The devil you know and the devil you don't: current status and challenges of bovine tuberculosis eradication in the United States.

Having entered into its second century, the eradication program for bovine tuberculosis (bTB, caused by Mycobacterium bovis) in the United States of America occupies a position both enviable and daunting. Excepting four counties in Michigan comprising only 6109 km2 (0.06% of US land area) classified as Modified Accredited, as of April 2022 the entire country was considered Accredited Free of bTB by the US Department of Agriculture for cattle and bison. On the surface, the now well-described circumstances of endemic bTB in Michigan, where white-tailed deer (Odocoileus virginianus) serve as a free-ranging wildlife maintenance host, may appear to be the principal remaining barrier to national eradication. However, the situation there is unique in the U.S., and far-removed from the broader issues of bTB control in the remainder of the country. In Michigan, extensive surveillance for bTB in deer over the last quarter century, and regulatory measures to maximize the harvest of publicly-owned wildlife, have been implemented and sustained. Prevalence of bTB in deer has remained at a low level, although not sufficiently low to eliminate cattle herd infections. Public attitudes towards bTB, cattle and deer, and their relative importance, have been more influential in the management of the disease than any limitations of biological science. However, profound changes in the demographics and social attitudes of Michigan's human population are underway, changes which are likely to force a critical reevaluation of the bTB control strategies thus far considered integral. In the rest of the U.S. where bTB is not self-sustaining in wildlife, changes in the scale of cattle production, coupled with both technical and non-technical issues have created their own substantial challenges. It is against this diverse backdrop that the evolution of whole genome sequencing of M. bovis has revolutionized understanding of the history and ecology of bTB in Michigan, resolved previously undiscernible epidemiological puzzles, provided insights into zoonotic transmission, and unified eradication efforts across species and agencies. We describe the current status of bTB eradication in the U.S., how circumstances and management have changed, what has been learned, and what remains more elusive than ever.

A Needle-Free Transdermal Patch for Sampling Interstitial Fluid.

OBJECTIVE: Modern diagnostics is pivoting towards less invasive health monitoring in dermal interstitial fluid, rather than blood or urine. However, the skin's outermost layer, the stratum corneum, makes accessing the fluid more difficult without invasive, needle-based technology. Simple, minimally invasive means for surpassing this hurdle are needed. METHODS: To address this problem, a flexible, Band-Aid-like patch for sampling interstitial fluid was developed and tested. This patch uses simple resistive heating elements to thermally porate the stratum corneum, allowing the fluid to exude from the deeper skin tissue without applying external pressure. Fluid is then transported to an on-patch reservoir through self-driving hydrophilic microfluidic channels. RESULTS: Testing with living, ex-vivo human skin models demonstrated the device's ability to rapidly collect sufficient interstitial fluid for biomarker quantification. Further, finite-element modeling showed that the patch can porate the stratum corneum without raising the skin's temperature to pain-inducing levels in the nerve-laden dermis. CONCLUSION: Relying only on simple, commercially scalable fabrication methods, this patch outperforms the collection rate of various microneedle-based patches, painlessly sampling a human bodily fluid without entering the body. SIGNIFICANCE: The technology holds potential as a clinical device for an array of biomedical applications, especially with the integration of on-patch testing.

Shape-morphing into 3D curved surfaces with nacre-like composite architectures.

Inhomogeneous in-plane deformation of soft materials or cutting and folding of inextensible flat sheets enables shape-morphing from two dimensional (2D) to three-dimensional (3D), while the resulting structures often have weakened mechanical strength. Shells like nacre are known for the superior fracture toughness due to the "brick and mortar" composite layers, enabling stress redistribution and crack stopping. Here, we report an optimal and universal cutting and stacking strategy that transforms composite plies into 3D doubly curved shapes with nacre-like architectures. The multilayered laminate exhibits staggered cut distributions, while the interlaminar shear mitigates the cut-induced mechanical weakness. The experimentally consolidated hemispherical shells exhibit, on average, 37 and 69% increases of compression peak forces, versus those with random cut distributions, when compressed in different directions. Our approach opens a previously unidentified paradigm for shape-conforming arbitrarily curved surfaces while achieving high mechanical performance.

GEOGRAPHIC SPREAD OF CANINE DISTEMPER IN WILD CARNIVORES IN MICHIGAN, USA: PATHOLOGY AND EPIDEMIOLOGY, 2008-18.

Canine distemper is a widespread disease affecting both domestic and wild carnivores. This investigation of the geographic distribution, wildlife species infected, and relative prevalence rates was conducted over an 11-yr period and helps to document the disease spread, most highly infected wildlife species, and histologic lesions. Animals were collected as found dead, hunter and trapper harvested, and euthanized for displaying signs of abnormal behavior or neurologic disease. This disease appeared to spread from the Lower Peninsula of Michigan into the Upper Peninsula, was most frequently documented in raccoons (Procyon lotor), striped skunks (Mephitis mephitis), and gray fox (Urocyon cinereoargenteus), but also involved additional wildlife species. Three unique wildlife virus strains were identified. Two of these grouped within a separate subclade of the America 2 lineage. A third strain appeared to be a unique sequence type that is not associated with any existing subclade of America 2. We recommend the combined use of routine histology and immunohistochemical staining to confirm the diagnosis, and further recommend that both the lungs and spleen be collected as the optimal tissues to utilize for surveillance purposes.

FOOT INJURIES IN MICHIGAN, USA, GRAY WOLVES (CANIS LUPUS), 1992-2014.

The range of gray wolves (Canis lupus) in the contiguous US is expanding. Research and monitoring to support population recovery and management often involves capture via foothold traps. A population-level epidemiologic assessment of the effect of trap injuries on wolf survival remains needed to inform management. We describe the baseline rate, type, and severity of foot injuries of wolves born 1992-2013 in Michigan's Upper Peninsula, evaluate the reliability of field-scoring trap-related injuries, and the effect of injuries on wolf survival. We assessed foot injuries by physical and radiographic exam at postmortem and/or time of capture for 351 wolves using the International Organization for Standardization 10990-5 standard and the effects of injuries, sex, age, previous capture and body condition on survival using proportional hazards regression. We used ordinal regression to evaluate epidemiologic associations between sex, age, previous capture, body condition, cause of death and injury severity. Most wolves (53%) experienced no physically or radiographically discernable foot injuries over their lifetimes. Among those wolves that did experience injuries, 33% scored as mild. Foot injuries had little epidemiologically discernable effect on survival rates. Wolves with higher foot trauma scores did experience an increased risk of dying, but the magnitude of the increase was modest. Most limb injuries occurred below the carpus or tarsus, and scoring upper-limb injuries added little predictive information to population-level epidemiologic measures of survival and injury severity. There was little association between injury severity and cause of death. Based on necropsy exams, previous trap injuries likely contributed to death in only four wolves (1.1%). Our results suggest that injuries resulting from foothold traps are unlikely to be a limiting factor in recovery and ongoing survival of the Michigan gray wolf population.

Modeling Dynamic Surface Tension on Surfactant-Enhanced Polydimethylsiloxane.

Surfactants are often added to aqueous solutions to induce spreading on otherwise unwettable hydrophobic surfaces. Alternatively, they can be introduced directly into solid hydrophobic materials─such as the soft elastomer, polydimethylsiloxane─to induce autonomous wetting without requiring additional surface or liquid modifications. Given the similarity between mechanisms of these two approaches, models that describe wetting by aqueous surfactant solutions should also characterize wetting on surfactant-solid systems. To investigate this theory, multiple surfactants of varying size and chemical composition were added to prepolymerized PDMS samples. After cross-linking, water droplets were placed on the surfaces at set time points, and their contact angles were recorded to track the temporal evolution of the interfacial tension. Multiple nonlinear models were fitted to this data, their parameters were analyzed, and each goodness of fit was compared. An empirical model of dynamic surface tension was found to describe the wetting process better than the single established model found in the literature. The proposed model adapted better to the longer time scales induced by slow molecular diffusivity in PDMS. Siloxane ethoxylate surfactants induced faster and more complete wetting of PDMS by water than oxyoctylphenol ethoxylates did. The generalizability of this model for characterizing nonionic surfactants of a wide range of physiochemical properties was demonstrated.

Marginal support for a trophic cascade among sympatric canids in peripheral wolf range.

Trophic cascades reportedly structure ecological communities through indirect species interactions. Though the predator-herbivore-autotroph relationship has received much attention, mechanistic evidence supporting intraguild trophic cascades is rare. We established 348 remote camera sites (1 August-5 September 2019) across seven study areas of varying wolf (Canis lupus) density including one study area where wolves were absent in northern Michigan, USA. Using multi-species occupancy modeling at species-relevant spatial scales, we evaluated the hypothesis that increased wolf occurrence suppresses coyote (C. latrans) occurrence with corresponding increased red fox (Vulpes vulpes) occurrence mediated by land cover edge density, human presence, and temporal partitioning. Remote cameras recorded >600,000 images and included 6,370, 10,137, and 4,876 detections of wolves, coyotes, and foxes, respectively. Fox occupancy probability was more than three times as high (0.29) at camera sites where wolves were present, relative to sites wolves were absent (0.09). Pairwise species interactions supported expected size-based dominance patterns among canids and insignificant effects were directionally consistent with reported reduced strength of top-down effects in peripheral wolf range. Increased edge density also increased co-occurrence of coyote and wolves, likely a function of increased prey availability and refugia for coyotes. Though foxes occurred in spatial proximity to wolves, competition was limited by greater temporal partitioning than observed between coyotes and foxes that were spatially segregated. Collectively, our results provide marginal support for the reported trophic cascade among wolves, coyotes, and foxes wherein top-down effects may be reduced near the edge of current wolf distributions. As predators continue to recolonize portions of their historic range, knowledge of the effects on intraguild predators has implications for species management and predicting prey population responses.

Isolation of time-dependent DNA damage induced by energetic carbon ions and their fragments using fluorescent nuclear track detectors.

PURPOSE: High energetic carbon (C-) ion beams undergo nuclear interactions with tissue, producing secondary nuclear fragments. Thus, at depth, C-ion beams are composed of a mixture of different particles with different linear energy transfer (LET) values. We developed a technique to enable isolation of DNA damage response (DDR) in mixed radiation fields using beam line microscopy coupled with fluorescence nuclear track detectors (FNTDs). METHODS: We imaged live cells on a coverslip made of FNTDs right after C-ion, proton or photon irradiation using an in-house built confocal microscope placed in the beam path. We used the FNTD to link track traversals with DNA damage and separated DNA damage induced by primary particles from fragments. RESULTS: We were able to spatially link physical parameters of radiation tracks to DDR in live cells to investigate spatiotemporal DDR in multi-ion radiation fields in real time, which was previously not possible. We demonstrated that the response of lesions produced by the high-LET primary particles associates most strongly with cell death in a multi-LET radiation field, and that this association is not seen when analyzing radiation induced foci in aggregate without primary/fragment classification. CONCLUSIONS: We report a new method that uses confocal microscopy in combination with FNTDs to provide submicrometer spatial-resolution measurements of radiation tracks in live cells. Our method facilitates expansion of the radiation-induced DDR research because it can be used in any particle beam line including particle therapy beam lines. CATEGORY: Biological Physics and Response Prediction.

Disease management at the wildlife-livestock interface: Using whole-genome sequencing to study the role of elk in Mycobacterium bovis transmission in Michigan, USA.

The role of wildlife in the persistence and spread of livestock diseases is difficult to quantify and control. These difficulties are exacerbated when several wildlife species are potentially involved. Bovine tuberculosis (bTB), caused by Mycobacterium bovis, has experienced an ecological shift in Michigan, with spillover from cattle leading to an endemically infected white-tailed deer (deer) population. It has potentially substantial implications for the health and well-being of both wildlife and livestock and incurs a significant economic cost to industry and government. Deer are known to act as a reservoir of infection, with evidence of M. bovis transmission to sympatric elk and cattle populations. However, the role of elk in the circulation of M. bovis is uncertain; they are few in number, but range further than deer, so may enable long distance spread. Combining Whole Genome Sequences (WGS) for M. bovis isolates from exceptionally well-observed populations of elk, deer and cattle with spatiotemporal locations, we use spatial and Bayesian phylogenetic analyses to show strong spatiotemporal admixture of M. bovis isolates. Clustering of bTB in elk and cattle suggests either intraspecies transmission within the two populations, or exposure to a common source. However, there is no support for significant pathogen transfer amongst elk and cattle, and our data are in accordance with existing evidence that interspecies transmission in Michigan is likely only maintained by deer. This study demonstrates the value of whole genome population studies of M. bovis transmission at the wildlife-livestock interface, providing insights into bTB management in an endemic system.

Baiting and Feeding Revisited: Modeling Factors Influencing Transmission of Tuberculosis Among Deer and to Cattle.

Although tuberculosis caused by Mycobacterium bovis (bTB) is endemic in white-tailed deer (Odocoileus virginianus) in northeastern Michigan, USA, baiting and feeding of deer continue despite a regulatory ban. Previous modeling suggests aggregation at bait sites slows the rates at which harvest and/or vaccination decrease bTB prevalence, prolongs time to eradication, and increases the likelihood that once eradicated, bTB will re-establish following an incursion. However, the extent to which specific factors such as food density, attractiveness to deer, and persistence on the landscape influence bTB transmission is unknown. We used an individual-based, spatially-explicit stochastic simulation model of bTB in deer and cattle to investigate effects of feed density, attractiveness, and spatial and temporal persistence on bTB prevalence in deer and the probability of breakdowns in adjacent cattle herds. Because hunter harvest remains key to controlling bTB in deer, and harvest rates are in long term decline, we modeled these feeding-associated factors at harvest rates prevailing both when the model was developed (2003-2007) and in 2018. Food placement at randomized locations vs. fixed sites had little effect on bTB prevalence in deer, whereas increasing the probability that deer move to food piles (attractiveness) had the greatest effect of factors studied on both prevalence and herd breakdowns. Reducing food pile density reduced prevalence, but decreased herd breakdowns only modestly. Consistent availability of food over longer periods of time, as would occur with supplemental winter feeding or persistent recreational feeding, increased both prevalence in deer and cattle herd breakdowns dramatically. Though perhaps implausible to the public, altering how bait and feed for deer are used can reduce cattle herd breakdowns. Baiting and feeding bans have contributed to declining bTB prevalence, but non-compliance and continued legal sales of feed impede eradication. Requiring hunters to move food piles is unlikely to mitigate effects on transmission and is not a useful management tool. Compared to baiting, winter supplemental feeding or extended recreational feeding is likely to magnify bTB transmission by prolonging temporal availability. Because attractiveness of feed is influenced both by type of feed and deer behavior, research to quantify factors influencing deer movement to food should be a priority.

Alteplase Causing Cardiac Tamponade after Recent Cardiac Pacemaker Placement.

A 56-year-old female presented to the emergency department with evolving cardiac tamponade after receiving alteplase for acute ischemic stroke. This is the first case report of cardiac tamponade from thrombolytics in the setting of recent pacemaker placement. Point-of-care ultrasound was used to make the diagnosis quickly and expedite the patient to the operating room where a pericardial window was performed.

Relative dosimetry with an MR-linac: Response of ion chambers, diamond, and diode detectors for off-axis, depth dose, and output factor measurements.

PURPOSE: The purpose of this study was to acquire beam data for an MR-linac, with and without a 1.5 T magnetic field, by using a variety of commercially available detectors to assess their relative response in the magnetic field. The impact of the magnetic field on the measured dose distribution was also assessed. METHODS: An MR-safe 3D scanning water phantom was used to measure output factors, depth dose curves, and off-axis profiles for various depths and for field sizes between 2 × 2 cm2 and 22 × 22 cm2 for an Elekta MR-linac beam with the orthogonal 1.5 T magnetic field on or off. An on-board MV portal imaging system was used to ensure that the reproducibility of the detector position, both with and without the magnetic field, was within 0.1 mm. The detectors used included ionization chambers with large, medium, and small sensitive volumes; a diamond detector; a shielded diode; and an unshielded diode. RESULTS: The offset of the effective point of measurement of the ionization chambers was found to be reduced by at least half for each chamber in the direction parallel with the beam. A lateral shift of similar magnitude was also introduced to the chambers' effective point of measurement toward the average direction of the Lorentz force. A similar lateral shift (but in the opposite direction) was also observed for the diamond and diode detectors. The measured lateral shift in the dose distribution was independent of depth and field size for each detector for fields between 2 × 2 cm2 and 10 × 10 cm2 . The shielded diode significantly misrepresented the dose distribution in the lateral direction perpendicular to the magnetic field, making it seem more symmetric. The percentage depth dose was generally found to be lower with the magnetic field than without, but this difference was reduced as field size increased. The depth of maximum dose showed little dependence on field size in the presence of the magnetic field, with values from 1.2 cm to 1.3 cm between the 2 × 2 cm2 and 22 × 22 cm2 fields. Output factors measured in the magnetic field at the center of the beam profile produced a larger spread of values between detectors for fields smaller than 10 × 10 cm2 (with a spread of 2% at 3 × 3 cm2 ). The spread of values was more consistent when the output factors were measured at the point of peak intensity of the lateral dose distribution instead (except for the shielded diode which differed by up to 2% depending on field size). CONCLUSIONS: The magnetic field of the MR-linac alters the effective point of measurement of ionization chambers, shifting it both downstream and laterally. Shielded diodes produce incorrect and misleading dose profiles. The output factor measured at the point of peak intensity in the lateral dose distribution is more robust than the conventional output factor (measured at central axis). Diodes are not recommended for output factor measurements in the magnetic field.

Use of whole-genome sequencing and evaluation of the apparent sensitivity and specificity of antemortem tuberculosis tests in the investigation of an unusual outbreak of Mycobacterium bovis infection in a Michigan dairy herd.

OBJECTIVE To describe use of whole-genome sequencing (WGS) and evaluate the apparent sensitivity and specificity of antemortem tuberculosis tests during investigation of an unusual outbreak of Mycobacterium bovis infection in a Michigan dairy herd. DESIGN Bovine tuberculosis (bTB) outbreak investigation. ANIMALS Cattle, cats, dog, and wildlife. PROCEDURES All cattle in the index dairy herd were screened for bTB with the caudal fold test (CFT), and cattle ≥ 6 months old were also screened with a γ-interferon (γIFN) assay. The index herd was depopulated along with all barn cats and a dog that were fed unpasteurized milk from the herd. Select isolates from M bovis-infected animals from the index herd and other bTB-affected herds underwent WGS. Wildlife around all affected premises was examined for bTB. RESULTS No evidence of bTB was found in any wildlife examined. Within the index herd, 53 of 451 (11.8%) cattle and 12 of 21 (57%) cats were confirmed to be infected with M bovis. Prevalence of M bovis-infected cattle was greatest among 4- to 7-month-old calves (16/49 [33%]) followed by adult cows (36/203 [18%]). The apparent sensitivity and specificity were 86.8% and 92.7% for the CFT and 80.4% and 96.5% for the γIFN assay when results for those tests were interpreted separately and 96.1% and 91.7% when results were interpreted in parallel. Results of WGS revealed that M bovis-infected barn cats and cattle from the index herd and 6 beef operations were infected with the same strain of M bovis. Of the 6 bTB-affected beef operations identified during the investigation, 3 were linked to the index herd only by WGS results; there was no record of movement of livestock or waste milk from the index herd to those operations. CONCLUSIONS AND CLINICAL RELEVANCE Whole-genome sequencing enhanced the epidemiological investigation and should be used in all disease investigations. Performing the CFT and γIFN assay in parallel improved the antemortem ability to detect M bovis-infected animals. Contact with M bovis-infected cattle and contaminated milk were major risk factors for transmission of bTB within and between herds of this outbreak.

Monte Carlo study of the chamber-phantom air gap effect in a magnetic field.

PURPOSE: The aim of this study was to examine the effect of submillimeter air gaps that may exist between an ionization chamber and solid phantoms when measurements are performed in a magnetic field. METHODS: Geant4 Monte Carlo simulations were performed using a model of a PTW 30013 Farmer chamber in a water phantom. Symmetrical and asymmetrical air gaps of various thicknesses were modeled surrounding the chamber, and the dose to the air cavity of the chamber was scored in each case. Magnetic fields were modeled parallel to the long axis of the chamber with strengths of 0, 0.35 T, 1.0 T, and 1.5 T. To examine the phenomenon in more detail, the gyroradii of the electrons responsible for the energy deposited in the chamber were scored as they entered the chamber and the total energy deposited was split into three components: energy originating from inside the chamber, in the immediate vacinity of the chamber, or outside the chamber. RESULTS: Differences in the chamber dose of 1.6% were observed for asymmetric air gaps just 0.2 mm thick. No effect greater than 0.5% was observed for the symmetrical air gaps investigated in this work (1.4 mm thick or less) for this chamber/magnetic field configuration. The mean gyroradius of contributing electrons as they first enter the chamber was 4 mm. The presence of the air gap reduced the energy contributions from electrons released in the immediate vicinity of the chamber, and this loss was not completely compensated for when a magnetic field was present. CONCLUSIONS: The gyroradius of most electrons was too large to be responsible for the air gap effect via the electron return effect; instead, the effect is attributed to the loss of energy contributions from electrons originating inside the air gap volume, which is not completely compensated for by more distant electrons owing to their reduced range in the magnetic field. When the chamber is parallel with the magnetic field, symmetric air gaps have a smaller effect (< 0.5%) compared to asymmetric air-gaps (up to 1.6%) on the chamber response.

PREVALENCE AND DISTRIBUTION OF PSEUDOGYMNOASCUS DESTRUCTANS IN MICHIGAN BATS SUBMITTED FOR RABIES SURVEILLANCE.

Since 2006, bat populations in North America have suffered devastating mortality from an emerging disease known as white-nose syndrome (WNS). The causal agent of WNS is the fungus Pseudogymnoascus destructans. In April 2014, WNS was discovered in little brown bats ( Myotis lucifugus ) in Michigan, US, and has since been documented in 12 counties. Because current surveillance for WNS focuses primarily on mine-hibernating species in winter, it is subject to geographic, species, and seasonal bias. To investigate species affected and potential associations of gender, seasonal life cycle, and region with P. destructans prevalence, 1,040 rabies-negative bats were sampled from May 2014 to May 2015 from animals submitted as part of statewide rabies surveillance. The vast majority (96%) of the sample population consisted of big brown bats ( Eptesicus fuscus ), a noncavernicolous species. Two methods were used to detect P. destructans: fluorescence of the muzzle, wing, and tail membranes under ultraviolet light and PCR targeting genomic DNA on wing samples. Only five bats (0.5%), all M. lucifugus , were confirmed positive after nucleic acid sequencing of PCR amplicons. No other species were infected. All infected bats were collected from April to May, coinciding with their emergence from hibernation. As P. destructans and WNS spread westward, novel surveillance streams may provide a useful tool for wildlife management agencies seeking to detect the fungus where winter hibernacula such as caves and mines are absent or otherwise inaccessible.

Management of on-farm risk to livestock from bovine tuberculosis in Michigan, USA, white-tailed deer: Predictions from a spatially-explicit stochastic model.

The eradication of bovine tuberculosis (bTB), caused by Mycobacterium bovis, from cattle in many locations worldwide is complicated by endemic foci of the disease in free-ranging wildlife. Recent simulation modeling of the bTB outbreak in white-tailed deer (WTD) in Michigan, USA, suggests current management is unlikely to eradicate bTB from the core outbreak area (DMU 452) within the next three decades. However, some level of control short of eradication might sufficiently reduce transmission from deer to cattle to a point at which the negative effects of bTB on the cattle industry could be reduced or eliminated, while minimizing the negative consequences of reducing deer numbers. We extended our existing spatially-explicit, individual-based stochastic simulation model of bTB transmission in WTD to incorporate transmission to cattle, to characterize the effects of vaccination and increased harvest of WTD on cattle herd breakdown rates, to examine the effects of localized culling or vaccination of WTD in the vicinity of cattle farms, to assess the effects of concurrent deer baiting, and to determine the effect of progressive restriction of deer/cattle contact on herd breakdowns. A spatially-explicit "cattle layer" was constructed describing the spatial locations, farm size and cattle density of all farms within and directly adjacent to DMU452. Increased hunter harvest or vaccination of deer, or a combination, would likely decrease the number of cattle herd breakdowns to <1 per year in less than 15 years. Concurrent deer baiting variably increased the time necessary to achieve zero breakdowns. The prevalence of bTB in deer needed to fall below ∼0.5% before ≤1 herd breakdown per year could be expected, and below 0.1% before zero breakdowns were likely. Locally applied post-harvest deer culling or vaccination also rapidly reduced herd breakdowns. On farm biosecurity measures needed to reduce deer to cattle contact by >95% in order to reliably reduce herd breakdowns, and did not achieve zero breakdowns in the absence of other deer controls.

Polarised light sheet tomography.

The various benefits of light sheet microscopy have made it a widely used modality for capturing three-dimensional images. It is mostly used for fluorescence imaging, but recently another technique called light sheet tomography solely relying on scattering was presented. The method was successfully applied to imaging of plant roots in transparent soil, but is limited when it comes to more turbid samples. This study presents a polarised light sheet tomography system and its advantages when imaging in highly scattering turbid media. The experimental configuration is guided by Monte Carlo radiation transfer methods, which model the propagation of a polarised light sheet in the sample. Images of both reflecting and absorbing phantoms in a complex collagenous matrix were acquired, and the results for different polarisation configurations are compared. Focus scanning methods were then used to reduce noise and produce three-dimensional reconstructions of absorbing targets.

Phase correlation applied to the 3D registration of CT and CBCT image volumes.

PURPOSE: In this study, a 3D phase correlation algorithm was investigated to test feasibility for use in determining the anatomical changes that occur throughout a patient's radiotherapy treatment. The algorithm determines the transformations between two image volumes through analysis in the Fourier domain and has not previously been used in radiotherapy for 3D registration of CT and CBCT volumes. METHODS: Various known transformations were applied to a patient's prostate CT image volume to create 12 different test cases. The mean absolute error and standard deviation were determined by evaluating the difference between the known contours and those calculated from the registration process on a point-by-point basis. Similar evaluations were performed on images with increasing levels of noise added. The improvement in structure overlap offered by the algorithm in registering clinical CBCT to CT images was evaluated using the Dice Similarity Coefficient (DSC). RESULTS: A mean error of 2.35 (σ = 1.54) mm was calculated for the 12 deformations applied. When increasing levels of noise were introduced to the images, the mean errors were observed to rise up to a maximum increase of 1.77 mm. For CBCT to CT registration, maximum improvements in the DSC of 0.09 and 0.46 were observed for the bladder and rectum, respectively. CONCLUSIONS: The Fourier-based 3D phase correlation registration algorithm investigated displayed promising results in CT to CT and CT to CBCT registration, offers potential in terms of efficiency and robustness to noise, and is suitable for use in radiotherapy for monitoring patient anatomy throughout treatment.