Site of breast cancer metastasis is independent of single nutrient levels.

Cancer metastasis is a major contributor to patient morbidity and mortality, yet the factors that determine the organs where cancers can metastasize are incompletely understood. In this study, we quantify the absolute levels of over 100 nutrients available across multiple tissues in mice and investigate how this relates to the ability of breast cancer cells to grow in different organs. We engineered breast cancer cells with broad metastatic potential to be auxotrophic for specific nutrients and assessed their ability to colonize different organs.

A Machine Learning-Optimized System for Pulsatile, Photo- and Chemotherapeutic Treatment Using Near-Infrared Responsive MoS-Based Microparticles in a Breast Cancer Model.

Multimodal cancer therapies are often required for progressive cancers due to the high persistence and mortality of the disease and the negative systemic side effects of traditional therapeutic methods. Thus, the development of less invasive modalities for recurring treatment cycles is of clinical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation.

Texaphyrin-Based Calcium Sensor for Multimodal Imaging.

The ability to monitor intracellular calcium concentrations using fluorescent probes has led to important insights into biological signaling processes at the cellular level. An important challenge is to relate such measurements to broader patterns of signaling across fields of view that are inaccessible to optical techniques. To meet this need, we synthesized molecular probes that couple calcium-binding moieties to lanthanide texaphyrins, resulting in complexes endowed with a diverse complement of magnetic and photophysical properties.

A Machine Learning-optimized system for on demand, pulsatile, photo- and chemo-therapeutic treatment using near-infrared responsive MoS -based microparticles in a breast cancer model.

Cancer therapy research is of high interest because of the persistence and mortality of the disease and the side effects of traditional therapeutic methods, while often multimodal treatments are necessary based on the patient's needs. The development of less invasive modalities for recurring treatment cycles is thus of critical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation, by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation.

Maximizing response to intratumoral immunotherapy in mice by tuning local retention.

Direct injection of therapies into tumors has emerged as an administration route capable of achieving high local drug exposure and strong anti-tumor response. A diverse array of immune agonists ranging in size and target are under development as local immunotherapies. However, due to the relatively recent adoption of intratumoral administration, the pharmacokinetics of locally-injected biologics remains poorly defined, limiting rational design of tumor-localized immunotherapies.

Magnetic Retrieval of Encapsulated Beta Cell Transplants from Diabetic Mice Using Dual-Function MRI Visible and Retrievable Microcapsules.

Encapsulated beta cell transplantation offers a potential cure for a subset of diabetic patients. Once transplanted, beta cell grafts can help to restore glycemic control; however, locating and retrieving cells in the event of graft failure may pose a surgical challenge. Here, a dual-function nanoparticle-loaded hydrogel microcapsule is developed that enables graft retrieval under an applied magnetic field.

Wireless resonant circuits for the minimally invasive sensing of biophysical processes in magnetic resonance imaging.

Biological electromagnetic fields arise throughout all tissue depths and types, and correlate with physiological processes and signalling in organs of the body. Most of the methods for monitoring these fields are either highly invasive or spatially coarse. Here, we show that implantable active coil-based transducers that are detectable via magnetic resonance imaging enable the remote sensing of biological fields.

Simultaneous spatiotemporal tracking and oxygen sensing of transient implants in vivo using hot-spot MRI and machine learning.

A varying oxygen environment is known to affect cellular function in disease as well as activity of various therapeutics. For transient structures, whether they are unconstrained therapeutic transplants, migrating cells during tumor metastasis, or cell populations induced by an immunological response, the role of oxygen in their fate and function is known to be pivotal albeit not well understood in vivo. To address such a challenge in the case of generation of a bioartificial pancreas, we have combined fluorine magnetic resonance imaging and unsupervised machine learning to monitor over time the spatial arrangement and the oxygen content of implants encapsulating pancreatic islets that are unconstrained in the intraperitoneal (IP) space of healthy and diabetic mice.

Investigation of a clinical PET detector module design that employs large-area avalanche photodetectors.

We investigated the feasibility of designing an Anger-logic PET detector module using large-area high-gain avalanche photodiodes (APDs) for a brain-dedicated PET/MRI system. Using Monte Carlo simulations, we systematically optimized the detector design with regard to the scintillation crystal, optical diffuser, surface treatment, layout of large-area APDs, and signal-to-noise ratio (SNR, defined as the 511 keV photopeak position divided by the standard deviation of noise floor in an energy spectrum) of the APD devices. A detector prototype was built comprising an 8 × 8 array of 2.

Scintillation induced response in passively-quenched Si-based single photon counting avalanche diode arrays.

An optical electrical model which studies the response of Si-based single photon counting arrays, specifically silicon photomultipliers (SiPMs), to scintillation light has been developed and validated with analytically derived and experimental data. The scintillator-photodetector response in terms of relative pulse height, 10%-90% rise/decay times to light stimuli of different rise times (ranging from 0.1 to 5 ns) and decay times (ranging from 1 to 50 ns), as well as for different decay times of the photodetector are compared in theory and simulation.

Photo-detectors for time of flight positron emission tomography (ToF-PET).

We present the most recent advances in photo-detector design employed in time of flight positron emission tomography (ToF-PET). PET is a molecular imaging modality that collects pairs of coincident (temporally correlated) annihilation photons emitted from the patient body. The annihilation photon detector typically comprises a scintillation crystal coupled to a fast photo-detector.

PET & SPECT instrumentation.

The nuclear medical imaging methods, positron emission tomography (PET) and single photon emission computed tomography (SPECT), utilize the detection of gamma rays leaving the body after a radioactive tracer has been administered. The sensitivity of PET allows the detection of picomolar tracer amounts in vivo and current technology offers millimeter (PET) or submillimeter (SPECT) spatial resolution. These techniques are used in clinical and preclinical applications.