ROBOT Assisted Laparoscopic Surgeries For Nononcological Urologic Disease: Initial Experience With Hugo Ras System.

OBJECTIVE: To report our initial experience with the use of HUGO Robotic Assisted Surgery System (RAS) for nononcological urologic disease. METHODS: We collected retrospective data describing clinical outcomes from patients undergoing surgeries for nononcological urologic disease with the new HUGO RAS. Analysis included: total surgery and console time, docking time, estimated bleeding, complications, and pain after surgery. RESULTS: There were 5 patients operated for nononcological urologic disease. The mean age was 50 years (range 32-70), comorbidities were mild (2 patients with chronic hypertension) and American Society of Anesthesiologists (ASA) classification was 2. Total surgical time ranged from 150 to 257 minutes, and console time from 89 to 164 minutes, each depending on the intervention. The mean docking time was 8.5 minutes (range 5.7-11). No intraoperative complications, instrument clashes, or system failure that compromised the surgery's completion were recorded. Mean blood loss ranged from 10-30 mL, and there were no postoperative complications. Postoperative pain classified from 0-10 at 1, 6, and 12 hours was low (range 0-3), and pain before discharge was 0 for all patients. Hospital stay ranged from 2 to 5 days, depending on the intervention. CONCLUSION: Robotic surgery was introduced in early 2000s and was rapidly adopted. Initially, this technology was reserved for oncological surgery, later expanding to nononcological conditions. These preliminary results are comparable to the previous robotic systems, suggesting the multiple potential uses of the HUGO RAS. The adoption of this technology has the potential to improve patient accessibility for less-invasive therapies in developing countries.

Temperature effect of Moses™ 2.0 during flexible ureteroscopy: an in vitro assessment.

Introduction: One of the main issues related to the use of high-power lasers is the associated rise in temperature. The aim of this study was to characterize temperature variations with activation of the Moses™ 2.0 laser. Material and methods: An in vitro experimental study was designed using a high-fidelity uretero-nephroscope simulation model to assess changes in temperature during intracorporeal laser lithotripsy. Renal and ureteral temperature records were obtained from the treatment of BegoStones positioned in the renal pelvis. Different laser settings over three time periods and two possible irrigation flow speeds were evaluated. We considered 43°C as the threshold since it is associated with denaturation of proteins. The Wilcoxon-Mann-Whitney test was used to assess quantitative variables and the Kruskal-Wallis test for categorical variables. Results: The highest increase in intrarenal temperature was reached with 30 seconds of laser activation at a laser setting of 0.5 J/100 Hz (50 W) and a flow of 10 mL/min. Only 15 seconds of activation was sufficient for most settings to exceed 43°C. The ureteral temperature did not increase significantly, regardless of the combination of laser setting, time, or irrigation flow, except when 30 W was used for a 30 second period. Multivariate analysis showed that an irrigation flow of 20 mL/min produced an intrarenal temperature decrease of 4.7-9.2°C (p <0.001). Conclusions: Use of high-power lasers, both for the ureter and kidney, should involve consideration of temperature increases evidenced in this study, due to the potential biological risk entailed.

Spatial resolution of an integrated C4+CAM photosynthetic metabolism.

C4 and CAM photosynthesis have repeatedly evolved in plants over the past 30 million years. Because both repurpose the same set of enzymes but differ in their spatial and temporal deployment, they have long been considered as distinct and incompatible adaptations. Portulaca contains multiple C4 species that perform CAM when droughted. Spatially explicit analyses of gene expression reveal that C4 and CAM systems are completely integrated in Portulaca oleracea, with CAM and C4 carbon fixation occurring in the same cells and CAM-generated metabolites likely incorporated directly into the C4 cycle. Flux balance analysis corroborates the gene expression findings and predicts an integrated C4+CAM system under drought. This first spatially explicit description of a C4+CAM photosynthetic metabolism presents a potential new blueprint for crop improvement.

Gene co-expression reveals the modularity and integration of C4 and CAM in Portulaca.

C4 photosynthesis and Crassulacean acid metabolism (CAM) have been considered as largely independent adaptations despite sharing key biochemical modules. Portulaca is a geographically widespread clade of over 100 annual and perennial angiosperm species that primarily use C4 but facultatively exhibit CAM when drought stressed, a photosynthetic system known as C4 + CAM. It has been hypothesized that C4 + CAM is rare because of pleiotropic constraints, but these have not been deeply explored. We generated a chromosome-level genome assembly of Portulaca amilis and sampled mRNA from P. amilis and Portulaca oleracea during CAM induction. Gene co-expression network analyses identified C4 and CAM gene modules shared and unique to both Portulaca species. A conserved CAM module linked phosphoenolpyruvate carboxylase to starch turnover during the day-night transition and was enriched in circadian clock regulatory motifs in the P. amilis genome. Preservation of this co-expression module regardless of water status suggests that Portulaca constitutively operate a weak CAM cycle that is transcriptionally and posttranscriptionally upregulated during drought. C4 and CAM mostly used mutually exclusive genes for primary carbon fixation, and it is likely that nocturnal CAM malate stores are shuttled into diurnal C4 decarboxylation pathways, but we found evidence that metabolite cycling may occur at low levels. C4 likely evolved in Portulaca through co-option of redundant genes and integration of the diurnal portion of CAM. Thus, the ancestral CAM system did not strongly constrain C4 evolution because photosynthetic gene networks are not co-regulated for both daytime and nighttime functions.

Experiencia y resultados de un proceso educativo interdisciplinario para la promoción de salud en universitarios / Experience and results of an interdisciplinary educational process for the promotion of health with university students / Experiência e resultados dum processo educativo interdisciplinario para a promoção de saúde em universitarios

Objetivo: Capacitar a un grupo interdisciplinario de estudiantes de pregrado como promotores universitarios de salud y evaluar los resultados. Metodología: Investigación acción participativa con 13 estudiantes de pregrado de la Pontificia Universidad Católica del Ecuador durante el periodo 2012-2014. El proceso se desarrolló en cuatro fases: 1) capacitación en promoción de salud del grupo; 2) diagnóstico de la situación de salud general de los estudiantes; 3) diseño, planificación e implementación de un proyecto ejecutado por los estudiantes capacitados; y 4) evaluación de la intervención. En cada fase se aplicaron técnicas cualitativas y cuantitativas para el diagnóstico y evaluación de resultados. Resultados: Fase 1: 100% de los estudiantes completaron el proceso de capacitación. Fase 2: se identificó como principales problemas de salud en la población estudiantil universitaria a los relacionados con salud mental (estrés, ansiedad, depresión), alimentación inadecuada y violencia. Fase 3: Se diseñó y ejecutó un proyecto de intervención a partir del diagnóstico realizado, que benefició a 2916 pares. Fase 4: Como resultado de la intervención, el 76,2% de los beneficiarios manifestaron enfrentar los problemas cotidianos, 90,6% lo consideraron importante para su desarrollo personal espiritual, afectivo y corporal, 94% mejoró las relaciones con sus compañeros, 68,9% aprendieron sobre sus derechos y 38% reconocieron que modificaron sus hábitos de vida. Conclusiones: La metodología implementada otorgó a los estudiantes herramientas para diseñar, ejecutar y evaluar proyectos interdisciplinarios de promoción de salud. La investigación-acción posibilita transformaciones de las realidades en salud en entornos universitarios y es factible de ser aplicada en otros contextos.

Objective: To train an interdisciplinary group of undergraduate students as university health promoters and evaluate their results. Methodology: Participatory action research with 13 undergraduate students of the Pontificia Universidad Católica de Ecuador during the period 2012-2014. The process was developed in four phases: 1) training in health promotion of the group; 2) diagnosis of the general health situation of the students; 3) design, planning and implementation of a project executed by trained students; and 4) evaluation of the intervention. Qualitative and quantitative techniques were applied in each phase for the diagnosis and evaluation of results. Results: Phase 1: 100% of the students completed the training process; Phase 2: The main health problems in the university student population were identified as related to mental health (stress, anxiety, and depression), inadequate diet and violence; Phase 3: An intervention project was designed and executed based on the diagnosis made, which benefited 2916 peers; Phase 4: As a result of the intervention, 76.2% of the beneficiaries stated that they faced daily problems, 90.6% considered it important for their personal spiritual, emotional and corporal development, 94% improved relations with their peers, 68, 9% learned about their rights and 38% acknowledged that they modified their life habits. Conclusions: The methodology implemented gave students tools to design, execute and evaluate interdisciplinary health promotion projects. Action research enables transformations of realities in health in university settings and is feasible to be applied in other contexts.

Objetivo: Capacitar a um grupo interdisciplinares de estudantes de formatura como promotores universitários de saúde e avaliar os resultados. Metodologia: Pesquisa ação participativa com 13 estudantes de formatura da Pontifícia Universidade Católica do Equador durante o período 2012-2014. O processo de desenvolvimento em quatro fases: 1) capacitação em promoção de saúde do grupo; 2) diagnóstico da situação de saúde geral dos estudantes; 3) design, planificação e execução dum projeto executado pelos estudantes capacitados; e 4) avaliação da intervenção. Em cada fase se aplicação técnicas qualitativas e quantitativas para o diagnóstico e avaliação de resultados. Resultados: Fase 1: 100% dos estudantes terminaram o processo de capacitação. Fase 2: Identificou- se como principais problemas de saúde na população estudantil universitária aos relacionados com saúde mental (estresse, ansiedade, depressão), alimentação inadequada e violência. Fase 3: Desenhou-se e executou um projeto de intervenção a partir do diagnóstico realizado, que beneficiou a 2916 pares. Fase 4: Como resultado da intervenção, o 76,2% dos beneficiários manifestaram enfrentar os problemas cotidianos, 90,6% o consideraram importante para seu desenvolvimento pessoal espiritual, afetivo e corporal, 94% melhorou as relações com seus colegas, 68,9% aprenderam sobre seus direitos e 38% reconheceram que modificaram seus hábitos de vida. Conclusões: A metodologia executada deu aos estudantes ferramentas para desenhar, executar e avaliar projetos interdisciplinares de promoção de saúde. A pesquisa-ação possibilita transformações das realidades em saúde em entornos universitários e é possível de ser aplicada em outros contextos.

Experiencia y resultados de un proceso educativo interdisciplinario para la promoción de salud en universitarios / Experience and results of an interdisciplinary educational process for the promotion of health with university students / Experiência e resultados dum processo educativo interdisciplinario para a promoção de saúde em universitarios

Resumen Objetivo: Capacitar a un grupo interdisciplinario de estudiantes de pregrado como promotores universitarios de salud y evaluar los resultados. Metodología: Investigación acción participativa con 13 estudiantes de pregrado de la Pontificia Universidad Católica del Ecuador durante el periodo 2012-2014. El proceso se desarrolló en cuatro fases: 1) capacitación en promoción de salud del grupo; 2) diagnóstico de la situación de salud general de los estudiantes; 3) diseño, planificación e implementación de un proyecto ejecutado por los estudiantes capacitados; y 4) evaluación de la intervención. En cada fase se aplicaron técnicas cualitativas y cuantitativas para el diagnóstico y evaluación de resultados. Resultados: Fase 1: 100% de los estudiantes completaron el proceso de capacitación. Fase 2: se identificó como principales problemas de salud en la población estudiantil universitaria a los relacionados con salud mental (estrés, ansiedad, depresión), alimentación inadecuada y violencia. Fase 3: Se diseñó y ejecutó un proyecto de intervención a partir del diagnóstico realizado, que benefició a 2916 pares. Fase 4: Como resultado de la intervención, el 76,2% de los beneficiarios manifestaron enfrentar los problemas cotidianos, 90,6% lo consideraron importante para su desarrollo personal espiritual, afectivo y corporal, 94% mejoró las relaciones con sus compañeros, 68,9% aprendieron sobre sus derechos y 38% reconocieron que modificaron sus hábitos de vida. Conclusiones: La metodología implementada otorgó a los estudiantes herramientas para diseñar, ejecutar y evaluar proyectos interdisciplinarios de promoción de salud. La investigación-acción posibilita transformaciones de las realidades en salud en entornos universitarios y es factible de ser aplicada en otros contextos.

Abstract Objective: To train an interdisciplinary group of undergraduate students as university health promoters and evaluate their results. Methodology: Participatory action research with 13 undergraduate students of the Pontificia Universidad Católica de Ecuador during the period 2012-2014. The process was developed in four phases: 1) training in health promotion of the group; 2) diagnosis of the general health situation of the students; 3) design, planning and implementation of a project executed by trained students; and 4) evaluation of the intervention. Qualitative and quantitative techniques were applied in each phase for the diagnosis and evaluation of results. Results: Phase 1: 100% of the students completed the training process; Phase 2: The main health problems in the university student population were identified as related to mental health (stress, anxiety, and depression), inadequate diet and violence; Phase 3: An intervention project was designed and executed based on the diagnosis made, which benefited 2916 peers; Phase 4: As a result of the intervention, 76.2% of the beneficiaries stated that they faced daily problems, 90.6% considered it important for their personal spiritual, emotional and corporal development, 94% improved relations with their peers, 68, 9% learned about their rights and 38% acknowledged that they modified their life habits. Conclusions: The methodology implemented gave students tools to design, execute and evaluate interdisciplinary health promotion projects. Action research enables transformations of realities in health in university settings and is feasible to be applied in other contexts.

Resumo Objetivo: Capacitar a um grupo interdisciplinares de estudantes de formatura como promotores universitários de saúde e avaliar os resultados. Metodologia: Pesquisa ação participativa com 13 estudantes de formatura da Pontifícia Universidade Católica do Equador durante o período 2012-2014. O processo de desenvolvimento em quatro fases: 1) capacitação em promoção de saúde do grupo; 2) diagnóstico da situação de saúde geral dos estudantes; 3) design, planificação e execução dum projeto executado pelos estudantes capacitados; e 4) avaliação da intervenção. Em cada fase se aplicação técnicas qualitativas e quantitativas para o diagnóstico e avaliação de resultados. Resultados: Fase 1: 100% dos estudantes terminaram o processo de capacitação. Fase 2: Identificouse como principais problemas de saúde na população estudantil universitária aos relacionados com saúde mental (estresse, ansiedade, depressão), alimentação inadequada e violência. Fase 3: Desenhou-se e executou um projeto de intervenção a partir do diagnóstico realizado, que beneficiou a 2916 pares. Fase 4: Como resultado da intervenção, o 76,2% dos beneficiários manifestaram enfrentar os problemas cotidianos, 90,6% o consideraram importante para seu desenvolvimento pessoal espiritual, afetivo e corporal, 94% melhorou as relações com seus colegas, 68,9% aprenderam sobre seus direitos e 38% reconheceram que modificaram seus hábitos de vida. Conclusões: A metodologia executada deu aos estudantes ferramentas para desenhar, executar e avaliar projetos interdisciplinares de promoção de saúde. A pesquisa-ação possibilita transformações das realidades em saúde em entornos universitários e é possível de ser aplicada em outros contextos.

C4 and crassulacean acid metabolism within a single leaf: deciphering key components behind a rare photosynthetic adaptation.

Although biochemically related, C4 and crassulacean acid metabolism (CAM) systems are expected to be incompatible. However, Portulaca species, including P. oleracea, operate C4 and CAM within a single leaf, and the mechanisms behind this unique photosynthetic arrangement remain largely unknown. Here, we employed RNA-seq to identify candidate genes involved exclusively or shared by C4 or CAM, and provided an in-depth characterization of their transcript abundance patterns during the drought-induced photosynthetic transitions in P. oleracea. Data revealed fewer candidate CAM-specific genes than those recruited to function in C4 . The putative CAM-specific genes were predominantly involved in night-time primary carboxylation reactions and malate movement across the tonoplast. Analysis of gene transcript-abundance regulation and photosynthetic physiology indicated that C4 and CAM coexist within a single P. oleracea leaf under mild drought conditions. Developmental and environmental cues were shown to regulate CAM expression in stems, whereas the shift from C4 to C4 -CAM hybrid photosynthesis in leaves was strictly under environmental control. Moreover, efficient starch turnover was identified as part of the metabolic adjustments required for CAM operation in both organs. These findings provide insights into C4 /CAM connectivity and compatibility, contributing to a deeper understanding of alternative ways to engineer CAM into C4 crop species.

Key changes in gene expression identified for different stages of C4 evolution in Alloteropsis semialata.

C4 photosynthesis is a complex trait that boosts productivity in tropical conditions. Compared with C3 species, the C4 state seems to require numerous novelties, but species comparisons can be confounded by long divergence times. Here, we exploit the photosynthetic diversity that exists within a single species, the grass Alloteropsis semialata, to detect changes in gene expression associated with different photosynthetic phenotypes. Phylogenetically informed comparative transcriptomics show that intermediates with a weak C4 cycle are separated from the C3 phenotype by increases in the expression of 58 genes (0.22% of genes expressed in the leaves), including those encoding just three core C4 enzymes: aspartate aminotransferase, phosphoenolpyruvate carboxykinase, and phosphoenolpyruvate carboxylase. The subsequent transition to full C4 physiology was accompanied by increases in another 15 genes (0.06%), including only the core C4 enzyme pyruvate orthophosphate dikinase. These changes probably created a rudimentary C4 physiology, and isolated populations subsequently improved this emerging C4 physiology, resulting in a patchwork of expression for some C4 accessory genes. Our work shows how C4 assembly in A. semialata happened in incremental steps, each requiring few alterations over the previous step. These create short bridges across adaptive landscapes that probably facilitated the recurrent origins of C4 photosynthesis through a gradual process of evolution.

The genetics of convergent evolution: insights from plant photosynthesis.

The tree of life is resplendent with examples of convergent evolution, whereby distinct species evolve the same trait independently. Many highly convergent adaptations are also complex, which makes their repeated emergence surprising. In plants, the evolutionary history of two carbon concentrating mechanisms (CCMs) - C4 and crassulacean acid metabolism (CAM) photosynthesis - presents such a paradox. Both of these modifications of ancestral C3 photosynthesis require the integration of multiple anatomical and biochemical components, yet together they have evolved more than one hundred times. The presence of CCM enzymes in all plants suggests that a rudimentary CCM might emerge via relatively few genetic changes in potentiated lineages. Here, we propose that many of the complexities often associated with C4 and CAM photosynthesis may have evolved during a post-emergence optimization phase. The ongoing development of new model clades for young, emerging CCMs is enabling the comparative studies needed to test these ideas.

Lateral transfers of large DNA fragments spread functional genes among grasses.

A fundamental tenet of multicellular eukaryotic evolution is that vertical inheritance is paramount, with natural selection acting on genetic variants transferred from parents to offspring. This lineal process means that an organism's adaptive potential can be restricted by its evolutionary history, the amount of standing genetic variation, and its mutation rate. Lateral gene transfer (LGT) theoretically provides a mechanism to bypass many of these limitations, but the evolutionary importance and frequency of this process in multicellular eukaryotes, such as plants, remains debated. We address this issue by assembling a chromosome-level genome for the grass Alloteropsis semialata, a species surmised to exhibit two LGTs, and screen it for other grass-to-grass LGTs using genomic data from 146 other grass species. Through stringent phylogenomic analyses, we discovered 57 additional LGTs in the A. semialata nuclear genome, involving at least nine different donor species. The LGTs are clustered in 23 laterally acquired genomic fragments that are up to 170 kb long and have accumulated during the diversification of Alloteropsis. The majority of the 59 LGTs in A. semialata are expressed, and we show that they have added functions to the recipient genome. Functional LGTs were further detected in the genomes of five other grass species, demonstrating that this process is likely widespread in this globally important group of plants. LGT therefore appears to represent a potent evolutionary force capable of spreading functional genes among distantly related grass species.

C4 anatomy can evolve via a single developmental change.

C4 photosynthesis is a complex trait that boosts productivity in warm environments. Paradoxically, it evolved independently in numerous plant lineages, despite requiring specialised leaf anatomy. The anatomical modifications underlying C4 evolution have previously been evaluated through interspecific comparisons, which capture numerous changes besides those needed for C4 functionality. Here, we quantify the anatomical changes accompanying the transition between non-C4 and C4 phenotypes by sampling widely across the continuum of leaf anatomical traits in the grass Alloteropsis semialata. Within this species, the only trait that is shared among and specific to C4 individuals is an increase in vein density, driven specifically by minor vein development that yields multiple secondary effects facilitating C4 function. For species with the necessary anatomical preconditions, developmental proliferation of veins can therefore be sufficient to produce a functional C4 leaf anatomy, creating an evolutionary entry point to complex C4 syndromes that can become more specialised.

Gene duplication and dosage effects during the early emergence of C4 photosynthesis in the grass genus Alloteropsis.

The importance of gene duplication for evolutionary diversification has been mainly discussed in terms of genetic redundancy allowing neofunctionalization. In the case of C4 photosynthesis, which evolved via the co-option of multiple enzymes to boost carbon fixation in tropical conditions, the importance of genetic redundancy has not been consistently supported by genomic studies. Here, we test for a different role for gene duplication in the early evolution of C4 photosynthesis, via dosage effects creating rapid step changes in expression levels. Using genome-wide data for accessions of the grass genus Alloteropsis that recently diversified into different photosynthetic types, we estimate gene copy numbers and demonstrate that recurrent duplications in two important families of C4 genes coincided with increases in transcript abundance along the phylogeny, in some cases via a pure dosage effect. While increased gene copy number during the initial emergence of C4 photosynthesis probably offered a rapid route to enhanced expression, we also find losses of duplicates following the acquisition of genes encoding better-suited isoforms. The dosage effect of gene duplication might therefore act as a transient process during the evolution of a C4 biochemistry, rendered obsolete by the fixation of regulatory mutations increasing expression levels.

Highly Expressed Genes Are Preferentially Co-Opted for C4 Photosynthesis.

Novel adaptations are generally assembled by co-opting pre-existing genetic components, but the factors dictating the suitability of genes for new functions remain poorly known. In this work, we used comparative transcriptomics to determine the attributes that increased the likelihood of some genes being co-opted for C4 photosynthesis, a convergent complex trait that boosts productivity in tropical conditions. We show that independent lineages of grasses repeatedly co-opted the gene lineages that were the most highly expressed in non-C4 ancestors to produce their C4 pathway. Although ancestral abundance in leaves explains which genes were used for the emergence of a C4 pathway, the tissue specificity has surprisingly no effect. Our results suggest that levels of key genes were elevated during the early diversification of grasses and subsequently repeatedly used to trigger a weak C4 cycle via relatively few mutations. The abundance of C4-suitable transcripts therefore facilitated physiological innovation, but the transition to a strong C4 pathway still involved consequent changes in expression levels, leaf specificity, and coding sequences. The direction and amount of changes required for the strong C4 pathway depended on the identity of the genes co-opted, so that ancestral gene expression both facilitates adaptive transitions and constrains subsequent evolutionary trajectories.

Introgression and repeated co-option facilitated the recurrent emergence of C4 photosynthesis among close relatives.

The origins of novel traits are often studied using species trees and modeling phenotypes as different states of the same character, an approach that cannot always distinguish multiple origins from fewer origins followed by reversals. We address this issue by studying the origins of C4 photosynthesis, an adaptation to warm and dry conditions, in the grass Alloteropsis. We dissect the C4 trait into its components, and show two independent origins of the C4 phenotype via different anatomical modifications, and the use of distinct sets of genes. Further, inference of enzyme adaptation suggests that one of the two groups encompasses two transitions to a full C4 state from a common ancestor with an intermediate phenotype that had some C4 anatomical and biochemical components. Molecular dating of C4 genes confirms the introgression of two key C4 components between species, while the inheritance of all others matches the species tree. The number of origins consequently varies among C4 components, a scenario that could not have been inferred from analyses of the species tree alone. Our results highlight the power of studying individual components of complex traits to reconstruct trajectories toward novel adaptations.

Quarter-millimeter-resolution molecular mouse imaging with U-SPECT⁺.

Limited spatial resolution of preclinical positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has slowed down applications of molecular imaging in small animals. Here we present the latest-generation U-SPECT system (U-SPECT⁺, MILabs, Utrecht, the Netherlands) enabling radionuclide imaging of mice with quarter-millimeter resolution. The system was equipped with the newest high-resolution collimator with 0.25 mm diameter circular pinholes. It was calibrated with technetium-99 m point source measurements from which the system matrix was calculated. Images were reconstructed using pixel-based ordered subset expectation maximization (OSEM). Various phantoms and mouse SPECT scans were acquired. The reconstructed spatial resolution (the smallest visible capillary diameter in a hot-rod resolution phantom) was 0.25 mm. Knee joint images show tiny structures such as the femur epicondyle sulcus, as well as a clear separation between cortical and trabecular bone structures. In addition, time-activity curves of the lumbar spine illustrated that tracer dynamics in tiny tissue amounts could be measured. U-SPECT⁺ allows discrimination between molecular concentrations in adjacent volumes of as small as 0.015 µL, which is significantly better than can be imaged by any existing SPECT or PET system. This increase in the level of detail makes it more and more attractive to replace ex vivo methods and allows monitoring biological processes in tiny parts of organs in vivo.