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Maintaining persistent migration in complex environments is critical for neutrophils to reach infection sites. Neutrophils avoid getting trapped, even when obstacles split their front into multiple leading edges. How they re-establish polarity to move productively while incorporating receptor inputs under such conditions remains unclear. Here, we challenge chemotaxing HL60 neutrophil-like cells with symmetric bifurcating microfluidic channels to probe cell-intrinsic processes during the resolution of competing fronts. Using supervised statistical learning, we demonstrate that cells commit to one leading edge late in the process, rather than amplifying structural asymmetries or early fluctuations. Using optogenetic tools, we show that receptor inputs only bias the decision similarly late, once mechanical stretching begins to weaken each front. Finally, a retracting edge commits to retraction, with ROCK limiting sensitivity to receptor inputs until the retraction completes. Collectively, our results suggest that cell edges locally adopt highly stable protrusion/retraction programs that are modulated by mechanical feedback.

To migrate efficiently to target locations, cells must integrate receptor inputs while maintaining polarity: a distinct front that leads and a rear that follows. Here we investigate what is necessary to overwrite pre-existing front-rear polarity in neutrophil-like HL60 cells migrating inside straight microfluidic channels. Using subcellular optogenetic receptor activation, we show that receptor inputs can reorient weakly polarized cells, but the rear of strongly polarized cells is refractory to new inputs. Transient stimulation reveals a multi-step repolarization process, confirming that cell rear sensitivity to receptor input is the primary determinant of large-scale directional reversal. We demonstrate that the RhoA/ROCK/myosin II pathway limits the ability of receptor inputs to signal to Cdc42 and reorient migrating neutrophils. We discover that by tuning the phosphorylation of myosin regulatory light chain we can modulate the activity and localization of myosin II and thus the amenability of the cell rear to 'listen' to receptor inputs and respond to directional reprogramming.

Efficient chemotaxis requires rapid coordination between different parts of the cell in response to changing directional cues. Here, we investigate the mechanism of front-rear coordination in chemotactic neutrophils. We find that changes in the protrusion rate at the cell front are instantaneously coupled to changes in retraction at the cell rear, while myosin II accumulation at the rear exhibits a reproducible 9-15-s lag. In turning cells, myosin II exhibits dynamic side-to-side relocalization at the cell rear in response to turning of the leading edge and facilitates efficient turning by rapidly re-orienting the rear. These manifestations of front-rear coupling can be explained by a simple quantitative model incorporating reversible actin-myosin interactions with a rearward-flowing actin network. Finally, the system can be tuned by the degree of myosin regulatory light chain (MRLC) phosphorylation, which appears to be set in an optimal range to balance persistence of movement and turning ability.

Efficient chemotaxis requires rapid coordination between different parts of the cell in response to changing directional cues. Here, we investigate the mechanism of front-rear coordination in chemotactic neutrophils. We find that changes in the protrusion rate at the cell front are instantaneously coupled to changes in retraction at the cell rear, while myosin II accumulation at the rear exhibits a reproducible 9-15-s lag. In turning cells, myosin II exhibits dynamic side-to-side relocalization at the cell rear in response to turning of the leading edge and facilitates efficient turning by rapidly re-orienting the rear. These manifestations of front-rear coupling can be explained by a simple quantitative model incorporating reversible actin-myosin interactions with a rearward-flowing actin network. Finally, the system can be tuned by the degree of myosin regulatory light chain (MRLC) phosphorylation, which appears to be set in an optimal range to balance persistence of movement and turning ability.

• EFOMP QC PET/CT and PET/MRI protocol document. • QC tests to guarantee image quality, quantification accuracy and adequate radiation dose. • Consists of easy-to-integrate practical tests for use in clinical practice. • Allows users to detect changes in PET/CT/MRI system performance. • Crucial for avoiding the short- and long-term system and image quality deterioration. This article presents the protocol on Quality Controls in PET/CT and PET/MRI published online in May 2022 by the European Federation of Organisations for Medical Physics (EFOMP), which was developed by the Working group for PET/CT and PET/MRI Quality Control (QC) protocol. The main objective of this protocol was to comprehensively provide simple and practical procedures that may be integrated into clinical practice to identify changes in the PET/CT/MRI system's performance and avoid short- and long-term quality deterioration. The protocol describes the quality control procedures on radionuclide calibrators, weighing scales, PET, CT and MRI systems using selected and measurable parameters that are directly linked to clinical images quality. It helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantification accuracy and patient radiation dose. CT and MRI QCs are described only in the context of their use for PET (attenuation correction and anatomical localization) imaging. Detailed step-by-step instructions have been provided, limiting any misinterpretations or interpersonal variations as much as possible. This paper presents the main characteristics of the protocol illustrated together with a brief summary of the content of each chapter. A regular QC based on the proposed protocol would guarantee that PET/CT and PET/MRI systems operate under optimal conditions, resulting in the best performance for routine clinical tasks. [ABSTRACT FROM AUTHOR]

Purpose In an oncology nuclear medicine department, radioisotopes are not only used for tumor detecting, staging, evaluation of therapy response but also for therapeutic purposes. This study documents the radiation exposure of departmental staff, related to cyclotron operation and service during the production and injection of 18 F radiopharmaceuticals for PET/CT examination. In addition, it investigates exposure in a multiple holding tank system used for the storage of 131 I waste generated from patients undergoing thyroid therapy, in order to optimize environmental protection procedures. Methods Measurements for the dose rates of neutrons and photons in the room of ABT-BG-75 self-shielded mini-cyclotron were recorded during bombardment for 18 F-FDG production using a neutron detector and a scintillation dosimeter. The correlation between the duration of bombardment and required time to reach a dose rate equal to background level was investigated. An electronic dosimeter was used to record staff exposure for 18 F production, dispensing, administration and imaging using PET-CT. Finally, the decay rate of 131 I waste was measured using a dose rate meter positioned in the decay tank system of the radioactive iodine isolation ward. Results The time required for the cyclotron room to reach background level following completion of bombardment (3 × 50 min each) was approximately 2 h. The dose rate from neutrons was found to be negligible and from photons was less than 7.5  μ Sv/h. Therefore, personnel can safely enter the room during bombardment. The staff mean whole-body dose per 18 F-administered patient was 1–2  μ Sv, depending on patient condition. The values obtained from the 131 I radioactive waste stored in a delay tank system were comparable with theoretical values. Conclusion This study is useful for optimizing radiation exposure in an oncology nuclear medicine department. It is shown that during 18 F production exposure is mostly attributed to photons. The level of the dose permits staff entry into the cyclotron room. Staff responsible for administration received 1–2  μ Sv per 18 F-patient, considered to be on the lower end of the acceptable limit for a radiation worker. The study also documents the decay rate of 131 I waste over the period which the suggested activity level for release in the environment is reached. [ABSTRACT FROM AUTHOR]