Patch-based nonlinear image registration for gigapixel whole slide images

Producción CientíficaImage registration of whole slide histology images allows the fusion of fine-grained information-like different immunohistochemical stains-from neighboring tissue slides. Traditionally, pathologists fuse this information by looking subsequently at one slide at a time. If the slides are digitized and accurately aligned at cell level, automatic analysis can be used to ease the pathologist's work. However, the size of those images exceeds the memory capacity of regular computers. Methods: We address the challenge to combine a global motion model that takes the physical cutting process of the tissue into account with image data that is not simultaneously globally available. Typical approaches either reduce the amount of data to be processed or partition the data into smaller chunks to be processed separately. Our novel method first registers the complete images on a low resolution with a nonlinear deformation model and later refines this result on patches by using a second nonlinear registration on each patch. Finally, the deformations computed on all patches are combined by interpolation to form one globally smooth nonlinear deformation. The NGF distance measure is used to handle multistain images. Results: The method is applied to ten whole slide image pairs of human lung cancer data. The alignment of 85 corresponding structures is measured by comparing manual segmentations from neighboring slides. Their offset improves significantly, by at least 15%, compared to the low-resolution nonlinear registration. Conclusion/Significance: The proposed method significantly improves the accuracy of multistain registration which allows us to compare different antibodies at cell level

Modified constraint-induced movement therapy or bimanual occupational therapy following injection of Botulinum toxin-A to improve bimanual performance in young children with hemiplegic cerebral palsy: a randomised controlled trial methods paper

<p>Abstract</p> <p>Background</p> <p>Use of Botulinum toxin-A (BoNT-A) for treatment of upper limb spasticity in children with cerebral palsy has become routine clinical practice in many paediatric treatment centres worldwide. There is now high-level evidence that upper limb BoNT-A injection, in combination with occupational therapy, improves outcomes in children with cerebral palsy at both the body function/structure and activity level domains of the International Classification of Functioning, Disability and Health. Investigation is now required to establish what amount and specific type of occupational therapy will further enhance functional outcomes and prolong the beneficial effects of BoNT-A.</p> <p>Methods/Design</p> <p>A randomised, controlled, evaluator blinded, prospective parallel-group trial. Eligible participants were children aged 18 months to 6 years, diagnosed with spastic hemiplegic cerebral palsy and who were able to demonstrate selective motor control of the affected upper limb. Both groups received upper limb injections of BoNT-A. Children were randomised to either the modified constraint-induced movement therapy group (experimental) or bimanual occupational therapy group (control). Outcome assessments were undertaken at pre-injection and 1, 3 and 6 months following injection of BoNT-A. The primary outcome measure was the Assisting Hand Assessment. Secondary outcomes included: the Quality of Upper Extremity Skills Test; Pediatric Evaluation of Disability Inventory; Canadian Occupational Performance Measure; Goal Attainment Scaling; Pediatric Motor Activity Log; modified Ashworth Scale and; the modified Tardieu Scale.</p> <p>Discussion</p> <p>The aim of this paper is to describe the methodology of a randomised controlled trial comparing the effects of modified constraint-induced movement therapy (a uni-manual therapy) versus bimanual occupational therapy (a bimanual therapy) on improving bimanual upper limb performance of children with hemiplegic cerebral palsy following upper limb injection of BoNT-A. The paper outlines the background to the study, the study hypotheses, outcome measures and trial methodology. It also provides a comprehensive description of the interventions provided.</p> <p>Trial Registration</p> <p>ACTRN12605000002684</p

Study of kinetic recrystallization and growing of grains in alloys with memory of form

Dissertação (mestrado)—Universidade de Brasília, Faculdade UnB Gama, Faculdade de Tecnologia, Programa de Pós-Graduação em Integridade de Materiais da Engenharia, 2013.Ligas com memória de forma, como as dos sistemas de Cu-Al-Ni, Cu-Al-Be e Ni- Ti, possuem uma vasta gama de utilização, a qual inclui elementos funcionais de sensores e atuadores que funcionam através da variação das temperaturas dos materiais. A diversidade de suas aplicações depende não só de sua composição química, mas evitar a perda da capacidade de executar sua correta função com o tempo (envelhecimento/ crescimento de grão). Assim, o estudo da cinética de recristalização assume um papel importante por possibilitar o controle do estado encruado em função do tempo de tratamento. O objetivo deste trabalho é determinar e comparar as cinéticas de recristalização em função das temperaturas de tratamento das ligas Cu-14Al-4Ni , Cu-12Al-0,5Be e Ni-42Ti, com base na lei empírica de Johnson-Mehl-Avrami (J-M-A), assim como suas energias de ativação para crescimento de grãos, segundo equação baseada na lei empírica de Arrhenius. Para isso, foram realizadas análises dinâmicas em DSC para determinação da temperatura de recristalização das ligas encruadas. Em seguida, diferentes amostras foram recozidas em temperaturas próximas à de pico, de início e fim de recristalização da curva DSC, em tempos que variaram de 1 a 120 minutos. Depois de tratadas, as amostras foram submetidas a ensaios de microdureza Vickers, cujos resultados foram relacionados com o tempo e a fração transformada para determinação da cinética de recristalização. Para a caracterização do processo e de seus mecanismos, foram realizadas análises de Fluorescência de raios-X e de microscopia óptica. Foi verificado que a liga menos suscetível ao crescimento de grão, para temperaturas inferiores à de pico de recristalização, é a Ni-42Ti, a qual apresentou a maior energia de ativação, seguida da liga Cu-14Al-4Ni. Verificou-se, também, que a cinética de recristalização acompanhada pela variação de dureza, apesar das limitações deste processo, mostra-se uma importante ferramenta, atuando como orientadora para seleção dos tempos de tratamento em função da temperatura. _______________________________________________________________________________________ ABSTRACTAlloys with shape memory, such as the Cu-Al -Ni , Cu -Al- Be and Ni -Ti systems, have a wide range of use, like functional elements that operate sensors and actuators according to the variation of the material temperature. The diversity of its application depends not only on its chemical composition, but avoid the loss of ability to perform its proper function over time (aging / grain growth). Thus, the study of recrystallization kinetics is important for enabling the control of hardened state as a function of treatment time. The objective of this study is to determine and compare the kinetics of recrystallization depending on the treatment temperatures of Cu-14Al-4Ni, Cu-12Al-0,5Be e Ni-42Ti alloys , based on the empirical law of Johnson - Mehl - Avrami ( JMA ), as well as their activation energies for grain growth, according to empirical law based on the Arrhenius equation. For this, dynamic DSC analyzes were performed to determine the recrystallization temperature of the strain hardened alloys. Then, the different samples were treated termically at temperatures close to the peak, start and end of recrystallization of the DSC curve at times ranging from 1 to 120 minutes. After treated termically, the samples were tested for microhardness, whose results were related to the time and the fraction transformed to determine the recrystallization kinetics. For the characterization of the process and its mechanisms, analysis of X-ray fluorescence and optical microscopy were performed. The alloy less susceptible to grain growth, for temperatures below the recrystallization peak, is the Ni-42Ti, which showed the highest activation energy, followed by Cu-14Al-4Ni. The recrystallization kinetics accompanied by varying hardness, despite the limitations of this process, is showed as an important tool, acting as advisor for selection of treatment times as a function of temperature

Landmark constrained non-parametric image registration with isotropic tolerances

The incorporation of additional user knowledge into a nonrigid registration process is a promising topic in modern registration schemes. The combination of intensity based registration and some interactively chosen landmark pairs is a major approach in this direction. There exist different possibilities to incorporate landmark pairs into a variational non-parametric registration framework. As the interactive localization of point landmarks is always prone to errors, a demand for precise landmark matching is bound to fail. Here, the treatment of the distances of corresponding landmarks as penalties within a constrained optimization problem offers the possibility to control the quality of the matching of each landmark pair individually. More precisely, we introduce inequality constraints, which allow for a sphere-like tolerance around each landmark. We illustrate the performance of this new approach for artificial 2D images as well as for the challenging registration of preoperative CT data to intra-operative 3D ultrasound data of the liver

Landmark constrained non-rigid image registration with anisotropic tolerances

The registration of medical images containing soft tissue like inner organs, muscles, fat , etc., is challenging due to complex deformations between different image acquisitions. Despite different approaches to get smooth transformations the number of feasible transformations is still huge and ambiguous local image contents may lead to unwanted results. The incorporation of additional user knowledge is a promising way to restrict the number of possible non-rigid transformations and to increase the probability to find a clinically reasonable solution. A small number of pre-operatively and interactively defined landmarks is a straight forward example for such expert knowledge. Typically, when vessels appear in the image data, a natural way is to determine landmarks as vessel branchings. Here, we present a generalization that allows also the usage of corresponding vessel segments. Therefor, we introduce a registration scheme that can handle anisotropic localization uncertainties. The contribution of this work is a consistent modeling of a combined intensity and landmark registration approach as an inequality constrained optimization problem. This guarantees that each reference landmark lies within an error ellipsoid around the corresponding template landmark at the end of the registration process. First results are presented for the registration of preoperative CT images to intra-operative 3D ultrasound data of the liver as an important issue in an intra-operative navigation system

Patch-Based Nonlinear Image Registration For Gigapixel Whole Slide Images

INTRODUCTION / BACKGROUND: Image Registration of whole slide histology images allows the fusion of fine-grained information – like different immunohistochemical stains – from neighboring tissue slides. Traditionally, pathologists fuse this information by looking subsequently at one slide at a time. If the slides are digitized and accurately aligned at cell-level, automatic analysis can be used to ease the pathologist’s work. However, the size of those images exceeds the memory capacity of regular computers, preventing the application of established image registration methods at a high magnification. AIMS: An accurate and automatic alignment helps the pathologist to analyze the combination of different antibodies without memorizing multiple slides. For some applications, cell-level accuracy is needed. This also enables automatic image analysis to take advantage of multislide information. METHODS: We extend available registration methods by using image data at fine spatial resolution. However, this data is not simultaneously globally available due to the computer’s memory restrictions. Typical approaches either reduce the amount of data to be processed by downsampling or partition the data into smaller chunks to be processed separately. We combine the patch based approach with an elastic deformation model to obtain a global registration result. Our method first registers the complete images on a low resolution with a nonlinear deformation model and later refines this result on patches by using a second nonlinear registration on each patch. The deformation information on the individual patches can be contradictory and needs to be combined into one global model. As an extension to our previous work, the global solution is computed by minimizing an energy function that preserves the patch-wise deformation and establishes global smoothness. The NGF distance measure is used to handle multi-stain images. RESULTS: The method will be applied to whole slide image pairs. The alignment of corresponding structures will be measured by comparing manual segmentations from neighboring slides. First results show an improvement of the registration accuracy compared to the low-resolution nonlinear registration