Beckman Laser Institute & Medical Clinic

Background

Methods

Results

Conclusion

Electroacoustic imaging is an imaging modality used to detect electric field energy distribution during electroporation, offering valuable guidance for clinical procedures, particularly in deep tissues. Traditionally, single-element piezoelectric transducers or arrays have been employed for this purpose. However, these piezoelectric sensors are sensitive to electromagnetic interference and require physical contact with the sample through a coupling medium, raising concerns for both clinical and preclinical applications. To overcome these limitations, a multi-channel random quadrature ultrasonics system has been developed, enabling non-contact detection of electroacoustic signals. In this study, we demonstrated that this non-contact technique effectively detects electroacoustic signals, identifies electroporation regions, and reconstructs electric energy distribution, offering a promising approach for monitoring electroporation therapy.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue's stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without "packing foam-like" extracellular matrix.

BACKGROUND: The ALLEGRO phase 2b/3 study investigated the efficacy and safety of ritlecitinib in patients with alopecia areata (AA). OBJECTIVE: To describe the impact of ritlecitinib on patient-reported hair loss using the Alopecia Areata Patient Priority Outcomes (AAPPO) instrument and evaluate the relationship between clinically meaningful hair regrowth and improvements in patient-reported impacts. METHODS: In ALLEGRO-2b/3, patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (± 4-week 200-mg daily loading dose), 10 mg, or placebo for 24 weeks and then continued ritlecitinib or switched from placebo to ritlecitinib 200/50 or 50 mg for 24 weeks. The AAPPO instrument evaluated improvement in hair loss, emotional symptoms (ES), and activity limitations (AL) from weeks 4 to 48 (secondary endpoint). Mean changes in ES and AL domain scores and individual items at weeks 24 and 48 were calculated for Severity of Alopecia Tool (SALT) score ≤ 20 responders and nonresponders (exploratory endpoint). RESULTS: Overall, 718 patients were randomized. At week 24, 5-36% of patients receiving ritlecitinib 10-200/50 mg reported improvement in scalp hair loss versus 9% receiving placebo. The results for eyebrow, eyelash, and body hair loss were similar. Mean change from baseline in ES and AL scores at weeks 24 and 48 was small and similar between groups. Mean change was larger for individual hair loss and ES items at weeks 24 and 48 in SALT score ≤ 20 responders versus nonresponders. CONCLUSIONS: The AAPPO instrument demonstrated the beneficial impact of ritlecitinib on patient-reported hair growth, which was consistent with improvements in clinician-reported outcomes. CLINICAL TRIAL REGISTRATION: NCT03732807. INFOGRAPHIC.

Background

Main body

Conclusions

Background: K-edge subtraction (KES) imaging is a dual-energy imaging technique that enhances contrast by subtracting images taken with x-rays that are above and below the K-edge energy of a specified contrast agent. The resulting reconstruction spatially identifies where the contrast agent accumulates, even when obscured by complex and heterogeneous distributions of human tissue. This method is most successful when x-ray sources are quasimonoenergetic and tunable, conditions that have traditionally only been met at synchrotrons. Laser-Compton x-ray sources (LCSs) are a compact alternative to synchrotron radiation with a quasimonoenergetic x-ray spectrum. One limitation in the clinical application of KES imaging with LCSs has been the extensive time required to tune the x-ray spectrum to two different energies. Purpose: We introduce an imaging technique called scanning K-edge subtraction (SKES) that leverages the angle-correlated laser-Compton x-ray spectrum in the setting of mammography. The feasibility and utility of this technique will be evaluated through a series of simulation studies. The goal of SKES imaging is to enable rapid K-edge subtraction imaging using a laser-Compton x-ray source. The technique does not rely on the time-consuming process of tuning laser-Compton interaction parameters. Methods: Laser-Compton interaction physics are modeled using conditions based on an X-band linear electron accelerator architecture currently under development using a combination of 3D particle tracking software and Mathematica. The resulting angle-correlated laser-Compton x-ray beam is propagated through digitally compressed breast phantoms containing iodine contrast-enhanced inserts and then to a digital flat-panel detector using a Matlab Monte Carlo propagation software. This scanning acquisition technique is compared to the direct energy tuning method (DET), as well as to a clinically available dual-energy contrast-enhanced mammography (CEM) system. Results: KES imaging in a scanning configuration using an LCS was able to generate a KES image of comparable quality to the direct energy tuning method. SKES was able to detect tumors with iodine contrast concentrations lower than what is clinically available today including lesions that are typically obscured by dense fibroglandular tissue. After normalizing to mean glandular dose, SKES is able to generate a KES image with equal contrast to CEM using only 3% of the dose. Conclusions: By leveraging the unique quasimonochromatic and angle-correlated x-ray spectrum offered by LCSs, a contrast-enhanced subtraction image can be obtained with significantly more contrast and less dose compared to conventional systems, and improve tumor detection in patients with dense breast tissue. The scanning configuration of this technique could accelerate the clinical translation of this technology.

Many contemporary imaging systems seek tunable focusing components with minimal form factors and versatile functionalities; however, existing solutions are typically limited in size, efficiency, and tuning speed. Here, low-loss all-dielectric metasurfaces integrated with liquid crystals (LCs) are used to demonstrate highly compact multifunctional zoom components. The phase profiles imparted by the metalens are modulated in real time by means of field-dependent LCs, enabling electrically driven continuous focal length variation and active bifocal imaging with low applied voltages (<10 V). These applications are achieved through the systematic design and validation of resonant metasurface elements that ensure the desired metalens response in each LC state. We engineer and fabricate a high-contrast voltage-actuated continuous-zoom LC-metalens with up to 18% total shift in focal length. Additionally, we fabricate simplified large-diameter LC-metalenses, composed of only a few resonator types, that facilitate electrically tunable multidepth imaging. These results demonstrate the promise of electrically controlled LC-embedded zoom-metasurfaces to serve as lightweight and ultrathin multifunctional focusing components, with prospective uses in next-generation imaging devices.

Background

Objective

Methods

Results

Conclusion

Objectives

Methods

Results

Conclusions

Conventional refractive microscope objective lenses have limited applicability to a range of imaging modalities due to the dispersive nature of their optical elements. Designing a conventional refractive microscope objective that provides well-corrected imaging over a broad spectral range can be challenging, if not impossible. In contrast, reflective optics are inherently achromatic, so a system composed entirely of reflective elements is free from chromatic aberrations and, as a result, can image over an ultra-wide spectral range with perfect color correction. This study explores the design space of unobscured high numerical aperture, allreflective microscope objectives. In particular, using freeform optical elements we obviate the need for a center obscuration, rendering the objective's modulation transfer function comparable to that of refractive lens systems of similar numerical aperture. We detail the design process of the reflective objective, from determining the design specifications to the system optimization and sensitivity analysis. The outcome is an all-reflective freeform microscope objective lens with a 0.65 numerical aperture that provides diffraction-limited imaging and is compatible with the geometric constraints of commercial microscope systems.