Patients with brain metastases (BMs) are surviving longer and returning for multiple courses of stereotactic radiosurgery. BMs are monitored after radiation with follow-up magnetic resonance (MR) ...imaging every 2–3 months. This study investigated whether it is possible to automatically track BMs on longitudinal imaging and quantify the tumor response after radiotherapy.
The METRO process (MEtastasis Tracking with Repeated Observations was developed to automatically process patient data and track BMs. A longitudinal intrapatient registration method for T1 MR post-Gd was conceived and validated on 20 patients. Detections and volumetric measurements of BMs were obtained from a deep learning model. BM tracking was validated on 32 separate patients by comparing results with manual measurements of BM response and radiologists’ assessments of new BMs. Linear regression and residual analysis were used to assess accuracy in determining tumor response and size change.
A total of 123 irradiated BMs and 38 new BMs were successfully tracked. 66 irradiated BMs were visible on follow-up imaging 3–9 months after radiotherapy. Comparing their longest diameter changes measured manually vs. METRO, the Pearson correlation coefficient was 0.88 (p < 0.001); the mean residual error was −8 ± 17%. The mean registration error was 1.5 ± 0.2 mm.
Automatic, longitudinal tracking of BMs using deep learning methods is feasible. In particular, the software system METRO fulfills a need to automatically track and quantify volumetric changes of BMs prior to, and in response to, radiation therapy.
Abstract
Background
Evaluation of treatment response for brain metastases (BMs) following stereotactic radiosurgery (SRS) becomes complex as the number of treated BMs increases. This study uses ...artificial intelligence (AI) to track BMs after SRS and validates its output compared with manual measurements.
Methods
Patients with BMs who received at least one course of SRS and followed up with MRI scans were retrospectively identified. A tool for automated detection, segmentation, and tracking of intracranial metastases on longitudinal imaging, MEtastasis Tracking with Repeated Observations (METRO), was applied to the dataset. The longest three-dimensional (3D) diameter identified with METRO was compared with manual measurements of maximum axial BM diameter, and their correlation was analyzed. Change in size of the measured BM identified with METRO after SRS treatment was used to classify BMs as responding, or not responding, to treatment, and its accuracy was determined relative to manual measurements.
Results
From 71 patients, 176 BMs were identified and measured with METRO and manual methods. Based on a one-to-one correlation analysis, the correlation coefficient was R2 = 0.76 (P = .0001). Using modified BM response classifications of BM change in size, the longest 3D diameter data identified with METRO had a sensitivity of 0.72 and a specificity of 0.95 in identifying lesions that responded to SRS, when using manual axial diameter measurements as the ground truth.
Conclusions
Using AI to automatically measure and track BM volumes following SRS treatment, this study showed a strong correlation between AI-driven measurements and the current clinically used method: manual axial diameter measurements.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Thesis: Ph. D., Massachusetts Institute of ...Technology, Department of Physics, 2019
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 241-256).
A measurement of the differential Z boson production cross section in proton-proton collisions is presented. It furnishes a precision test of the Standard Model, and constrains the parton distribution functions of the proton. Moreover, it is a building block for future measurements of the mass of the W± boson. A study of the efficiency of lepton identification algorithms is performed which drives the precision of the measurement at lower values of transverse momentum. In tandem, a search for new physics in events with a Z boson produced in association with large missing transverse momentum is presented. The results of this search are interpreted in the context of several dark matter models: generic spin-0 or spin-1 mediators, invisible decays of a Higgs-like boson, unparticles, and large extra spatial dimensions. A multivariate analysis was developed to enhance the sensitivity of the invisible Higgs interpretation. The theoretical uncertainty on the irreducible background from electroweak diboson processes is constrained by emulating the missing energy using pure control samples in the fully leptonic final states. The data were collected with the Compact Muon Solenoid detector at the Large Hadron Collider and correspond to an integrated luminosity of 35.9 fb-1. No significant deviations from the Standard Model are found.
by Dylan George Hsu.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Physics
Sensitization, defined as the presence of circulating antibodies, presents challenges for heart transplant recipients and physicians. When present, sensitization can limit a transplantation ...candidate's access to organs, prolong wait time, and, in some cases, exclude the candidate from heart transplantation altogether. The management of sensitization is not yet standardized, and current therapies have not yielded consistent results. Although current strategies involve antibody suppression and removal with intravenous immunoglobulin, plasmapheresis, and antibody therapy, newer strategies with more specific targets are being investigated.
: In medical sciences, statistical analyses based on observational studies are common phenomena. One peril of drawing inferences about the effect of a treatment on subjects using observational ...studies is the lack of randomized assignment of subjects to the treatment. After adjusting for measured pretreatment covariates, perhaps by matching, a sensitivity analysis examines the impact of an unobserved covariate, u, in an observational study. One type of sensitivity analysis uses two sensitivity parameters to measure the degree of departure of an observational study from randomized assignment. One sensitivity parameter relates u to treatment and the other relates u to response. For subject matter experts, it may be difficult to specify plausible ranges of values for the sensitivity parameters on their absolute scales. We propose an approach that calibrates the values of the sensitivity parameters to the observed covariates and is more interpretable to subject matter experts. We will illustrate our method using data from the U.S. National Health and Nutrition Examination Survey regarding the relationship between cigarette smoking and blood lead levels.
Fear conditioning in animals has been used extensively to model clinical anxiety disorders. While individual animals exhibit marked differences in their propensity to undergo fear conditioning, the ...physiologically relevant mediators have not yet been fully characterized. Here, we demonstrate that C57BL/6 inbred mouse strain subjected to a regimen of chronic social defeat stress (CSDS) can be separated into susceptible and resistant subpopulations that display different levels of fear responses in an auditory fear conditioning paradigm. Susceptible mice had significantly more c-Fos protein expression in neurons of the basolateral amygdala (BLA) following CSDS and showed exaggerated conditioned fear responses, while there were no significant differences between groups in innate anxiety- and depressive-like behaviors. Through the use of conditional brain-derived neurotrophic factor (BDNF) knockout strategies, we find that elevated BLA BDNF level following fear conditioning training is a key mediator contributing to determine the levels of conditioned fear responses. Our results also show that relative to susceptible mice, resistant mice had a much faster recovery from conditioned stimuli-induced cardiovascular and corticosterone responses. Systemic administration of norepinephrine reuptake inhibitor atomoxetine increased c-Fos protein expression in BLA neurons following fear conditioning training and promoted the expression of conditioned fear in resistant mice. Conversely, administration of β-adrenergic receptor antagonist propranolol reduced fear conditioning training-induced c-Fos protein expression in BLA neurons and reduced conditioned fear responses in susceptible mice. These findings reveal a novel role for the BDNF signaling within the BLA in mediating individual differences in autonomic, neuroendocrine and behavioral reactivity to fear conditioning.
•Individuals exhibit differences in their propensity to undergo fear conditioning.•BDNF level in the BLA determines the magnitude of conditioned fear response.•Increased adrenergic activity promotes the acquisition of conditioned fear.
Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer ...programmable RNA-guided RNA recognition that triggers cleavage and release of a fluorescent reporter molecule, but long reaction times hamper their detection sensitivity and speed. Here, we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 molecules per µl of RNA in 20 min. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA extracted from respiratory swab samples with quantitative reverse transcriptase PCR (qRT-PCR)-derived cycle threshold (C
) values up to 33, using a compact detector. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables sensitive, direct RNA detection in a format that is amenable to point-of-care infection diagnosis as well as to a wide range of other diagnostic or research applications.
A new methodology capable of concurrently resolving free surface wave field, bottom boundary layer, and sediment transport processes throughout the entire water column was recently developed in the ...OpenFOAM framework, called SedWaveFoam. In this study, SedWaveFoam is validated with large wave flume data for sheet flow driven by near-breaking waves. Good agreements are obtained for free surface elevation, flow velocity, turbulence kinetic energy, sediment concentration, and sheet flow sediment fluxes. Model results are used to investigate the joint effects of velocity skewness, acceleration skewness, and progressive wave streaming on sheet flow sediment transport. SedWaveFoam results are contrasted with rigid-lid one-dimensional-vertical model results to isolate the effect of the free surface. Onshore directed near-bed flow velocity and sediment flux are enhanced due to the presence of the free surface via progressive wave streaming. However, the enhancement of net onshore sediment transport for the near-breaking condition with both high velocity and acceleration skewness is several factors greater than that found in the nonbreaking condition with only high velocity skewness. Model results suggest that the large horizontal pressure gradient, which has a Sleath parameter exceeding 0.2, may play a key role. Momentary bed failure is identified via near-bed instability of the sheet flow layer, associated with a large bed shear stress and horizontal pressure gradient. Instantaneous near-bed vortices due to the near-bed instability correspond to the increase of horizontal pore pressure gradient during the wave crest, consistent with measured data. Model inter-comparison suggests that a two-dimensional model is crucial to capture the effect of momentary bed failure that increases sediment suspension during wave crest passage and net onshore sediment transport.
•A free surface resolving Eulerian two-phase flow model is validated for sheet flow driven by near-breaking waves on a sandbar.•Onshore-directed sediment flux is enhanced due to progressive wave streaming effect for both velocity and acceleration skewed waves.•The enhancement of onshore transport is more significant for acceleration-skewed waves due to momentary bed failure.
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