Dataset Information

Assessment of a Silicon-Photomultiplier-Based Platform for the Measurement of Intracellular Calcium Dynamics with Targeted Aequorin.

ABSTRACT: Ca²⁺ is among the most important intracellular second messengers participating in a plethora of biological processes, and the measurement of Ca²⁺ fluctuations is significant in the phenomenology of the underlying processes. Aequorin-based Ca²⁺ probes represent an invaluable tool for reliable measurement of Ca²⁺ concentrations and dynamics in different subcellular compartments. However, their use is limited due to the lack on the market of ready-to-use, cost-effective, and portable devices for the detection and readout of the low-intensity bioluminescence signal produced by these probes. Silicon photomultipliers (SiPMs) are rapidly evolving solid-state sensors for low light detection, with single photon sensitivity and photon number resolving capability, featuring low cost, low voltage, and compact format. Thus, they may represent the sensors of choice for the development of such devices and, more in general, of a new generation of multipurpose bioluminescence detectors suitable for cell biology studies. Ideally, a detector customized for these purposes must combine high dynamic range with high fidelity in reconstructing the light intensity signal temporal profile. In this article, the ability to perform aequorin-based intracellular Ca²⁺ measurements using a multipurpose, low-cost setup exploiting SiPMs as the sensors is demonstrated. SiPMs turn out to assure performances comparable to those exhibited by a custom-designed photomultiplier tube-based aequorinometer. Moreover, the flexibility of SiPM-based devices might pave the way toward routinely and wide scale application of innovative biophysical protocols.

SUBMITTER: Ruffinatti FA

PROVIDER: S-EPMC8009593 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Assessment of a Silicon-Photomultiplier-Based Platform for the Measurement of Intracellular Calcium Dynamics with Targeted Aequorin.

Ruffinatti Federico Alessandro FA Lomazzi Samuela S Nardo Luca L Santoro Romualdo R Martemiyanov Alexander A Dionisi Marianna M Tapella Laura L Genazzani Armando A AA Lim Dmitry D Distasi Carla C Caccia Massimo M

ACS sensors 20200805 8

Ca2+ is among the most important intracellular second messengers participating in a plethora of biological processes, and the measurement of Ca2+ fluctuations is significant in the phenomenology of the underlying processes. Aequorin-based Ca2+ probes represent an invaluable tool for reliable measurement of Ca2+ concentrations and dynamics in different subcellular compartments. However, their use is limited due to the lack on the market of ready-to-use, ...[more]

PMID: 32701269

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Project description:PurposeThe implementation of photon-counting detectors is widely expected to be the next breakthrough in X-ray computed tomography (CT) instrumentation. A small number of prototype scanners equipped with direct-conversion detectors based on room-temperature semiconductors, such as CdTe and CdZnTe (CZT), are currently installed at medical centers. Here, we investigate the feasibility of using silicon photomultiplier (SiPM)-based scintillation detectors in photon-counting computed tomography (PCCT) scanners, as a potential alternative to CdTe and CZT detectors.MethodsWe introduce a model that allows us to compute the expected energy resolution as well as the expected pulse shape and associated rate capability of SiPM-based PCCT detectors. The model takes into account SiPM saturation and optical crosstalk, because these phenomena may substantially affect the performance of SiPM-based PCCT detectors with sub-mm pixels. We present model validation experiments using a single-pixel detector consisting of a 0.9 × 0.9 × 1.0 mm3 LuAP:Ce scintillation crystal coupled to a 1 × 1 mm2 SiPM. We subsequently use the validated model to compute the expected performance of the fast scintillators LYSO:Ce, LuAP:Ce, and LaBr3 :Ce, coupled to currently available SiPMs, as well as to a more advanced SiPM prototype with improved dynamic range, for sub-mm pixel sizes.ResultsThe model was found to be in good agreement with the validation experiments, both with respect to energy resolution and pulse shape. It shows how saturation progressively degrades the energy resolution of detectors equipped with currently available SiPMs as the pixel size decreases. Moreover, the expected pulse duration is relatively long (~200 ns) with these SiPMs. However, when LuAP:Ce and LaBr3 :Ce are coupled to the more advanced SiPM prototype, the pulse duration improves to less than 60 ns, which is in the same order of magnitude as pulses from CdTe and CZT detectors. It follows that sufficient rate capability can be achieved with pixel sizes of 400 μm or smaller. Moreover, LaBr3 :Ce detectors can provide an energy resolution of 11.5%-13.5% at 60 keV, comparable to CdTe and CZT detectors.ConclusionsThis work provides first evidence that it may be feasible to develop SiPM-based scintillation detectors for PCCT that can compete with CdTe and CZT detectors in terms of energy resolution and rate capability.

Project description:The radioiodine isotope pair 124I/131I is used in a theranostic approach for patient-specific treatment of differentiated thyroid cancer. Lesion detectability is notably higher for 124I PET (positron emission tomography) than for 131I gamma camera imaging but can be limited for small and low uptake lesions. The recently introduced silicon-photomultiplier-based (SiPM-based) PET/CT (computed tomography) systems outperform previous-generation systems in detector sensitivity, coincidence time resolution, and spatial resolution. Hence, SiPM-based PET/CT shows an improved detectability, particularly for small lesions. In this study, we compare the size-dependant minimum detectable 124I activity (MDA) between the SiPM-based Biograph Vision and the previous-generation Biograph mCT PET/CT systems and we attempt to predict the response to 131I radioiodine therapy of lesions additionally identified on the SiPM-based system. A tumour phantom mimicking challenging conditions (derived from published patient data) was used; i.e., 6 small spheres (diameter of 3.7-9.7 mm), 9 low activity concentrations (0.25-25 kBq/mL), and a very low signal-to-background ratio (20:1). List-mode emission data (single-bed position) were divided into frames of 4, 8, 16, and 30 min. Images were reconstructed with ordinary Poisson ordered-subsets expectation maximization (OSEM), additional time-of-flight (OSEM-TOF) or TOF and point spread function modelling (OSEM-TOF+PSF). The signal-to-noise ratio and the MDA were determined. Absorbed dose estimations were performed to assess possible treatment response to high-activity 131I radioiodine therapy. The signal-to-noise ratio and the MDA were improved from the mCT to the Vision, from OSEM to OSEM-TOF and from OSEM-TOF to OSEM-TOF+PSF reconstructed images, and from shorter to longer emission times. The overall mean MDA ratio of the Vision to the mCT was 0.52 ± 0.18. The absorbed dose estimations indicate that lesions ≥ 6.5 mm with expected response to radioiodine therapy would be detectable on both systems at 4-min emission time. Additional smaller lesions of therapeutic relevance could be detected when using a SiPM-based PET system at clinically reasonable emission times. This study demonstrates that additional lesions with predicted response to 131I radioiodine therapy can be detected. Further clinical evaluation is warranted to evaluate if negative 124I PET scans on a SiPM-based system can be sufficient to preclude patients from blind radioiodine therapy.

Dataset Information

Assessment of a Silicon-Photomultiplier-Based Platform for the Measurement of Intracellular Calcium Dynamics with Targeted Aequorin.

Publications

Assessment of a Silicon-Photomultiplier-Based Platform for the Measurement of Intracellular Calcium Dynamics with Targeted Aequorin.

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