evaluate methods for automatically mitigating the effect of content mismatch by leveraging the surgical planning data to assign greater weight to anatomical regions known to be reliable for registration and vital to the surgical task while removing problematic regions that are highly deformable or often occluded by surgical tools. We investigated two approaches to assigning variable weight (i.e., "masking") to image content and/or the similarity metric: (1) masking the preoperative 3D CT ("volumetric masking"); and (2) masking within the 2D similarity metric calculation ("projection masking"). The accuracy of registration was evaluated in terms of projection distance error (PDE) in 61 cases selected from an IRB-approved clinical study. The best performing of the masking techniques was found to reduce the rate of gross failure (PDE > 20 mm) from 11.48% to 5.57% in this challenging retrospective data set. These approaches provided robustness to content mismatch and eliminated distinct failure modes of registration. Such improvement was gained without additional workflow and has motivated incorporation of the masking methods within a system under development for prospective clinical studies.

A fast and mobile system for registration of low-altitude visual and thermal aerial images using multiple small-scale UAVs

NASA Astrophysics Data System (ADS)

Yahyanejad, Saeed; Rinner, Bernhard

2015-06-01

The use of multiple small-scale UAVs to support first responders in disaster management has become popular because of their speed and low deployment costs. We exploit such UAVs to perform real-time monitoring of target areas by fusing individual images captured from heterogeneous aerial sensors. Many approaches have already been presented to register images from homogeneous sensors. These methods have demonstrated robustness against scale, rotation and illumination variations and can also cope with limited overlap among individual images. In this paper we focus on thermal and visual image registration and propose different methods to improve the quality of interspectral registration for the purpose of real-time monitoring and mobile mapping. Images captured by low-altitude UAVs represent a very challenging scenario for interspectral registration due to the strong variations in overlap, scale, rotation, point of view and structure of such scenes. Furthermore, these small-scale UAVs have limited processing and communication power. The contributions of this paper include (i) the introduction of a feature descriptor for robustly identifying corresponding regions of images in different spectrums, (ii) the registration of image mosaics, and (iii) the registration of depth maps. We evaluated the first method using a test data set consisting of 84 image pairs. In all instances our approach combined with SIFT or SURF feature-based registration was superior to the standard versions. Although we focus mainly on aerial imagery, our evaluation shows that the presented approach would also be beneficial in other scenarios such as surveillance and human detection. Furthermore, we demonstrated the advantages of the other two methods in case of multiple image pairs.

Automatic masking for robust 3D-2D image registration in image-guided spine surgery

NASA Astrophysics Data System (ADS)

Ketcha, M. D.; De Silva, T.; Uneri, A.; Kleinszig, G.; Vogt, S.; Wolinsky, J.-P.; Siewerdsen, J. H.

2016-03-01

During spinal neurosurgery, patient-specific information, planning, and annotation such as vertebral labels can be mapped from preoperative 3D CT to intraoperative 2D radiographs via image-based 3D-2D registration. Such registration has been shown to provide a potentially valuable means of decision support in target localization as well as quality assurance of the surgical product. However, robust registration can be challenged by mismatch in image content between the preoperative CT and intraoperative radiographs, arising, for example, from anatomical deformation or the presence of surgical tools within the radiograph. In this work, we develop and evaluate methods for automatically mitigating the effect of content mismatch by leveraging the surgical planning data to assign greater weight to anatomical regions known to be reliable for registration and vital to the surgical task while removing problematic regions that are highly deformable or often occluded by surgical tools. We investigated two approaches to assigning variable weight (i.e., "masking") to image content and/or the similarity metric: (1) masking the preoperative 3D CT ("volumetric masking"); and (2) masking within the 2D similarity metric calculation ("projection masking"). The accuracy of registration was evaluated in terms of projection distance error (PDE) in 61 cases selected from an IRB-approved clinical study. The best performing of the masking techniques was found to reduce the rate of gross failure (PDE > 20 mm) from 11.48% to 5.57% in this challenging retrospective data set. These approaches provided robustness to content mismatch and eliminated distinct failure modes of registration. Such improvement was gained without additional workflow and has motivated incorporation of the masking methods within a system under development for prospective clinical studies.

Comparative study to evaluate the accuracy of polyether occlusal bite registration material and occlusal registration wax as a guide for occlusal reduction during tooth preparation.

PubMed

Joshi, Niranjan; Shetty, Sridhar N; Prasad, Krishna D

2013-01-01

The use of different materials and techniques has been studied to decide the safest quantum of reduction of the occlusal surfaces. However, these methods provide limited information as to the actual amount of reduction with limitations in accuracy, accessibility and complexity. The objective of this study was to compare and evaluate the reliability of the most commonly used occlusal registration wax that with polyether bite registration material as a guide for occlusal reduction required during tooth preparations. For the purpose of this study, 25 abutment teeth requiring tooth preparation for fixed prosthesis were selected and tooth preparations carried out. Modeling wax strips of specific dimensions were placed onto the cast of prepared tooth, which was mounted on maximum intercuspation on the articulator and the articulator was closed. The thickness of the wax registration was measured at three zones namely two functional cusps and central fossa. Similar measurements were made using the polyether bite registration material and prosthesis at the same zones. The data was tabulated and was subjected to statistical analysis using anova test and Tukey honestly significant difference test. The differences in thickness between wax record and prosthesis by 0.1346 mm, whereas the difference between polyether and prosthesis was 0.02 mm with a P value of 0.042, which is statistically significant. This means that the wax record was 8.25% larger than the prosthesis while polyether was just 1.27% larger than the prosthesis. The clinical significance of the above analysis is that Ramitec polyether bite registration material is most suitable material when compared with commonly used modeling wax during the tooth preparation.

Registration of angiographic image on real-time fluoroscopic image for image-guided percutaneous coronary intervention.

PubMed

Kim, Dongkue; Park, Sangsoo; Jeong, Myung Ho; Ryu, Jeha

2018-02-01

In percutaneous coronary intervention (PCI), cardiologists must study two different X-ray image sources: a fluoroscopic image and an angiogram. Manipulating a guidewire while alternately monitoring the two separate images on separate screens requires a deep understanding of the anatomy of coronary vessels and substantial training. We propose 2D/2D spatiotemporal image registration of the two images in a single image in order to provide cardiologists with enhanced visual guidance in PCI. The proposed 2D/2D spatiotemporal registration method uses a cross-correlation of two ECG series in each image to temporally synchronize two separate images and register an angiographic image onto the fluoroscopic image. A guidewire centerline is then extracted from the fluoroscopic image in real time, and the alignment of the centerline with vessel outlines of the chosen angiographic image is optimized using the iterative closest point algorithm for spatial registration. A proof-of-concept evaluation with a phantom coronary vessel model with engineering students showed an error reduction rate greater than 74% on wrong insertion to nontarget branches compared to the non-registration method and more than 47% reduction in the task completion time in performing guidewire manipulation for very difficult tasks. Evaluation with a small number of experienced doctors shows a potentially significant reduction in both task completion time and error rate for difficult tasks. The total registration time with real procedure X-ray (angiographic and fluoroscopic) images takes [Formula: see text] 60 ms, which is within the fluoroscopic image acquisition rate of 15 Hz. By providing cardiologists with better visual guidance in PCI, the proposed spatiotemporal image registration method is shown to be useful in advancing the guidewire to the coronary vessel branches, especially those difficult to insert into.

A Multistage Approach for Image Registration.

PubMed

Bowen, Francis; Hu, Jianghai; Du, Eliza Yingzi

2016-09-01

Successful image registration is an important step for object recognition, target detection, remote sensing, multimodal content fusion, scene blending, and disaster assessment and management. The geometric and photometric variations between images adversely affect the ability for an algorithm to estimate the transformation parameters that relate the two images. Local deformations, lighting conditions, object obstructions, and perspective differences all contribute to the challenges faced by traditional registration techniques. In this paper, a novel multistage registration approach is proposed that is resilient to view point differences, image content variations, and lighting conditions. Robust registration is realized through the utilization of a novel region descriptor which couples with the spatial and texture characteristics of invariant feature points. The proposed region descriptor is exploited in a multistage approach. A multistage process allows the utilization of the graph-based descriptor in many scenarios thus allowing the algorithm to be applied to a broader set of images. Each successive stage of the registration technique is evaluated through an effective similarity metric which determines subsequent action. The registration of aerial and street view images from pre- and post-disaster provide strong evidence that the proposed method estimates more accurate global transformation parameters than traditional feature-based methods. Experimental results show the robustness and accuracy of the proposed multistage image registration methodology.

A quantitative comparison of the performance of three deformable registration algorithms in radiotherapy

PubMed Central

Fabri, Daniella; Zambrano, Valentina; Bhatia, Amon; Furtado, Hugo; Bergmann, Helmar; Stock, Markus; Bloch, Christoph; Lütgendorf-Caucig, Carola; Pawiro, Supriyanto; Georg, Dietmar; Birkfellner, Wolfgang; Figl, Michael

2013-01-01

We present an evaluation of various non-rigid registration algorithms for the purpose of compensating interfractional motion of the target volume and organs at risk areas when acquiring CBCT image data prior to irradiation. Three different deformable registration (DR) methods were used: the Demons algorithm implemented in the iPlan Software (BrainLAB AG, Feldkirchen, Germany) and two custom-developed piecewise methods using either a Normalized Correlation or a Mutual Information metric (featureletNC and featureletMI). These methods were tested on data acquired using a novel purpose-built phantom for deformable registration and clinical CT/CBCT data of prostate and lung cancer patients. The Dice similarity coefficient (DSC) between manually drawn contours and the contours generated by a derived deformation field of the structures in question was compared to the result obtained with rigid registration (RR). For the phantom, the piecewise methods were slightly superior, the featureletNC for the intramodality and the featureletMI for the intermodality registrations. For the prostate cases in less than 50% of the images studied the DSC was improved over RR. Deformable registration methods improved the outcome over a rigid registration for lung cases and in the phantom study, but not in a significant way for the prostate study. A significantly superior deformation method could not be identified. PMID:23969092

Prospective registration trends, reasons for retrospective registration and mechanisms to increase prospective registration compliance: descriptive analysis and survey.

PubMed

Hunter, Kylie Elizabeth; Seidler, Anna Lene; Askie, Lisa M

2018-03-01

To analyse prospective versus retrospective trial registration trends on the Australian New Zealand Clinical Trials Registry (ANZCTR) and to evaluate the reasons for non-compliance with prospective registration. Part 1: Descriptive analysis of trial registration trends from 2006 to 2015. Part 2: Online registrant survey. Part 1: All interventional trials registered on ANZCTR from 2006 to 2015. Part 2: Random sample of those who had retrospectively registered a trial on ANZCTR between 2010 and 2015. Part 1: Proportion of prospective versus retrospective clinical trial registrations (ie, registration before versus after enrolment of the first participant) on the ANZCTR overall and by various key metrics, such as sponsor, funder, recruitment country and sample size. Part 2: Reasons for non-compliance with prospective registration and perceived usefulness of various proposed mechanisms to improve prospective registration compliance. Part 1: Analysis of the complete dataset of 9450 trials revealed that compliance with prospective registration increased from 48% (216 out of 446 trials) in 2006 to 63% (723/1148) in 2012 and has since plateaued at around 64%. Patterns of compliance were relatively consistent across sponsor and funder types (industry vs non-industry), type of intervention (drug vs non-drug) and size of trial (n<100, 100-500, >500). However, primary sponsors from Australia/New Zealand were almost twice as likely to register prospectively (62%; 4613/7452) compared with sponsors from other countries with a WHO Network Registry (35%; 377/1084) or sponsors from countries without a WHO Registry (29%; 230/781). Part 2: The majority (56%; 84/149) of survey respondents cited lack of awareness as a reason for not registering their study prospectively. Seventy-four per cent (111/149) stated that linking registration to ethics approval would facilitate prospective registration. Despite some progress, compliance with prospective registration remains suboptimal. Linking registration to ethics approval was the favoured strategy among those sampled for improving compliance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Regulation (EC) No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations.

PubMed

Lehmann, Birka

2008-12-08

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective.The same approach may not always be applied to medicinal products used to treat children.Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions.The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children.The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products and in particular relating to the implementation of good clinical practice. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The CTD is addressed to all investigators conducting clinical trials including clinical trials in the paediatric population and had to be applied accordingly.In the framework of the authorisation of medicinal products regulated by the Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended and the CTD, and additional implementing Directives and guidelines, the new Regulation (EC) No 1901/2006 is an important new piece of legislation focusing on the requirements to improve the situation for the paediatric population. All Regulations/Directives to be found: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol1_en.htm.

The legal framework governing the quality of (traditional) herbal medicinal products in the European Union.

PubMed

Kroes, Burt H

2014-12-02

In the European Union a complex regulatory framework is in place for the regulation of (traditional) herbal medicinal products. It is based on the principle that a marketing authorisation granted by the competent authorities is required for placing medicinal products on the market. The requirements and procedures for acquiring such a marketing authorisation are laid down in regulations, directives and scientific guidelines. This paper gives an overview of the quality requirements for (traditional) herbal medicinal products that are contained in European pharmaceutical legislation. Pharmaceutical quality of medicinal product is the basis for ensuring safe and effective medicines. The basic principles governing the assurance of the quality of medicinal products in the European Union are primarily defined in the amended Directive 2001/83/EC and Directive 2003/63/EC. Quality requirements of herbal medicinal products are also laid down in scientific guidelines. Scientific guidelines provide a basis for practical harmonisation of how the competent authorities of EU Member States interpret and apply the detailed requirements for the demonstration of quality laid down in regulations and directives. Detailed quality requirements for herbal medicinal products on the European market are contained in European Union (EU) pharmaceutical legislation. They include a system of manufacturing authorisations which ensures that all herbal medicinal products on the European market are manufactured/imported only by authorised manufacturers, whose activities are regularly inspected by the competent authorities. Additionally, as starting materials only active substances are allowed which have been manufactured in accordance with the GMP for starting materials as adopted by the Community. The European regulatory framework encompasses specific requirements for herbal medicinal products. These requirements are independent from the legal status. Thus, the same quality standards equally apply to herbal products based on clinical evidence and traditional herbal medicinal products. The basic principle is that the quality of herbal medicinal products is intrinsically associated with the quality standard of the herbal substances and/or herbal preparations. Furthermore, the herbal substance or herbal preparation in its entirety is regarded as the active substance. Consequently, a mere determination of the content of marker(s) or constituents with known therapeutic activity is not sufficient for the quality control of herbal medicinal products. Specific quality requirements include thorough product characterisation, adherence to the Good Agricultural and Collection Practices, good manufacturing practices and validated manufacturing process, e.g., raw material testing, in-process testing, fingerprint characterisation etc. Quality control of herbal medicinal products is primarily intended to define the quality of the herbal substance/preparation and herbal medicinal product rather than to establish full characterisation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Regulation (EC) No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations

PubMed Central

Lehmann, Birka

2008-01-01

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective. The same approach may not always be applied to medicinal products used to treat children. Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions. The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children. The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products and in particular relating to the implementation of good clinical practice. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The CTD is addressed to all investigators conducting clinical trials including clinical trials in the paediatric population and had to be applied accordingly. In the framework of the authorisation of medicinal products regulated by the Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended and the CTD, and additional implementing Directives and guidelines, the new Regulation (EC) No 1901/2006 is an important new piece of legislation focusing on the requirements to improve the situation for the paediatric population. All Regulations/Directives to be found: PMID:19063722

SU-F-BRA-01: A Procedure for the Fast Semi-Automatic Localization of Catheters Using An Electromagnetic Tracker (EMT) for Image-Guided Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Damato, A; Viswanathan, A; Cormack, R

2015-06-15

Purpose: To evaluate the feasibility of brachytherapy catheter localization through use of an EMT and 3D image set. Methods: A 15-catheter phantom mimicking an interstitial implantation was built and CT-scanned. Baseline catheter reconstruction was performed manually. An EMT was used to acquire the catheter coordinates in the EMT frame of reference. N user-identified catheter tips, without catheter number associations, were used to establish registration with the CT frame of reference. Two algorithms were investigated: brute-force registration (BFR), in which all possible permutation of N identified tips with the EMT tips were evaluated; and signature-based registration (SBR), in which a distancemore » matrix was used to generate a list of matching signatures describing possible N-point matches with the registration points. Digitization error (average of the distance between corresponding EMT and baseline dwell positions; average, standard deviation, and worst-case scenario over all possible registration-point selections) and algorithm inefficiency (maximum number of rigid registrations required to find the matching fusion for all possible selections of registration points) were calculated. Results: Digitization errors on average <2 mm were observed for N ≥5, with standard deviation <2 mm for N ≥6, and worst-case scenario error <2 mm for N ≥11. Algorithm inefficiencies were: N = 5, 32,760 (BFR) and 9900 (SBR); N = 6, 360,360 (BFR) and 21,660 (SBR); N = 11, 5.45*1010 (BFR) and 12 (SBR). Conclusion: A procedure was proposed for catheter reconstruction using EMT and only requiring user identification of catheter tips without catheter localization. Digitization errors <2 mm were observed on average with 5 or more registration points, and in any scenario with 11 or more points. Inefficiency for N = 11 was 9 orders of magnitude lower for SBR than for BFR. Funding: Kaye Family Award.« less

larvalign: Aligning Gene Expression Patterns from the Larval Brain of Drosophila melanogaster.

PubMed

Muenzing, Sascha E A; Strauch, Martin; Truman, James W; Bühler, Katja; Thum, Andreas S; Merhof, Dorit

2018-01-01

The larval brain of the fruit fly Drosophila melanogaster is a small, tractable model system for neuroscience. Genes for fluorescent marker proteins can be expressed in defined, spatially restricted neuron populations. Here, we introduce the methods for 1) generating a standard template of the larval central nervous system (CNS), 2) spatial mapping of expression patterns from different larvae into a reference space defined by the standard template. We provide a manually annotated gold standard that serves for evaluation of the registration framework involved in template generation and mapping. A method for registration quality assessment enables the automatic detection of registration errors, and a semi-automatic registration method allows one to correct registrations, which is a prerequisite for a high-quality, curated database of expression patterns. All computational methods are available within the larvalign software package: https://github.com/larvalign/larvalign/releases/tag/v1.0.

An effective non-rigid registration approach for ultrasound image based on "demons" algorithm.

PubMed

Liu, Yan; Cheng, H D; Huang, Jianhua; Zhang, Yingtao; Tang, Xianglong; Tian, Jiawei

2013-06-01

Medical image registration is an important component of computer-aided diagnosis system in diagnostics, therapy planning, and guidance of surgery. Because of its low signal/noise ratio (SNR), ultrasound (US) image registration is a difficult task. In this paper, a fully automatic non-rigid image registration algorithm based on demons algorithm is proposed for registration of ultrasound images. In the proposed method, an "inertia force" derived from the local motion trend of pixels in a Moore neighborhood system is produced and integrated into optical flow equation to estimate the demons force, which is helpful to handle the speckle noise and preserve the geometric continuity of US images. In the experiment, a series of US images and several similarity measure metrics are utilized for evaluating the performance. The experimental results demonstrate that the proposed method can register ultrasound images efficiently, robust to noise, quickly and automatically.

Image registration assessment in radiotherapy image guidance based on control chart monitoring.

PubMed

Xia, Wenyao; Breen, Stephen L

2018-04-01

Image guidance with cone beam computed tomography in radiotherapy can guarantee the precision and accuracy of patient positioning prior to treatment delivery. During the image guidance process, operators need to take great effort to evaluate the image guidance quality before correcting a patient's position. This work proposes an image registration assessment method based on control chart monitoring to reduce the effort taken by the operator. According to the control chart plotted by daily registration scores of each patient, the proposed method can quickly detect both alignment errors and image quality inconsistency. Therefore, the proposed method can provide a clear guideline for the operators to identify unacceptable image quality and unacceptable image registration with minimal effort. Experimental results demonstrate that by using control charts from a clinical database of 10 patients undergoing prostate radiotherapy, the proposed method can quickly identify out-of-control signals and find special cause of out-of-control registration events.

Evaluation of body-wise and organ-wise registrations for abdominal organs

NASA Astrophysics Data System (ADS)

Xu, Zhoubing; Panjwani, Sahil A.; Lee, Christopher P.; Burke, Ryan P.; Baucom, Rebeccah B.; Poulose, Benjamin K.; Abramson, Richard G.; Landman, Bennett A.

2016-03-01

Identifying cross-sectional and longitudinal correspondence in the abdomen on computed tomography (CT) scans is necessary for quantitatively tracking change and understanding population characteristics, yet abdominal image registration is a challenging problem. The key difficulty in solving this problem is huge variations in organ dimensions and shapes across subjects. The current standard registration method uses the global or body-wise registration technique, which is based on the global topology for alignment. This method (although producing decent results) has substantial influence of outliers, thus leaving room for significant improvement. Here, we study a new image registration approach using local (organ-wise registration) by first creating organ-specific bounding boxes and then using these regions of interest (ROIs) for aligning references to target. Based on Dice Similarity Coefficient (DSC), Mean Surface Distance (MSD) and Hausdorff Distance (HD), the organ-wise approach is demonstrated to have significantly better results by minimizing the distorting effects of organ variations. This paper compares exclusively the two registration methods by providing novel quantitative and qualitative comparison data and is a subset of the more comprehensive problem of improving the multi-atlas segmentation by using organ normalization.

Marker-free registration for the accurate integration of CT images and the subject's anatomy during navigation surgery of the maxillary sinus

PubMed Central

Kang, S-H; Kim, M-K; Kim, J-H; Park, H-K; Park, W

2012-01-01

Objective This study compared three marker-free registration methods that are applicable to a navigation system that can be used for maxillary sinus surgery, and evaluated the associated errors, with the aim of determining which registration method is the most applicable for operations that require accurate navigation. Methods The CT digital imaging and communications in medicine (DICOM) data of ten maxillary models in DICOM files were converted into stereolithography file format. All of the ten maxillofacial models were scanned three dimensionally using a light-based three-dimensional scanner. The methods applied for registration of the maxillofacial models utilized the tooth cusp, bony landmarks and maxillary sinus anterior wall area. The errors during registration were compared between the groups. Results There were differences between the three registration methods in the zygoma, sinus posterior wall, molar alveolar, premolar alveolar, lateral nasal aperture and the infraorbital areas. The error was smallest using the overlay method for the anterior wall of the maxillary sinus, and the difference was statistically significant. Conclusion The navigation error can be minimized by conducting registration using the anterior wall of the maxillary sinus during image-guided surgery of the maxillary sinus. PMID:22499127

MARS: a mouse atlas registration system based on a planar x-ray projector and an optical camera

NASA Astrophysics Data System (ADS)

Wang, Hongkai; Stout, David B.; Taschereau, Richard; Gu, Zheng; Vu, Nam T.; Prout, David L.; Chatziioannou, Arion F.

2012-10-01

This paper introduces a mouse atlas registration system (MARS), composed of a stationary top-view x-ray projector and a side-view optical camera, coupled to a mouse atlas registration algorithm. This system uses the x-ray and optical images to guide a fully automatic co-registration of a mouse atlas with each subject, in order to provide anatomical reference for small animal molecular imaging systems such as positron emission tomography (PET). To facilitate the registration, a statistical atlas that accounts for inter-subject anatomical variations was constructed based on 83 organ-labeled mouse micro-computed tomography (CT) images. The statistical shape model and conditional Gaussian model techniques were used to register the atlas with the x-ray image and optical photo. The accuracy of the atlas registration was evaluated by comparing the registered atlas with the organ-labeled micro-CT images of the test subjects. The results showed excellent registration accuracy of the whole-body region, and good accuracy for the brain, liver, heart, lungs and kidneys. In its implementation, the MARS was integrated with a preclinical PET scanner to deliver combined PET/MARS imaging, and to facilitate atlas-assisted analysis of the preclinical PET images.

MARS: a mouse atlas registration system based on a planar x-ray projector and an optical camera.

PubMed

Wang, Hongkai; Stout, David B; Taschereau, Richard; Gu, Zheng; Vu, Nam T; Prout, David L; Chatziioannou, Arion F

2012-10-07

This paper introduces a mouse atlas registration system (MARS), composed of a stationary top-view x-ray projector and a side-view optical camera, coupled to a mouse atlas registration algorithm. This system uses the x-ray and optical images to guide a fully automatic co-registration of a mouse atlas with each subject, in order to provide anatomical reference for small animal molecular imaging systems such as positron emission tomography (PET). To facilitate the registration, a statistical atlas that accounts for inter-subject anatomical variations was constructed based on 83 organ-labeled mouse micro-computed tomography (CT) images. The statistical shape model and conditional Gaussian model techniques were used to register the atlas with the x-ray image and optical photo. The accuracy of the atlas registration was evaluated by comparing the registered atlas with the organ-labeled micro-CT images of the test subjects. The results showed excellent registration accuracy of the whole-body region, and good accuracy for the brain, liver, heart, lungs and kidneys. In its implementation, the MARS was integrated with a preclinical PET scanner to deliver combined PET/MARS imaging, and to facilitate atlas-assisted analysis of the preclinical PET images.

Estimation of Mouse Organ Locations Through Registration of a Statistical Mouse Atlas With Micro-CT Images

PubMed Central

Stout, David B.; Chatziioannou, Arion F.

2012-01-01

Micro-CT is widely used in preclinical studies of small animals. Due to the low soft-tissue contrast in typical studies, segmentation of soft tissue organs from noncontrast enhanced micro-CT images is a challenging problem. Here, we propose an atlas-based approach for estimating the major organs in mouse micro-CT images. A statistical atlas of major trunk organs was constructed based on 45 training subjects. The statistical shape model technique was used to include inter-subject anatomical variations. The shape correlations between different organs were described using a conditional Gaussian model. For registration, first the high-contrast organs in micro-CT images were registered by fitting the statistical shape model, while the low-contrast organs were subsequently estimated from the high-contrast organs using the conditional Gaussian model. The registration accuracy was validated based on 23 noncontrast-enhanced and 45 contrast-enhanced micro-CT images. Three different accuracy metrics (Dice coefficient, organ volume recovery coefficient, and surface distance) were used for evaluation. The Dice coefficients vary from 0.45 ± 0.18 for the spleen to 0.90 ± 0.02 for the lungs, the volume recovery coefficients vary from for the liver to 1.30 ± 0.75 for the spleen, the surface distances vary from 0.18 ± 0.01 mm for the lungs to 0.72 ± 0.42 mm for the spleen. The registration accuracy of the statistical atlas was compared with two publicly available single-subject mouse atlases, i.e., the MOBY phantom and the DIGIMOUSE atlas, and the results proved that the statistical atlas is more accurate than the single atlases. To evaluate the influence of the training subject size, different numbers of training subjects were used for atlas construction and registration. The results showed an improvement of the registration accuracy when more training subjects were used for the atlas construction. The statistical atlas-based registration was also compared with the thin-plate spline based deformable registration, commonly used in mouse atlas registration. The results revealed that the statistical atlas has the advantage of improving the estimation of low-contrast organs. PMID:21859613

Improved multimodality data fusion of late gadolinium enhancement MRI to left ventricular voltage maps in ventricular tachycardia ablation.

PubMed

Roujol, Sebastien; Basha, Tamer A; Tan, Alex; Khanna, Varun; Chan, Raymond H; Moghari, Mehdi H; Rayatzadeh, Hussein; Shaw, Jaime L; Josephson, Mark E; Nezafat, Reza

2013-05-01

Electroanatomical voltage mapping (EAVM) is commonly performed prior to catheter ablation of scar-related ventricular tachycardia (VT) to locate the arrhythmic substrate and to guide the ablation procedure. EAVM is used to locate the position of the ablation catheter and to provide a 3-D reconstruction of left-ventricular anatomy and scar. However, EAVM measurements only represent the endocardial scar with no transmural or epicardial information. Furthermore, EAVM is a time-consuming procedure, with a high operator dependence and has low sampling density, i.e., spatial resolution. Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) allows noninvasive assessment of scar morphology that can depict 3-D scar architecture. Despite the potential use of LGE as a roadmap for VT ablation for identification of arrhythmogenic substrate, its utility has been very limited. To allow for identification of VT substrate, a correlation is needed between the substrates identified by EAVM as the gold standard and LGE-MRI scar characteristics. To do so, a system must be developed to fuse the datasets from these modalities. In this study, a registration pipeline for the fusion of LGE-MRI and EAVM data is presented. A novel surface registration algorithm is proposed, integrating the matching of global scar areas as an additional constraint in the registration process. A preparatory landmark registration is initially performed to expedite the convergence of the algorithm. Numerical simulations were performed to evaluate the accuracy of the registration in the presence of errors in identifying landmarks in EAVM or LGE-MRI datasets as well as additional errors due to respiratory or cardiac motion. Subsequently, the accuracy of the proposed fusion system was evaluated in a cohort of ten patients undergoing VT ablation where both EAVM and LGE-MRI data were available. Compared to landmark registration and surface registration, the presented method achieved significant improvement in registration error. The proposed data fusion system allows the fusion of EAVM and LGE-MRI data in VT ablation with registration errors less than 3.5  mm.

WE-AB-BRA-01: 3D-2D Image Registration for Target Localization in Spine Surgery: Comparison of Similarity Metrics Against Robustness to Content Mismatch

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Silva, T; Ketcha, M; Siewerdsen, J H

Purpose: In image-guided spine surgery, mapping 3D preoperative images to 2D intraoperative images via 3D-2D registration can provide valuable assistance in target localization. However, the presence of surgical instrumentation, hardware implants, and soft-tissue resection/displacement causes mismatches in image content, confounding existing registration methods. Manual/semi-automatic methods to mask such extraneous content is time consuming, user-dependent, error prone, and disruptive to clinical workflow. We developed and evaluated 2 novel similarity metrics within a robust registration framework to overcome such challenges in target localization. Methods: An IRB-approved retrospective study in 19 spine surgery patients included 19 preoperative 3D CT images and 50 intraoperativemore » mobile radiographs in cervical, thoracic, and lumbar spine regions. A neuroradiologist provided truth definition of vertebral positions in CT and radiography. 3D-2D registration was performed using the CMA-ES optimizer with 4 gradient-based image similarity metrics: (1) gradient information (GI); (2) gradient correlation (GC); (3) a novel variant referred to as gradient orientation (GO); and (4) a second variant referred to as truncated gradient correlation (TGC). Registration accuracy was evaluated in terms of the projection distance error (PDE) of the vertebral levels. Results: Conventional similarity metrics were susceptible to gross registration error and failure modes associated with the presence of surgical instrumentation: for GI, the median PDE and interquartile range was 33.0±43.6 mm; similarly for GC, PDE = 23.0±92.6 mm respectively. The robust metrics GO and TGC, on the other hand, demonstrated major improvement in PDE (7.6 ±9.4 mm and 8.1± 18.1 mm, respectively) and elimination of gross failure modes. Conclusion: The proposed GO and TGC similarity measures improve registration accuracy and robustness to gross failure in the presence of strong image content mismatch. Such registration capability could offer valuable assistance in target localization without disruption of clinical workflow. G. Kleinszig and S. Vogt are employees of Siemens Healthcare.« less

Is autologous chondrocyte implantation (ACI) an adequate treatment option for repair of cartilage defects in paediatric patients?

PubMed

Kaszkin-Bettag, Marietta

2013-08-01

Cartilage lesions in the knee of juvenile patients require an effective repair to regain life-long functional activity of the joint. Autologous chondrocyte implantation (ACI) is discussed to be advantageous over other methods for cartilage repair regarding long-term outcome. ACI has successfully been applied in juvenile patients, although currently recommended for patients ≥18 years of age. Only few controlled clinical trials present evidence of efficacy and safety of ACI in adolescent patients. ACI products have to undergo the process of a marketing authorisation application, including the submission of a paediatric investigation plan (PIP). Data from prospective clinical studies or retrospective collection of long-term data in paediatric patients should be submitted for risk-benefit evaluation by the Paediatric Committee (PDCO). Copyright © 2013 Elsevier Ltd. All rights reserved.

Towards local estimation of emphysema progression using image registration

NASA Astrophysics Data System (ADS)

Staring, M.; Bakker, M. E.; Shamonin, D. P.; Stolk, J.; Reiber, J. H. C.; Stoel, B. C.

2009-02-01

Progression measurement of emphysema is required to evaluate the health condition of a patient and the effect of drugs. To locally estimate progression we use image registration, which allows for volume correction using the determinant of the Jacobian of the transformation. We introduce an adaptation of the so-called sponge model that circumvents its constant-mass assumption. Preliminary results from CT scans of a lung phantom and from CT data sets of three patients suggest that image registration may be a suitable method to locally estimate emphysema progression.

Conventional 3D staging PET/CT in CT simulation for lung cancer: impact of rigid and deformable target volume alignments for radiotherapy treatment planning.

PubMed

Hanna, G G; Van Sörnsen De Koste, J R; Carson, K J; O'Sullivan, J M; Hounsell, A R; Senan, S

2011-10-01

Positron emission tomography (PET)/CT scans can improve target definition in radiotherapy for non-small cell lung cancer (NSCLC). As staging PET/CT scans are increasingly available, we evaluated different methods for co-registration of staging PET/CT data to radiotherapy simulation (RTP) scans. 10 patients underwent staging PET/CT followed by RTP PET/CT. On both scans, gross tumour volumes (GTVs) were delineated using CT (GTV(CT)) and PET display settings. Four PET-based contours (manual delineation, two threshold methods and a source-to-background ratio method) were delineated. The CT component of the staging scan was co-registered using both rigid and deformable techniques to the CT component of RTP PET/CT. Subsequently rigid registration and deformation warps were used to transfer PET and CT contours from the staging scan to the RTP scan. Dice's similarity coefficient (DSC) was used to assess the registration accuracy of staging-based GTVs following both registration methods with the GTVs delineated on the RTP PET/CT scan. When the GTV(CT) delineated on the staging scan after both rigid registration and deformation was compared with the GTV(CT)on the RTP scan, a significant improvement in overlap (registration) using deformation was observed (mean DSC 0.66 for rigid registration and 0.82 for deformable registration, p = 0.008). A similar comparison for PET contours revealed no significant improvement in overlap with the use of deformable registration. No consistent improvements in similarity measures were observed when deformable registration was used for transferring PET-based contours from a staging PET/CT. This suggests that currently the use of rigid registration remains the most appropriate method for RTP in NSCLC.

Determination of optimal ultrasound planes for the initialisation of image registration during endoscopic ultrasound-guided procedures.

PubMed

Bonmati, Ester; Hu, Yipeng; Gibson, Eli; Uribarri, Laura; Keane, Geri; Gurusami, Kurinchi; Davidson, Brian; Pereira, Stephen P; Clarkson, Matthew J; Barratt, Dean C

2018-06-01

Navigation of endoscopic ultrasound (EUS)-guided procedures of the upper gastrointestinal (GI) system can be technically challenging due to the small fields-of-view of ultrasound and optical devices, as well as the anatomical variability and limited number of orienting landmarks during navigation. Co-registration of an EUS device and a pre-procedure 3D image can enhance the ability to navigate. However, the fidelity of this contextual information depends on the accuracy of registration. The purpose of this study was to develop and test the feasibility of a simulation-based planning method for pre-selecting patient-specific EUS-visible anatomical landmark locations to maximise the accuracy and robustness of a feature-based multimodality registration method. A registration approach was adopted in which landmarks are registered to anatomical structures segmented from the pre-procedure volume. The predicted target registration errors (TREs) of EUS-CT registration were estimated using simulated visible anatomical landmarks and a Monte Carlo simulation of landmark localisation error. The optimal planes were selected based on the 90th percentile of TREs, which provide a robust and more accurate EUS-CT registration initialisation. The method was evaluated by comparing the accuracy and robustness of registrations initialised using optimised planes versus non-optimised planes using manually segmented CT images and simulated ([Formula: see text]) or retrospective clinical ([Formula: see text]) EUS landmarks. The results show a lower 90th percentile TRE when registration is initialised using the optimised planes compared with a non-optimised initialisation approach (p value [Formula: see text]). The proposed simulation-based method to find optimised EUS planes and landmarks for EUS-guided procedures may have the potential to improve registration accuracy. Further work will investigate applying the technique in a clinical setting.

TU-AB-202-06: Quantitative Evaluation of Deformable Image Registration in MRI-Guided Adaptive Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mooney, K; Zhao, T; Green, O

Purpose: To assess the performance of the deformable image registration algorithm used for MRI-guided adaptive radiation therapy using image feature analysis. Methods: MR images were collected from five patients treated on the MRIdian (ViewRay, Inc., Oakwood Village, OH), a three head Cobalt-60 therapy machine with an 0.35 T MR system. The images were acquired immediately prior to treatment with a uniform 1.5 mm resolution. Treatment sites were as follows: head/neck, lung, breast, stomach, and bladder. Deformable image registration was performed using the ViewRay software between the first fraction MRI and the final fraction MRI, and the DICE similarity coefficient (DSC)more » for the skin contours was reported. The SIFT and Harris feature detection and matching algorithms identified point features in each image separately, then found matching features in the other image. The target registration error (TRE) was defined as the vector distance between matched features on the two image sets. Each deformation was evaluated based on comparison of average TRE and DSC. Results: Image feature analysis produced between 2000–9500 points for evaluation on the patient images. The average (± standard deviation) TRE for all patients was 3.3 mm (±3.1 mm), and the passing rate of TRE<3 mm was 60% on the images. The head/neck patient had the best average TRE (1.9 mm±2.3 mm) and the best passing rate (80%). The lung patient had the worst average TRE (4.8 mm±3.3 mm) and the worst passing rate (37.2%). DSC was not significantly correlated with either TRE (p=0.63) or passing rate (p=0.55). Conclusions: Feature matching provides a quantitative assessment of deformable image registration, with a large number of data points for analysis. The TRE of matched features can be used to evaluate the registration of many objects throughout the volume, whereas DSC mainly provides a measure of gross overlap. We have a research agreement with ViewRay Inc.« less

Degrees of Doubt? Towards Eradicating Fraudulent Cross-Border Institutions and Diplomas

ERIC Educational Resources Information Center

Observatory on Borderless Higher Education, 2010

2010-01-01

Six higher education institutions in Singapore and four universities in New Zealand have reportedly been placed on a list of unaccredited institutions and so-called "degree mills", which has been compiled by the Office of Degree Authorisation of the state of Oregon in the United States (US). As one of the first US states that introduced…

Threat Modelling Adobe PDF

DTIC Science & Technology

2012-08-01

this attack sensitive information relating to their two-factor authentication process, employed within RSA’s products, was stolen; potentially... authenticated session the victim has with another website. This could allow the attacker to impersonate the victim or obtain sensitive information...all that is not blacklisted is authorised . We will outline relevant security settings in this section. 4.1 Adobe End-User Security Modification

Using State-Wide Multiple Measures for School Leadership and Management: Costs Incurred vs. Benefits Gained

ERIC Educational Resources Information Center

Hentschke, Guilbert; Wohlstetter, Priscilla; Hirman, Jennifer; Zeehandelaar, Dara

2011-01-01

In this article, we examine the utility and value of multiple measures of school performance for school leaders and managers. The research was conducted within the context of the state of California through an investigation of how operators, managers and authorisers of autonomous "charter" (publicly financed but privately operated)…

75 FR 34111 - Notice of Intent to Suspend Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... a person adversely affected by the Notice of Intent to Suspend or the registrant has satisfied the... Notice of Intent to Suspend). FOR FURTHER INFORMATION CONTACT: Terria Northern, Pesticide Re- evaluation..., consult the person listed under FOR FURTHER INFORMATION CONTACT. B. How Can I Get Copies of this Document...

21 CFR 607.25 - Information required for establishment registration and blood product listing.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Information required for establishment registration and blood product listing. 607.25 Section 607.25 Food and Drugs FOOD AND DRUG ADMINISTRATION... the manufacturer issued by the Center for Biologics Evaluation and Research, Food and Drug...

21 CFR 607.25 - Information required for establishment registration and blood product listing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Information required for establishment registration and blood product listing. 607.25 Section 607.25 Food and Drugs FOOD AND DRUG ADMINISTRATION... the manufacturer issued by the Center for Biologics Evaluation and Research, Food and Drug...

75 FR 53976 - Risks and Benefits of Long-Term Use of Nicotine Replacement Therapy Products; Public Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

...-0002, 301-796-3519, email: [email protected] ; or Dominic Chiapperino, Center for Drug Evaluation... Spring, MD 20993-0002, 301- 796-1183, email: [email protected] . Registration to Attend the... public hearing, please email your registration to [email protected] by October 5, 2010. Those...

Registration of 4D cardiac CT sequences under trajectory constraints with multichannel diffeomorphic demons.

PubMed

Peyrat, Jean-Marc; Delingette, Hervé; Sermesant, Maxime; Xu, Chenyang; Ayache, Nicholas

2010-07-01

We propose a framework for the nonlinear spatiotemporal registration of 4D time-series of images based on the Diffeomorphic Demons (DD) algorithm. In this framework, the 4D spatiotemporal registration is decoupled into a 4D temporal registration, defined as mapping physiological states, and a 4D spatial registration, defined as mapping trajectories of physical points. Our contribution focuses more specifically on the 4D spatial registration that should be consistent over time as opposed to 3D registration that solely aims at mapping homologous points at a given time-point. First, we estimate in each sequence the motion displacement field, which is a dense representation of the point trajectories we want to register. Then, we perform simultaneously 3D registrations of corresponding time-points with the constraints to map the same physical points over time called the trajectory constraints. Under these constraints, we show that the 4D spatial registration can be formulated as a multichannel registration of 3D images. To solve it, we propose a novel version of the Diffeomorphic Demons (DD) algorithm extended to vector-valued 3D images, the Multichannel Diffeomorphic Demons (MDD). For evaluation, this framework is applied to the registration of 4D cardiac computed tomography (CT) sequences and compared to other standard methods with real patient data and synthetic data simulated from a physiologically realistic electromechanical cardiac model. Results show that the trajectory constraints act as a temporal regularization consistent with motion whereas the multichannel registration acts as a spatial regularization. Finally, using these trajectory constraints with multichannel registration yields the best compromise between registration accuracy, temporal and spatial smoothness, and computation times. A prospective example of application is also presented with the spatiotemporal registration of 4D cardiac CT sequences of the same patient before and after radiofrequency ablation (RFA) in case of atrial fibrillation (AF). The intersequence spatial transformations over a cardiac cycle allow to analyze and quantify the regression of left ventricular hypertrophy and its impact on the cardiac function.

Multi-template tensor-based morphometry: Application to analysis of Alzheimer's disease

PubMed Central

Koikkalainen, Juha; Lötjönen, Jyrki; Thurfjell, Lennart; Rueckert, Daniel; Waldemar, Gunhild; Soininen, Hilkka

2012-01-01

In this paper methods for using multiple templates in tensor-based morphometry (TBM) are presented and comparedtothe conventional single-template approach. TBM analysis requires non-rigid registrations which are often subject to registration errors. When using multiple templates and, therefore, multiple registrations, it can be assumed that the registration errors are averaged and eventually compensated. Four different methods are proposed for multi-template TBM. The methods were evaluated using magnetic resonance (MR) images of healthy controls, patients with stable or progressive mild cognitive impairment (MCI), and patients with Alzheimer's disease (AD) from the ADNI database (N=772). The performance of TBM features in classifying images was evaluated both quantitatively and qualitatively. Classification results show that the multi-template methods are statistically significantly better than the single-template method. The overall classification accuracy was 86.0% for the classification of control and AD subjects, and 72.1%for the classification of stable and progressive MCI subjects. The statistical group-level difference maps produced using multi-template TBM were smoother, formed larger continuous regions, and had larger t-values than the maps obtained with single-template TBM. PMID:21419228

Evaluation of registration accuracy between Sentinel-2 and Landsat 8

NASA Astrophysics Data System (ADS)

Barazzetti, Luigi; Cuca, Branka; Previtali, Mattia

2016-08-01

Starting from June 2015, Sentinel-2A is delivering high resolution optical images (ground resolution up to 10 meters) to provide a global coverage of the Earth's land surface every 10 days. The planned launch of Sentinel-2B along with the integration of Landsat images will provide time series with an unprecedented revisit time indispensable for numerous monitoring applications, in which high resolution multi-temporal information is required. They include agriculture, water bodies, natural hazards to name a few. However, the combined use of multi-temporal images requires an accurate geometric registration, i.e. pixel-to-pixel correspondence for terrain-corrected products. This paper presents an analysis of spatial co-registration accuracy for several datasets of Sentinel-2 and Landsat 8 images distributed all around the world. Images were compared with digital correlation techniques for image matching, obtaining an evaluation of registration accuracy with an affine transformation as geometrical model. Results demonstrate that sub-pixel accuracy was achieved between 10 m resolution Sentinel-2 bands (band 3) and 15 m resolution panchromatic Landsat images (band 8).

A gaussian mixture + demons deformable registration method for cone-beam CT-guided robotic transoral base-of-tongue surgery

NASA Astrophysics Data System (ADS)

Reaungamornrat, S.; Liu, W. P.; Schafer, S.; Otake, Y.; Nithiananthan, S.; Uneri, A.; Richmon, J.; Sorger, J.; Siewerdsen, J. H.; Taylor, R. H.

2013-03-01

Purpose: An increasingly popular minimally invasive approach to resection of oropharyngeal / base-of-tongue cancer is made possible by a transoral technique conducted with the assistance of a surgical robot. However, the highly deformed surgical setup (neck flexed, mouth open, and tongue retracted) compared to the typical patient orientation in preoperative images poses a challenge to guidance and localization of the tumor target and adjacent critical anatomy. Intraoperative cone-beam CT (CBCT) can account for such deformation, but due to the low contrast of soft-tissue in CBCT images, direct localization of the target and critical tissues in CBCT images can be difficult. Such structures may be more readily delineated in preoperative CT or MR images, so a method to deformably register such information to intraoperative CBCT could offer significant value. This paper details the initial implementation of a deformable registration framework to align preoperative images with the deformed intraoperative scene and gives preliminary evaluation of the geometric accuracy of registration in CBCT-guided TORS. Method: The deformable registration aligns preoperative CT or MR to intraoperative CBCT by integrating two established approaches. The volume of interest is first segmented (specifically, the region of the tongue from the tip to the hyoid), and a Gaussian mixture (GM) mode1 of surface point clouds is used for rigid initialization (GMRigid) as well as an initial deformation (GMNonRigid). Next, refinement of the registration is performed using the Demons algorithm applied to distance transformations of the GM-registered and CBCT volumes. The registration accuracy of the framework was quantified in preliminary studies using a cadaver emulating preoperative and intraoperative setups. Geometric accuracy of registration was quantified in terms of target registration error (TRE) and surface distance error. Result: With each step of the registration process, the framework demonstrated improved registration, achieving mean TRE of 3.0 mm following the GM rigid, 1.9 mm following GM nonrigid, and 1.5 mm at the output of the registration process. Analysis of surface distance demonstrated a corresponding improvement of 2.2, 0.4, and 0.3 mm, respectively. The evaluation of registration error revealed the accurate alignment in the region of interest for base-of-tongue robotic surgery owing to point-set selection in the GM steps and refinement in the deep aspect of the tongue in the Demons step. Conclusions: A promising framework has been developed for CBCT-guided TORS in which intraoperative CBCT provides a basis for registration of preoperative images to the highly deformed intraoperative setup. The registration framework is invariant to imaging modality (accommodating preoperative CT or MR) and is robust against CBCT intensity variations and artifact, provided corresponding segmentation of the volume of interest. The approach could facilitate overlay of preoperative planning data directly in stereo-endoscopic video in support of CBCT-guided TORS.

Deformable and rigid registration of MRI and microPET images for photodynamic therapy of cancer in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fei Baowei; Wang Hesheng; Muzic, Raymond F. Jr.

2006-03-15

We are investigating imaging techniques to study the tumor response to photodynamic therapy (PDT). Positron emission tomography (PET) can provide physiological and functional information. High-resolution magnetic resonance imaging (MRI) can provide anatomical and morphological changes. Image registration can combine MRI and PET images for improved tumor monitoring. In this study, we acquired high-resolution MRI and microPET {sup 18}F-fluorodeoxyglucose (FDG) images from C3H mice with RIF-1 tumors that were treated with Pc 4-based PDT. We developed two registration methods for this application. For registration of the whole mouse body, we used an automatic three-dimensional, normalized mutual information algorithm. For tumor registration,more » we developed a finite element model (FEM)-based deformable registration scheme. To assess the quality of whole body registration, we performed slice-by-slice review of both image volumes; manually segmented feature organs, such as the left and right kidneys and the bladder, in each slice; and computed the distance between corresponding centroids. Over 40 volume registration experiments were performed with MRI and microPET images. The distance between corresponding centroids of organs was 1.5{+-}0.4 mm which is about 2 pixels of microPET images. The mean volume overlap ratios for tumors were 94.7% and 86.3% for the deformable and rigid registration methods, respectively. Registration of high-resolution MRI and microPET images combines anatomical and functional information of the tumors and provides a useful tool for evaluating photodynamic therapy.« less

Nonrigid registration of carotid ultrasound and MR images using a "twisting and bending" model

NASA Astrophysics Data System (ADS)

Nanayakkara, Nuwan D.; Chiu, Bernard; Samani, Abbas; Spence, J. David; Parraga, Grace; Samarabandu, Jagath; Fenster, Aaron

2008-03-01

Atherosclerosis at the carotid bifurcation resulting in cerebral emboli is a major cause of ischemic stroke. Most strokes associated with carotid atherosclerosis can be prevented by lifestyle/dietary changes and pharmacological treatments if identified early by monitoring carotid plaque changes. Plaque composition information from magnetic resonance (MR) carotid images and dynamic characteristics information from 3D ultrasound (US) are necessary for developing and validating US imaging tools to identify vulnerable carotid plaques. Combining these images requires nonrigid registration to correct the non-linear miss-alignments caused by relative twisting and bending in the neck due to different head positions during the two image acquisitions sessions. The high degree of freedom and large number of parameters associated with existing nonrigid image registration methods causes several problems including unnatural plaque morphology alteration, computational complexity, and low reliability. Our approach was to model the normal movement of the neck using a "twisting and bending model" with only six parameters for nonrigid registration. We evaluated our registration technique using intra-subject in-vivo 3D US and 3D MR carotid images acquired on the same day. We calculated the Mean Registration Error (MRE) between the segmented vessel surfaces in the target image and the registered image using a distance-based error metric after applying our "twisting bending model" based nonrigid registration algorithm. We achieved an average registration error of 1.33+/-0.41mm using our nonrigid registration technique. Visual inspection of segmented vessel surfaces also showed a substantial improvement of alignment with our non-rigid registration technique.

Validation of a deformable image registration technique for cone beam CT-based dose verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, M., E-mail: mmoteabbed@partners.org; Sharp, G. C.; Wang, Y.

2015-01-15

Purpose: As radiation therapy evolves toward more adaptive techniques, image guidance plays an increasingly important role, not only in patient setup but also in monitoring the delivered dose and adapting the treatment to patient changes. This study aimed to validate a method for evaluation of delivered intensity modulated radiotherapy (IMRT) dose based on multimodal deformable image registration (DIR) for prostate treatments. Methods: A pelvic phantom was scanned with CT and cone-beam computed tomography (CBCT). Both images were digitally deformed using two realistic patient-based deformation fields. The original CT was then registered to the deformed CBCT resulting in a secondary deformedmore » CT. The registration quality was assessed as the ability of the DIR method to recover the artificially induced deformations. The primary and secondary deformed CT images as well as vector fields were compared to evaluate the efficacy of the registration method and it’s suitability to be used for dose calculation. PLASTIMATCH, a free and open source software was used for deformable image registration. A B-spline algorithm with optimized parameters was used to achieve the best registration quality. Geometric image evaluation was performed through voxel-based Hounsfield unit (HU) and vector field comparison. For dosimetric evaluation, IMRT treatment plans were created and optimized on the original CT image and recomputed on the two warped images to be compared. The dose volume histograms were compared for the warped structures that were identical in both warped images. This procedure was repeated for the phantom with full, half full, and empty bladder. Results: The results indicated mean HU differences of up to 120 between registered and ground-truth deformed CT images. However, when the CBCT intensities were calibrated using a region of interest (ROI)-based calibration curve, these differences were reduced by up to 60%. Similarly, the mean differences in average vector field lengths decreased from 10.1 to 2.5 mm when CBCT was calibrated prior to registration. The results showed no dependence on the level of bladder filling. In comparison with the dose calculated on the primary deformed CT, differences in mean dose averaged over all organs were 0.2% and 3.9% for dose calculated on the secondary deformed CT with and without CBCT calibration, respectively, and 0.5% for dose calculated directly on the calibrated CBCT, for the full-bladder scenario. Gamma analysis for the distance to agreement of 2 mm and 2% of prescribed dose indicated a pass rate of 100% for both cases involving calibrated CBCT and on average 86% without CBCT calibration. Conclusions: Using deformable registration on the planning CT images to evaluate the IMRT dose based on daily CBCTs was found feasible. The proposed method will provide an accurate dose distribution using planning CT and pretreatment CBCT data, avoiding the additional uncertainties introduced by CBCT inhomogeneity and artifacts. This is a necessary initial step toward future image-guided adaptive radiotherapy of the prostate.« less

Registration uncertainties between 3D cone beam computed tomography and different reference CT datasets in lung stereotactic body radiation therapy.

PubMed

Oechsner, Markus; Chizzali, Barbara; Devecka, Michal; Combs, Stephanie Elisabeth; Wilkens, Jan Jakob; Duma, Marciana Nona

2016-10-26

The aim of this study was to analyze differences in couch shifts (setup errors) resulting from image registration of different CT datasets with free breathing cone beam CTs (FB-CBCT). As well automatic as manual image registrations were performed and registration results were correlated to tumor characteristics. FB-CBCT image registration was performed for 49 patients with lung lesions using slow planning CT (PCT), average intensity projection (AIP), maximum intensity projection (MIP) and mid-ventilation CTs (MidV) as reference images. Both, automatic and manual image registrations were applied. Shift differences were evaluated between the registered CT datasets for automatic and manual registration, respectively. Furthermore, differences between automatic and manual registration were analyzed for the same CT datasets. The registration results were statistically analyzed and correlated to tumor characteristics (3D tumor motion, tumor volume, superior-inferior (SI) distance, tumor environment). Median 3D shift differences over all patients were between 0.5 mm (AIPvsMIP) and 1.9 mm (MIPvsPCT and MidVvsPCT) for the automatic registration and between 1.8 mm (AIPvsPCT) and 2.8 mm (MIPvsPCT and MidVvsPCT) for the manual registration. For some patients, large shift differences (>5.0 mm) were found (maximum 10.5 mm, automatic registration). Comparing automatic vs manual registrations for the same reference CTs, ∆AIP achieved the smallest (1.1 mm) and ∆MIP the largest (1.9 mm) median 3D shift differences. The standard deviation (variability) for the 3D shift differences was also the smallest for ∆AIP (1.1 mm). Significant correlations (p < 0.01) between 3D shift difference and 3D tumor motion (AIPvsMIP, MIPvsMidV) and SI distance (AIPvsMIP) (automatic) and also for 3D tumor motion (∆PCT, ∆MidV; automatic vs manual) were found. Using different CT datasets for image registration with FB-CBCTs can result in different 3D couch shifts. Manual registrations achieved partly different 3D shifts than automatic registrations. AIP CTs yielded the smallest shift differences and might be the most appropriate CT dataset for registration with 3D FB-CBCTs.

Using reusable learning objects (rlos) in injection skills teaching: Evaluations from multiple user types.

PubMed

Williams, Julia; O'Connor, Mórna; Windle, Richard; Wharrad, Heather J

2015-12-01

Clinical skills are a critical component of pre-registration nurse education in the United Kingdom, yet there is widespread concern about the clinical skills displayed by newly-qualified nurses. Novel means of supporting clinical skills education are required to address this. A package of Reusable Learning Objects (RLOs) was developed to supplement pre-registration teaching on the clinical skill of administering injection medication. RLOs are electronic resources addressing a single learning objective whose interactivity facilitates learning. This article evaluates a package of five injection RLOs across three studies: (1) questionnaires administered to pre-registration nursing students at University of Nottingham (UoN) (n=46) evaluating the RLO package as a whole; (2) individual RLOs evaluated in online questionnaires by educators and students from UoN; from other national and international institutions; and healthcare professionals (n=265); (3) qualitative evaluation of the RLO package by UoN injection skills tutors (n=6). Data from all studies were assessed for (1) access to, (2) usefulness, (3) impact and (4) integration of the RLOs. Study one found that pre-registration nursing students rate the RLO package highly across all categories, particularly underscoring the value of their self-test elements. Study two found high ratings in online assessments of individual RLOs by multiple users. The global reach is particularly encouraging here. Tutors reported insufficient levels of student-RLO access, which might be explained by the timing of their student exposure. Tutors integrate RLOs into teaching and agree on their use as teaching supplements, not substitutes for face-to-face education. This evaluation encompasses the first years postpackage release. Encouraging data on evaluative categories in this early review suggest that future evaluations are warranted to track progress as the package is adopted and evaluated more widely. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fast interactive elastic registration of 12-bit multi-spectral images with subvoxel accuracy using display hardware

NASA Astrophysics Data System (ADS)

Noordmans, Herke Jan; de Roode, Rowland; Verdaasdonk, Rudolf

2007-03-01

Multi-spectral images of human tissue taken in-vivo often contain image alignment problems as patients have difficulty in retaining their posture during the acquisition time of 20 seconds. Previously, it has been attempted to correct motion errors with image registration software developed for MR or CT data but these algorithms have been proven to be too slow and erroneous for practical use with multi-spectral images. A new software package has been developed which allows the user to play a decisive role in the registration process as the user can monitor the progress of the registration continuously and force it in the right direction when it starts to fail. The software efficiently exploits videocard hardware to gain speed and to provide a perfect subvoxel correspondence between registration field and display. An 8 bit graphic card was used to efficiently register and resample 12 bit images using the hardware interpolation modes present on the graphic card. To show the feasibility of this new registration process, the software was applied in clinical practice evaluating the dosimetry for psoriasis and KTP laser treatment. The microscopic differences between images of normal skin and skin exposed to UV light proved that an affine registration step including zooming and slanting is critical for a subsequent elastic match to have success. The combination of user interactive registration software with optimal addressing the potentials of PC video card hardware greatly improves the speed of multi spectral image registration.

Ultrasound guidance system for prostate biopsy

NASA Astrophysics Data System (ADS)

Hummel, Johann; Kerschner, Reinhard; Kaar, Marcus; Birkfellner, Wolfgang; Figl, Michael

2017-03-01

We designed a guidance system for prostate biopsy based on PET/MR images and 3D ultrasound (US). With our proposed method common inter-modal MR-US (or CT-US in case of PET/CTs) registration can be replaced by an intra-modal 3D/3D-US/US registration and an optical tracking system (OTS). On the pre-operative site, a PET/MR calibration allows to link both hybrid modalities with an abdominal 3D-US. On the interventional site, another abdominal 3D US is taken to merge the pre-operative images with the real-time 3D-US via 3D/3D-US/US registration. Finally, the images of a tracked trans-rectal US probe can be displayed with the pre-operative images by overlay. For PET/MR image fusion we applied a point-to-point registration between PET and OTS and MR and OTS, respectively. 3D/3D-US/US registration was evaluated for images taken in supine and lateral patient position. To enable table shifts between PET/MR and US image acquisition a table calibration procedure is presented. We found fiducial registration errors of 0.9 mm and 2.8 mm, respectively, with respect to the MR and PET calibration. A target registration error between MR and 3D US amounted to 1.4 mm. The registration error for the 3D/3D-US/US registration was found to be 3.7 mm. Furthermore, we have shown that ultrasound is applicable in an MR environment.

Optimization of PET-MR Registrations for Nonhuman Primates Using Mutual Information Measures: A Multi-Transform Method (MTM)

PubMed Central

Sandiego, Christine M.; Weinzimmer, David; Carson, Richard E.

2012-01-01

An important step in PET brain kinetic analysis is the registration of functional data to an anatomical MR image. Typically, PET-MR registrations in nonhuman primate neuroreceptor studies used PET images acquired early post-injection, (e.g., 0–10 min) to closely resemble the subject’s MR image. However, a substantial fraction of these registrations (~25%) fail due to the differences in kinetics and distribution for various radiotracer studies and conditions (e.g., blocking studies). The Multi-Transform Method (MTM) was developed to improve the success of registrations between PET and MR images. Two algorithms were evaluated, MTM-I and MTM-II. The approach involves creating multiple transformations by registering PET images of different time intervals, from a dynamic study, to a single reference (i.e., MR image) (MTM-I) or to multiple reference images (i.e., MR and PET images pre-registered to the MR) (MTM-II). Normalized mutual information was used to compute similarity between the transformed PET images and the reference image(s) to choose the optimal transformation. This final transformation is used to map the dynamic dataset into the animal’s anatomical MR space, required for kinetic analysis. The chosen transformed from MTM-I and MTM-II were evaluated using visual rating scores to assess the quality of spatial alignment between the resliced PET and reference. One hundred twenty PET datasets involving eleven different tracers from 3 different scanners were used to evaluate the MTM algorithms. Studies were performed with baboons and rhesus monkeys on the HR+, HRRT, and Focus-220. Successful transformations increased from 77.5%, 85.8%, to 96.7% using the 0–10 min method, MTM-I, and MTM-II, respectively, based on visual rating scores. The Multi-Transform Methods proved to be a robust technique for PET-MR registrations for a wide range of PET studies. PMID:22926293

Slice-to-Volume Nonrigid Registration of Histological Sections to MR Images of the Human Brain

PubMed Central

Osechinskiy, Sergey; Kruggel, Frithjof

2011-01-01

Registration of histological images to three-dimensional imaging modalities is an important step in quantitative analysis of brain structure, in architectonic mapping of the brain, and in investigation of the pathology of a brain disease. Reconstruction of histology volume from serial sections is a well-established procedure, but it does not address registration of individual slices from sparse sections, which is the aim of the slice-to-volume approach. This study presents a flexible framework for intensity-based slice-to-volume nonrigid registration algorithms with a geometric transformation deformation field parametrized by various classes of spline functions: thin-plate splines (TPS), Gaussian elastic body splines (GEBS), or cubic B-splines. Algorithms are applied to cross-modality registration of histological and magnetic resonance images of the human brain. Registration performance is evaluated across a range of optimization algorithms and intensity-based cost functions. For a particular case of histological data, best results are obtained with a TPS three-dimensional (3D) warp, a new unconstrained optimization algorithm (NEWUOA), and a correlation-coefficient-based cost function. PMID:22567290

Efficient Multi-Atlas Registration using an Intermediate Template Image

PubMed Central

Dewey, Blake E.; Carass, Aaron; Blitz, Ari M.; Prince, Jerry L.

2017-01-01

Multi-atlas label fusion is an accurate but time-consuming method of labeling the human brain. Using an intermediate image as a registration target can allow researchers to reduce time constraints by storing the deformations required of the atlas images. In this paper, we investigate the effect of registration through an intermediate template image on multi-atlas label fusion and propose a novel registration technique to counteract the negative effects of through-template registration. We show that overall computation time can be decreased dramatically with minimal impact on final label accuracy and time can be exchanged for improved results in a predictable manner. We see almost complete recovery of Dice similarity over a simple through-template registration using the corrected method and still maintain a 3–4 times speed increase. Further, we evaluate the effectiveness of this method on brains of patients with normal-pressure hydrocephalus, where abnormal brain shape presents labeling difficulties, specifically the ventricular labels. Our correction method creates substantially better ventricular labeling than traditional methods and maintains the speed increase seen in healthy subjects. PMID:28943702

MRI and CBCT image registration of temporomandibular joint: a systematic review.

PubMed

Al-Saleh, Mohammed A Q; Alsufyani, Noura A; Saltaji, Humam; Jaremko, Jacob L; Major, Paul W

2016-05-10

The purpose of the present review is to systematically and critically analyze the available literature regarding the importance, applicability, and practicality of (MRI), computerized tomography (CT) or cone-beam CT (CBCT) image registration for TMJ anatomy and assessment. A systematic search of 4 databases; MEDLINE, EMBASE, EBM reviews and Scopus, was conducted by 2 reviewers. An additional manual search of the bibliography was performed. All articles discussing the magnetic resonance imaging MRI and CT or CBCT image registration for temporomandibular joint (TMJ) visualization or assessment were included. Only 3 articles satisfied the inclusion criteria. All included articles were published within the last 7 years. Two articles described MRI to CT multimodality image registration as a complementary tool to visualize TMJ. Both articles used images of one patient only to introduce the complementary concept of MRI-CT fused image. One article assessed the reliability of using MRI-CBCT registration to evaluate the TMJ disc position and osseous pathology for 10 temporomandibular disorder (TMD) patients. There are very limited studies of MRI-CT/CBCT registration to reach a conclusion regarding its accuracy or clinical use in the temporomandibular joints.

Efficient multi-atlas registration using an intermediate template image

NASA Astrophysics Data System (ADS)

Dewey, Blake E.; Carass, Aaron; Blitz, Ari M.; Prince, Jerry L.

2017-03-01

Multi-atlas label fusion is an accurate but time-consuming method of labeling the human brain. Using an intermediate image as a registration target can allow researchers to reduce time constraints by storing the deformations required of the atlas images. In this paper, we investigate the effect of registration through an intermediate template image on multi-atlas label fusion and propose a novel registration technique to counteract the negative effects of through-template registration. We show that overall computation time can be decreased dramatically with minimal impact on final label accuracy and time can be exchanged for improved results in a predictable manner. We see almost complete recovery of Dice similarity over a simple through-template registration using the corrected method and still maintain a 3-4 times speed increase. Further, we evaluate the effectiveness of this method on brains of patients with normal-pressure hydrocephalus, where abnormal brain shape presents labeling difficulties, specifically the ventricular labels. Our correction method creates substantially better ventricular labeling than traditional methods and maintains the speed increase seen in healthy subjects.

Evaluation of non-rigid constrained CT/CBCT registration algorithms for delineation propagation in the context of prostate cancer radiotherapy

NASA Astrophysics Data System (ADS)

Rubeaux, Mathieu; Simon, Antoine; Gnep, Khemara; Colliaux, Jérémy; Acosta, Oscar; de Crevoisier, Renaud; Haigron, Pascal

2013-03-01

Image-Guided Radiation Therapy (IGRT) aims at increasing the precision of radiation dose delivery. In the context of prostate cancer, a planning Computed Tomography (CT) image with manually defined prostate and organs at risk (OAR) delineations is usually associated with daily Cone Beam Computed Tomography (CBCT) follow-up images. The CBCT images allow to visualize the prostate position and to reposition the patient accordingly. They also should be used to evaluate the dose received by the organs at each fraction of the treatment. To do so, the first step is a prostate and OAR segmentation on the daily CBCTs, which is very timeconsuming. To simplify this task, CT to CBCT non-rigid registration could be used in order to propagate the original CT delineations in the CBCT images. For this aim, we compared several non-rigid registration methods. They are all based on the Mutual Information (MI) similarity measure, and use a BSpline transformation model. But we add different constraints to this global scheme in order to evaluate their impact on the final results. These algorithms are investigated on two real datasets, representing a total of 70 CBCT on which a reference delineation has been realized. The evaluation is led using the Dice Similarity Coefficient (DSC) as a quality criteria. The experiments show that a rigid penalty term on the bones improves the final registration result, providing high quality propagated delineations.

Improved image alignment method in application to X-ray images and biological images.

PubMed

Wang, Ching-Wei; Chen, Hsiang-Chou

2013-08-01

Alignment of medical images is a vital component of a large number of applications throughout the clinical track of events; not only within clinical diagnostic settings, but prominently so in the area of planning, consummation and evaluation of surgical and radiotherapeutical procedures. However, image registration of medical images is challenging because of variations on data appearance, imaging artifacts and complex data deformation problems. Hence, the aim of this study is to develop a robust image alignment method for medical images. An improved image registration method is proposed, and the method is evaluated with two types of medical data, including biological microscopic tissue images and dental X-ray images and compared with five state-of-the-art image registration techniques. The experimental results show that the presented method consistently performs well on both types of medical images, achieving 88.44 and 88.93% averaged registration accuracies for biological tissue images and X-ray images, respectively, and outperforms the benchmark methods. Based on the Tukey's honestly significant difference test and Fisher's least square difference test tests, the presented method performs significantly better than all existing methods (P ≤ 0.001) for tissue image alignment, and for the X-ray image registration, the proposed method performs significantly better than the two benchmark b-spline approaches (P < 0.001). The software implementation of the presented method and the data used in this study are made publicly available for scientific communities to use (http://www-o.ntust.edu.tw/∼cweiwang/ImprovedImageRegistration/). cweiwang@mail.ntust.edu.tw.

Evaluation of an Automatic Registration-Based Algorithm for Direct Measurement of Volume Change in Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarkar, Saradwata; Johnson, Timothy D.; Ma, Bing

2012-07-01

Purpose: Assuming that early tumor volume change is a biomarker for response to therapy, accurate quantification of early volume changes could aid in adapting an individual patient's therapy and lead to shorter clinical trials. We investigated an image registration-based approach for tumor volume change quantification that may more reliably detect smaller changes that occur in shorter intervals than can be detected by existing algorithms. Methods and Materials: Variance and bias of the registration-based approach were evaluated using retrospective, in vivo, very-short-interval diffusion magnetic resonance imaging scans where true zero tumor volume change is unequivocally known and synthetic data, respectively. Themore » interval scans were nonlinearly registered using two similarity measures: mutual information (MI) and normalized cross-correlation (NCC). Results: The 95% confidence interval of the percentage volume change error was (-8.93% to 10.49%) for MI-based and (-7.69%, 8.83%) for NCC-based registrations. Linear mixed-effects models demonstrated that error in measuring volume change increased with increase in tumor volume and decreased with the increase in the tumor's normalized mutual information, even when NCC was the similarity measure being optimized during registration. The 95% confidence interval of the relative volume change error for the synthetic examinations with known changes over {+-}80% of reference tumor volume was (-3.02% to 3.86%). Statistically significant bias was not demonstrated. Conclusion: A low-noise, low-bias tumor volume change measurement algorithm using nonlinear registration is described. Errors in change measurement were a function of tumor volume and the normalized mutual information content of the tumor.« less

The heart of the matter: Outcome reporting bias and registration status in cardio-thoracic surgery.

PubMed

Wiebe, Jordan; Detten, Grant; Scheckel, Caleb; Gearhart, David; Wheeler, Denna; Sanders, Donald; Vassar, Matt

2017-01-15

Our objective is to compare registered outcomes to published reports; to evaluate for discrepancies favoring statistically significant outcomes; to examine funding source and likelihood of outcome reporting bias; and to evaluate for any temporal trends in outcome reporting bias. PubMed was searched for randomized controlled trials published between 2008 and 2015 from 4 high impact cardio-thoracic journals: European Journal of Cardio-thoracic Surgery (EJCS), The Journal of Cardiothoracic Surgery (JCS), The Journal of Thoracic and Cardiovascular Surgery (JTCS), and Annals of Cardiothoracic Surgery (ACS). Data was collected using a standardized extraction form. We reviewed 287 articles, of which 214 (74.6%) did not meet registration criteria. Of those 214, 94 (43.9%) were published in the EJCS, 34 (15.9%) in JCS, 86 (40.2%) in JTCS, and 0 (0%) in the ACS. Of the remaining 73 articles, 34 (46.6%) had a discrepancy between the primary outcome registered and the published outcome, and 11 of the 34 reported p-values favoring the change. We also found that 12 of the 73 registrations had updated primary outcomes from the initial report to the final report. The timing of registration was an incidental finding showing 14 (19.1%) articles retrospectively registered, 29 (39.7%) registered during patient enrollment, and 30 (41.1%) registered prospectively. The results indicated that selective outcome reporting is prevalent in cardio-thoracic surgery journals. The more concerning issue, however, is the lack of registration or provision of registration number for randomized controlled trials within these journals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Text messaging as a new method for injury registration in sports: a methodological study in elite female football.

PubMed

Nilstad, A; Bahr, R; Andersen, T E

2014-02-01

Methodological differences in epidemiologic studies have led to significant discrepancies in injury incidences reported. The aim of this study was to evaluate text messaging as a new method for injury registration in elite female football players and to compare this method with routine medical staff registration. Twelve teams comprising 228 players prospectively recorded injuries and exposure through one competitive football season. Players reported individually by answering three text messages once a week. A designated member of the medical staff conducted concurrent registrations of injuries and exposure. Injuries and exposure were compared between medical staff registrations from nine teams and their 159 affiliated players. During the football season, a total of 232 time-loss injuries were recorded. Of these, 62% were captured through individual registration only, 10% by the medical staff only, and 28% were reported through both methods. The incidence of training injuries was 3.7 per 1000 player hours when calculated from individual registration vs 2.2 from medical staff registration [rate ratio (RR): 1.7, 1.2-2.4]. For match injuries, the corresponding incidences were 18.6 vs 5.4 (RR: 3.4, 2.4-4.9), respectively. There was moderate agreement for severity classifications in injury cases reported by both methods (kappa correlation coefficient: 0.48, confidence interval: 0.30-0.66). © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Coarse Point Cloud Registration by Egi Matching of Voxel Clusters

NASA Astrophysics Data System (ADS)

Wang, Jinhu; Lindenbergh, Roderik; Shen, Yueqian; Menenti, Massimo

2016-06-01

Laser scanning samples the surface geometry of objects efficiently and records versatile information as point clouds. However, often more scans are required to fully cover a scene. Therefore, a registration step is required that transforms the different scans into a common coordinate system. The registration of point clouds is usually conducted in two steps, i.e. coarse registration followed by fine registration. In this study an automatic marker-free coarse registration method for pair-wise scans is presented. First the two input point clouds are re-sampled as voxels and dimensionality features of the voxels are determined by principal component analysis (PCA). Then voxel cells with the same dimensionality are clustered. Next, the Extended Gaussian Image (EGI) descriptor of those voxel clusters are constructed using significant eigenvectors of each voxel in the cluster. Correspondences between clusters in source and target data are obtained according to the similarity between their EGI descriptors. The random sampling consensus (RANSAC) algorithm is employed to remove outlying correspondences until a coarse alignment is obtained. If necessary, a fine registration is performed in a final step. This new method is illustrated on scan data sampling two indoor scenarios. The results of the tests are evaluated by computing the point to point distance between the two input point clouds. The presented two tests resulted in mean distances of 7.6 mm and 9.5 mm respectively, which are adequate for fine registration.

An ITK framework for deterministic global optimization for medical image registration

NASA Astrophysics Data System (ADS)

Dru, Florence; Wachowiak, Mark P.; Peters, Terry M.

2006-03-01

Similarity metric optimization is an essential step in intensity-based rigid and nonrigid medical image registration. For clinical applications, such as image guidance of minimally invasive procedures, registration accuracy and efficiency are prime considerations. In addition, clinical utility is enhanced when registration is integrated into image analysis and visualization frameworks, such as the popular Insight Toolkit (ITK). ITK is an open source software environment increasingly used to aid the development, testing, and integration of new imaging algorithms. In this paper, we present a new ITK-based implementation of the DIRECT (Dividing Rectangles) deterministic global optimization algorithm for medical image registration. Previously, it has been shown that DIRECT improves the capture range and accuracy for rigid registration. Our ITK class also contains enhancements over the original DIRECT algorithm by improving stopping criteria, adaptively adjusting a locality parameter, and by incorporating Powell's method for local refinement. 3D-3D registration experiments with ground-truth brain volumes and clinical cardiac volumes show that combining DIRECT with Powell's method improves registration accuracy over Powell's method used alone, is less sensitive to initial misorientation errors, and, with the new stopping criteria, facilitates adequate exploration of the search space without expending expensive iterations on non-improving function evaluations. Finally, in this framework, a new parallel implementation for computing mutual information is presented, resulting in near-linear speedup with two processors.

SU-E-J-218: Novel Validation Paradigm of MRI to CT Deformation of Prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Padgett, K; University of Miami School of Medicine - Radiology, Miami, FL; Pirozzi, S

2015-06-15

Purpose: Deformable registration algorithms are inherently difficult to characterize in the multi-modality setting due to a significant differences in the characteristics of the different modalities (CT and MRI) as well as tissue deformations. We present a unique paradigm where this is overcome by utilizing a planning-MRI acquired within an hour of the planning-CT serving as a surrogate for quantifying MRI to CT deformation by eliminating the issues of multi-modality comparisons. Methods: For nine subjects, T2 fast-spin-echo images were acquired at two different time points, the first several weeks prior to planning (diagnostic-MRI) and the second on the same day asmore » the planning-CT (planning-MRI). Significant effort in patient positioning and bowel/bladder preparation was undertaken to minimize distortion of the prostate in all datasets. The diagnostic-MRI was rigidly and deformably aligned to the planning-CT utilizing a commercially available deformable registration algorithm synthesized from local registrations. Additionally, the quality of rigid alignment was ranked by an imaging physicist. The distances between corresponding anatomical landmarks on rigid and deformed registrations (diagnostic-MR to planning-CT) were evaluated. Results: It was discovered that in cases where the rigid registration was of acceptable quality the deformable registration didn’t improve the alignment, this was true of all metrics employed. If the analysis is separated into cases where the rigid alignment was ranked as unacceptable the deformable registration significantly improved the alignment, 4.62mm residual error in landmarks as compared to 5.72mm residual error in rigid alignments with a p-value of 0.0008. Conclusion: This paradigm provides an ideal testing ground for MR to CT deformable registration algorithms by allowing for inter-modality comparisons of multi-modality registrations. Consistent positioning, bowel and bladder preparation may Result in higher quality rigid registrations than typically achieved which limits the impact of deformable registrations. In this study cases where significant differences exist, deformable registrations provide significant value.« less

Three-dimensional nonrigid landmark-based magnetic resonance to transrectal ultrasound registration for image-guided prostate biopsy.

PubMed

Sun, Yue; Qiu, Wu; Yuan, Jing; Romagnoli, Cesare; Fenster, Aaron

2015-04-01

Registration of three-dimensional (3-D) magnetic resonance (MR) to 3-D transrectal ultrasound (TRUS) prostate images is an important step in the planning and guidance of 3-D TRUS guided prostate biopsy. In order to accurately and efficiently perform the registration, a nonrigid landmark-based registration method is required to account for the different deformations of the prostate when using these two modalities. We describe a nonrigid landmark-based method for registration of 3-D TRUS to MR prostate images. The landmark-based registration method first makes use of an initial rigid registration of 3-D MR to 3-D TRUS images using six manually placed approximately corresponding landmarks in each image. Following manual initialization, the two prostate surfaces are segmented from 3-D MR and TRUS images and then nonrigidly registered using the following steps: (1) rotationally reslicing corresponding segmented prostate surfaces from both 3-D MR and TRUS images around a specified axis, (2) an approach to find point correspondences on the surfaces of the segmented surfaces, and (3) deformation of the surface of the prostate in the MR image to match the surface of the prostate in the 3-D TRUS image and the interior using a thin-plate spline algorithm. The registration accuracy was evaluated using 17 patient prostate MR and 3-D TRUS images by measuring the target registration error (TRE). Experimental results showed that the proposed method yielded an overall mean TRE of [Formula: see text] for the rigid registration and [Formula: see text] for the nonrigid registration, which is favorably comparable to a clinical requirement for an error of less than 2.5 mm. A landmark-based nonrigid 3-D MR-TRUS registration approach is proposed, which takes into account the correspondences on the prostate surface, inside the prostate, as well as the centroid of the prostate. Experimental results indicate that the proposed method yields clinically sufficient accuracy.

Hierarchical and symmetric infant image registration by robust longitudinal-example-guided correspondence detection

PubMed Central

Wu, Yao; Wu, Guorong; Wang, Li; Munsell, Brent C.; Wang, Qian; Lin, Weili; Feng, Qianjin; Chen, Wufan; Shen, Dinggang

2015-01-01

Purpose: To investigate anatomical differences across individual subjects, or longitudinal changes in early brain development, it is important to perform accurate image registration. However, due to fast brain development and dynamic tissue appearance changes, it is very difficult to align infant brain images acquired from birth to 1-yr-old. Methods: To solve this challenging problem, a novel image registration method is proposed to align two infant brain images, regardless of age at acquisition. The main idea is to utilize the growth trajectories, or spatial-temporal correspondences, learned from a set of longitudinal training images, for guiding the registration of two different time-point images with different image appearances. Specifically, in the training stage, an intrinsic growth trajectory is first estimated for each training subject using the longitudinal images. To register two new infant images with potentially a large age gap, the corresponding images patches between each new image and its respective training images with similar age are identified. Finally, the registration between the two new images can be assisted by the learned growth trajectories from one time point to another time point that have been established in the training stage. To further improve registration accuracy, the proposed method is combined with a hierarchical and symmetric registration framework that can iteratively add new key points in both images to steer the estimation of the deformation between the two infant brain images under registration. Results: To evaluate image registration accuracy, the proposed method is used to align 24 infant subjects at five different time points (2-week-old, 3-month-old, 6-month-old, 9-month-old, and 12-month-old). Compared to the state-of-the-art methods, the proposed method demonstrated superior registration performance. Conclusions: The proposed method addresses the difficulties in the infant brain registration and produces better results compared to existing state-of-the-art registration methods. PMID:26133617

76 FR 45268 - Center for Drug Evaluation and Research, Approach to Addressing Drug Shortage; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-28

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21 CFR 1271.37 - Will establishment registrations and HCT/P listings be available for inspection, and how do I...

Code of Federal Regulations, 2011 CFR

2011-04-01

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Objective and expert-independent validation of retinal image registration algorithms by a projective imaging distortion model.

PubMed

Lee, Sangyeol; Reinhardt, Joseph M; Cattin, Philippe C; Abràmoff, Michael D

2010-08-01

Fundus camera imaging of the retina is widely used to diagnose and manage ophthalmologic disorders including diabetic retinopathy, glaucoma, and age-related macular degeneration. Retinal images typically have a limited field of view, and multiple images can be joined together using an image registration technique to form a montage with a larger field of view. A variety of methods for retinal image registration have been proposed, but evaluating such methods objectively is difficult due to the lack of a reference standard for the true alignment of the individual images that make up the montage. A method of generating simulated retinal images by modeling the geometric distortions due to the eye geometry and the image acquisition process is described in this paper. We also present a validation process that can be used for any retinal image registration method by tracing through the distortion path and assessing the geometric misalignment in the coordinate system of the reference standard. The proposed method can be used to perform an accuracy evaluation over the whole image, so that distortion in the non-overlapping regions of the montage components can be easily assessed. We demonstrate the technique by generating test image sets with a variety of overlap conditions and compare the accuracy of several retinal image registration models. Copyright 2010 Elsevier B.V. All rights reserved.

A MULTICORE BASED PARALLEL IMAGE REGISTRATION METHOD

PubMed Central

Yang, Lin; Gong, Leiguang; Zhang, Hong; Nosher, John L.; Foran, David J.

2012-01-01

Image registration is a crucial step for many image-assisted clinical applications such as surgery planning and treatment evaluation. In this paper we proposed a landmark based nonlinear image registration algorithm for matching 2D image pairs. The algorithm was shown to be effective and robust under conditions of large deformations. In landmark based registration, the most important step is establishing the correspondence among the selected landmark points. This usually requires an extensive search which is often computationally expensive. We introduced a nonregular data partition algorithm using the K-means clustering algorithm to group the landmarks based on the number of available processing cores. The step optimizes the memory usage and data transfer. We have tested our method using IBM Cell Broadband Engine (Cell/B.E.) platform. PMID:19964921

Registration of interferometric SAR images

NASA Technical Reports Server (NTRS)

Lin, Qian; Vesecky, John F.; Zebker, Howard A.

1992-01-01

Interferometric synthetic aperture radar (INSAR) is a new way of performing topography mapping. Among the factors critical to mapping accuracy is the registration of the complex SAR images from repeated orbits. A new algorithm for registering interferometric SAR images is presented. A new figure of merit, the average fluctuation function of the phase difference image, is proposed to evaluate the fringe pattern quality. The process of adjusting the registration parameters according to the fringe pattern quality is optimized through a downhill simplex minimization algorithm. The results of applying the proposed algorithm to register two pairs of Seasat SAR images with a short baseline (75 m) and a long baseline (500 m) are shown. It is found that the average fluctuation function is a very stable measure of fringe pattern quality allowing very accurate registration.

Towards operational multisensor registration

NASA Technical Reports Server (NTRS)

Rignot, Eric J. M.; Kwok, Ronald; Curlander, John C.

1991-01-01

To use data from a number of different remote sensors in a synergistic manner, a multidimensional analysis of the data is necessary. However, prior to this analysis, processing to correct for the systematic geometric distortion characteristic of each sensor is required. Furthermore, the registration process must be fully automated to handle a large volume of data and high data rates. A conceptual approach towards an operational multisensor registration algorithm is presented. The performance requirements of the algorithm are first formulated given the spatially, temporally, and spectrally varying factors that influence the image characteristics and the science requirements of various applications. Several registration techniques that fit within the structure of this algorithm are also presented. Their performance was evaluated using a multisensor test data set assembled from LANDSAT TM, SEASAT, SIR-B, Thermal Infrared Multispectral Scanner (TIMS), and SPOT sensors.

Position tracking of moving liver lesion based on real-time registration between 2D ultrasound and 3D preoperative images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weon, Chijun; Hyun Nam, Woo; Lee, Duhgoon

Purpose: Registration between 2D ultrasound (US) and 3D preoperative magnetic resonance (MR) (or computed tomography, CT) images has been studied recently for US-guided intervention. However, the existing techniques have some limits, either in the registration speed or the performance. The purpose of this work is to develop a real-time and fully automatic registration system between two intermodal images of the liver, and subsequently an indirect lesion positioning/tracking algorithm based on the registration result, for image-guided interventions. Methods: The proposed position tracking system consists of three stages. In the preoperative stage, the authors acquire several 3D preoperative MR (or CT) imagesmore » at different respiratory phases. Based on the transformations obtained from nonrigid registration of the acquired 3D images, they then generate a 4D preoperative image along the respiratory phase. In the intraoperative preparatory stage, they properly attach a 3D US transducer to the patient’s body and fix its pose using a holding mechanism. They then acquire a couple of respiratory-controlled 3D US images. Via the rigid registration of these US images to the 3D preoperative images in the 4D image, the pose information of the fixed-pose 3D US transducer is determined with respect to the preoperative image coordinates. As feature(s) to use for the rigid registration, they may choose either internal liver vessels or the inferior vena cava. Since the latter is especially useful in patients with a diffuse liver disease, the authors newly propose using it. In the intraoperative real-time stage, they acquire 2D US images in real-time from the fixed-pose transducer. For each US image, they select candidates for its corresponding 2D preoperative slice from the 4D preoperative MR (or CT) image, based on the predetermined pose information of the transducer. The correct corresponding image is then found among those candidates via real-time 2D registration based on a gradient-based similarity measure. Finally, if needed, they obtain the position information of the liver lesion using the 3D preoperative image to which the registered 2D preoperative slice belongs. Results: The proposed method was applied to 23 clinical datasets and quantitative evaluations were conducted. With the exception of one clinical dataset that included US images of extremely low quality, 22 datasets of various liver status were successfully applied in the evaluation. Experimental results showed that the registration error between the anatomical features of US and preoperative MR images is less than 3 mm on average. The lesion tracking error was also found to be less than 5 mm at maximum. Conclusions: A new system has been proposed for real-time registration between 2D US and successive multiple 3D preoperative MR/CT images of the liver and was applied for indirect lesion tracking for image-guided intervention. The system is fully automatic and robust even with images that had low quality due to patient status. Through visual examinations and quantitative evaluations, it was verified that the proposed system can provide high lesion tracking accuracy as well as high registration accuracy, at performance levels which were acceptable for various clinical applications.« less

Increasing the automation of a 2D-3D registration system.

PubMed

Varnavas, Andreas; Carrell, Tom; Penney, Graeme

2013-02-01

Routine clinical use of 2D-3D registration algorithms for Image Guided Surgery remains limited. A key aspect for routine clinical use of this technology is its degree of automation, i.e., the amount of necessary knowledgeable interaction between the clinicians and the registration system. Current image-based registration approaches usually require knowledgeable manual interaction during two stages: for initial pose estimation and for verification of produced results. We propose four novel techniques, particularly suited to vertebra-based registration systems, which can significantly automate both of the above stages. Two of these techniques are based upon the intraoperative "insertion" of a virtual fiducial marker into the preoperative data. The remaining two techniques use the final registration similarity value between multiple CT vertebrae and a single fluoroscopy vertebra. The proposed methods were evaluated with data from 31 operations (31 CT scans, 419 fluoroscopy images). Results show these methods can remove the need for manual vertebra identification during initial pose estimation, and were also very effective for result verification, producing a combined true positive rate of 100% and false positive rate equal to zero. This large decrease in required knowledgeable interaction is an important contribution aiming to enable more widespread use of 2D-3D registration technology.

Registration of in vivo MR to histology of rodent brains using blockface imaging

NASA Astrophysics Data System (ADS)

Uberti, Mariano; Liu, Yutong; Dou, Huanyu; Mosley, R. Lee; Gendelman, Howard E.; Boska, Michael

2009-02-01

Registration of MRI to histopathological sections can enhance bioimaging validation for use in pathobiologic, diagnostic, and therapeutic evaluations. However, commonly used registration methods fall short of this goal due to tissue shrinkage and tearing after brain extraction and preparation. In attempts to overcome these limitations we developed a software toolbox using 3D blockface imaging as the common space of reference. This toolbox includes a semi-automatic brain extraction technique using constraint level sets (CLS), 3D reconstruction methods for the blockface and MR volume, and a 2D warping technique using thin-plate splines with landmark optimization. Using this toolbox, the rodent brain volume is first extracted from the whole head MRI using CLS. The blockface volume is reconstructed followed by 3D brain MRI registration to the blockface volume to correct the global deformations due to brain extraction and fixation. Finally, registered MRI and histological slices are warped to corresponding blockface images to correct slice specific deformations. The CLS brain extraction technique was validated by comparing manual results showing 94% overlap. The image warping technique was validated by calculating target registration error (TRE). Results showed a registration accuracy of a TRE < 1 pixel. Lastly, the registration method and the software tools developed were used to validate cell migration in murine human immunodeficiency virus type one encephalitis.

Deformable registration of CT and cone-beam CT with local intensity matching.

PubMed

Park, Seyoun; Plishker, William; Quon, Harry; Wong, John; Shekhar, Raj; Lee, Junghoon

2017-02-07

Cone-beam CT (CBCT) is a widely used intra-operative imaging modality in image-guided radiotherapy and surgery. A short scan followed by a filtered-backprojection is typically used for CBCT reconstruction. While data on the mid-plane (plane of source-detector rotation) is complete, off-mid-planes undergo different information deficiency and the computed reconstructions are approximate. This causes different reconstruction artifacts at off-mid-planes depending on slice locations, and therefore impedes accurate registration between CT and CBCT. In this paper, we propose a method to accurately register CT and CBCT by iteratively matching local CT and CBCT intensities. We correct CBCT intensities by matching local intensity histograms slice by slice in conjunction with intensity-based deformable registration. The correction-registration steps are repeated in an alternating way until the result image converges. We integrate the intensity matching into three different deformable registration methods, B-spline, demons, and optical flow that are widely used for CT-CBCT registration. All three registration methods were implemented on a graphics processing unit for efficient parallel computation. We tested the proposed methods on twenty five head and neck cancer cases and compared the performance with state-of-the-art registration methods. Normalized cross correlation (NCC), structural similarity index (SSIM), and target registration error (TRE) were computed to evaluate the registration performance. Our method produced overall NCC of 0.96, SSIM of 0.94, and TRE of 2.26 → 2.27 mm, outperforming existing methods by 9%, 12%, and 27%, respectively. Experimental results also show that our method performs consistently and is more accurate than existing algorithms, and also computationally efficient.

Deformable registration of CT and cone-beam CT with local intensity matching

NASA Astrophysics Data System (ADS)

Park, Seyoun; Plishker, William; Quon, Harry; Wong, John; Shekhar, Raj; Lee, Junghoon

2017-02-01

Cone-beam CT (CBCT) is a widely used intra-operative imaging modality in image-guided radiotherapy and surgery. A short scan followed by a filtered-backprojection is typically used for CBCT reconstruction. While data on the mid-plane (plane of source-detector rotation) is complete, off-mid-planes undergo different information deficiency and the computed reconstructions are approximate. This causes different reconstruction artifacts at off-mid-planes depending on slice locations, and therefore impedes accurate registration between CT and CBCT. In this paper, we propose a method to accurately register CT and CBCT by iteratively matching local CT and CBCT intensities. We correct CBCT intensities by matching local intensity histograms slice by slice in conjunction with intensity-based deformable registration. The correction-registration steps are repeated in an alternating way until the result image converges. We integrate the intensity matching into three different deformable registration methods, B-spline, demons, and optical flow that are widely used for CT-CBCT registration. All three registration methods were implemented on a graphics processing unit for efficient parallel computation. We tested the proposed methods on twenty five head and neck cancer cases and compared the performance with state-of-the-art registration methods. Normalized cross correlation (NCC), structural similarity index (SSIM), and target registration error (TRE) were computed to evaluate the registration performance. Our method produced overall NCC of 0.96, SSIM of 0.94, and TRE of 2.26 → 2.27 mm, outperforming existing methods by 9%, 12%, and 27%, respectively. Experimental results also show that our method performs consistently and is more accurate than existing algorithms, and also computationally efficient.

Stopping Criteria for Log-Domain Diffeomorphic Demons Registration: An Experimental Survey for Radiotherapy Application.

PubMed

Peroni, M; Golland, P; Sharp, G C; Baroni, G

2016-02-01

A crucial issue in deformable image registration is achieving a robust registration algorithm at a reasonable computational cost. Given the iterative nature of the optimization procedure an algorithm must automatically detect convergence, and stop the iterative process when most appropriate. This paper ranks the performances of three stopping criteria and six stopping value computation strategies for a Log-Domain Demons Deformable registration method simulating both a coarse and a fine registration. The analyzed stopping criteria are: (a) velocity field update magnitude, (b) mean squared error, and (c) harmonic energy. Each stoping condition is formulated so that the user defines a threshold ∊, which quantifies the residual error that is acceptable for the particular problem and calculation strategy. In this work, we did not aim at assigning a value to e, but to give insights in how to evaluate and to set the threshold on a given exit strategy in a very popular registration scheme. Experiments on phantom and patient data demonstrate that comparing the optimization metric minimum over the most recent three iterations with the minimum over the fourth to sixth most recent iterations can be an appropriate algorithm stopping strategy. The harmonic energy was found to provide best trade-off between robustness and speed of convergence for the analyzed registration method at coarse registration, but was outperformed by mean squared error when all the original pixel information is used. This suggests the need of developing mathematically sound new convergence criteria in which both image and vector field information could be used to detect the actual convergence, which could be especially useful when considering multi-resolution registrations. Further work should be also dedicated to study same strategies performances in other deformable registration methods and body districts. © The Author(s) 2014.

Registration and fusion quantification of augmented reality based nasal endoscopic surgery.

PubMed

Chu, Yakui; Yang, Jian; Ma, Shaodong; Ai, Danni; Li, Wenjie; Song, Hong; Li, Liang; Chen, Duanduan; Chen, Lei; Wang, Yongtian

2017-12-01

This paper quantifies the registration and fusion display errors of augmented reality-based nasal endoscopic surgery (ARNES). We comparatively investigated the spatial calibration process for front-end endoscopy and redefined the accuracy level of a calibrated endoscope by using a calibration tool with improved structural reliability. We also studied how registration accuracy was combined with the number and distribution of the deployed fiducial points (FPs) for positioning and the measured registration time. A physically integrated ARNES prototype was customarily configured for performance evaluation in skull base tumor resection surgery with an innovative approach of dynamic endoscopic vision expansion. As advised by surgical experts in otolaryngology, we proposed a hierarchical rendering scheme to properly adapt the fused images with the required visual sensation. By constraining the rendered sight in a known depth and radius, the visual focus of the surgeon can be induced only on the anticipated critical anatomies and vessel structures to avoid misguidance. Furthermore, error analysis was conducted to examine the feasibility of hybrid optical tracking based on point cloud, which was proposed in our previous work as an in-surgery registration solution. Measured results indicated that the error of target registration for ARNES can be reduced to 0.77 ± 0.07 mm. For initial registration, our results suggest that a trade-off for a new minimal time of registration can be reached when the distribution of five FPs is considered. For in-surgery registration, our findings reveal that the intrinsic registration error is a major cause of performance loss. Rigid model and cadaver experiments confirmed that the scenic integration and display fluency of ARNES are smooth, as demonstrated by three clinical trials that surpassed practicality. Copyright © 2017 Elsevier B.V. All rights reserved.

"Good Girls": Emphasised Femininity as Cloning Culture in Academia

ERIC Educational Resources Information Center

Mattsson, Tina

2015-01-01

Gender inequality in academia might be understood as an effect of the belief of a contradiction between woman and science, which make it difficult for women to appropriate the right to author and authorise acts of knowing and thinking in science. In relation to this concern, the aim of this article is to explore how a group of successful women…

Investigating "Race" and Social Cohesion at the University of KwaZulu-Natal

ERIC Educational Resources Information Center

Pattman, R.

2010-01-01

In the light of the notorious video made by white students at the University of Free State (UFS) in which black middle aged cleaners were subjected to forms of degradation in a mock initiation ceremony (which included being given food mixed with urine) the Minister of Education authorised an investigation on social cohesion in universities. The…

Interrogating the Nature of the "Universal" in South Africa's New Educational Order

ERIC Educational Resources Information Center

Soudien, Crain

2011-01-01

This paper examines the relationship between the South African knowledge enterprise and citizenship in terms of the ontologies it authorises. It is especially interested in how education comes to be used in particular settings to privilege particular ways of being. In relation to this it asks what notions of the subject and his or her relation to…

Principles for consistent value assessment and sustainable funding of orphan drugs in Europe.

PubMed

Gutierrez, Laura; Patris, Julien; Hutchings, Adam; Cowell, Warren

2015-05-03

The European Orphan Medicinal Products (OMP) Regulation has successfully encouraged research to develop treatments for rare diseases resulting in the authorisation of new OMPs in Europe. While decisions on OMP designation and marketing authorisation are made at the European Union level, reimbursement decisions are made at the national level. OMP value and affordability are high priority issues for policymakers and decisions regarding their pricing and funding are highly complex. There is currently no European consensus on how OMP value should be assessed and inequalities of access to OMPs have previously been observed. Against this background, policy makers in many countries are considering reforms to improve access to OMPs. This paper proposes ten principles to be considered when undertaking such reforms, from the perspective of an OMP manufacturer. We recommend the continued prioritisation of rare diseases by policymakers, an increased alignment between payer and regulatory frameworks, pricing centred on OMP value, and mechanisms to ensure long-term financial sustainability allowing a continuous and virtuous development of OMPs. Our recommendations support the development of more consistent frameworks and encourage collaboration between all stakeholders, including research-based industry, payers, clinicians, and patients.

Improving drug policy: The potential of broader democratic participation.

PubMed

Ritter, Alison; Lancaster, Kari; Diprose, Rosalyn

2018-05-01

Policies concerned with illicit drugs vex governments. While the 'evidence-based policy' paradigm argues that governments should be informed by 'what works', in practice policy makers rarely operate this way. Moreover the evidence-based policy paradigm fails to account for democratic participatory processes, particularly how community members and people who use drugs might be included. The aim of this paper is to explore the political science thinking about democratic participation and the potential afforded in 'deliberative democracy' approaches, such as Citizens Juries and other mini-publics for improved drug policy processes. Deliberative democracy, through its focus on inclusion, equality and reasoned discussion, shows potential for drug policy reform and shifts the focus from reliance on and privileging of experts and scientific evidence. But the very nature of this kind of 'deliberation' may delimit participation, notably through its insistence on authorised modes of communication. Other forms of participation beyond reasoned deliberation aligned with the ontological view that participatory processes themselves are constitutive of subject positions and policy problems, may generate opportunities for considering how the deleterious effects of authorised modes of communication might be overcome. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of real-time PCR tests for the detection of Tenebrio molitor in food and feed.

PubMed

Debode, Frédéric; Marien, Aline; Gérard, Amaury; Francis, Frédéric; Fumière, Olivier; Berben, Gilbert

2017-08-01

Insects are rich in proteins and could be an alternative source of proteins to feed animals and humans. Numerous companies have started the production of insects for feed purposes. In Europe, these processed animal proteins are not yet authorised by legislation as many questions still need to be answered concerning this 'novel food'. Authorisations will be possible when methods of authentication of the products are available. In this study we propose real-time PCR methods for the specific detection of the mealworm (Tenebriomolitor), one of the most widely used insects for food and feed production. Two PCR assays are proposed: the first based on the wingless gene and the second based on the cadherin gene. The PCR tests amplify fragments of 87 bp. These qualitative methods were tested according to several performance criteria. The specificity was tested on 34 insect species' DNA, but also on non-insect species including crustacean, mammals, birds and plants. The limit of detection was determined and was below 20 copies for the two PCR tests. The applicability of the tests was demonstrated by the analysis of real-life processed samples containing T. molitor.

Implementation and evaluation of a new workflow for registration and segmentation of pulmonary MRI data for regional lung perfusion assessment.

PubMed

Böttger, T; Grunewald, K; Schöbinger, M; Fink, C; Risse, F; Kauczor, H U; Meinzer, H P; Wolf, Ivo

2007-03-07

Recently it has been shown that regional lung perfusion can be assessed using time-resolved contrast-enhanced magnetic resonance (MR) imaging. Quantification of the perfusion images has been attempted, based on definition of small regions of interest (ROIs). Use of complete lung segmentations instead of ROIs could possibly increase quantification accuracy. Due to the low signal-to-noise ratio, automatic segmentation algorithms cannot be applied. On the other hand, manual segmentation of the lung tissue is very time consuming and can become inaccurate, as the borders of the lung to adjacent tissues are not always clearly visible. We propose a new workflow for semi-automatic segmentation of the lung from additionally acquired morphological HASTE MR images. First the lung is delineated semi-automatically in the HASTE image. Next the HASTE image is automatically registered with the perfusion images. Finally, the transformation resulting from the registration is used to align the lung segmentation from the morphological dataset with the perfusion images. We evaluated rigid, affine and locally elastic transformations, suitable optimizers and different implementations of mutual information (MI) metrics to determine the best possible registration algorithm. We located the shortcomings of the registration procedure and under which conditions automatic registration will succeed or fail. Segmentation results were evaluated using overlap and distance measures. Integration of the new workflow reduces the time needed for post-processing of the data, simplifies the perfusion quantification and reduces interobserver variability in the segmentation process. In addition, the matched morphological data set can be used to identify morphologic changes as the source for the perfusion abnormalities.

Evolving prevalence of haematological malignancies in orphan designation procedures in the European Union.

PubMed

Polsinelli, Benedetta; Tsigkos, Stelios; Naumann-Winter, Frauke; Mariz, Segundo; Sepodes, Bruno

2017-01-21

The Committee for Orphan Medicinal Products (COMP) evaluates prevalence of rare conditions as one of the criteria for granting an orphan designation with a prevalence threshold of 5 in 10.000. At the time of Marketing Authorisation (MA) these criteria are reassessed to ensure they are still met. The COMP has noted discordance between the prevalence of certain haematological malignancies at the time of Orphan Designation and at the time of Marketing Authorisation. Consequently, we conducted a retrospective assessment of Chronic Lymphocytic Lymphoma and Multiple Myeloma/Plasma cell Myeloma as well as several other haematological rare aetiologies frequently subject of orphan designation. These were: Diffuse large B-Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Cutaneous T-Cell Lymphoma (CTCL), Mantle Cell Lymphoma (MCL) and Chronic Myeloid Leukaemia (CML). The review used submissions as well as recent publications and results from external and EMA databases. As a first step in the analysis, an increase over time in the number of people affected was evident for four conditions in the COMP designation documents, whereas for DLBCL, FL, CTCL and MCL there had been no significant change, since the introduction of the Regulation in 2000. Specifically, the prevalence estimates increased from 1.2 to 3.6 per 10,000 for multiple myeloma, from 0.4 to 1.7 in acute lymphoblastic leukaemia, and from 2.7 to 4.85 for chronic lymphocytic leukaemia/small lymphocytic leukaemia and 1 to 2 in 10,000 for chronic myeloid leukaemia. The reasons for the changes in the prevalence of these four haematological conditions over the last 15 years were not assessed but recent publications have alluded to better outcomes due to new treatments being made available. In addition, many orphan diseases have a median age of onset over 60 years so that also the aging of the population may be a relevant contributing factor.

Pirfenidone. First, do no harm.

PubMed

2013-05-01

Idiopathic pulmonary fibrosis is a rare disorder due to progressive, widespread fibrotic damage of the lung parenchyma. It usually occurs after the age of 50, and its cause is unknown. Symptoms include progressive shortness of breath and nonproductive cough. The course of the disease is marked by exacerbations. Death from respiratory failure occurs about 2 to 5 years after diagnosis. There are currently no drugs that can control or slow the fibrotic process. Pirfenidone, an immunosuppressant, has been authorised in the European Union for the treatment of mild to moderate idiopathic pulmonary fibrosis. Clinical evaluation is based on two double-blind randomised placebo-controlled trials lasting 72 weeks in a total of 779 patients. Mortality, the frequency of exacerbations and the number of lung transplants did not differ significantly between the pirfenidone and placebo groups in either trial. Decline in forced vital capacity was smaller with pirfenidone than with placebo, but the difference was statistically significant in only one of the trials. The small difference in this surrogate endpoint is of questionable clinical relevance. 14.8% of the patients taking pirfenidone 2403 mg/day (maintenance dose according to the marketing authorisation) discontinued treatment because of adverse events, versus 8.6% of patients in the placebo groups. Serious adverse effects included 3 cases of bladder cancer in the pirfenidone groups versus 1 case in the placebo groups. Photosensitivity and skin rash, cardiac arrhythmias and coronary artery disease were more frequent with pirfenidone 2403 mg/day than with placebo. Abnormal transaminase elevation occurred in 4.1% of patients on pirfenidone 2403 mg/day versus 0.6% of patients on placebo. A few cases of acute renal failure were also observed. In practice, there is no evidence that pirfenidone improves quality of life in patients with mild to moderate idiopathic pulmonary fibrosis, or that it slows the progression of pulmonary fibrosis. The adverse effect profile is already burdensome. Pending real therapeutic advance, it is best to avoid pirfenidone altogether and to focus on symptomatic treatment.

Regulatory considerations on new adjuvants and delivery systems.

PubMed

Sesardic, D

2006-04-12

New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

European Medicines Agency approval summary: Zaltrap for the treatment of patients with oxaliplatin-resistant metastatic colorectal cancer.

PubMed

Stanel, Stefan Cristian; Sjöberg, Jan; Salmonson, Tomas; Foggi, Paolo; Caleno, Mariapaola; Melchiorri, Daniela; Gravanis, Iordanis; Tzogani, Kyriaki; Pignatti, Francesco

2017-01-01

On 1 February 2013, a marketing authorisation valid throughout the European Union was issued for aflibercept (Zaltrap) in combination with irinotecan/5-fluorouracil/folinic acid chemotherapy for the treatment of adults with metastatic colorectal cancer resistant to or progressive after an oxaliplatin-containing regimen. Aflibercept is a recombinant fusion protein which blocks the activation of vascular endothelial growth factor (VEGF) receptors and the proliferation of endothelial cells, acting as a soluble decoy receptor that binds to VEGF-A with higher affinity than its native receptors, as well as placental growth factor and VEGF-B. The use of aflibercept was studied in a randomised, double-blind, placebo-controlled phase III study, in patients with metastatic colorectal cancer (mCRC) who had previously been treated with an oxaliplatin-based treatment with or without prior bevacizumab. Aflibercept (n=612) was compared with placebo (n=614), both in combination with FOLFIRI (infusional fluorouracil, leucovorin and irinotecan). The primary endpoint of the study was overall survival (OS). The median OS in the intent-to-treat population was 13.5 months in subjects treated with aflibercept compared with 12.1 months for subjects in the control arm (stratified HR=0.817, 95% CI 0.714 to 0.935, stratified pvalue=0.0032). The frequency of adverse events was higher in the aflibercept arm compared with the placebo arm, reflecting the toxicity profile of anti-VEGF agents in combination with chemotherapy. This paper is based on the scientific review of the application leading to approval of aflibercept in the EU. The detailed scientific assessment report and product information for this product are available on the European Medicines Agency website (http://www.ema.europa.eu). Trial registration number NCT00561470, Results.

Impact of electronic clinical decision support on adherence to guideline-recommended treatment for hyperlipidaemia, atrial fibrillation and heart failure: protocol for a cluster randomised trial

PubMed Central

Kessler, Maya Elizabeth; Cook, David A; Kor, Daryl Jon; McKie, Paul M; Pencille, Laurie J; Scheitel, Marianne R; Chaudhry, Rajeev

2017-01-01

Introduction Clinical practice guidelines facilitate optimal clinical practice. Point of care access, interpretation and application of such guidelines, however, is inconsistent. Informatics-based tools may help clinicians apply guidelines more consistently. We have developed a novel clinical decision support tool that presents guideline-relevant information and actionable items to clinicians at the point of care. We aim to test whether this tool improves the management of hyperlipidaemia, atrial fibrillation and heart failure by primary care clinicians. Methods/analysis Clinician care teams were cluster randomised to receive access to the clinical decision support tool or passive access to institutional guidelines on 16 May 2016. The trial began on 1 June 2016 when access to the tool was granted to the intervention clinicians. The trial will be run for 6 months to ensure a sufficient number of patient encounters to achieve 80% power to detect a twofold increase in the primary outcome at the 0.05 level of significance. The primary outcome measure will be the percentage of guideline-based recommendations acted on by clinicians for hyperlipidaemia, atrial fibrillation and heart failure. We hypothesise care teams with access to the clinical decision support tool will act on recommendations at a higher rate than care teams in the standard of care arm. Ethics and dissemination The Mayo Clinic Institutional Review Board approved all study procedures. Informed consent was obtained from clinicians. A waiver of informed consent and of Health Insurance Portability and Accountability Act (HIPAA) authorisation for patients managed by clinicians in the study was granted. In addition to publication, results will be disseminated via meetings and newsletters. Trial registration number NCT02742545. PMID:29208620

The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial

PubMed Central

Neubert, Antje; Baarslag, Manuel Alberto; van Dijk, Monique; van Rosmalen, Joost; Standing, Joseph F; Sheng, Yucheng; Rascher, Wolfgang; Roberts, Deborah; Winslade, Jackie; Rawcliffe, Louise; Hanning, Sara M; Metsvaht, Tuuli; Giannuzzi, Viviana; Larsson, Peter; Pokorná, Pavla; Simonetti, Alessandra; Tibboel, Dick

2017-01-01

Introduction Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. Methods and analysis The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2–18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. Ethics Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial Registration EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results. PMID:28637741

Line-Based Registration of Panoramic Images and LiDAR Point Clouds for Mobile Mapping.

PubMed

Cui, Tingting; Ji, Shunping; Shan, Jie; Gong, Jianya; Liu, Kejian

2016-12-31

For multi-sensor integrated systems, such as the mobile mapping system (MMS), data fusion at sensor-level, i.e., the 2D-3D registration between an optical camera and LiDAR, is a prerequisite for higher level fusion and further applications. This paper proposes a line-based registration method for panoramic images and a LiDAR point cloud collected by a MMS. We first introduce the system configuration and specification, including the coordinate systems of the MMS, the 3D LiDAR scanners, and the two panoramic camera models. We then establish the line-based transformation model for the panoramic camera. Finally, the proposed registration method is evaluated for two types of camera models by visual inspection and quantitative comparison. The results demonstrate that the line-based registration method can significantly improve the alignment of the panoramic image and the LiDAR datasets under either the ideal spherical or the rigorous panoramic camera model, with the latter being more reliable.

Line-Based Registration of Panoramic Images and LiDAR Point Clouds for Mobile Mapping

PubMed Central

Cui, Tingting; Ji, Shunping; Shan, Jie; Gong, Jianya; Liu, Kejian

2016-01-01

For multi-sensor integrated systems, such as the mobile mapping system (MMS), data fusion at sensor-level, i.e., the 2D-3D registration between an optical camera and LiDAR, is a prerequisite for higher level fusion and further applications. This paper proposes a line-based registration method for panoramic images and a LiDAR point cloud collected by a MMS. We first introduce the system configuration and specification, including the coordinate systems of the MMS, the 3D LiDAR scanners, and the two panoramic camera models. We then establish the line-based transformation model for the panoramic camera. Finally, the proposed registration method is evaluated for two types of camera models by visual inspection and quantitative comparison. The results demonstrate that the line-based registration method can significantly improve the alignment of the panoramic image and the LiDAR datasets under either the ideal spherical or the rigorous panoramic camera model, with the latter being more reliable. PMID:28042855

Markerless laser registration in image-guided oral and maxillofacial surgery.

PubMed

Marmulla, Rüdiger; Lüth, Tim; Mühling, Joachim; Hassfeld, Stefan

2004-07-01

The use of registration markers in computer-assisted surgery is combined with high logistic costs and efforts. Markerless patient registration using laser scan surface registration techniques is a new challenging method. The present study was performed to evaluate the clinical accuracy in finding defined target points within the surgical site after markerless patient registration in image-guided oral and maxillofacial surgery. Twenty consecutive patients with different cranial diseases were scheduled for computer-assisted surgery. Data set alignment between the surgical site and the computed tomography (CT) data set was performed by markerless laser scan surface registration of the patient's face. Intraoral rigidly attached registration markers were used as target points, which had to be detected by an infrared pointer. The Surgical Segment Navigator SSN++ has been used for all procedures. SSN++ is an investigative product based on the SSN system that had previously been developed by the presenting authors with the support of Carl Zeiss (Oberkochen, Germany). SSN++ is connected to a Polaris infrared camera (Northern Digital, Waterloo, Ontario, Canada) and to a Minolta VI 900 3D digitizer (Tokyo, Japan) for high-resolution laser scanning. Minimal differences in shape between the laser scan surface and the surface generated from the CT data set could be detected. Nevertheless, high-resolution laser scan of the skin surface allows for a precise patient registration (mean deviation 1.1 mm, maximum deviation 1.8 mm). Radiation load, logistic costs, and efforts arising from the planning of computer-assisted surgery of the head can be reduced because native (markerless) CT data sets can be used for laser scan-based surface registration.

Automatic elastic image registration by interpolation of 3D rotations and translations from discrete rigid-body transformations.

PubMed

Walimbe, Vivek; Shekhar, Raj

2006-12-01

We present an algorithm for automatic elastic registration of three-dimensional (3D) medical images. Our algorithm initially recovers the global spatial mismatch between the reference and floating images, followed by hierarchical octree-based subdivision of the reference image and independent registration of the floating image with the individual subvolumes of the reference image at each hierarchical level. Global as well as local registrations use the six-parameter full rigid-body transformation model and are based on maximization of normalized mutual information (NMI). To ensure robustness of the subvolume registration with low voxel counts, we calculate NMI using a combination of current and prior mutual histograms. To generate a smooth deformation field, we perform direct interpolation of six-parameter rigid-body subvolume transformations obtained at the last subdivision level. Our interpolation scheme involves scalar interpolation of the 3D translations and quaternion interpolation of the 3D rotational pose. We analyzed the performance of our algorithm through experiments involving registration of synthetically deformed computed tomography (CT) images. Our algorithm is general and can be applied to image pairs of any two modalities of most organs. We have demonstrated successful registration of clinical whole-body CT and positron emission tomography (PET) images using this algorithm. The registration accuracy for this application was evaluated, based on validation using expert-identified anatomical landmarks in 15 CT-PET image pairs. The algorithm's performance was comparable to the average accuracy observed for three expert-determined registrations in the same 15 image pairs.

Non-rigid registration between 3D ultrasound and CT images of the liver based on intensity and gradient information

NASA Astrophysics Data System (ADS)

Lee, Duhgoon; Nam, Woo Hyun; Lee, Jae Young; Ra, Jong Beom

2011-01-01

In order to utilize both ultrasound (US) and computed tomography (CT) images of the liver concurrently for medical applications such as diagnosis and image-guided intervention, non-rigid registration between these two types of images is an essential step, as local deformation between US and CT images exists due to the different respiratory phases involved and due to the probe pressure that occurs in US imaging. This paper introduces a voxel-based non-rigid registration algorithm between the 3D B-mode US and CT images of the liver. In the proposed algorithm, to improve the registration accuracy, we utilize the surface information of the liver and gallbladder in addition to the information of the vessels inside the liver. For an effective correlation between US and CT images, we treat those anatomical regions separately according to their characteristics in US and CT images. Based on a novel objective function using a 3D joint histogram of the intensity and gradient information, vessel-based non-rigid registration is followed by surface-based non-rigid registration in sequence, which improves the registration accuracy. The proposed algorithm is tested for ten clinical datasets and quantitative evaluations are conducted. Experimental results show that the registration error between anatomical features of US and CT images is less than 2 mm on average, even with local deformation due to different respiratory phases and probe pressure. In addition, the lesion registration error is less than 3 mm on average with a maximum of 4.5 mm that is considered acceptable for clinical applications.

Object-constrained meshless deformable algorithm for high speed 3D nonrigid registration between CT and CBCT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Ting; Kim, Sung; Goyal, Sharad

2010-01-15

Purpose: High-speed nonrigid registration between the planning CT and the treatment CBCT data is critical for real time image guided radiotherapy (IGRT) to improve the dose distribution and to reduce the toxicity to adjacent organs. The authors propose a new fully automatic 3D registration framework that integrates object-based global and seed constraints with the grayscale-based ''demons'' algorithm. Methods: Clinical objects were segmented on the planning CT images and were utilized as meshless deformable models during the nonrigid registration process. The meshless models reinforced a global constraint in addition to the grayscale difference between CT and CBCT in order to maintainmore » the shape and the volume of geometrically complex 3D objects during the registration. To expedite the registration process, the framework was stratified into hierarchies, and the authors used a frequency domain formulation to diffuse the displacement between the reference and the target in each hierarchy. Also during the registration of pelvis images, they replaced the air region inside the rectum with estimated pixel values from the surrounding rectal wall and introduced an additional seed constraint to robustly track and match the seeds implanted into the prostate. The proposed registration framework and algorithm were evaluated on 15 real prostate cancer patients. For each patient, prostate gland, seminal vesicle, bladder, and rectum were first segmented by a radiation oncologist on planning CT images for radiotherapy planning purpose. The same radiation oncologist also manually delineated the tumor volumes and critical anatomical structures in the corresponding CBCT images acquired at treatment. These delineated structures on the CBCT were only used as the ground truth for the quantitative validation, while structures on the planning CT were used both as the input to the registration method and the ground truth in validation. By registering the planning CT to the CBCT, a displacement map was generated. Segmented volumes in the CT images deformed using the displacement field were compared against the manual segmentations in the CBCT images to quantitatively measure the convergence of the shape and the volume. Other image features were also used to evaluate the overall performance of the registration. Results: The algorithm was able to complete the segmentation and registration process within 1 min, and the superimposed clinical objects achieved a volumetric similarity measure of over 90% between the reference and the registered data. Validation results also showed that the proposed registration could accurately trace the deformation inside the target volume with average errors of less than 1 mm. The method had a solid performance in registering the simulated images with up to 20 Hounsfield unit white noise added. Also, the side by side comparison with the original demons algorithm demonstrated its improved registration performance over the local pixel-based registration approaches. Conclusions: Given the strength and efficiency of the algorithm, the proposed method has significant clinical potential to accelerate and to improve the CBCT delineation and targets tracking in online IGRT applications.« less

Recruitment, selection and retention of nursing and midwifery students in Scottish Universities.

PubMed

Rodgers, Sheila; Stenhouse, Rosie; McCreaddie, May; Small, Pauline

2013-11-01

High attrition rates from pre-registration nursing and midwifery programmes have been reported in both the UK and in other countries. A study was conducted to identify best practice in recruitment, selection and retention across Scottish Universities providing pre-registration programmes. A survey of all universities providing pre-registration programmes in Scotland was conducted. Semi-structured interviews were conducted with key personnel in each university. Documentary evidence was collected to supplement interview data and evidence recruitment, selection and retention practices. All universities in Scotland providing pre-registration nursing and/or midwifery programmes. All 10 identified universities agreed to take part and a total of 18 interviews were conducted. Semi-structured face to face and telephone interviews were conducted. Relevant documentary evidence was collected. All data were subject to thematic analysis. Universities are predominantly concerned with recruiting to the institution and not to the professions. Interviews are widely used, and are a requirement in the United Kingdom. However, there is no evidence base within the literature that they have predictive validity despite creating scales and scoring systems which are largely unvalidated. The study identified initiatives aimed at addressing attrition/retention, however most had not been evaluated often due to the multi-factorial nature of attrition/retention and difficulties with measurement. Recruitment selection and retention initiatives were rarely evaluated, and if so, adopted a relatively superficial approach. Evidence from existing studies to support practices was mostly weakly supportive or absent. The study highlights the need for a coordinated approach, supporting the development of a robust evidence base through the evaluation of local initiatives, and evaluation of new strategies. Evaluation strategies must take account of the local context to facilitate transferability of findings across different settings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Implementation of Remote 3-Dimensional Image Guided Radiation Therapy Quality Assurance for Radiation Therapy Oncology Group Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui Yunfeng; Galvin, James M.; Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania

2013-01-01

Purpose: To report the process and initial experience of remote credentialing of three-dimensional (3D) image guided radiation therapy (IGRT) as part of the quality assurance (QA) of submitted data for Radiation Therapy Oncology Group (RTOG) clinical trials; and to identify major issues resulting from this process and analyze the review results on patient positioning shifts. Methods and Materials: Image guided radiation therapy datasets including in-room positioning CT scans and daily shifts applied were submitted through the Image Guided Therapy QA Center from institutions for the IGRT credentialing process, as required by various RTOG trials. A centralized virtual environment is establishedmore » at the RTOG Core Laboratory, containing analysis tools and database infrastructure for remote review by the Physics Principal Investigators of each protocol. The appropriateness of IGRT technique and volumetric image registration accuracy were evaluated. Registration accuracy was verified by repeat registration with a third-party registration software system. With the accumulated review results, registration differences between those obtained by the Physics Principal Investigators and from the institutions were analyzed for different imaging sites, shift directions, and imaging modalities. Results: The remote review process was successfully carried out for 87 3D cases (out of 137 total cases, including 2-dimensional and 3D) during 2010. Frequent errors in submitted IGRT data and challenges in the review of image registration for some special cases were identified. Workarounds for these issues were developed. The average differences of registration results between reviewers and institutions ranged between 2 mm and 3 mm. Large discrepancies in the superior-inferior direction were found for megavoltage CT cases, owing to low spatial resolution in this direction for most megavoltage CT cases. Conclusion: This first experience indicated that remote review for 3D IGRT as part of QA for RTOG clinical trials is feasible and effective. The magnitude of registration discrepancy between institution and reviewer was presented, and the major issues were investigated to further improve this remote evaluation process.« less

Deformable image registration with local rigidity constraints for cone-beam CT-guided spine surgery

NASA Astrophysics Data System (ADS)

Reaungamornrat, S.; Wang, A. S.; Uneri, A.; Otake, Y.; Khanna, A. J.; Siewerdsen, J. H.

2014-07-01

Image-guided spine surgery (IGSS) is associated with reduced co-morbidity and improved surgical outcome. However, precise localization of target anatomy and adjacent nerves and vessels relative to planning information (e.g., device trajectories) can be challenged by anatomical deformation. Rigid registration alone fails to account for deformation associated with changes in spine curvature, and conventional deformable registration fails to account for rigidity of the vertebrae, causing unrealistic distortions in the registered image that can confound high-precision surgery. We developed and evaluated a deformable registration method capable of preserving rigidity of bones while resolving the deformation of surrounding soft tissue. The method aligns preoperative CT to intraoperative cone-beam CT (CBCT) using free-form deformation (FFD) with constraints on rigid body motion imposed according to a simple intensity threshold of bone intensities. The constraints enforced three properties of a rigid transformation—namely, constraints on affinity (AC), orthogonality (OC), and properness (PC). The method also incorporated an injectivity constraint (IC) to preserve topology. Physical experiments involving phantoms, an ovine spine, and a human cadaver as well as digital simulations were performed to evaluate the sensitivity to registration parameters, preservation of rigid body morphology, and overall registration accuracy of constrained FFD in comparison to conventional unconstrained FFD (uFFD) and Demons registration. FFD with orthogonality and injectivity constraints (denoted FFD+OC+IC) demonstrated improved performance compared to uFFD and Demons. Affinity and properness constraints offered little or no additional improvement. The FFD+OC+IC method preserved rigid body morphology at near-ideal values of zero dilatation ({ D} = 0.05, compared to 0.39 and 0.56 for uFFD and Demons, respectively) and shear ({ S} = 0.08, compared to 0.36 and 0.44 for uFFD and Demons, respectively). Target registration error (TRE) was similarly improved for FFD+OC+IC (0.7 mm), compared to 1.4 and 1.8 mm for uFFD and Demons. Results were validated in human cadaver studies using CT and CBCT images, with FFD+OC+IC providing excellent preservation of rigid morphology and equivalent or improved TRE. The approach therefore overcomes distortions intrinsic to uFFD and could better facilitate high-precision IGSS.

Rendering-based video-CT registration with physical constraints for image-guided endoscopic sinus surgery

NASA Astrophysics Data System (ADS)

Otake, Y.; Leonard, S.; Reiter, A.; Rajan, P.; Siewerdsen, J. H.; Ishii, M.; Taylor, R. H.; Hager, G. D.

2015-03-01

We present a system for registering the coordinate frame of an endoscope to pre- or intra- operatively acquired CT data based on optimizing the similarity metric between an endoscopic image and an image predicted via rendering of CT. Our method is robust and semi-automatic because it takes account of physical constraints, specifically, collisions between the endoscope and the anatomy, to initialize and constrain the search. The proposed optimization method is based on a stochastic optimization algorithm that evaluates a large number of similarity metric functions in parallel on a graphics processing unit. Images from a cadaver and a patient were used for evaluation. The registration error was 0.83 mm and 1.97 mm for cadaver and patient images respectively. The average registration time for 60 trials was 4.4 seconds. The patient study demonstrated robustness of the proposed algorithm against a moderate anatomical deformation.

Aircraft MSS data registration and vegetation classification of wetland change detection

USGS Publications Warehouse

Christensen, E.J.; Jensen, J.R.; Ramsey, Elijah W.; Mackey, H.E.

1988-01-01

Portions of the Savannah River floodplain swamp were evaluated for vegetation change using high resolution (5a??6 m) aircraft multispectral scanner (MSS) data. Image distortion from aircraft movement prevented precise image-to-image registration in some areas. However, when small scenes were used (200-250 ha), a first-order linear transformation provided registration accuracies of less than or equal to one pixel. A larger area was registered using a piecewise linear method. Five major wetland classes were identified and evaluated for change. Phenological differences and the variable distribution of vegetation limited wetland type discrimination. Using unsupervised methods and ground-collected vegetation data, overall classification accuracies ranged from 84 per cent to 87 per cent for each scene. Results suggest that high-resolution aircraft MSS data can be precisely registered, if small areas are used, and that wetland vegetation change can be accurately detected and monitored.

Social media and internet driven study recruitment: evaluating a new model for promoting collaborator engagement and participation.

PubMed

Khatri, Chetan; Chapman, Stephen J; Glasbey, James; Kelly, Michael; Nepogodiev, Dmitri; Bhangu, Aneel; Fitzgerald, J Edward

2015-01-01

A substantial challenge facing multicentre audit and research projects is timely recruitment of collaborators and their study centres. Cost-effective strategies are required and fee-free social media has previously been identified as a potential conduit. We investigated and evaluated the effectiveness of a novel multi-format social media and Internet strategy for targeted recruitment to a national multicentre cohort study. Interventions involved a new Twitter account, including weekly live question-and-answer sessions, a new Facebook group page, online YouTube presentations and an information page on a national association website. Link tracking analysis was undertaken using Google Analytics, which was then related to subsequent registration. Social influence was calculated using the proprietary Klout score. Internet traffic analysis identified a total of 1562 unique registration site views, of which 285 originated from social media (18.2%). Some 528 unique registrations were received, with 96 via social media platforms (18.2%). Traffic source analysis identified a separate national association webpage as resulting in the majority of registration page views (15.8%), followed by Facebook (11.9%), Twitter (4.8%) and YouTube (1.5%). A combination of publicity through Facebook, Twitter and the dedicated national association webpage contributed to the greatest rise in registration traffic and accounted for 312 (48%) of the total registrations within a 2-week period. A Twitter 'social influence' (Klout) score of 42/100 was obtained during this period. Targeted social media substantially aided study dissemination and collaborator recruitment. It acted as an adjunct to traditional methods, accounting for 18.2% of collaborator registration in a short time period with no associated financial costs. We provide a practical model for designing future recruitment campaigns, and recommend Facebook, Twitter and targeted websites as the most effective adjuncts for maximising cost-effective study recruitment.

Social Media and Internet Driven Study Recruitment: Evaluating a New Model for Promoting Collaborator Engagement and Participation

PubMed Central

Khatri, Chetan; Chapman, Stephen J.; Glasbey, James; Kelly, Michael; Nepogodiev, Dmitri; Bhangu, Aneel; Fitzgerald, J. Edward

2015-01-01

Aims A substantial challenge facing multicentre audit and research projects is timely recruitment of collaborators and their study centres. Cost-effective strategies are required and fee-free social media has previously been identified as a potential conduit. We investigated and evaluated the effectiveness of a novel multi-format social media and Internet strategy for targeted recruitment to a national multicentre cohort study. Methods Interventions involved a new Twitter account, including weekly live question-and-answer sessions, a new Facebook group page, online YouTube presentations and an information page on a national association website. Link tracking analysis was undertaken using Google Analytics, which was then related to subsequent registration. Social influence was calculated using the proprietary Klout score. Results Internet traffic analysis identified a total of 1562 unique registration site views, of which 285 originated from social media (18.2%). Some 528 unique registrations were received, with 96 via social media platforms (18.2%). Traffic source analysis identified a separate national association webpage as resulting in the majority of registration page views (15.8%), followed by Facebook (11.9%), Twitter (4.8%) and YouTube (1.5%). A combination of publicity through Facebook, Twitter and the dedicated national association webpage contributed to the greatest rise in registration traffic and accounted for 312 (48%) of the total registrations within a 2-week period. A Twitter ‘social influence’ (Klout) score of 42/100 was obtained during this period. Conclusions Targeted social media substantially aided study dissemination and collaborator recruitment. It acted as an adjunct to traditional methods, accounting for 18.2% of collaborator registration in a short time period with no associated financial costs. We provide a practical model for designing future recruitment campaigns, and recommend Facebook, Twitter and targeted websites as the most effective adjuncts for maximising cost-effective study recruitment. PMID:25775005

A surgical robot with augmented reality visualization for stereoelectroencephalography electrode implantation.

PubMed

Zeng, Bowei; Meng, Fanle; Ding, Hui; Wang, Guangzhi

2017-08-01

Using existing stereoelectroencephalography (SEEG) electrode implantation surgical robot systems, it is difficult to intuitively validate registration accuracy and display the electrode entry points (EPs) and the anatomical structure around the electrode trajectories in the patient space to the surgeon. This paper proposes a prototype system that can realize video see-through augmented reality (VAR) and spatial augmented reality (SAR) for SEEG implantation. The system helps the surgeon quickly and intuitively confirm the registration accuracy, locate EPs and visualize the internal anatomical structure in the image space and patient space. We designed and developed a projector-camera system (PCS) attached to the distal flange of a robot arm. First, system calibration is performed. Second, the PCS is used to obtain the point clouds of the surface of the patient's head, which are utilized for patient-to-image registration. Finally, VAR is produced by merging the real-time video of the patient and the preoperative three-dimensional (3D) operational planning model. In addition, SAR is implemented by projecting the planning electrode trajectories and local anatomical structure onto the patient's scalp. The error of registration, the electrode EPs and the target points are evaluated on a phantom. The fiducial registration error is [Formula: see text] mm (max 1.22 mm), and the target registration error is [Formula: see text] mm (max 1.18 mm). The projection overlay error is [Formula: see text] mm, and the TP error after the pre-warped projection is [Formula: see text] mm. The TP error caused by a surgeon's viewpoint deviation is also evaluated. The presented system can help surgeons quickly verify registration accuracy during SEEG procedures and can provide accurate EP locations and internal structural information to the surgeon. With more intuitive surgical information, the surgeon may have more confidence and be able to perform surgeries with better outcomes.

SU-E-J-91: FFT Based Medical Image Registration Using a Graphics Processing Unit (GPU).

PubMed

Luce, J; Hoggarth, M; Lin, J; Block, A; Roeske, J

2012-06-01

To evaluate the efficiency gains obtained from using a Graphics Processing Unit (GPU) to perform a Fourier Transform (FT) based image registration. Fourier-based image registration involves obtaining the FT of the component images, and analyzing them in Fourier space to determine the translations and rotations of one image set relative to another. An important property of FT registration is that by enlarging the images (adding additional pixels), one can obtain translations and rotations with sub-pixel resolution. The expense, however, is an increased computational time. GPUs may decrease the computational time associated with FT image registration by taking advantage of their parallel architecture to perform matrix computations much more efficiently than a Central Processor Unit (CPU). In order to evaluate the computational gains produced by a GPU, images with known translational shifts were utilized. A program was written in the Interactive Data Language (IDL; Exelis, Boulder, CO) to performCPU-based calculations. Subsequently, the program was modified using GPU bindings (Tech-X, Boulder, CO) to perform GPU-based computation on the same system. Multiple image sizes were used, ranging from 256×256 to 2304×2304. The time required to complete the full algorithm by the CPU and GPU were benchmarked and the speed increase was defined as the ratio of the CPU-to-GPU computational time. The ratio of the CPU-to- GPU time was greater than 1.0 for all images, which indicates the GPU is performing the algorithm faster than the CPU. The smallest improvement, a 1.21 ratio, was found with the smallest image size of 256×256, and the largest speedup, a 4.25 ratio, was observed with the largest image size of 2304×2304. GPU programming resulted in a significant decrease in computational time associated with a FT image registration algorithm. The inclusion of the GPU may provide near real-time, sub-pixel registration capability. © 2012 American Association of Physicists in Medicine.

Analysis of deformable image registration accuracy using computational modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhong Hualiang; Kim, Jinkoo; Chetty, Indrin J.

2010-03-15

Computer aided modeling of anatomic deformation, allowing various techniques and protocols in radiation therapy to be systematically verified and studied, has become increasingly attractive. In this study the potential issues in deformable image registration (DIR) were analyzed based on two numerical phantoms: One, a synthesized, low intensity gradient prostate image, and the other a lung patient's CT image data set. Each phantom was modeled with region-specific material parameters with its deformation solved using a finite element method. The resultant displacements were used to construct a benchmark to quantify the displacement errors of the Demons and B-Spline-based registrations. The results showmore » that the accuracy of these registration algorithms depends on the chosen parameters, the selection of which is closely associated with the intensity gradients of the underlying images. For the Demons algorithm, both single resolution (SR) and multiresolution (MR) registrations required approximately 300 iterations to reach an accuracy of 1.4 mm mean error in the lung patient's CT image (and 0.7 mm mean error averaged in the lung only). For the low gradient prostate phantom, these algorithms (both SR and MR) required at least 1600 iterations to reduce their mean errors to 2 mm. For the B-Spline algorithms, best performance (mean errors of 1.9 mm for SR and 1.6 mm for MR, respectively) on the low gradient prostate was achieved using five grid nodes in each direction. Adding more grid nodes resulted in larger errors. For the lung patient's CT data set, the B-Spline registrations required ten grid nodes in each direction for highest accuracy (1.4 mm for SR and 1.5 mm for MR). The numbers of iterations or grid nodes required for optimal registrations depended on the intensity gradients of the underlying images. In summary, the performance of the Demons and B-Spline registrations have been quantitatively evaluated using numerical phantoms. The results show that parameter selection for optimal accuracy is closely related to the intensity gradients of the underlying images. Also, the result that the DIR algorithms produce much lower errors in heterogeneous lung regions relative to homogeneous (low intensity gradient) regions, suggests that feature-based evaluation of deformable image registration accuracy must be viewed cautiously.« less

PCA-based groupwise image registration for quantitative MRI.

PubMed

Huizinga, W; Poot, D H J; Guyader, J-M; Klaassen, R; Coolen, B F; van Kranenburg, M; van Geuns, R J M; Uitterdijk, A; Polfliet, M; Vandemeulebroucke, J; Leemans, A; Niessen, W J; Klein, S

2016-04-01

Quantitative magnetic resonance imaging (qMRI) is a technique for estimating quantitative tissue properties, such as the T1 and T2 relaxation times, apparent diffusion coefficient (ADC), and various perfusion measures. This estimation is achieved by acquiring multiple images with different acquisition parameters (or at multiple time points after injection of a contrast agent) and by fitting a qMRI signal model to the image intensities. Image registration is often necessary to compensate for misalignments due to subject motion and/or geometric distortions caused by the acquisition. However, large differences in image appearance make accurate image registration challenging. In this work, we propose a groupwise image registration method for compensating misalignment in qMRI. The groupwise formulation of the method eliminates the requirement of choosing a reference image, thus avoiding a registration bias. The method minimizes a cost function that is based on principal component analysis (PCA), exploiting the fact that intensity changes in qMRI can be described by a low-dimensional signal model, but not requiring knowledge on the specific acquisition model. The method was evaluated on 4D CT data of the lungs, and both real and synthetic images of five different qMRI applications: T1 mapping in a porcine heart, combined T1 and T2 mapping in carotid arteries, ADC mapping in the abdomen, diffusion tensor mapping in the brain, and dynamic contrast-enhanced mapping in the abdomen. Each application is based on a different acquisition model. The method is compared to a mutual information-based pairwise registration method and four other state-of-the-art groupwise registration methods. Registration accuracy is evaluated in terms of the precision of the estimated qMRI parameters, overlap of segmented structures, distance between corresponding landmarks, and smoothness of the deformation. In all qMRI applications the proposed method performed better than or equally well as competing methods, while avoiding the need to choose a reference image. It is also shown that the results of the conventional pairwise approach do depend on the choice of this reference image. We therefore conclude that our groupwise registration method with a similarity measure based on PCA is the preferred technique for compensating misalignments in qMRI. Copyright © 2015 Elsevier B.V. All rights reserved.

Depth-resolved registration of transesophageal echo to x-ray fluoroscopy using an inverse geometry fluoroscopy system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatt, Charles R.; Tomkowiak, Michael T.; Dunkerley, David A. P.

2015-12-15

Purpose: Image registration between standard x-ray fluoroscopy and transesophageal echocardiography (TEE) has recently been proposed. Scanning-beam digital x-ray (SBDX) is an inverse geometry fluoroscopy system designed for cardiac procedures. This study presents a method for 3D registration of SBDX and TEE images based on the tomosynthesis and 3D tracking capabilities of SBDX. Methods: The registration algorithm utilizes the stack of tomosynthetic planes produced by the SBDX system to estimate the physical 3D coordinates of salient key-points on the TEE probe. The key-points are used to arrive at an initial estimate of the probe pose, which is then refined using amore » 2D/3D registration method adapted for inverse geometry fluoroscopy. A phantom study was conducted to evaluate probe pose estimation accuracy relative to the ground truth, as defined by a set of coregistered fiducial markers. This experiment was conducted with varying probe poses and levels of signal difference-to-noise ratio (SDNR). Additional phantom and in vivo studies were performed to evaluate the correspondence of catheter tip positions in TEE and x-ray images following registration of the two modalities. Results: Target registration error (TRE) was used to characterize both pose estimation and registration accuracy. In the study of pose estimation accuracy, successful pose estimates (3D TRE < 5.0 mm) were obtained in 97% of cases when the SDNR was 5.9 or higher in seven out of eight poses. Under these conditions, 3D TRE was 2.32 ± 1.88 mm, and 2D (projection) TRE was 1.61 ± 1.36 mm. Probe localization error along the source-detector axis was 0.87 ± 1.31 mm. For the in vivo experiments, mean 3D TRE ranged from 2.6 to 4.6 mm and mean 2D TRE ranged from 1.1 to 1.6 mm. Anatomy extracted from the echo images appeared well aligned when projected onto the SBDX images. Conclusions: Full 6 DOF image registration between SBDX and TEE is feasible and accurate to within 5 mm. Future studies will focus on real-time implementation and application-specific analysis.« less

Testing nano-silver food packaging to evaluate silver migration and food spoilage bacteria on chicken meat.

PubMed

Gallocchio, Federica; Cibin, Veronica; Biancotto, Giancarlo; Roccato, Anna; Muzzolon, Orietta; Carmen, Losasso; Simone, Belluco; Manodori, Laura; Fabrizi, Alberto; Patuzzi, Ilaria; Ricci, Antonia

2016-06-01

Migration of nanomaterials from food containers into food is a matter of concern because of the potential risk for exposed consumers. The aims of this study were to evaluate silver migration from a commercially available food packaging containing silver nanoparticles into a real food matrix (chicken meat) under plausible domestic storage conditions and to test the contribution of such packaging to limit food spoilage bacteria proliferation. Chemical analysis revealed the absence of silver in chicken meatballs under the experimental conditions in compliance with current European Union legislation, which establishes a maximum level of 0.010 mg kg(-1) for the migration of non-authorised substances through a functional barrier (Commission Regulation (EU) No. 10/2011). On the other hand, microbiological tests (total microbial count, Pseudomonas spp. and Enterobacteriaceae) showed no relevant difference in the tested bacteria levels between meatballs stored in silver-nanoparticle plastic bags or control bags. This study shows the importance of testing food packaging not only to verify potential silver migration as an indicator of potential nanoparticle migration, but also to evaluate the benefits in terms of food preservation so as to avoid unjustified usage of silver nanoparticles and possible negative impacts on the environment.

GT-57633 catalogue of Martian impact craters developed for evaluation of crater detection algorithms

NASA Astrophysics Data System (ADS)

Salamunićcar, Goran; Lončarić, Sven

2008-12-01

Crater detection algorithms (CDAs) are an important subject of the recent scientific research. A ground truth (GT) catalogue, which contains the locations and sizes of known craters, is important for the evaluation of CDAs in a wide range of CDA applications. Unfortunately, previous catalogues of craters by other authors cannot be easily used as GT. In this paper, we propose a method for integration of several existing catalogues to obtain a new craters catalogue. The methods developed and used during this work on the GT catalogue are: (1) initial screening of used catalogues; (2) evaluation of self-consistency of used catalogues; (3) initial registration from three different catalogues; (4) cross-evaluation of used catalogues; (5) additional registrations and registrations from additional catalogues; and (6) fine-tuning and registration with additional data-sets. During this process, all craters from all major currently available manually assembled catalogues were processed, including catalogues by Barlow, Rodionova, Boyce, Kuzmin, and our previous work. Each crater from the GT catalogue contains references to crater(s) that are used for its registration. This provides direct access to all properties assigned to craters from the used catalogues, which can be of interest even to those scientists that are not directly interested in CDAs. Having all these craters in a single catalogue also provides a good starting point for searching for craters still not catalogued manually, which is also expected to be one of the challenges of CDAs. The resulting new GT catalogue contains 57,633 craters, significantly more than any previous catalogue. From this point of view, GT-57633 catalogue is currently the most complete catalogue of large Martian impact craters. Additionally, each crater from the resulting GT-57633 catalogue is aligned with MOLA topography and, during the final review phase, additionally registered/aligned with 1/256° THEMIS-DIR, 1/256° MDIM and 1/256° MOC data-sets. Accordingly, the resulting GT-57633 catalogue can successfully be used as a part of the framework for evaluation of CDAs.

Critical review on the Environmental Risk Assessment of medicinal products for human use in the centralised procedure.

PubMed

Caneva, Laura; Bonelli, Milton; Papaluca-Amati, Marisa; Vidal, Jean-Marc

2014-04-01

In this article we analyse the Environmental Risk Assessment (ERA) of 59 medicinal products for human use authorised in the EU through the centralised procedure between 2011 and 2012, to establish whether company submissions are compliant with the European Medicines Agency (EMA) guideline and complete in terms of data and study reports provided. The most frequent questions raised by EU regulatory authorities are described, together with an evaluation of the presence and quality of ERA-related information in published regulatory assessment documents. The results of this review show recent improvement in ERA-related data presented in regulatory assessment documents available to the public while also highlighting a need to develop further guidance on environmental issues in order to assist applicants improve their ERA dossiers and overcome current shortcomings. Copyright © 2014 Elsevier Inc. All rights reserved.

Regulation of sporicides under the European Biocidal Products Directive.

PubMed

Low, A

2011-03-01

Disinfectants (including sporicides) used in the healthcare setting fall within the scope of the European Biocidal Products Directive (98/8/EC). The active substances used in these products will be evaluated as part of an EU wide review programme, to determine whether they can be used in biocidal products without undue risks to humans, animals and the environment, and that these products will be effective. Following the review of an active substance, biocidal products containing the active substance will become subject to regulatory controls in all EU Member States. This paper discusses how the Directive operates, both through the review programme and the authorisation of biocidal products at the Member State level, together with the requirements to provide data on the efficacy of both the active substances and end-use biocidal products. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Biodegradable stents for the treatment of refractory or recurrent benign esophageal stenosis.

PubMed

Imaz-Iglesia, Iñaki; García-Pérez, Sonia; Nachtnebel, Anna; Martín-Águeda, Belén; Sánchez-Piedra, Carlos; Karadayi, Bilgehan; Demirbaş, Ali Rıza

2016-06-01

Esophageal stents are used for the treatment of refractory and recurrent dyphagias. In 2007, esophageal biodegradable stents (EBS) were authorised as an alternative to existing metal and plastic stents in Europe. The advantages claimed for EBS are fewer complications concerning tissue ingrowth, stent migration and stent removal. We performed a systematic review to evaluate the efficacy and safety of EBS compared to fully-covered self-expanding metal stents, self-expanding plastic stents, and esophageal dilation for the treatment of refractory or recurrent benign esophageal stenosis. Three comparative studies (one randomized controlled trial and two cohort studies) were assessed. The studies used different inclusion criteria, had a very small (sample) size and the quality of the evidence was very low. Expert commentary: The current evidence is insufficient to determine the relative efficacy or safety of esophageal biodegradable stents. The results of this systematic review should be updated once new evidence is available.

Joint multi-object registration and segmentation of left and right cardiac ventricles in 4D cine MRI

NASA Astrophysics Data System (ADS)

Ehrhardt, Jan; Kepp, Timo; Schmidt-Richberg, Alexander; Handels, Heinz

2014-03-01

The diagnosis of cardiac function based on cine MRI requires the segmentation of cardiac structures in the images, but the problem of automatic cardiac segmentation is still open, due to the imaging characteristics of cardiac MR images and the anatomical variability of the heart. In this paper, we present a variational framework for joint segmentation and registration of multiple structures of the heart. To enable the simultaneous segmentation and registration of multiple objects, a shape prior term is introduced into a region competition approach for multi-object level set segmentation. The proposed algorithm is applied for simultaneous segmentation of the myocardium as well as the left and right ventricular blood pool in short axis cine MRI images. Two experiments are performed: first, intra-patient 4D segmentation with a given initial segmentation for one time-point in a 4D sequence, and second, a multi-atlas segmentation strategy is applied to unseen patient data. Evaluation of segmentation accuracy is done by overlap coefficients and surface distances. An evaluation based on clinical 4D cine MRI images of 25 patients shows the benefit of the combined approach compared to sole registration and sole segmentation.

Explicit B-spline regularization in diffeomorphic image registration

PubMed Central

Tustison, Nicholas J.; Avants, Brian B.

2013-01-01

Diffeomorphic mappings are central to image registration due largely to their topological properties and success in providing biologically plausible solutions to deformation and morphological estimation problems. Popular diffeomorphic image registration algorithms include those characterized by time-varying and constant velocity fields, and symmetrical considerations. Prior information in the form of regularization is used to enforce transform plausibility taking the form of physics-based constraints or through some approximation thereof, e.g., Gaussian smoothing of the vector fields [a la Thirion's Demons (Thirion, 1998)]. In the context of the original Demons' framework, the so-called directly manipulated free-form deformation (DMFFD) (Tustison et al., 2009) can be viewed as a smoothing alternative in which explicit regularization is achieved through fast B-spline approximation. This characterization can be used to provide B-spline “flavored” diffeomorphic image registration solutions with several advantages. Implementation is open source and available through the Insight Toolkit and our Advanced Normalization Tools (ANTs) repository. A thorough comparative evaluation with the well-known SyN algorithm (Avants et al., 2008), implemented within the same framework, and its B-spline analog is performed using open labeled brain data and open source evaluation tools. PMID:24409140

Multiscale multimodal fusion of histological and MRI volumes for characterization of lung inflammation

NASA Astrophysics Data System (ADS)

Rusu, Mirabela; Wang, Haibo; Golden, Thea; Gow, Andrew; Madabhushi, Anant

2013-03-01

Mouse lung models facilitate the investigation of conditions such as chronic inflammation which are associated with common lung diseases. The multi-scale manifestation of lung inflammation prompted us to use multi-scale imaging - both in vivo, ex vivo MRI along with ex vivo histology, for its study in a new quantitative way. Some imaging modalities, such as MRI, are non-invasive and capture macroscopic features of the pathology, while others, e.g. ex vivo histology, depict detailed structures. Registering such multi-modal data to the same spatial coordinates will allow the construction of a comprehensive 3D model to enable the multi-scale study of diseases. Moreover, it may facilitate the identification and definition of quantitative of in vivo imaging signatures for diseases and pathologic processes. We introduce a quantitative, image analytic framework to integrate in vivo MR images of the entire mouse with ex vivo histology of the lung alone, using lung ex vivo MRI as conduit to facilitate their co-registration. In our framework, we first align the MR images by registering the in vivo and ex vivo MRI of the lung using an interactive rigid registration approach. Then we reconstruct the 3D volume of the ex vivo histological specimen by efficient group wise registration of the 2D slices. The resulting 3D histologic volume is subsequently registered to the MRI volumes by interactive rigid registration, directly to the ex vivo MRI, and implicitly to in vivo MRI. Qualitative evaluation of the registration framework was performed by comparing airway tree structures in ex vivo MRI and ex vivo histology where airways are visible and may be annotated. We present a use case for evaluation of our co-registration framework in the context of studying chronic inammation in a diseased mouse.

SU-E-J-264: Comparison of Two Commercially Available Software Platforms for Deformable Image Registration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuohy, R; Stathakis, S; Mavroidis, P

2014-06-01

Purpose: To evaluate and compare the deformable image registration algorithms available in the Velocity (Velocity Medical Solutions, Atlanta, GA) and RayStation (RaySearch Americas, Inc., Garden city NY). Methods: Ten consecutive patient cone beam CTs (CBCT) for each fraction were collected. The CBCTs along with the simulation CT were exported to the Velocity and the RayStation software. Each CBCT was registered using deformable image registration to the simulation CT and the resulting deformable vector matrix was generated. Each registration was visually inspected by a physicist and the prescribing physician. The volumes of the critical organs were calculated for each deformable CTmore » and used for comparison. Results: The resulting deformable registrations revealed differences between the two algorithms. These differences were realized when the organs at risk were contoured on each deformed CBCT. Differences in the order of 10% ±30% in volume were observed for bladder, 17 ±21% for rectum and 16±10% for sigmoid. The prostate and PTV volume differences were in the order of 3±5%. The volumetric differences observed had a respective impact on the DVHs of all organs at risk. Differences of 8–10% in the mean dose were observed for all organs above. Conclusion: Deformable registration is a powerful tool that aids in the definition of critical structures and is often used for the evaluation of daily dose delivered to the patient. It should be noted that extended QA should be performed before clinical implementation of the software and the users should be aware of advantages and limitations of the methods.« less

Multiview marker-free registration of forest terrestrial laser scanner data with embedded confidence metrics

DOE PAGES

Kelbe, David; Oak Ridge National Lab.; van Aardt, Jan; ...

2016-10-18

Terrestrial laser scanning has demonstrated increasing potential for rapid comprehensive measurement of forest structure, especially when multiple scans are spatially registered in order to reduce the limitations of occlusion. Although marker-based registration techniques (based on retro-reflective spherical targets) are commonly used in practice, a blind marker-free approach is preferable, insofar as it supports rapid operational data acquisition. To support these efforts, we extend the pairwise registration approach of our earlier work, and develop a graph-theoretical framework to perform blind marker-free global registration of multiple point cloud data sets. Pairwise pose estimates are weighted based on their estimated error, in ordermore » to overcome pose conflict while exploiting redundant information and improving precision. The proposed approach was tested for eight diverse New England forest sites, with 25 scans collected at each site. Quantitative assessment was provided via a novel embedded confidence metric, with a mean estimated root-mean-square error of 7.2 cm and 89% of scans connected to the reference node. Lastly, this paper assesses the validity of the embedded multiview registration confidence metric and evaluates the performance of the proposed registration algorithm.« less

Fast time-of-flight camera based surface registration for radiotherapy patient positioning.

PubMed

Placht, Simon; Stancanello, Joseph; Schaller, Christian; Balda, Michael; Angelopoulou, Elli

2012-01-01

This work introduces a rigid registration framework for patient positioning in radiotherapy, based on real-time surface acquisition by a time-of-flight (ToF) camera. Dynamic properties of the system are also investigated for future gating/tracking strategies. A novel preregistration algorithm, based on translation and rotation-invariant features representing surface structures, was developed. Using these features, corresponding three-dimensional points were computed in order to determine initial registration parameters. These parameters became a robust input to an accelerated version of the iterative closest point (ICP) algorithm for the fine-tuning of the registration result. Distance calibration and Kalman filtering were used to compensate for ToF-camera dependent noise. Additionally, the advantage of using the feature based preregistration over an "ICP only" strategy was evaluated, as well as the robustness of the rigid-transformation-based method to deformation. The proposed surface registration method was validated using phantom data. A mean target registration error (TRE) for translations and rotations of 1.62 ± 1.08 mm and 0.07° ± 0.05°, respectively, was achieved. There was a temporal delay of about 65 ms in the registration output, which can be seen as negligible considering the dynamics of biological systems. Feature based preregistration allowed for accurate and robust registrations even at very large initial displacements. Deformations affected the accuracy of the results, necessitating particular care in cases of deformed surfaces. The proposed solution is able to solve surface registration problems with an accuracy suitable for radiotherapy cases where external surfaces offer primary or complementary information to patient positioning. The system shows promising dynamic properties for its use in gating/tracking applications. The overall system is competitive with commonly-used surface registration technologies. Its main benefit is the usage of a cost-effective off-the-shelf technology for surface acquisition. Further strategies to improve the registration accuracy are under development.

Elastic registration of prostate MR images based on state estimation of dynamical systems

NASA Astrophysics Data System (ADS)

Marami, Bahram; Ghoul, Suha; Sirouspour, Shahin; Capson, David W.; Davidson, Sean R. H.; Trachtenberg, John; Fenster, Aaron

2014-03-01

Magnetic resonance imaging (MRI) is being increasingly used for image-guided biopsy and focal therapy of prostate cancer. A combined rigid and deformable registration technique is proposed to register pre-treatment diagnostic 3T magnetic resonance (MR) images, with the identified target tumor(s), to the intra-treatment 1.5T MR images. The pre-treatment 3T images are acquired with patients in strictly supine position using an endorectal coil, while 1.5T images are obtained intra-operatively just before insertion of the ablation needle with patients in the lithotomy position. An intensity-based registration routine rigidly aligns two images in which the transformation parameters is initialized using three pairs of manually selected approximate corresponding points. The rigid registration is followed by a deformable registration algorithm employing a generic dynamic linear elastic deformation model discretized by the finite element method (FEM). The model is used in a classical state estimation framework to estimate the deformation of the prostate based on a similarity metric between pre- and intra-treatment images. Registration results using 10 sets of prostate MR images showed that the proposed method can significantly improve registration accuracy in terms of target registration error (TRE) for all prostate substructures. The root mean square (RMS) TRE of 46 manually identified fiducial points was found to be 2.40+/-1.20 mm, 2.51+/-1.20 mm, and 2.28+/-1.22mm for the whole gland (WG), central gland (CG), and peripheral zone (PZ), respectively after deformable registration. These values are improved from 3.15+/-1.60 mm, 3.09+/-1.50 mm, and 3.20+/-1.73mm in the WG, CG and PZ, respectively resulted from rigid registration. Registration results are also evaluated based on the Dice similarity coefficient (DSC), mean absolute surface distances (MAD) and maximum absolute surface distances (MAXD) of the WG and CG in the prostate images.

Simultaneous 3D–2D image registration and C-arm calibration: Application to endovascular image-guided interventions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitrović, Uroš; Pernuš, Franjo; Likar, Boštjan

Purpose: Three-dimensional to two-dimensional (3D–2D) image registration is a key to fusion and simultaneous visualization of valuable information contained in 3D pre-interventional and 2D intra-interventional images with the final goal of image guidance of a procedure. In this paper, the authors focus on 3D–2D image registration within the context of intracranial endovascular image-guided interventions (EIGIs), where the 3D and 2D images are generally acquired with the same C-arm system. The accuracy and robustness of any 3D–2D registration method, to be used in a clinical setting, is influenced by (1) the method itself, (2) uncertainty of initial pose of the 3Dmore » image from which registration starts, (3) uncertainty of C-arm’s geometry and pose, and (4) the number of 2D intra-interventional images used for registration, which is generally one and at most two. The study of these influences requires rigorous and objective validation of any 3D–2D registration method against a highly accurate reference or “gold standard” registration, performed on clinical image datasets acquired in the context of the intervention. Methods: The registration process is split into two sequential, i.e., initial and final, registration stages. The initial stage is either machine-based or template matching. The latter aims to reduce possibly large in-plane translation errors by matching a projection of the 3D vessel model and 2D image. In the final registration stage, four state-of-the-art intrinsic image-based 3D–2D registration methods, which involve simultaneous refinement of rigid-body and C-arm parameters, are evaluated. For objective validation, the authors acquired an image database of 15 patients undergoing cerebral EIGI, for which accurate gold standard registrations were established by fiducial marker coregistration. Results: Based on target registration error, the obtained success rates of 3D to a single 2D image registration after initial machine-based and template matching and final registration involving C-arm calibration were 36%, 73%, and 93%, respectively, while registration accuracy of 0.59 mm was the best after final registration. By compensating in-plane translation errors by initial template matching, the success rates achieved after the final stage improved consistently for all methods, especially if C-arm calibration was performed simultaneously with the 3D–2D image registration. Conclusions: Because the tested methods perform simultaneous C-arm calibration and 3D–2D registration based solely on anatomical information, they have a high potential for automation and thus for an immediate integration into current interventional workflow. One of the authors’ main contributions is also comprehensive and representative validation performed under realistic conditions as encountered during cerebral EIGI.« less

Law tightened to protect adults who lack capacity.

PubMed

2009-05-21

VULNERABLE OLDER people will be better protected from abuse and poor care after new legislation came into force last month. Under the Mental Capacity Act Deprivation of Liberty Safeguards, a care home or hospital wanting to deprive a person who lacks capacity of their liberty, for their own safety or wellbeing, must now apply for permission. A rigorous, standardised assessment and authorisation process must then be completed.

Rituximab

PubMed Central

Storz, Ulrich

2014-01-01

Because drug development is not a static process, a drug’s market authorisation may change over time. In many cases, the number of indications for which a drug is approved increases. Because this facet of drug development also comes at significant costs, a corresponding patent filing strategy is required to protect these investments. The strategy as applied to rituximab, which is approved for a variety of indications, is discussed in this review. PMID:24866199

Caspofungin in the treatment of invasive fungal infections.

PubMed

Keady, Simon; Thacker, Meera

2006-02-01

Caspofungin is a member of a new class of antifungals called Echinocandins and is the first to have marketing authorisation in the United Kingdom. This article reviews the clinical efficacy, side effect profile, dosing and administration schedule of caspofungin. The article also discusses the warnings and precautions associated with the use of this drug. Caspofungin is an effective treatment option in the management of fungal infections.

Direct endoscopic video registration for sinus surgery

NASA Astrophysics Data System (ADS)

Mirota, Daniel; Taylor, Russell H.; Ishii, Masaru; Hager, Gregory D.

2009-02-01

Advances in computer vision have made possible robust 3D reconstruction of monocular endoscopic video. These reconstructions accurately represent the visible anatomy and, once registered to pre-operative CT data, enable a navigation system to track directly through video eliminating the need for an external tracking system. Video registration provides the means for a direct interface between an endoscope and a navigation system and allows a shorter chain of rigid-body transformations to be used to solve the patient/navigation-system registration. To solve this registration step we propose a new 3D-3D registration algorithm based on Trimmed Iterative Closest Point (TrICP)1 and the z-buffer algorithm.2 The algorithm takes as input a 3D point cloud of relative scale with the origin at the camera center, an isosurface from the CT, and an initial guess of the scale and location. Our algorithm utilizes only the visible polygons of the isosurface from the current camera location during each iteration to minimize the search area of the target region and robustly reject outliers of the reconstruction. We present example registrations in the sinus passage applicable to both sinus surgery and transnasal surgery. To evaluate our algorithm's performance we compare it to registration via Optotrak and present closest distance point to surface error. We show our algorithm has a mean closest distance error of .2268mm.

Study protocol for a transversal study to develop a screening model for excessive gambling behaviours on a representative sample of users of French authorised gambling websites.

PubMed

Perrot, Bastien; Hardouin, Jean-Benoit; Costes, Jean-Michel; Caillon, Julie; Grall-Bronnec, Marie; Challet-Bouju, Gaëlle

2017-05-17

Since the legalisation of online gambling in France in 2010, gambling operators must implement responsible gambling measures to prevent excessive gambling practices. However, actually there is no screening procedure for identifying problematic gamblers. Although several studies have already been performed using several data sets from online gambling operators, the authors deplored several methodological and clinical limits that prevent scientifically validating the existence of problematic gambling behaviour. The aim of this study is to develop a model for screening excessive gambling practices based on the gambling behaviours observed on French gambling websites, coupled with a clinical validation. The research is divided into three successive stages. All analyses will be performed for each major type of authorised online gambling in France. The first stage aims at defining a typology of users of French authorised gambling websites based on their gambling behaviour. This analysis will be based on data from the Authority for Regulating Online Gambling (ARJEL) and the Française Des Jeux (FDJ). For the second stage aiming at determining a score to predict whether a gambler is problematic or not, we will cross answers from the Canadian Problem Gambling Index with real gambling data. The objective of the third stage is to clinically validate the score previously developed. Results from the screening model will be compared (using sensitivity, specificity, area under the curve, and positive and negative predictive values) with the diagnosis obtained with a telephone clinical interview, including diagnostic criteria for gambling addiction. This study was approved by the local Research Ethics Committee (GNEDS) on 25 March 2015. Results will be presented in national and international conferences, submitted to peer-reviewed journals and will be part of a PhD thesis. A final report with the study results will be presented to the ARJEL, especially the final screening model. NCT02415296. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of limbal marking prior to laser ablation on the magnitude of cyclotorsional error.

PubMed

Chen, Xiangjun; Stojanovic, Aleksandar; Stojanovic, Filip; Eidet, Jon Roger; Raeder, Sten; Øritsland, Haakon; Utheim, Tor Paaske

2012-05-01

To evaluate the residual registration error after limbal-marking-based manual adjustment in cyclotorsional tracker-controlled laser refractive surgery. Two hundred eyes undergoing custom surface ablation with the iVIS Suite (iVIS Technologies) were divided into limbal marked (marked) and non-limbal marked (unmarked) groups. Iris registration information was acquired preoperatively from all eyes. Preoperatively, the horizontal axis was recorded in the marked group for use in manual cyclotorsional alignment prior to surgical iris registration. During iris registration, the preoperative iris information was compared to the eye-tracker captured image. The magnitudes of the registration error angle and cyclotorsional movement during the subsequent laser ablation were recorded and analyzed. Mean magnitude of registration error angle (absolute value) was 1.82°±1.31° (range: 0.00° to 5.50°) and 2.90°±2.40° (range: 0.00° to 13.50°) for the marked and unmarked groups, respectively (P<.001). Mean magnitude of cyclotorsional movement during the laser ablation (absolute value) was 1.15°±1.34° (range: 0.00° to 7.00°) and 0.68°±0.97° (range: 0.00° to 6.00°) for the marked and unmarked groups, respectively (P=.005). Forty-six percent and 60% of eyes had registration error >2°, whereas 22% and 20% of eyes had cyclotorsional movement during ablation >2° in the marked and unmarked groups, respectively. Limbal-marking-based manual alignment prior to laser ablation significantly reduced cyclotorsional registration error. However, residual registration misalignment and cyclotorsional movements remained during ablation. Copyright 2012, SLACK Incorporated.

Splint sterilization--a potential registration hazard in computer-assisted surgery.

PubMed

Figl, Michael; Weber, Christoph; Assadian, Ojan; Toma, Cyril D; Traxler, Hannes; Seemann, Rudolf; Guevara-Rojas, Godoberto; Pöschl, Wolfgang P; Ewers, Rolf; Schicho, Kurt

2012-04-01

Registration of preoperative targeting information for the intraoperative situation is a crucial step in computer-assisted surgical interventions. Point-to-point registration using acrylic splints is among the most frequently used procedures. There are, however, no generally accepted recommendations for sterilization of the splint. An appropriate method for the thermolabile splint would be hydrogen peroxide-based plasma sterilization. This study evaluated the potential deformation of the splint undergoing such sterilization. Deformation was quantified using image-processing methods applied to computed tomographic (CT) volumes before and after sterilization. An acrylic navigation splint was used as the study object. Eight metallic markers placed in the splint were used for registration. Six steel spheres in the mouthpiece were used as targets. Two CT volumes of the splint were acquired before and after 5 sterilization cycles using a hydrogen peroxide sterilizer. Point-to-point registration was applied, and fiducial and target registration errors were computed. Surfaces were extracted from CT scans and Hausdorff distances were derived. Effectiveness of sterilization was determined using Geobacillus stearothermophilus. Fiducial-based registration of CT scans before and after sterilization resulted in a mean fiducial registration error of 0.74 mm; the target registration error in the mouthpiece was 0.15 mm. The Hausdorff distance, describing the maximal deformation of the splint, was 2.51 mm. Ninety percent of point-surface distances were shorter than 0.61 mm, and 95% were shorter than 0.73 mm. No bacterial growth was found after the sterilization process. Hydrogen peroxide-based low-temperature plasma sterilization does not deform the splint, which is the base for correct computer-navigated surgery. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

21 CFR 207.7 - Establishment registration and product listing for human blood and blood products and for medical...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Establishment registration and product listing for human blood and blood products and for medical devices. 207.7 Section 207.7 Food and Drugs FOOD AND DRUG... Repository Team (HFD-143), Center for Drug Evaluation and Research, FDA, and list their drug products in...

21 CFR 207.7 - Establishment registration and product listing for human blood and blood products and for medical...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Establishment registration and product listing for human blood and blood products and for medical devices. 207.7 Section 207.7 Food and Drugs FOOD AND DRUG... Repository Team (HFD-143), Center for Drug Evaluation and Research, FDA, and list their drug products in...

Evaluation of nonrigid registration models for interfraction dose accumulation in radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janssens, Guillaume; Orban de Xivry, Jonathan; Fekkes, Stein

2009-09-15

Purpose: Interfraction dose accumulation is necessary to evaluate the dose distribution of an entire course of treatment by adding up multiple dose distributions of different treatment fractions. This accumulation of dose distributions is not straightforward as changes in the patient anatomy may occur during treatment. For this purpose, the accuracy of nonrigid registration methods is assessed for dose accumulation based on the calculated deformations fields. Methods: A phantom study using a deformable cubic silicon phantom with implanted markers and a cylindrical silicon phantom with MOSFET detectors has been performed. The phantoms were deformed and images were acquired using a cone-beammore » CT imager. Dose calculations were performed on these CT scans using the treatment planning system. Nonrigid CT-based registration was performed using two different methods, the Morphons and Demons. The resulting deformation field was applied on the dose distribution. For both phantoms, accuracy of the registered dose distribution was assessed. For the cylindrical phantom, also measured dose values in the deformed conditions were compared with the dose values of the registered dose distributions. Finally, interfraction dose accumulation for two treatment fractions of a patient with primary rectal cancer has been performed and evaluated using isodose lines and the dose volume histograms of the target volume and normal tissue. Results: A significant decrease in the difference in marker or MOSFET position was observed after nonrigid registration methods (p<0.001) for both phantoms and with both methods, as well as a significant decrease in the dose estimation error (p<0.01 for the cubic phantom and p<0.001 for the cylindrical) with both methods. Considering the whole data set at once, the difference between estimated and measured doses was also significantly decreased using registration (p<0.001 for both methods). The patient case showed a slightly underdosed planning target volume and an overdosed bladder volume due to anatomical deformations. Conclusions: Dose accumulation using nonrigid registration methods is possible using repeated CT imaging. This opens possibilities for interfraction dose accumulation and adaptive radiotherapy to incorporate possible differences in dose delivered to the target volume and organs at risk due to anatomical deformations.« less

Registration of 3D ultrasound computer tomography and MRI for evaluation of tissue correspondences

NASA Astrophysics Data System (ADS)

Hopp, T.; Dapp, R.; Zapf, M.; Kretzek, E.; Gemmeke, H.; Ruiter, N. V.

2015-03-01

3D Ultrasound Computer Tomography (USCT) is a new imaging method for breast cancer diagnosis. In the current state of development it is essential to correlate USCT with a known imaging modality like MRI to evaluate how different tissue types are depicted. Due to different imaging conditions, e.g. with the breast subject to buoyancy in USCT, a direct correlation is demanding. We present a 3D image registration method to reduce positioning differences and allow direct side-by-side comparison of USCT and MRI volumes. It is based on a two-step approach including a buoyancy simulation with a biomechanical model and free form deformations using cubic B-Splines for a surface refinement. Simulation parameters are optimized patient-specifically in a simulated annealing scheme. The method was evaluated with in-vivo datasets resulting in an average registration error below 5mm. Correlating tissue structures can thereby be located in the same or nearby slices in both modalities and three-dimensional non-linear deformations due to the buoyancy are reduced. Image fusion of MRI volumes and USCT sound speed volumes was performed for intuitive display. By applying the registration to data of our first in-vivo study with the KIT 3D USCT, we could correlate several tissue structures in MRI and USCT images and learn how connective tissue, carcinomas and breast implants observed in the MRI are depicted in the USCT imaging modes.

Promoting learning transfer in post registration education: a collaborative approach.

PubMed

Finn, Frances L; Fensom, Sue A; Chesser-Smyth, Patricia

2010-01-01

Pre-registration nurse education in Ireland became a four year undergraduate honors degree programme in 2002 (Government of Ireland, 2000. The Nursing Education Forum Report. Dublin, Dublin Stationary Office.). Consequently, the Irish Government invested significant resources in post registration nursing education in order to align certificate and diploma trained nurses with the qualification levels of new graduates. However, a general concern amongst academic and clinical staff in the South East of Ireland was that there was limited impact of this initiative on practice. These concerns were addressed through a collaborative approach to the development and implementation of a new part-time post registration degree that incorporated an enquiry and practice based learning philosophy. The principles of learning transfer (Ford, K., 1994. Defining transfer of learning the meaning is in the answers. Adult Learning 5 (4), p. 2214.) underpinned the curriculum development and implementation process with the goal of reducing the theory practice gap. This paper reports on all four stages of the curriculum development process: exploration, design, implementation and evaluation (Quinn, F.M., 2002. Principles and Practices of Nurse Education, fourth ed. Nelson Thornes, Cheltenham), and the subsequent impact of learning transfer on practice development. Eclectic approaches of quantitative and qualitative data collection techniques were utilised in the evaluation. The evaluation of this project to date supports our view that this practice based enquiry curriculum promotes the transfer of learning in the application of knowledge to practice, impacting both student and service development.

On the nature of data collection for soft-tissue image-to-physical organ registration: a noise characterization study

NASA Astrophysics Data System (ADS)

Collins, Jarrod A.; Heiselman, Jon S.; Weis, Jared A.; Clements, Logan W.; Simpson, Amber L.; Jarnagin, William R.; Miga, Michael I.

2017-03-01

In image-guided liver surgery (IGLS), sparse representations of the anterior organ surface may be collected intraoperatively to drive image-to-physical space registration. Soft tissue deformation represents a significant source of error for IGLS techniques. This work investigates the impact of surface data quality on current surface based IGLS registration methods. In this work, we characterize the robustness of our IGLS registration methods to noise in organ surface digitization. We study this within a novel human-to-phantom data framework that allows a rapid evaluation of clinically realistic data and noise patterns on a fully characterized hepatic deformation phantom. Additionally, we implement a surface data resampling strategy that is designed to decrease the impact of differences in surface acquisition. For this analysis, n=5 cases of clinical intraoperative data consisting of organ surface and salient feature digitizations from open liver resection were collected and analyzed within our human-to-phantom validation framework. As expected, results indicate that increasing levels of noise in surface acquisition cause registration fidelity to deteriorate. With respect to rigid registration using the raw and resampled data at clinically realistic levels of noise (i.e. a magnitude of 1.5 mm), resampling improved TRE by 21%. In terms of nonrigid registration, registrations using resampled data outperformed the raw data result by 14% at clinically realistic levels and were less susceptible to noise across the range of noise investigated. These results demonstrate the types of analyses our novel human-to-phantom validation framework can provide and indicate the considerable benefits of resampling strategies.

Improving transparency and reproducibility through registration: The status of intervention trials published in clinical psychology journals.

PubMed

Cybulski, Lukasz; Mayo-Wilson, Evan; Grant, Sean

2016-09-01

Prospective registration increases the validity of randomized controlled trials (RCTs). In the United States, registration is a legal requirement for drugs and devices regulated by the Food and Drug Administration (FDA), and many biomedical journals refuse to publish trials that are not registered. Trials in clinical psychology have not been subject to these requirements; it is unknown to what extent they are registered. We searched the 25 highest-impact clinical psychology journals that published at least 1 RCT of a health-related psychological intervention in 2013. For included trials, we evaluated their registration status (prospective, retrospective, not registered) and the completeness of their outcome definitions. We identified 163 articles that reported 165 RCTs; 73 (44%) RCTs were registered, of which only 25 (15%) were registered prospectively. Of registered RCTs, only 42 (58%) indicated their registration status in the publication. Only 2 (1% of all trials) were registered prospectively and defined their primary outcomes completely. For the primary outcome(s), 72 (99%) of all registrations defined the domain, 67 (92%) the time frame, and 48 (66%) the specific measurements. Only 19 (26%) and 5 (7%) defined the specific metric and method of aggregation, respectively, for all primary outcomes. Very few reports of RCTs published in clinical psychology journals were registered prospectively and completely. Clinical psychology journals could improve transparency and reproducibility, as well as reduce bias, by requiring complete prospective trial registration for publication and by including trial registration numbers in all reports of RCTs. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Influence of image registration on ADC images computed from free-breathing diffusion MRIs of the abdomen

NASA Astrophysics Data System (ADS)

Guyader, Jean-Marie; Bernardin, Livia; Douglas, Naomi H. M.; Poot, Dirk H. J.; Niessen, Wiro J.; Klein, Stefan

2014-03-01

The apparent diffusion coefficient (ADC) is an imaging biomarker providing quantitative information on the diffusion of water in biological tissues. This measurement could be of relevance in oncology drug development, but it suffers from a lack of reliability. ADC images are computed by applying a voxelwise exponential fitting to multiple diffusion-weighted MR images (DW-MRIs) acquired with different diffusion gradients. In the abdomen, respiratory motion induces misalignments in the datasets, creating visible artefacts and inducing errors in the ADC maps. We propose a multistep post-acquisition motion compensation pipeline based on 3D non-rigid registrations. It corrects for motion within each image and brings all DW-MRIs to a common image space. The method is evaluated on 10 datasets of free-breathing abdominal DW-MRIs acquired from healthy volunteers. Regions of interest (ROIs) are segmented in the right part of the abdomen and measurements are compared in the three following cases: no image processing, Gaussian blurring of the raw DW-MRIs and registration. Results show that both blurring and registration improve the visual quality of ADC images, but compared to blurring, registration yields visually sharper images. Measurement uncertainty is reduced both by registration and blurring. For homogeneous ROIs, blurring and registration result in similar median ADCs, which are lower than without processing. In a ROI at the interface between liver and kidney, registration and blurring yield different median ADCs, suggesting that uncorrected motion introduces a bias. Our work indicates that averaging procedures on the scanner should be avoided, as they remove the opportunity to perform motion correction.

Deformable image registration with content mismatch: a demons variant to account for added material and surgical devices in the target image

NASA Astrophysics Data System (ADS)

Nithiananthan, S.; Uneri, A.; Schafer, S.; Mirota, D.; Otake, Y.; Stayman, J. W.; Zbijewski, W.; Khanna, A. J.; Reh, D. D.; Gallia, G. L.; Siewerdsen, J. H.

2013-03-01

Fast, accurate, deformable image registration is an important aspect of image-guided interventions. Among the factors that can confound registration is the presence of additional material in the intraoperative image - e.g., contrast bolus or a surgical implant - that was not present in the prior image. Existing deformable registration methods generally fail to account for tissue excised between image acquisitions and typically simply "move" voxels within the images with no ability to account for tissue that is removed or introduced between scans. We present a variant of the Demons algorithm to accommodate such content mismatch. The approach combines segmentation of mismatched content with deformable registration featuring an extra pseudo-spatial dimension representing a reservoir from which material can be drawn into the registered image. Previous work tested the registration method in the presence of tissue excision ("missing tissue"). The current paper tests the method in the presence of additional material in the target image and presents a general method by which either missing or additional material can be accommodated. The method was tested in phantom studies, simulations, and cadaver models in the context of intraoperative cone-beam CT with three examples of content mismatch: a variable-diameter bolus (contrast injection); surgical device (rod), and additional material (bone cement). Registration accuracy was assessed in terms of difference images and normalized cross correlation (NCC). We identify the difficulties that traditional registration algorithms encounter when faced with content mismatch and evaluate the ability of the proposed method to overcome these challenges.

On the appropriate feature for general SAR image registration

NASA Astrophysics Data System (ADS)

Li, Dong; Zhang, Yunhua

2012-09-01

An investigation to the appropriate feature for SAR image registration is conducted. The commonly-used features such as tie points, Harris corner, the scale invariant feature transform (SIFT), and the speeded up robust feature (SURF) are comprehensively evaluated in terms of several criteria such as the geometrical invariance of feature, the extraction speed, the localization accuracy, the geometrical invariance of descriptor, the matching speed, the robustness to decorrelation, and the flexibility to image speckling. It is shown that SURF outperforms others. It is particularly indicated that SURF has good flexibility to image speckling because the Fast-Hessian detector of SURF has a potential relation with the refined Lee filter. It is recommended to perform SURF on the oversampled image with unaltered sampling step so as to improve the subpixel registration accuracy and speckle immunity. Thus SURF is more appropriate and competent for general SAR image registration.

Joint detection of anatomical points on surface meshes and color images for visual registration of 3D dental models

NASA Astrophysics Data System (ADS)

Destrez, Raphaël.; Albouy-Kissi, Benjamin; Treuillet, Sylvie; Lucas, Yves

2015-04-01

Computer aided planning for orthodontic treatment requires knowing occlusion of separately scanned dental casts. A visual guided registration is conducted starting by extracting corresponding features in both photographs and 3D scans. To achieve this, dental neck and occlusion surface are firstly extracted by image segmentation and 3D curvature analysis. Then, an iterative registration process is conducted during which feature positions are refined, guided by previously found anatomic edges. The occlusal edge image detection is improved by an original algorithm which follows Canny's poorly detected edges using a priori knowledge of tooth shapes. Finally, the influence of feature extraction and position optimization is evaluated in terms of the quality of the induced registration. Best combination of feature detection and optimization leads to a positioning average error of 1.10 mm and 2.03°.

aMAP is a validated pipeline for registration and segmentation of high-resolution mouse brain data

PubMed Central

Niedworok, Christian J.; Brown, Alexander P. Y.; Jorge Cardoso, M.; Osten, Pavel; Ourselin, Sebastien; Modat, Marc; Margrie, Troy W.

2016-01-01

The validation of automated image registration and segmentation is crucial for accurate and reliable mapping of brain connectivity and function in three-dimensional (3D) data sets. While validation standards are necessarily high and routinely met in the clinical arena, they have to date been lacking for high-resolution microscopy data sets obtained from the rodent brain. Here we present a tool for optimized automated mouse atlas propagation (aMAP) based on clinical registration software (NiftyReg) for anatomical segmentation of high-resolution 3D fluorescence images of the adult mouse brain. We empirically evaluate aMAP as a method for registration and subsequent segmentation by validating it against the performance of expert human raters. This study therefore establishes a benchmark standard for mapping the molecular function and cellular connectivity of the rodent brain. PMID:27384127

Multi-Objective Memetic Search for Robust Motion and Distortion Correction in Diffusion MRI.

PubMed

Hering, Jan; Wolf, Ivo; Maier-Hein, Klaus H

2016-10-01

Effective image-based artifact correction is an essential step in the analysis of diffusion MR images. Many current approaches are based on retrospective registration, which becomes challenging in the realm of high b -values and low signal-to-noise ratio, rendering the corresponding correction schemes more and more ineffective. We propose a novel registration scheme based on memetic search optimization that allows for simultaneous exploitation of different signal intensity relationships between the images, leading to more robust registration results. We demonstrate the increased robustness and efficacy of our method on simulated as well as in vivo datasets. In contrast to the state-of-art methods, the median target registration error (TRE) stayed below the voxel size even for high b -values (3000 s ·mm -2 and higher) and low SNR conditions. We also demonstrate the increased precision in diffusion-derived quantities by evaluating Neurite Orientation Dispersion and Density Imaging (NODDI) derived measures on a in vivo dataset with severe motion artifacts. These promising results will potentially inspire further studies on metaheuristic optimization in diffusion MRI artifact correction and image registration in general.

[Validation of an improved Demons deformable registration algorithm and its application in re-contouring in 4D-CT].

PubMed

Zhen, Xin; Zhou, Ling-hong; Lu, Wen-ting; Zhang, Shu-xu; Zhou, Lu

2010-12-01

To validate the efficiency and accuracy of an improved Demons deformable registration algorithm and evaluate its application in contour recontouring in 4D-CT. To increase the additional Demons force and reallocate the bilateral forces to accelerate convergent speed, we propose a novel energy function as the similarity measure, and utilize a BFGS method for optimization to avoid specifying the numbers of iteration. Mathematical transformed deformable CT images and home-made deformable phantom were used to validate the accuracy of the improved algorithm, and its effectiveness for contour recontouring was tested. The improved algorithm showed a relatively high registration accuracy and speed when compared with the classic Demons algorithm and optical flow based method. Visual inspection of the positions and shapes of the deformed contours agreed well with the physician-drawn contours. Deformable registration is a key technique in 4D-CT, and this improved Demons algorithm for contour recontouring can significantly reduce the workload of the physicians. The registration accuracy of this method proves to be sufficient for clinical needs.

Phantom study and accuracy evaluation of an image-to-world registration approach used with electro-magnetic tracking system for neurosurgery

NASA Astrophysics Data System (ADS)

Li, Senhu; Sarment, David

2015-12-01

Minimally invasive neurosurgery needs intraoperative imaging updates and high efficient image guide system to facilitate the procedure. An automatic image guided system utilized with a compact and mobile intraoperative CT imager was introduced in this work. A tracking frame that can be easily attached onto the commercially available skull clamp was designed. With known geometry of fiducial and tracking sensor arranged on this rigid frame that was fabricated through high precision 3D printing, not only was an accurate, fully automatic registration method developed in a simple and less-costly approach, but also it helped in estimating the errors from fiducial localization in image space through image processing, and in patient space through the calibration of tracking frame. Our phantom study shows the fiducial registration error as 0.348+/-0.028mm, comparing the manual registration error as 1.976+/-0.778mm. The system in this study provided a robust and accurate image-to-patient registration without interruption of routine surgical workflow and any user interactions involved through the neurosurgery.

Nonrigid Image Registration in Digital Subtraction Angiography Using Multilevel B-Spline

PubMed Central

2013-01-01

We address the problem of motion artifact reduction in digital subtraction angiography (DSA) using image registration techniques. Most of registration algorithms proposed for application in DSA, have been designed for peripheral and cerebral angiography images in which we mainly deal with global rigid motions. These algorithms did not yield good results when applied to coronary angiography images because of complex nonrigid motions that exist in this type of angiography images. Multiresolution and iterative algorithms are proposed to cope with this problem, but these algorithms are associated with high computational cost which makes them not acceptable for real-time clinical applications. In this paper we propose a nonrigid image registration algorithm for coronary angiography images that is significantly faster than multiresolution and iterative blocking methods and outperforms competing algorithms evaluated on the same data sets. This algorithm is based on a sparse set of matched feature point pairs and the elastic registration is performed by means of multilevel B-spline image warping. Experimental results with several clinical data sets demonstrate the effectiveness of our approach. PMID:23971026

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelbe, David; Oak Ridge National Lab.; van Aardt, Jan

Terrestrial laser scanning has demonstrated increasing potential for rapid comprehensive measurement of forest structure, especially when multiple scans are spatially registered in order to reduce the limitations of occlusion. Although marker-based registration techniques (based on retro-reflective spherical targets) are commonly used in practice, a blind marker-free approach is preferable, insofar as it supports rapid operational data acquisition. To support these efforts, we extend the pairwise registration approach of our earlier work, and develop a graph-theoretical framework to perform blind marker-free global registration of multiple point cloud data sets. Pairwise pose estimates are weighted based on their estimated error, in ordermore » to overcome pose conflict while exploiting redundant information and improving precision. The proposed approach was tested for eight diverse New England forest sites, with 25 scans collected at each site. Quantitative assessment was provided via a novel embedded confidence metric, with a mean estimated root-mean-square error of 7.2 cm and 89% of scans connected to the reference node. Lastly, this paper assesses the validity of the embedded multiview registration confidence metric and evaluates the performance of the proposed registration algorithm.« less

Deformable Image Registration for Cone-Beam CT Guided Transoral Robotic Base of Tongue Surgery

PubMed Central

Reaungamornrat, S.; Liu, W. P.; Wang, A. S.; Otake, Y.; Nithiananthan, S.; Uneri, A.; Schafer, S.; Tryggestad, E.; Richmon, J.; Sorger, J. M.; Siewerdsen, J. H.; Taylor, R. H.

2013-01-01

Transoral robotic surgery (TORS) offers a minimally invasive approach to resection of base of tongue tumors. However, precise localization of the surgical target and adjacent critical structures can be challenged by the highly deformed intraoperative setup. We propose a deformable registration method using intraoperative cone-beam CT (CBCT) to accurately align preoperative CT or MR images with the intraoperative scene. The registration method combines a Gaussian mixture (GM) model followed by a variation of the Demons algorithm. First, following segmentation of the volume of interest (i.e., volume of the tongue extending to the hyoid), a GM model is applied to surface point clouds for rigid initialization (GM rigid) followed by nonrigid deformation (GM nonrigid). Second, the registration is refined using the Demons algorithm applied to distance map transforms of the (GM-registered) preoperative image and intraoperative CBCT. Performance was evaluated in repeat cadaver studies (25 image pairs) in terms of target registration error (TRE), entropy correlation coefficient (ECC), and normalized pointwise mutual information (NPMI). Retraction of the tongue in the TORS operative setup induced gross deformation >30 mm. The mean TRE following the GM rigid, GM nonrigid, and Demons steps was 4.6, 2.1, and 1.7 mm, respectively. The respective ECC was 0.57, 0.70, and 0.73 and NPMI was 0.46, 0.57, and 0.60. Registration accuracy was best across the superior aspect of the tongue and in proximity to the hyoid (by virtue of GM registration of surface points on these structures). The Demons step refined registration primarily in deeper portions of the tongue further from the surface and hyoid bone. Since the method does not use image intensities directly, it is suitable to multi-modality registration of preoperative CT or MR with intraoperative CBCT. Extending the 3D image registration to the fusion of image and planning data in stereo-endoscopic video is anticipated to support safer, high-precision base of tongue robotic surgery. PMID:23807549

SU-F-J-57: Effectiveness of Daily CT-Based Three-Dimensional Image Guided and Adaptive Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moriya, S; National Cancer Center, Kashiwa, Chiba; Tachibana, H

Purpose: Daily CT-based three-dimensional image-guided and adaptive (CTIGRT-ART) proton therapy system was designed and developed. We also evaluated the effectiveness of the CTIGRT-ART. Methods: Retrospective analysis was performed in three lung cancer patients: Proton treatment planning was performed using CT image datasets acquired by Toshiba Aquilion ONE. Planning target volume and surrounding organs were contoured by a well-trained radiation oncologist. Dose distribution was optimized using 180-deg. and 270-deg. two fields in passive scattering proton therapy. Well commissioned Simplified Monte Carlo algorithm was used as dose calculation engine. Daily consecutive CT image datasets was acquired by an in-room CT (Toshiba Aquilionmore » LB). In our in-house program, two image registrations for bone and tumor were performed to shift the isocenter using treatment CT image dataset. Subsequently, dose recalculation was performed after the shift of the isocenter. When the dose distribution after the tumor registration exhibits change of dosimetric parameter of CTV D90% compared to the initial plan, an additional process of was performed that the range shifter thickness was optimized. Dose distribution with CTV D90% for the bone registration, the tumor registration only and adaptive plan with the tumor registration was compared to the initial plan. Results: In the bone registration, tumor dose coverage was decreased by 16% on average (Maximum: 56%). The tumor registration shows better coverage than the bone registration, however the coverage was also decreased by 9% (Maximum: 22%) The adaptive plan shows similar dose coverage of the tumor (Average: 2%, Maximum: 7%). Conclusion: There is a high possibility that only image registration for bone and tumor may reduce tumor coverage. Thus, our proposed methodology of image guidance and adaptive planning using the range adaptation after tumor registration would be effective for proton therapy. This research is partially supported by Japan Agency for Medical Research and Development (AMED).« less

Deformable image registration for cone-beam CT guided transoral robotic base-of-tongue surgery

NASA Astrophysics Data System (ADS)

Reaungamornrat, S.; Liu, W. P.; Wang, A. S.; Otake, Y.; Nithiananthan, S.; Uneri, A.; Schafer, S.; Tryggestad, E.; Richmon, J.; Sorger, J. M.; Siewerdsen, J. H.; Taylor, R. H.

2013-07-01

Transoral robotic surgery (TORS) offers a minimally invasive approach to resection of base-of-tongue tumors. However, precise localization of the surgical target and adjacent critical structures can be challenged by the highly deformed intraoperative setup. We propose a deformable registration method using intraoperative cone-beam computed tomography (CBCT) to accurately align preoperative CT or MR images with the intraoperative scene. The registration method combines a Gaussian mixture (GM) model followed by a variation of the Demons algorithm. First, following segmentation of the volume of interest (i.e. volume of the tongue extending to the hyoid), a GM model is applied to surface point clouds for rigid initialization (GM rigid) followed by nonrigid deformation (GM nonrigid). Second, the registration is refined using the Demons algorithm applied to distance map transforms of the (GM-registered) preoperative image and intraoperative CBCT. Performance was evaluated in repeat cadaver studies (25 image pairs) in terms of target registration error (TRE), entropy correlation coefficient (ECC) and normalized pointwise mutual information (NPMI). Retraction of the tongue in the TORS operative setup induced gross deformation >30 mm. The mean TRE following the GM rigid, GM nonrigid and Demons steps was 4.6, 2.1 and 1.7 mm, respectively. The respective ECC was 0.57, 0.70 and 0.73, and NPMI was 0.46, 0.57 and 0.60. Registration accuracy was best across the superior aspect of the tongue and in proximity to the hyoid (by virtue of GM registration of surface points on these structures). The Demons step refined registration primarily in deeper portions of the tongue further from the surface and hyoid bone. Since the method does not use image intensities directly, it is suitable to multi-modality registration of preoperative CT or MR with intraoperative CBCT. Extending the 3D image registration to the fusion of image and planning data in stereo-endoscopic video is anticipated to support safer, high-precision base-of-tongue robotic surgery.

Evaluation of the 2012 18th Maternal and Child Health (MCH) Epidemiology and 22nd CityMatCH MCH Urban Leadership Conference: Six Month Impact on Science, Program, and Policy

PubMed Central

Goodman, David A.; Howlette, Travis; Kroelinger, Charlan D.; Law, Mark; Phillips, Donna; Jones, Jessica; Brantley, Mary D.; Fitzgerald, Maureen

2015-01-01

The 18th Maternal and Child Health (MCH) Epidemiology and 22nd CityMatCH MCH Urban Leadership Conference took place in December 2012, covering MCH science, program, and policy issues. Assessing the impact of the Conference on attendees’ work 6 months post-Conference provides information critical to understanding the impact and the use of new partnerships, knowledge, and skills gained during the Conference. Evaluation assessments, which included collection of quantitative and qualitative data, were administered at two time points: at Conference registration and 6 months post-Conference. The evaluation files were merged using computer IP address, linking responses from each assessment. Percentages of attendees reporting Conference impacts were calculated from quantitative data, and common themes and supporting examples were identified from qualitative data. Online registration was completed by 650 individuals. Of registrants, 30 % responded to the 6 month post-Conference assessment. Between registration and 6 month post-Conference evaluation, the distribution of respondents did not significantly differ by organizational affiliation. In the 6 months following the Conference, 65 % of respondents reported pursuing a networking interaction; 96 % shared knowledge from the Conference with coworkers and others in their agency; and 74 % utilized knowledge from the Conference to translate data into public health action. The Conference produced far-reaching impacts among Conference attendees. The Conference served as a platform for networking, knowledge sharing, and attaining skills that advance the work of attendees, with the potential of impacting organizational and workforce capacity. Increasing capacity could improve MCH programs, policies, and services, ultimately impacting the health of women, infants, and children. PMID:25107597

Evaluation of the 2012 18th Maternal and Child Health (MCH) Epidemiology and 22nd CityMatCH MCH Urban Leadership Conference: six month impact on science, program, and policy.

PubMed

Arellano, Danielle E; Goodman, David A; Howlette, Travis; Kroelinger, Charlan D; Law, Mark; Phillips, Donna; Jones, Jessica; Brantley, Mary D; Fitzgerald, Maureen

2014-09-01

The 18th Maternal and Child Health (MCH) Epidemiology and 22nd CityMatCH MCH Urban Leadership Conference took place in December 2012, covering MCH science, program, and policy issues. Assessing the impact of the Conference on attendees' work 6 months post-Conference provides information critical to understanding the impact and the use of new partnerships, knowledge, and skills gained during the Conference. Evaluation assessments, which included collection of quantitative and qualitative data, were administered at two time points: at Conference registration and 6 months post-Conference. The evaluation files were merged using computer IP address, linking responses from each assessment. Percentages of attendees reporting Conference impacts were calculated from quantitative data, and common themes and supporting examples were identified from qualitative data. Online registration was completed by 650 individuals. Of registrants, 30 % responded to the 6 month post-Conference assessment. Between registration and 6 month post-Conference evaluation, the distribution of respondents did not significantly differ by organizational affiliation. In the 6 months following the Conference, 65 % of respondents reported pursuing a networking interaction; 96 % shared knowledge from the Conference with co-workers and others in their agency; and 74 % utilized knowledge from the Conference to translate data into public health action. The Conference produced far-reaching impacts among Conference attendees. The Conference served as a platform for networking, knowledge sharing, and attaining skills that advance the work of attendees, with the potential of impacting organizational and workforce capacity. Increasing capacity could improve MCH programs, policies, and services, ultimately impacting the health of women, infants, and children.

Image-guided radiotherapy quality control: Statistical process control using image similarity metrics.

PubMed

Shiraishi, Satomi; Grams, Michael P; Fong de Los Santos, Luis E

2018-05-01

The purpose of this study was to demonstrate an objective quality control framework for the image review process. A total of 927 cone-beam computed tomography (CBCT) registrations were retrospectively analyzed for 33 bilateral head and neck cancer patients who received definitive radiotherapy. Two registration tracking volumes (RTVs) - cervical spine (C-spine) and mandible - were defined, within which a similarity metric was calculated and used as a registration quality tracking metric over the course of treatment. First, sensitivity to large misregistrations was analyzed for normalized cross-correlation (NCC) and mutual information (MI) in the context of statistical analysis. The distribution of metrics was obtained for displacements that varied according to a normal distribution with standard deviation of σ = 2 mm, and the detectability of displacements greater than 5 mm was investigated. Then, similarity metric control charts were created using a statistical process control (SPC) framework to objectively monitor the image registration and review process. Patient-specific control charts were created using NCC values from the first five fractions to set a patient-specific process capability limit. Population control charts were created using the average of the first five NCC values for all patients in the study. For each patient, the similarity metrics were calculated as a function of unidirectional translation, referred to as the effective displacement. Patient-specific action limits corresponding to 5 mm effective displacements were defined. Furthermore, effective displacements of the ten registrations with the lowest similarity metrics were compared with a three dimensional (3DoF) couch displacement required to align the anatomical landmarks. Normalized cross-correlation identified suboptimal registrations more effectively than MI within the framework of SPC. Deviations greater than 5 mm were detected at 2.8σ and 2.1σ from the mean for NCC and MI, respectively. Patient-specific control charts using NCC evaluated daily variation and identified statistically significant deviations. This study also showed that subjective evaluations of the images were not always consistent. Population control charts identified a patient whose tracking metrics were significantly lower than those of other patients. The patient-specific action limits identified registrations that warranted immediate evaluation by an expert. When effective displacements in the anterior-posterior direction were compared to 3DoF couch displacements, the agreement was ±1 mm for seven of 10 patients for both C-spine and mandible RTVs. Qualitative review alone of IGRT images can result in inconsistent feedback to the IGRT process. Registration tracking using NCC objectively identifies statistically significant deviations. When used in conjunction with the current image review process, this tool can assist in improving the safety and consistency of the IGRT process. © 2018 American Association of Physicists in Medicine.

eHUGS: Enhanced Hierarchical Unbiased Graph Shrinkage for Efficient Groupwise Registration

PubMed Central

Wu, Guorong; Peng, Xuewei; Ying, Shihui; Wang, Qian; Yap, Pew-Thian; Shen, Dan; Shen, Dinggang

2016-01-01

Effective and efficient spatial normalization of a large population of brain images is critical for many clinical and research studies, but it is technically very challenging. A commonly used approach is to choose a certain image as the template and then align all other images in the population to this template by applying pairwise registration. To avoid the potential bias induced by the inappropriate template selection, groupwise registration methods have been proposed to simultaneously register all images to a latent common space. However, current groupwise registration methods do not make full use of image distribution information for more accurate registration. In this paper, we present a novel groupwise registration method that harnesses the image distribution information by capturing the image distribution manifold using a hierarchical graph with its nodes representing the individual images. More specifically, a low-level graph describes the image distribution in each subgroup, and a high-level graph encodes the relationship between representative images of subgroups. Given the graph representation, we can register all images to the common space by dynamically shrinking the graph on the image manifold. The topology of the entire image distribution is always maintained during graph shrinkage. Evaluations on two datasets, one for 80 elderly individuals and one for 285 infants, indicate that our method can yield promising results. PMID:26800361

Deformation field correction for spatial normalization of PET images

PubMed Central

Bilgel, Murat; Carass, Aaron; Resnick, Susan M.; Wong, Dean F.; Prince, Jerry L.

2015-01-01

Spatial normalization of positron emission tomography (PET) images is essential for population studies, yet the current state of the art in PET-to-PET registration is limited to the application of conventional deformable registration methods that were developed for structural images. A method is presented for the spatial normalization of PET images that improves their anatomical alignment over the state of the art. The approach works by correcting the deformable registration result using a model that is learned from training data having both PET and structural images. In particular, viewing the structural registration of training data as ground truth, correction factors are learned by using a generalized ridge regression at each voxel given the PET intensities and voxel locations in a population-based PET template. The trained model can then be used to obtain more accurate registration of PET images to the PET template without the use of a structural image. A cross validation evaluation on 79 subjects shows that the proposed method yields more accurate alignment of the PET images compared to deformable PET-to-PET registration as revealed by 1) a visual examination of the deformed images, 2) a smaller error in the deformation fields, and 3) a greater overlap of the deformed anatomical labels with ground truth segmentations. PMID:26142272

3D/2D image registration using weighted histogram of gradient directions

NASA Astrophysics Data System (ADS)

Ghafurian, Soheil; Hacihaliloglu, Ilker; Metaxas, Dimitris N.; Tan, Virak; Li, Kang

2015-03-01

Three dimensional (3D) to two dimensional (2D) image registration is crucial in many medical applications such as image-guided evaluation of musculoskeletal disorders. One of the key problems is to estimate the 3D CT- reconstructed bone model positions (translation and rotation) which maximize the similarity between the digitally reconstructed radiographs (DRRs) and the 2D fluoroscopic images using a registration method. This problem is computational-intensive due to a large search space and the complicated DRR generation process. Also, finding a similarity measure which converges to the global optimum instead of local optima adds to the challenge. To circumvent these issues, most existing registration methods need a manual initialization, which requires user interaction and is prone to human error. In this paper, we introduce a novel feature-based registration method using the weighted histogram of gradient directions of images. This method simplifies the computation by searching the parameter space (rotation and translation) sequentially rather than simultaneously. In our numeric simulation experiments, the proposed registration algorithm was able to achieve sub-millimeter and sub-degree accuracies. Moreover, our method is robust to the initial guess. It can tolerate up to +/-90°rotation offset from the global optimal solution, which minimizes the need for human interaction to initialize the algorithm.

Supervoxels for graph cuts-based deformable image registration using guided image filtering

NASA Astrophysics Data System (ADS)

Szmul, Adam; Papież, Bartłomiej W.; Hallack, Andre; Grau, Vicente; Schnabel, Julia A.

2017-11-01

We propose combining a supervoxel-based image representation with the concept of graph cuts as an efficient optimization technique for three-dimensional (3-D) deformable image registration. Due to the pixels/voxels-wise graph construction, the use of graph cuts in this context has been mainly limited to two-dimensional (2-D) applications. However, our work overcomes some of the previous limitations by posing the problem on a graph created by adjacent supervoxels, where the number of nodes in the graph is reduced from the number of voxels to the number of supervoxels. We demonstrate how a supervoxel image representation combined with graph cuts-based optimization can be applied to 3-D data. We further show that the application of a relaxed graph representation of the image, followed by guided image filtering over the estimated deformation field, allows us to model "sliding motion." Applying this method to lung image registration results in highly accurate image registration and anatomically plausible estimations of the deformations. Evaluation of our method on a publicly available computed tomography lung image dataset leads to the observation that our approach compares very favorably with state of the art methods in continuous and discrete image registration, achieving target registration error of 1.16 mm on average per landmark.

Supervoxels for Graph Cuts-Based Deformable Image Registration Using Guided Image Filtering.

PubMed

Szmul, Adam; Papież, Bartłomiej W; Hallack, Andre; Grau, Vicente; Schnabel, Julia A

2017-10-04

In this work we propose to combine a supervoxel-based image representation with the concept of graph cuts as an efficient optimization technique for 3D deformable image registration. Due to the pixels/voxels-wise graph construction, the use of graph cuts in this context has been mainly limited to 2D applications. However, our work overcomes some of the previous limitations by posing the problem on a graph created by adjacent supervoxels, where the number of nodes in the graph is reduced from the number of voxels to the number of supervoxels. We demonstrate how a supervoxel image representation, combined with graph cuts-based optimization can be applied to 3D data. We further show that the application of a relaxed graph representation of the image, followed by guided image filtering over the estimated deformation field, allows us to model 'sliding motion'. Applying this method to lung image registration, results in highly accurate image registration and anatomically plausible estimations of the deformations. Evaluation of our method on a publicly available Computed Tomography lung image dataset (www.dir-lab.com) leads to the observation that our new approach compares very favorably with state-of-the-art in continuous and discrete image registration methods achieving Target Registration Error of 1.16mm on average per landmark.

Joint image registration and fusion method with a gradient strength regularization

NASA Astrophysics Data System (ADS)

Lidong, Huang; Wei, Zhao; Jun, Wang

2015-05-01

Image registration is an essential process for image fusion, and fusion performance can be used to evaluate registration accuracy. We propose a maximum likelihood (ML) approach to joint image registration and fusion instead of treating them as two independent processes in the conventional way. To improve the visual quality of a fused image, a gradient strength (GS) regularization is introduced in the cost function of ML. The GS of the fused image is controllable by setting the target GS value in the regularization term. This is useful because a larger target GS brings a clearer fused image and a smaller target GS makes the fused image smoother and thus restrains noise. Hence, the subjective quality of the fused image can be improved whether the source images are polluted by noise or not. We can obtain the fused image and registration parameters successively by minimizing the cost function using an iterative optimization method. Experimental results show that our method is effective with transformation, rotation, and scale parameters in the range of [-2.0, 2.0] pixel, [-1.1 deg, 1.1 deg], and [0.95, 1.05], respectively, and variances of noise smaller than 300. It also demonstrated that our method yields a more visual pleasing fused image and higher registration accuracy compared with a state-of-the-art algorithm.

Supervoxels for Graph Cuts-Based Deformable Image Registration Using Guided Image Filtering

PubMed Central

Szmul, Adam; Papież, Bartłomiej W.; Hallack, Andre; Grau, Vicente; Schnabel, Julia A.

2017-01-01

In this work we propose to combine a supervoxel-based image representation with the concept of graph cuts as an efficient optimization technique for 3D deformable image registration. Due to the pixels/voxels-wise graph construction, the use of graph cuts in this context has been mainly limited to 2D applications. However, our work overcomes some of the previous limitations by posing the problem on a graph created by adjacent supervoxels, where the number of nodes in the graph is reduced from the number of voxels to the number of supervoxels. We demonstrate how a supervoxel image representation, combined with graph cuts-based optimization can be applied to 3D data. We further show that the application of a relaxed graph representation of the image, followed by guided image filtering over the estimated deformation field, allows us to model ‘sliding motion’. Applying this method to lung image registration, results in highly accurate image registration and anatomically plausible estimations of the deformations. Evaluation of our method on a publicly available Computed Tomography lung image dataset (www.dir-lab.com) leads to the observation that our new approach compares very favorably with state-of-the-art in continuous and discrete image registration methods achieving Target Registration Error of 1.16mm on average per landmark. PMID:29225433

Evaluation environment for digital and analog pathology: a platform for validation studies

PubMed Central

Gallas, Brandon D.; Gavrielides, Marios A.; Conway, Catherine M.; Ivansky, Adam; Keay, Tyler C.; Cheng, Wei-Chung; Hipp, Jason; Hewitt, Stephen M.

2014-01-01

Abstract. We present a platform for designing and executing studies that compare pathologists interpreting histopathology of whole slide images (WSIs) on a computer display to pathologists interpreting glass slides on an optical microscope. eeDAP is an evaluation environment for digital and analog pathology. The key element in eeDAP is the registration of the WSI to the glass slide. Registration is accomplished through computer control of the microscope stage and a camera mounted on the microscope that acquires real-time images of the microscope field of view (FOV). Registration allows for the evaluation of the same regions of interest (ROIs) in both domains. This can reduce or eliminate disagreements that arise from pathologists interpreting different areas and focuses on the comparison of image quality. We reduced the pathologist interpretation area from an entire glass slide (10 to 30  mm2) to small ROIs (<50  μm2). We also made possible the evaluation of individual cells. We summarize eeDAP’s software and hardware and provide calculations and corresponding images of the microscope FOV and the ROIs extracted from the WSIs. The eeDAP software can be downloaded from the Google code website (project: eeDAP) as a MATLAB source or as a precompiled stand-alone license-free application. PMID:26158076

Evaluation environment for digital and analog pathology: a platform for validation studies.

PubMed

Gallas, Brandon D; Gavrielides, Marios A; Conway, Catherine M; Ivansky, Adam; Keay, Tyler C; Cheng, Wei-Chung; Hipp, Jason; Hewitt, Stephen M

2014-10-01

We present a platform for designing and executing studies that compare pathologists interpreting histopathology of whole slide images (WSIs) on a computer display to pathologists interpreting glass slides on an optical microscope. eeDAP is an evaluation environment for digital and analog pathology. The key element in eeDAP is the registration of the WSI to the glass slide. Registration is accomplished through computer control of the microscope stage and a camera mounted on the microscope that acquires real-time images of the microscope field of view (FOV). Registration allows for the evaluation of the same regions of interest (ROIs) in both domains. This can reduce or eliminate disagreements that arise from pathologists interpreting different areas and focuses on the comparison of image quality. We reduced the pathologist interpretation area from an entire glass slide (10 to [Formula: see text]) to small ROIs ([Formula: see text]). We also made possible the evaluation of individual cells. We summarize eeDAP's software and hardware and provide calculations and corresponding images of the microscope FOV and the ROIs extracted from the WSIs. The eeDAP software can be downloaded from the Google code website (project: eeDAP) as a MATLAB source or as a precompiled stand-alone license-free application.

A multi-object statistical atlas adaptive for deformable registration errors in anomalous medical image segmentation

NASA Astrophysics Data System (ADS)

Botter Martins, Samuel; Vallin Spina, Thiago; Yasuda, Clarissa; Falcão, Alexandre X.

2017-02-01

Statistical Atlases have played an important role towards automated medical image segmentation. However, a challenge has been to make the atlas more adaptable to possible errors in deformable registration of anomalous images, given that the body structures of interest for segmentation might present significant differences in shape and texture. Recently, deformable registration errors have been accounted by a method that locally translates the statistical atlas over the test image, after registration, and evaluates candidate objects from a delineation algorithm in order to choose the best one as final segmentation. In this paper, we improve its delineation algorithm and extend the model to be a multi-object statistical atlas, built from control images and adaptable to anomalous images, by incorporating a texture classifier. In order to provide a first proof of concept, we instantiate the new method for segmenting, object-by-object and all objects simultaneously, the left and right brain hemispheres, and the cerebellum, without the brainstem, and evaluate it on MRT1-images of epilepsy patients before and after brain surgery, which removed portions of the temporal lobe. The results show efficiency gain with statistically significant higher accuracy, using the mean Average Symmetric Surface Distance, with respect to the original approach.