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

TRANSANTARCTIC BASIN: NEWINSIGHTS FROM FISSION TRACKAND STRUCTURAL DATA FROM THE USARP MOUNTAINS AND ADJACENT AREAS (NORTHERN VICTORIA LAND,ANTARCTICA)

The USARP Mountains comprise two N-S-aligned mountain ranges (Daniels Range, Pomerantz Tableland) located along the western margin of the RennickGlacier inNorthernVictoria Land (NVL). Four zircon and titanite ¢ssion track (FT) ages fromgranitic samples from the PomerantzTableland fall in a common range of 369^392Ma.The apatite FTages from20GraniteHarbour Intrusive rocks sampled throughout theUSARPMountains are distinctively younger (86^270Ma); their mean track lengths (MTL) vary between11.0 and13.9mm. Six samples fromRenirie Rocks and the Kavrayskiy Hills east of theUSARPMountains have even younger, concordant apatiteFTages of 43^71Ma, andMTL of 12.2^14.0 mm.Thermal history modelling of the thermochronological data indicate that both the Daniels Range and PomerantzTableland experienced a common Phanerozoic geologic history consisting of a mid-Devonian pulse of rapid denudation, followed by a protracted denudation stage between the Carboniferous and Jurassic.This latter period of denudationwas contemporaneous with the formation of theTransantarctic Basin to the east.We consequently suggest that theUSARP Mountains were one of the major source areas for the Beacon Supergroup that formed the ¢ll of the Transantarctic Basin.Subsequent to the deposition of the Beacon sequence, the now-outcropping rocks of theUSARPMountains were buried to a maximum depth of 4.2km. A palaeogeothermal gradient of 25 8 1Ckm1was inferred at the time of maximumburial. Inversion of theTransantarctic Basin due to the breakup of Gondwana, and in response to Cenozoic rifting and uplift of theTransantarctic Mountains, has triggered the ¢nal denudation stages recorded inNVL since the Cretaceous.Thereby, the amounts of denudation increase eastward.Whereas 2.4^4.2 km of crustal unloading are recognized for theUSARPMountains since the Cretaceous,more than 4 km of denudation has occurred towards the RennickGraben alone since the Eocene.This denudationwas associatedwith major fault activities involving earlyENE^WSWtoE^W-directed extension.Related structureswere reactivated bydominant NW^SEtoNNW^SSE-oriented right-lateral shear genetically linked to the formation and inversion of the structural depression of the RennickGraben in Cenozoic times