MR Imaging-Histology Correlation by Tailored 3D-Printed Slicer in Oncological Assessment.

3D printing and reverse engineering are innovative technologies that are revolutionizing scientific research in the health sciences and related clinical practice. Such technologies are able to improve the development of various custom-made medical devices while also lowering design and production costs. Recent advances allow the printing of particularly complex prototypes whose geometry is drawn from precise computer models designed on in vivo imaging data. This review summarizes a new method for histological sample processing (applicable to e.g., the brain, prostate, liver, and renal mass) which employs a personalized mold developed from diagnostic images through computer-aided design software and 3D printing. Through positioning the custom mold in a coherent manner with respect to the organ of interest (as delineated by in vivo imaging data), the cutting instrument can be precisely guided in order to obtain blocks of tissue which correspond with high accuracy to the slices imaged. This approach appeared crucial for validation of new quantitative imaging tools, for an accurate imaging-histopathological correlation and for the assessment of radiogenomic features extracted from oncological lesions. The aim of this review is to define and describe 3D printing technologies which are applicable to oncological assessment and slicer design, highlighting the radiological and pathological perspective as well as recent applications of this approach for the histological validation of and correlation with MR images.

3D printing from MRI Data: Harnessing strengths and minimizing weaknesses.

3D printing facilitates the creation of accurate physical models of patient-specific anatomy from medical imaging datasets. While the majority of models to date are created from computed tomography (CT) data, there is increasing interest in creating models from other datasets, such as ultrasound and magnetic resonance imaging (MRI). MRI, in particular, holds great potential for 3D printing, given its excellent tissue characterization and lack of ionizing radiation. There are, however, challenges to 3D printing from MRI data as well. Here we review the basics of 3D printing, explore the current strengths and weaknesses of printing from MRI data as they pertain to model accuracy, and discuss considerations in the design of MRI sequences for 3D printing. Finally, we explore the future of 3D printing and MRI, including creative applications and new materials. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2017;45:635-645.

3D-printing and the effect on medical costs: a new era?

3D-printing (3DP) is the art and science of printing in a new dimension using 3D printers to transform 3D computer aided designs (CAD) into life-changing products. This includes the design of more effective and patient-friendly pharmaceutical products as well as bio-inspired medical devices. It is poised as the next technology revolution for the pharmaceutical and medical-device industries. After decorous implementation scientists in collaboration with CAD designers have produced innovative medical devices ranging from pharmaceutical tablets to surgical transplants of the human face and skull, spinal implants, prosthetics, human organs and other biomaterials. While 3DP may be cost-efficient, a limitation exists in the availability of 3D printable biomaterials for most applications. In addition, the loss of skilled labor in producing medical devices such as prosthetics and other devices may affect developing economies. This review objectively explores the potential growth and impact of 3DP costs in the medical industry.

Use of digital technologies for nasal prosthesis manufacturing.

BACKGROUND AND AIM: Digital technology is becoming more accessible for common use in medical applications; however, their expansion in prosthetic and orthotic laboratories is not large because of the persistent image of difficult applicability to real patients. This article aims to offer real example in the area of human facial prostheses. TECHNIQUE: This article describes the utilization of optical digitization, computational modelling, rapid prototyping, mould fabrication and manufacturing of a nasal silicone prosthesis. This technical note defines the key points of the methodology and aspires to contribute to the introduction of a certified manufacturing procedure. DISCUSSION: The results show that the used technologies reduce the manufacturing time, reflect patient's requirements and allow the manufacture of high-quality prostheses for missing facial asymmetric parts. The methodology provides a good position for further development issues and is usable for clinical practice. Clinical relevance Utilization of digital technologies in facial prosthesis manufacturing process can be a good contribution for higher patient comfort and higher production efficiency but with higher initial investment and demands for experience with software tools.

If we designed airplanes like we design drugs....

In the early days, airplanes were put together with parts designed for other purposes (bicycles, farm equipment, textiles, automotive equipment, etc.). They were then flown by their brave designers to see if the design would work--often with disastrous results. Today, airplanes, helicopters, missiles, and rockets are designed in computers in a process that involves iterating through enormous numbers of designs before anything is made. Until very recently, novel drug-like molecules were nearly always made first like early airplanes, then tested to see if they were any good (although usually not on the brave scientists who created them!). The resulting extremely high failure rate is legendary. This article describes some of the evolution of computer-based design in the aerospace industry and compares it with the progress made to date in computer-aided drug design. Software development for pharmaceutical research has been largely entrepreneurial, with only relatively limited support from government and industry end-user organizations. The pharmaceutical industry is still about 30 years behind aerospace and other industries in fully recognizing the value of simulation and modeling and funding the development of the tools needed to catch up.

From chemical graphs in computer-aided drug design to general Markov-Galvez indices of drug-target, proteome, drug-parasitic disease, technological, and social-legal networks.

Complex Networks are useful in solving problems in drug research and industry, developing mathematical representations of different systems. These systems move in a wide range from relatively simple graph representations of drug molecular structures to large systems. We can cite for instance, drug-target protein interaction networks, drug policy legislation networks, or drug treatment in large geographical disease spreading networks. In any case, all these networks have essentially the same components: nodes (atoms, drugs, proteins, microorganisms and/or parasites, geographical areas, drug policy legislations, etc.) and edges (chemical bonds, drug-target interactions, drug-parasite treatment, drug use, etc.). Consequently, we can use the same type of numeric parameters called Topological Indices (TIs) to describe the connectivity patterns in all these kinds of Complex Networks despite the nature of the object they represent. The main reason for this success of TIs is the high flexibility of this theory to solve in a fast but rigorous way many apparently unrelated problems in all these disciplines. Another important reason for the success of TIs is that using these parameters as inputs we can find Quantitative Structure-Property Relationships (QSPR) models for different kind of problems in Computer-Aided Drug Design (CADD). Taking into account all the above-mentioned aspects, the present work is aimed at offering a common background to all the manuscripts presented in this special issue. In so doing, we make a review of the most common types of complex networks involving drugs or their targets. In addition, we review both classic TIs that have been used to describe the molecular structure of drugs and/or larger complex networks. Next, we use for the first time a Markov chain model to generalize Galvez TIs to higher order analogues coined here as the Markov-Galvez TIs of order k (MGk). Lastly, we illustrate the calculation of MGk values for different classes of networks found in drug research, nature, technology, and social-legal sciences.

Novel trends in high-throughput screening.

High-throughput screening (HTS) is a well-established process for lead discovery in Pharma and Biotech companies and is now also being used for basic and applied research in academia. It comprises the screening of large chemical libraries for activity against biological targets via the use of automation, miniaturized assays and large-scale data analysis. Since its first advent in the early to mid 1990s, the field of HTS has seen not only a continuous change in technology and processes, but also an adaptation to various needs in lead discovery. HTS has now evolved into a mature discipline that is a crucial source of chemical starting points for drug discovery. Whereas in previous years much emphasis has been put on a steady increase in screening capacity ('quantitative increase') via automation and miniaturization, the past years have seen a much greater emphasis on content and quality ('qualitative increase'). Today, many experts in the field see HTS at a crossroad with the need to decide on either higher throughput/more experimentation or a greater focus on assays of greater physiological relevance, both of which may lead to higher productivity in pharmaceutical R&D. In this paper, we describe the development of HTS over the past decade and point out our own ideas for future directions of HTS in biomedical research. We predict that the trend toward further miniaturization will slow down with the balanced implementation of 384 well, 1536 well, and 384 low volume well plates. Furthermore, we envisage that there will be much more emphasis on rigorous assay and chemical characterization, particularly considering that novel and more difficult target classes will be pursued. In recent years we have witnessed a clear trend in the drug discovery community toward rigorous hit validation by the use of orthogonal readout technologies, label free and biophysical methodologies. We also see a trend toward a more flexible use of the various screening approaches in lead discovery, that is, the use of both full deck compound screening as well as the use of focused screening and iterative screening approaches. Moreover, we expect greater usage of target identification strategies downstream of phenotypic screening and the more effective implementation of affinity selection technologies as a result of advances in chemical diversity methodologies. We predict that, ultimately, each hit finding strategy will be much more project-related, tailor-made, and better integrated into the broader drug discovery efforts.

Nuevos enfoques de las buenas prácticas de Manufactura / Good manufacturing practices new approaches

Durante los últimos años, el trabajo en Buenas Prácticas de Manufactura (bpm), además de contribuir a mejorar la calidad de los productos farmacéuticos disponibles en el mercado, ha permitido realizar un avance importante en la interpretación conceptual y en la aplicación práctica del verdadero significado del aseguramiento de la calidad en la industria farmacéutica. En ese sentido, este artículo analiza los aportes que sobre este tema han tenido las buenas prácticas de ingeniería, el desarrollo de producto, los programas de acciones correctivas y acciones preventivas, la gestión del riesgo en calidad, el control de procesos productivos en tiempo real y el sistema de gestión de la calidad para la industria farmacéutica. Sin duda, su adopción, que en la mayoría de los casos no corresponde a una exigencia explícita de la guía de bpm y que supone una inversión mayor de recursos, ofrece claros beneficios organizacionales y aporta evidencia para fortalecer la confianza, especialmente de las autoridades reguladoras, del cumplimiento del compromiso con la calidad que manifiesta una empresa determinada.

During the previous years, the Good Manufacturing Practices (gmp) work, besides contributing in improving the pharmaceutical products quality, has allowed an important progress in both the understanding and the practical application in the real meaning of the quality assurance in the pharmaceutical industry. As a contribution to this issue, this document studies the contributions of the good engineering practices, the product development, the corrective and preventive action system, the quality risk management, the process analytical technology and the pharmaceutical quality system. The implementation of these concepts, that in the majority of cases are not explicit gmp guide requirements, could suppose spending more money from the firm. However, on the contrary, it would give obvious benefits and contribute to have evidence, especially for the competent national authorities, about the fulfillment quality police implementation.

The future as I see it.

Predicting the future is always chancy, but when a young practitioner begins a career in dentistry, it is worthwhile to have some well-reasoned expectations. The critical dimensions in the next several decades in dentistry will include technology, marketing, and society.

Hunting for predictive computational drug-discovery models.

The Keystone Symposium on Computer-Aided Drug Design was held at Steamboat Springs (CO, USA), from March 29th to the 3rd of April, 2008. The organizers brought together approximately 180 participants, representing a cross-section of viewpoints from academia and the pharmaceutical industry. Since it is a young discipline, it was a privilege to have a keynote introduction from one of the original pioneers of the field, Irwin Kuntz. By avoiding pitfalls, and addressing active debates, the young field can become more reliably predictive. Accordingly, this report focuses on best practices. As reliability improves, drug-discovery programs will increasingly use models to determine which high-throughput screens to run.

Computer-assisted implantology: historical background and potential outcomes-a review.

BACKGROUND: The accurate transfer of preoperatively determined implant positions to the patient mouth is very beneficial to the dental practitioner as well as patients. The objective of this paper was to review the gradual development of computer-assisted implant surgery. METHODS: All of the major data sources including unpublished data in the internet are considered RESULTS AND CONCLUSIONS: Computer-assisted/-guided/-aided implantology has been founded to overcome the errors encountered during implant osteotomies and to position the implants more precisely. The protocols followed by this sophisticated technique are based upon the advocated concept of prosthetic-driven implantology and CT-scan analysis recently approved. Although several attempts have been made to improve this approach more and more, little has been done regarding the patient's demands, including cost. The inherent complexity of the techniques and materials utilized necessitates several degrees of training before attempting treatment and must be taken into account.

Computer-based de novo design of drug-like molecules.

Ever since the first automated de novo design techniques were conceived only 15 years ago, the computer-based design of hit and lead structure candidates has emerged as a complementary approach to high-throughput screening. Although many challenges remain, de novo design supports drug discovery projects by generating novel pharmaceutically active agents with desired properties in a cost- and time-efficient manner. In this review, we outline the various design concepts and highlight current developments in computer-based de novo design.

Virtual medical devices.

Virtual medical devices are set to have a major impact on the industry. This article explains the practicalities and benefits of a new approach to designing and constructing many types of medical devices.

Three generations of automatically designed robots.

The difficulties associated with designing, building, and controlling robots have led their development to a stasis: Applications are limited mostly to repetitive tasks with predefined behavior. Over the last few years we have been trying to address this challenge through an alternative approach: Rather than trying to control an existing machine or create a general-purpose robot, we propose that both the morphology and the controller should evolve at the same time. This process can lead to the automatic design of special-purpose mechanisms and controllers for specific short-term objectives. Here we provide a brief review of three generations of our recent research, which underlies the robots shown on the cover of this issue: Automatically designed static structures, automatically designed and manufactured dynamic electromechanical systems, and modular robots automatically designed through a generative DNA-like encoding.

Computer automated design and computer automated manufacture.

The introduction of computer aided design and computer aided manufacturing into the field of prosthetics and orthotics did not arrive without concern. Many prosthetists feared that the computer would provide other allied health practitioners who had little or no experience in prosthetics the ability to fit and manage amputees. Technicians in the field felt their jobs may be jeopardized by automated fabrication techniques. This has not turned out to be the case. Prosthetists who use CAD-CAM techniques are finding they have more time for patient care and clinical assessment. CAD-CAM is another tool for them to provide better care for the patients/clients they serve. One of the factors that deterred the acceptance of CAD-CAM techniques in its early stages was that of cost. It took a significant investment in software and hardware for the prosthetists to begin to use the new systems. This new technique was not reimbursed by insurance coverage. Practitioners did not have enough information about this new technique to make a sound decision on their investment of time and money. Ironically, it is the need to hold health care costs down that may prove to be the catalyst for the increased use of CAD-CAM in the field. Providing orthoses and prostheses to patients who require them is a very labor intensive process. Practitioners are looking for better, faster, and more economical ways in which to provide their services under the pressure of managed care. CAD-CAM may be the answer. The author foresees shape sensing departments in hospitals where patients would be sent to be digitized, similar to someone going for radiograph or ultrasound. Afterwards, an orthosis or prosthesis could be provided from a central fabrication facility at a remote site, most likely on the same day. Not long ago, highly skilled practitioners with extensive technical ability would custom make almost every orthosis. One now practices in an atmosphere where off-the-shelf orthoses are the standard. This reduced fabrication time, but compromised the accuracy of the fit of a custom made orthosis. Computer aided design and manufacturing has the ability to combine the accuracy of custom made with the speed and labor savings of off-the-shelf systems. This would be a substantial benefit to patients, practitioners, and third party payors as well. The field may run full circle and return to custom made systems at off-the-shelf costs. As scientific knowledge base increases and computer aided design improves, one still needs the interface between the design methodology and the patient. That interface is the prosthetist/orthotist. The clinician and the clients they serve have a lot to gain from further research in this field. If one does not lose focus on how one can improve prostheses and orthoses for the consumer, one can expect great things from the methodology of CAD-CAM. There is no question that computerization is here and will continue to influence the fields of prosthetics and orthotics.