ABSTRACT
PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) has gained increased interest in prostate cancer (PCa). This analysis aims to evaluate the feasibility, safety, and limitations of RGS with a novel drop-in gamma probe in primary PCa. PATIENTS AND METHODS: The data of 13 patients with primary PCa undergoing RGS were analyzed retrospectively. After preoperative administration of 99m Tc-PSMA-I&S, a SPECT/CT was conducted and a robotic radical prostatectomy was performed the following day including intraoperative assessment of the lymph node stations using a novel robotic drop-in gamma probe. This was followed by an extended pelvic lymph node dissection (ePLND) with ex vivo control measurement using the drop-in and a conventional rigid gamma probe. RESULTS: Eleven patients (median PSA value of 11 ng/mL) had high-risk and 2 patients had intermediate-risk PCa. Overall, a median of 22 ePLND lymph nodes were dissected. In 1 patient, preoperative SPECT/CT imaging showed suspicious lymph nodes, which could be confirmed intraoperatively with the robotic drop-in probe and subsequently in the final histopathological analysis. RGS failed to identify 2 patients with micrometastases (<3 mm) preoperatively and intraoperatively. No postoperative complications related to 99m Tc-PSMA-I&S RGS or ePLND occurred. CONCLUSIONS: RGS with the novel drop-in gamma probe and 99m Tc-PSMA-I&S allows for a reliable intraoperative screening for lymph node metastases in robot-assisted radical prostatectomy for primary PCa with an acceptable safety profile. However, limitations in the detection of micrometastases need to be overcome before omitting extended ePLND in patients at risk for lymphatic spread.
Subject(s)
Feasibility Studies , Prostatectomy , Prostatic Neoplasms , Robotic Surgical Procedures , Single Photon Emission Computed Tomography Computed Tomography , Humans , Male , Prostatic Neoplasms/surgery , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Middle Aged , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Lymph Nodes/pathology , Glutamate Carboxypeptidase II/metabolism , Organotechnetium Compounds , Retrospective Studies , Oligopeptides , Surgery, Computer-Assisted , Lymphatic Metastasis , Antigens, SurfaceABSTRACT
Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.
Subject(s)
Deafness , Hearing Loss , Male , Aged , Middle Aged , Female , Animals , Humans , Gerbillinae , Hearing/physiology , Evoked Potentials, Auditory, Brain Stem/physiology , Auditory Threshold , Auditory Perception/physiology , Acoustic StimulationABSTRACT
[This corrects the article DOI: 10.2196/44204.].
ABSTRACT
Shorebirds (order Charadriiformes) are among the world's most threatened avian taxa. Within the East Asian-Australasian Flyway (EAAF), a major threat to shorebirds' survival may be the gauntlet of pollution along the flyway. Metals, persistent organic pollutants (POPs), and per-/polyfluoroalkyl substances (PFASs) persist in the environment to the detriment of wildlife. In this study, we analysed element and PFAS concentrations in blood from 142 individuals across six species of Arctic-breeding migratory shorebirds with contrasting population trends, to discern species- and site-specific pollution differences, and determine how pollution correlated with population trends of EAAF shorebirds. Potential within-year pollution variations were investigated by blood-sampling birds at two sites, representing different points in the birds' annual migrations: staging in Taiwan on southward migrations and at non-breeding grounds in Western Australia (WA). Species' pollutant concentrations were compared to established population trends. Concentrations of potentially toxic elements were low in most individuals regardless of species. PFASs (range: <0.001-141 ng/g), Hg (<0.001-9910 ng/g) and Pb (<0.01-1210 ng/g) were higher in Taiwan than in WA (PFAS Taiwan median: 14.5 ng/g, WA median: 3.45 ng/g; Hg Taiwan: 338 ng/g, WA: 23.4 ng/g; Pb Taiwan: 36.8 ng/g, WA: 2.26 ng/g). Meanwhile As (range <0.001-8840 ng/g) and Se (290-47600 ng/g) were higher in WA than Taiwan (As Taiwan median: 500 ng/g, WA median: 1660 ng/g; Se Taiwan: 5490 ng/g, Se WA: 23700 ng/g). Nevertheless, pollutant concentrations in a subset of individuals may exceed sublethal effect thresholds (As, Se and PFASs). Finally, we found no consistent differences in pollution among species and demonstrated no correlation between pollution and population trends, suggesting pollution is likely not a major driver for population declines of EAAF shorebirds. However, ongoing and locally heavy environmental degradation and exposure to other contaminants not investigated here, such as POPs, warrants continued consideration when managing EAAF shorebird populations.
Subject(s)
Environmental Pollutants , Fluorocarbons , Mercury , Humans , Animals , Environmental Pollutants/analysis , Lead , Birds , Mercury/analysis , Fluorocarbons/analysisABSTRACT
The immune-fibrosis axis plays a critical role in cardiac remodeling after acute myocardial infarction. Imaging approaches to monitor temporal inflammation and fibroblast activation in mice have seen wide application in recent years. However, the repeatability of quantitative measurements remains challenging, particularly across multiple imaging centers. We aimed to determine reproducibility of quantitative inflammation and fibroblast activation images acquired at 2 facilities after myocardial infarction in mice. Methods: Mice underwent coronary artery ligation and sequential imaging with 68Ga-DOTA-ECL1i to assess chemokine receptor type 2 expression at 3 d after myocardial infarction and 68Ga-FAPI-46 to assess fibroblast activation protein expression at 7 d after myocardial infarction. Images were acquired at 1 center using either a local or a consensus protocol developed with the second center; the protocols differed in the duration of isoflurane anesthesia and the injected tracer dose. A second group of animals were scanned at the second site using the consensus protocol. Image analyses performed by each site and just by 1 site were also compared. Results: The uptake of 68Ga-DOTA-ECL1i in the infarct territory tended to be higher when the consensus protocol was used (P = 0.03). No difference was observed between protocol acquisitions for 68Ga-FAPI-46. Compared with the local protocol, the consensus protocol decreased variability between individual animals. When a matched consensus protocol was used, the 68Ga-DOTA-ECL1i infarct territory percentage injected dose per gram of tissue was higher on images acquired at site B than on those acquired at site A (P = 0.006). When normalized to body weight as SUV, this difference was mitigated. Both the percentage injected dose per gram of tissue and the SUV were comparable between sites for 68Ga-FAPI-46. Image analyses at the sites differed significantly, but this difference was mitigated when all images were analyzed at site A. Conclusion: The application of a standardized acquisition protocol may lower variability within datasets and facilitate comparison of molecular radiotracer distribution between preclinical imaging centers. Like clinical studies, multicenter preclinical studies should use centralized core-based image analysis to maximize reproducibility across sites.
Subject(s)
Gallium Radioisotopes , Myocardial Infarction , Mice , Animals , Reproducibility of Results , Myocardial Infarction/diagnostic imaging , Positron-Emission Tomography/methods , Inflammation , Positron Emission Tomography Computed Tomography/methodsABSTRACT
BACKGROUND: Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host's immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model. METHODS: PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis. RESULTS: The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site. CONCLUSION: Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation.
Subject(s)
Nanopores , Positron Emission Tomography Computed Tomography , Animals , Mice , Clodronic Acid , Gallium Radioisotopes , Tissue Distribution , Titanium , Disease Models, Animal , Magnetic PhenomenaABSTRACT
The rapid destruction of natural wetland habitats over past decades has been partially offset by an increase in artificial wetlands. However, these also include wastewater treatment plants, which may pose a pollution risk to the wildlife using them. We studied two long-distance Arctic-breeding migratory shorebird species, curlew sandpiper (Calidris ferruginea, n = 69) and red-necked stint (Calidris ruficollis, n = 103), while on their Australian non-breeding grounds using an artificial wetland at a wastewater treatment plant (WTP) and a natural coastal wetland. We compared pollutant exposure (elements and per- and poly-fluoroalkyl substances/PFASs), disease (avian influenza), physiological status (oxidative stress) of the birds at the two locations from 2011 to 2020, and population survival from 1978 to 2019. Our results indicated no significant differences in blood pellet pollutant concentrations between the habitats except mercury (WTP median: 224 ng/g, range: 19-873 ng/g; natural wetland: 160 ng/g, 22-998 ng/g) and PFASs (total PFASs WTP median: 85.1 ng/g, range: <0.01-836 ng/g; natural wetland: 8.02 ng/g, <0.01-85.3 ng/g) which were higher at the WTP, and selenium which was lower at the WTP (WTP median: 5000 ng/g, range: 1950-34,400 ng/g; natural wetland: 19,200 ng/g, 4130-65,200 ng/g). We also measured higher blood o,o'-dityrosine (an indicator of protein damage) at the WTP. No significant differences were found for adult survival, but survival of immature birds at the WTP appeared to be lower which could be due to higher dispersal to other wetlands. Interestingly, we found active avian influenza infections were higher in the natural habitat, while seropositivity was higher in the WTP, seemingly not directly related to pollutant exposure. Overall, we found limited differences in pollutant exposure, health and survival of the shorebirds in the two habitats. Our findings suggest that appropriately managed wastewater treatment wetlands could provide a suitable alternative habitat to these migratory species, which may aid in curbing the decline of shorebird populations from widespread habitat loss.
Subject(s)
Charadriiformes , Environmental Pollutants , Fluorocarbons , Influenza in Birds , Animals , Wetlands , Australia , Ecosystem , Birds/physiology , Environmental Pollutants/analysisABSTRACT
Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity. Methods: Twenty-three AS patients underwent 68Ga-FAP inhibitor 46 (68Ga-FAPI) PET, cardiac MRI, and echocardiography within 1-3 d before TAVR. Imaging parameters were correlated and then were integrated with clinical and blood biomarkers. Control cohorts of subjects without a history of cardiac disease and with (n = 5) and without (n = 9) arterial hypertension were compared with matched AS subgroups. Results: Myocardial FAP volume varied significantly among AS subjects (range, 1.54-138 cm3, mean ± SD, 42.2 ± 35.6 cm3) and was significantly higher than in controls with (7.42 ± 8.56 cm3, P = 0.007) and without (2.90 ± 6.67 cm3; P < 0.001) hypertension. FAP volume correlated with N-terminal prohormone of brain natriuretic peptide (r = 0.58, P = 0.005), left ventricular ejection fraction (r = -0.58, P = 0.02), mass (r = 0.47, P = 0.03), and global longitudinal strain (r = 0.55, P = 0.01) but not with cardiac MRI T1 (spin-lattice relaxation time) and extracellular volume (P = not statistically significant). In-hospital improvement in left ventricular ejection fraction after TAVR correlated with pre-TAVR FAP volume (r = 0.440, P = 0.035), N-terminal prohormone of brain natriuretic peptide, and strain but not with other imaging parameters. Conclusion: FAP-targeted PET identifies varying degrees of left ventricular fibroblast activation in TAVR candidates with advanced AS. 68Ga-FAPI signal does not match other imaging parameters, generating the hypothesis that it may become useful as a tool for personalized selection of optimal TAVR candidates.
Subject(s)
Aortic Valve Stenosis , Hypertension , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/methods , Pilot Projects , Stroke Volume/physiology , Ventricular Function, Left/physiology , Gallium Radioisotopes , Natriuretic Peptide, Brain , Treatment Outcome , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Hypertension/surgery , Molecular Imaging , Fibroblasts , Aortic Valve/diagnostic imaging , Aortic Valve/surgeryABSTRACT
BACKGROUND: We explored the interrelation between prostate-specific membrane antigen (PSMA) expression on circulating tumor cells (CTCs) and that of solid metastatic lesions as determined by whole-body PSMA-targeted positron emission tomography (PET) to refine the prediction of response to subsequent PSMA-targeted radioligand therapy (RLT). METHODS: A prospective study was performed in 20 patients with advanced mCRPC. Of these, 16 underwent subsequent RLT with [177 Lu]Lu-PSMA-617 at a dose of 7.4 GBq every 6-8 weeks. PSMA expression on CTCs using the CellSearch system was compared to clinical and serological results, and to marker expression in targeted imaging and available histological sections of prostatectomy specimens (19% of RLT patients). Clinical outcome was obtained after two cycles of RLT. RESULTS: Marked heterogeneity of PSMA expression was observed already at first diagnosis in available histological specimens. Targeted whole-body imaging also showed heterogeneous inter- and intra-patient PSMA expression between metastases. Heterogeneity of CTC PSMA expression was partially paralleled by heterogeneity of whole-body tumor burden PSMA expression. Twenty percent of CTC samples showed no PSMA expression, despite unequivocal PSMA expression of solid metastases at PET. A high fraction of PSMA-negative CTCs emerged as the sole predictor of poor RLT response (odds ratio [OR]: 0.9379 [95% confidence interval, CI, 0.8558-0.9902]; p = 0.0160), and was prognostic for both shorter progression-free survival (OR: 1.236 [95% CI, 1.035-2.587]; p = 0.0043) and overall survival (OR: 1.056 [95% CI, 1.008-1.141]; p = 0.0182). CONCLUSION: This proof-of-principle study suggests that liquid biopsy for CTC PSMA expression is complementary to PET for individual PSMA phenotyping of mCRPC.
Subject(s)
Neoplastic Cells, Circulating , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Prostatic Neoplasms, Castration-Resistant/drug therapy , Treatment Outcome , Prospective Studies , Tumor Burden , Prostate-Specific Antigen/metabolism , Retrospective StudiesABSTRACT
BACKGROUND: The COVID-19 pandemic is characterized by rapid increases in infection burden owing to the emergence of new variants with higher transmissibility and immune escape. To date, monitoring the COVID-19 pandemic has mainly relied on passive surveillance, yielding biased epidemiological measures owing to the disproportionate number of undetected asymptomatic cases. Active surveillance could provide accurate estimates of the true prevalence to forecast the evolution of the pandemic, enabling evidence-based decision-making. OBJECTIVE: This study compared 4 different approaches of active SARS-CoV-2 surveillance focusing on feasibility and epidemiological outcomes. METHODS: A 2-factor factorial randomized controlled trial was conducted in 2020 in a German district with 700,000 inhabitants. The epidemiological outcome comprised SARS-CoV-2 prevalence and its precision. The 4 study arms combined 2 factors: individuals versus households and direct testing versus testing conditioned on symptom prescreening. Individuals aged ≥7 years were eligible. Altogether, 27,908 addresses from 51 municipalities were randomly allocated to the arms and 15 consecutive recruitment weekdays. Data collection and logistics were highly digitized, and a website in 5 languages enabled low-barrier registration and tracking of results. Gargle sample collection kits were sent by post. Participants collected a gargle sample at home and mailed it to the laboratory. Samples were analyzed with reverse transcription loop-mediated isothermal amplification (RT-LAMP); positive and weak results were confirmed with real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Recruitment was conducted between November 18 and December 11, 2020. The response rates in the 4 arms varied between 34.31% (2340/6821) and 41.17% (2043/4962). The prescreening classified 16.61% (1207/7266) of the patients as COVID-19 symptomatic. Altogether, 4232 persons without prescreening and 7623 participating in the prescreening provided 5351 gargle samples, of which 5319 (99.4%) could be analyzed. This yielded 17 confirmed SARS-CoV-2 infections and a combined prevalence of 0.36% (95% CI 0.14%-0.59%) in the arms without prescreening and 0.05% (95% CI 0.00%-0.108%) in the arms with prescreening (initial contacts only). Specifically, we found a prevalence of 0.31% (95% CI 0.06%-0.58%) for individuals and 0.35% (95% CI 0.09%-0.61%) for households, and lower estimates with prescreening (0.07%, 95% CI 0.0%-0.15% for individuals and 0.02%, 95% CI 0.0%-0.06% for households). Asymptomatic infections occurred in 27% (3/11) of the positive cases with symptom data. The 2 arms without prescreening performed the best regarding effectiveness and accuracy. CONCLUSIONS: This study showed that postal mailing of gargle sample kits and returning home-based self-collected liquid gargle samples followed by high-sensitivity RT-LAMP analysis is a feasible way to conduct active SARS-CoV-2 population surveillance without burdening routine diagnostic testing. Efforts to improve participation rates and integration into the public health system may increase the potential to monitor the course of the pandemic. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (DRKS) DRKS00023271; https://tinyurl.com/3xenz68a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-021-05619-5.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , Pandemics/prevention & control , Specimen Handling , LaboratoriesABSTRACT
Challenges have become the state-of-the-art approach to benchmark image analysis algorithms in a comparative manner. While the validation on identical data sets was a great step forward, results analysis is often restricted to pure ranking tables, leaving relevant questions unanswered. Specifically, little effort has been put into the systematic investigation on what characterizes images in which state-of-the-art algorithms fail. To address this gap in the literature, we (1) present a statistical framework for learning from challenges and (2) instantiate it for the specific task of instrument instance segmentation in laparoscopic videos. Our framework relies on the semantic meta data annotation of images, which serves as foundation for a General Linear Mixed Models (GLMM) analysis. Based on 51,542 meta data annotations performed on 2,728 images, we applied our approach to the results of the Robust Medical Instrument Segmentation Challenge (ROBUST-MIS) challenge 2019 and revealed underexposure, motion and occlusion of instruments as well as the presence of smoke or other objects in the background as major sources of algorithm failure. Our subsequent method development, tailored to the specific remaining issues, yielded a deep learning model with state-of-the-art overall performance and specific strengths in the processing of images in which previous methods tended to fail. Due to the objectivity and generic applicability of our approach, it could become a valuable tool for validation in the field of medical image analysis and beyond.
Subject(s)
Algorithms , Laparoscopy , Humans , Image Processing, Computer-Assisted/methodsABSTRACT
Ischemic stroke imparts elevated risk of heart failure though the underlying mechanisms remain poorly described. We aimed to characterize the influence of cerebral ischemic injury on cardiac function using multimodality molecular imaging to investigate brain and cardiac morphology and tissue inflammation in two mouse models of variable stroke severity. Transient middle cerebral artery occlusion (MCAo) generated extensive stroke damage (56.31 ± 40.39 mm3). Positron emission tomography imaging of inflammation targeting the mitochondrial translocator protein (TSPO) revealed localized neuroinflammation at 7 days after stroke compared to sham (3.8 ± 0.8 vs 2.6 ± 0.7 %ID/g max, p < 0.001). By contrast, parenchyma topical application of vasoconstrictor endothelin-1 did not generate significant stroke damage or neuroinflammatory cell activity. MCAo evoked a modest reduction in left ventricle ejection fraction at both 1 weeks and 3 weeks after stroke (LVEF at 3 weeks: 54.3 ± 5.7 vs 66.1 ± 3.5%, p < 0.001). This contractile impairment was paralleled by elevated cardiac TSPO PET signal compared to sham (8.6 ± 2.4 vs 5.8 ± 0.7%ID/g, p = 0.022), but was independent of leukocyte infiltration defined by flow cytometry. Stroke size correlated with severity of cardiac dysfunction (r = 0.590, p = 0.008). Statistical parametric mapping identified a direct association between neuroinflammation at 7 days in a cluster of voxels including the insular cortex and reduced ejection fraction (ρ = - 0.396, p = 0.027). Suppression of microglia led to lower TSPO signal at 7 days which correlated with spared late cardiac function after MCAo (r = - 0.759, p = 0.029). Regional neuroinflammation early after cerebral ischemia influences subsequent cardiac dysfunction. Total body TSPO PET enables monitoring of neuroinflammation, providing insights into brain-heart inter-organ communication and may guide therapeutic intervention to spare cardiac function post-stroke.
Subject(s)
Brain Ischemia , Heart Diseases , Stroke , Animals , Mice , Brain/diagnostic imaging , Brain/metabolism , Brain Ischemia/metabolism , Endothelin-1/metabolism , Heart Diseases/metabolism , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/diagnostic imaging , Inflammation/metabolism , Molecular Imaging/methods , Positron-Emission Tomography/methods , Stroke/metabolism , Vasoconstrictor AgentsABSTRACT
Detecting Out-of-Distribution (OoD) data is one of the greatest challenges in safe and robust deployment of machine learning algorithms in medicine. When the algorithms encounter cases that deviate from the distribution of the training data, they often produce incorrect and over-confident predictions. OoD detection algorithms aim to catch erroneous predictions in advance by analysing the data distribution and detecting potential instances of failure. Moreover, flagging OoD cases may support human readers in identifying incidental findings. Due to the increased interest in OoD algorithms, benchmarks for different domains have recently been established. In the medical imaging domain, for which reliable predictions are often essential, an open benchmark has been missing. We introduce the Medical-Out-Of-Distribution-Analysis-Challenge (MOOD) as an open, fair, and unbiased benchmark for OoD methods in the medical imaging domain. The analysis of the submitted algorithms shows that performance has a strong positive correlation with the perceived difficulty, and that all algorithms show a high variance for different anomalies, making it yet hard to recommend them for clinical practice. We also see a strong correlation between challenge ranking and performance on a simple toy test set, indicating that this might be a valuable addition as a proxy dataset during anomaly detection algorithm development.
Subject(s)
Benchmarking , Machine Learning , Algorithms , HumansABSTRACT
Persistent inflammation following myocardial infarction (MI) precipitates adverse outcome including acute ventricular rupture and chronic heart failure. Molecular imaging allows longitudinal assessment of immune cell activity in the infarct territory and predicts severity of remodeling. We utilized a multiparametric imaging platform to assess the immune response and cardiac healing following MI in mice. Suppression of circulating macrophages prior to MI paradoxically resulted in higher total leukocyte content in the heart, demonstrated by increased CXC motif chemokine receptor 4 (CXCR4) positron emission tomography imaging. This supported the formation of a thrombus overlying the injured region, as identified by magnetic resonance imaging. The injured and thrombotic region in macrophage depeleted mice subsequently showed active calcification, as evidenced by accumulation of 18F-fluoride and by cardiac computed tomography. Importantly, macrophage suppression triggered a prolonged inflammatory response confirmed by post-mortem tissue analysis that was associated with higher mortality from ventricular rupture early after occlusion and with increased infarct size and worse chronic contractile function at 6 weeks after reperfusion. These findings establish a molecular imaging toolbox for monitoring the interplay between adverse immune response and tissue repair after MI. This may serve as a foundation for development and monitoring of novel targeted therapies that may include immune modulation and endogenous healing support.
Subject(s)
Myocardial Infarction , Ventricular Remodeling , Animals , Immunity , Mice , Myocardial Infarction/pathology , Myocardium/pathology , Positron-Emission Tomography/methods , Ventricular Remodeling/physiologyABSTRACT
After acute myocardial infarction (AMI), fibroblast activation protein (FAP) upregulation exceeds the infarct region. We sought further insights into the physiologic relevance by correlating FAP-targeted PET with tissue characteristics from cardiac MRI (CMR) and functional outcome. Methods: Thirty-five patients underwent CMR, perfusion SPECT, and 68Ga-FAP inhibitor (FAPI)-46 PET/CT within 11 d after AMI. Infarct size was determined from SPECT by comparison to a reference database. For PET, regional SUVs and isocontour volumes of interest determined the extent of cardiac FAP upregulation (FAP volume). CMR yielded functional parameters, area of injury (late gadolinium enhancement [LGE]) and T1/T2 mapping. Follow-up was available from echocardiography or CMR after 139.5 d (interquartile range, 80.5-188.25 d) (n = 14). Results: The area of FAP upregulation was significantly larger than the SPECT perfusion defect size (58% ± 15% vs. 23% ± 17%, P < 0.001) and infarct area by LGE (28% ± 11%, P < 0.001). FAP volume significantly correlated with CMR parameters at baseline (all P < 0.001): infarct area (r = 0.58), left ventricle (LV) mass (r = 0.69), end-systolic volume (r = 0.62), and end-diastolic volume (r = 0.57). Segmental analysis revealed FAP upregulation in 308 of 496 myocardial segments (62%). Significant LGE was found in only 56% of FAP-positive segments, elevated T1 in 74%, and elevated T2 in 68%. Fourteen percent (44/308) of FAP-positive segments exhibited neither prolonged T1 or T2 nor significant LGE. Of note, FAP volume correlated only weakly with simultaneously measured LV ejection fraction at baseline (r = -0.32, P = 0.07), whereas there was a significant inverse correlation with LV ejection fraction obtained at later follow-up (r = -0.58, P = 0.007). Conclusion: Early after AMI and reperfusion therapy, activation of fibroblasts markedly exceeds the hypoperfused infarct region and involves noninfarcted myocardium. The 68Ga-FAPI PET signal does not match regional myocardial tissue characteristics as defined by CMR but is predictive of the evolution of ventricular dysfunction. FAP-targeted imaging may provide a novel biomarker of LV remodeling that is complementary to existing techniques.
Subject(s)
Magnetic Resonance Imaging, Cine , Myocardial Infarction , Contrast Media , Fibroblasts , Gadolinium , Gallium Radioisotopes , Humans , Magnetic Resonance Imaging, Cine/methods , Myocardium , Positron Emission Tomography Computed Tomography , Predictive Value of Tests , Stroke Volume , Ventricular Function, LeftABSTRACT
BACKGROUND: Although digital and data-based technologies are widespread in various industries in the context of Industry 4.0, the use of smart connected devices in health care is still in its infancy. Innovative solutions for the medical environment are affected by difficult access to medical device data and high barriers to market entry because of proprietary systems. OBJECTIVE: In the proof-of-concept project OP 4.1, we show the business viability of connecting and augmenting medical devices and data through software add-ons by giving companies a technical and commercial platform for the development, implementation, distribution, and billing of innovative software solutions. METHODS: The creation of a central platform prototype requires the collaboration of several independent market contenders, including medical users, software developers, medical device manufacturers, and platform providers. A dedicated consortium of clinical and scientific partners as well as industry partners was set up. RESULTS: We demonstrate the successful development of the prototype of a user-centric, open, and extensible platform for the intelligent support of processes starting with the operating room. By connecting heterogeneous data sources and medical devices from different manufacturers and making them accessible for software developers and medical users, the cloud-based platform OP 4.1 enables the augmentation of medical devices and procedures through software-based solutions. The platform also allows for the demand-oriented billing of apps and medical devices, thus permitting software-based solutions to fast-track their economic development and become commercially successful. CONCLUSIONS: The technology and business platform OP 4.1 creates a multisided market for the successful development, implementation, distribution, and billing of new software solutions in the operating room and in the health care sector in general. Consequently, software-based medical innovation can be translated into clinical routine quickly, efficiently, and cost-effectively, optimizing the treatment of patients through smartly assisted procedures.
ABSTRACT
BACKGROUND: A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic neuroendocrine tumors, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated volumetric parameters for quantification of whole-body tumor burden from somatostatin receptor (SSR)-targeted PET/CT. METHODS: Thirty-two patients with metastastic grade1/grade 2 gastroenteropancreatic neuroendocrine tumors who underwent a 68Ga-DOTA-TATE PET/CT for staging of disease before initiation of peptide receptor radionuclide therapy were included in this retrospective cohort analysis. Volumetric parameters of tumor lesions, SSR-derived tumor volume (SSR-TV) and total lesion SSR (TL-SSR), were calculated for each patient using a computerized volumetric technique with a 40% SUV
Subject(s)
Neuroendocrine Tumors , Organometallic Compounds , Humans , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/pathology , Positron Emission Tomography Computed Tomography/methods , Gallium Radioisotopes , Tumor Burden , Retrospective Studies , Radiopharmaceuticals , Receptors, Somatostatin , BiomarkersABSTRACT
Recent developments in data science in general and machine learning in particular have transformed the way experts envision the future of surgery. Surgical Data Science (SDS) is a new research field that aims to improve the quality of interventional healthcare through the capture, organization, analysis and modeling of data. While an increasing number of data-driven approaches and clinical applications have been studied in the fields of radiological and clinical data science, translational success stories are still lacking in surgery. In this publication, we shed light on the underlying reasons and provide a roadmap for future advances in the field. Based on an international workshop involving leading researchers in the field of SDS, we review current practice, key achievements and initiatives as well as available standards and tools for a number of topics relevant to the field, namely (1) infrastructure for data acquisition, storage and access in the presence of regulatory constraints, (2) data annotation and sharing and (3) data analytics. We further complement this technical perspective with (4) a review of currently available SDS products and the translational progress from academia and (5) a roadmap for faster clinical translation and exploitation of the full potential of SDS, based on an international multi-round Delphi process.
Subject(s)
Data Science , Machine Learning , HumansABSTRACT
BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT. METHODS: In 46 mCRPC patients scheduled for Lu-177-PSMA-RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m2 ]), Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) clearance and baseline Ga-68-PSMA-ligand positron emission tomography (PET)-derived renal cortical uptake and PSMA-tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow-up. RESULTS: After 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/min/1.73 m2 (p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow-up, 16/46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m2 ), followed by Tc-99m-MAG3-derived tubular extraction rate (TER; AUC, 0.831, p < 0.001; best threshold, 200 ml/min/1.73 m2 ). Renal PET signal (p = 0.751) and PSMA-TV (p = 0.942), however, were not predictive. Kaplan-Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy-derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007). CONCLUSION: Serious adverse renal events are not a frequent phenomenon after PSMA-targeted RLT. However, in patients developing moderate CKD after RLT, pretherapeutic eGFR is an independent predictor for renal impairment during follow-up.