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Cover page of Toward real‐time, volumetric dosimetry for FLASH‐capable clinical synchrocyclotrons using protoacoustic imaging

Toward real‐time, volumetric dosimetry for FLASH‐capable clinical synchrocyclotrons using protoacoustic imaging

(2024)

Background

Radiation delivery with ultra-high dose rate (FLASH) radiotherapy (RT) holds promise for improving treatment outcomes and reducing side effects but poses challenges in radiation delivery accuracy due to its ultra-high dose rates. This necessitates the development of novel imaging and verification technologies tailored to these conditions.

Purpose

Our study explores the effectiveness of proton-induced acoustic imaging (PAI) in tracking the Bragg peak in three dimensions and in real time during FLASH proton irradiations, offering a method for volumetric beam imaging at both conventional and FLASH dose rates.

Methods

We developed a three-dimensional (3D) PAI technique using a 256-element ultrasound detector array for FLASH dose rate proton beams. In the study, we tested protoacoustic signal with a beamline of a FLASH-capable synchrocyclotron, setting the distal 90% of the Bragg peak around 35 mm away from the ultrasound array. This configuration allowed us to assess various total proton radiation doses, maintaining a consistent beam output of 21 pC/pulse. We also explored a spectrum of dose rates, from 15 Gy/s up to a FLASH rate of 48 Gy/s, by administering a set number of pulses. Furthermore, we implemented a three-dot scanning beam approach to observe the distinct movements of individual Bragg peaks using PAI. All these procedures utilized a proton beam energy of 180 MeV to achieve the maximum possible dose rate.

Results

Our findings indicate a strong linear relationship between protoacoustic signal amplitudes and delivered doses (R2 = 0.9997), with a consistent fit across different dose rates. The technique successfully provided 3D renderings of Bragg peaks at FLASH rates, validated through absolute Gamma index values.

Conclusions

The protoacoustic system demonstrates effectiveness in 3D visualization and tracking of the Bragg peak during FLASH proton therapy, representing a notable advancement in proton therapy quality assurance. This method promises enhancements in protoacoustic image guidance and real-time dosimetry, paving the way for more accurate and effective treatments in ultra-high dose rate therapy environments.

Cover page of Caring for Coma after Severe Brain Injury: Clinical Practices and Challenges to Improve Outcomes: An Initiative by the Curing Coma Campaign

Caring for Coma after Severe Brain Injury: Clinical Practices and Challenges to Improve Outcomes: An Initiative by the Curing Coma Campaign

(2024)

Severe brain injury can result in disorders of consciousness (DoC), including coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. Improved emergency and trauma medicine response, in addition to expanding efforts to prevent premature withdrawal of life-sustaining treatment, has led to an increased number of patients with prolonged DoC. High-quality bedside care of patients with DoC is key to improving long-term functional outcomes. However, there is a paucity of DoC-specific evidence guiding clinicians on efficacious bedside care that can promote medical stability and recovery of consciousness. This Viewpoint describes the state of current DoC bedside care and identifies knowledge and practice gaps related to patient care with DoC collated by the Care of the Patient in Coma scientific workgroup as part of the Neurocritical Care Society's Curing Coma Campaign. The gap analysis identified and organized domains of bedside care that could affect patient outcomes: clinical expertise, assessment and monitoring, timing of intervention, technology, family engagement, cultural considerations, systems of care, and transition to the post-acute continuum. Finally, this Viewpoint recommends future research and education initiatives to address and improve the care of patients with DoC.

Cover page of Correction: Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Neuroimaging

Correction: Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Neuroimaging

(2024)

The list of Curing Coma Campaign Collaborators included in the Acknowledgements section has been updated. Flora Hammond, Raimund Helbok, and Naomi Niznick have been added to the list. Several spelling errors have been corrected. A revised file has been included.

Cover page of 1.7-micron Optical Coherence Tomography Angiography for diagnosis and monitoring of Hereditary Hemorrhagic Telangiectasia - A pilot study

1.7-micron Optical Coherence Tomography Angiography for diagnosis and monitoring of Hereditary Hemorrhagic Telangiectasia - A pilot study

(2024)

Objective

Develop a multi-functional imaging system that combines 1.7μm optical coherence tomography/angiography (OCT/OCTA) to accurately interrogate Hereditary Hemorrhagic Telangiectasia (HHT) skin lesions.

Methods

The study involved imaging HHT skin lesions on five subjects including lips, hands, and chest. We assessed the attributes of both HHT lesions and the healthy vasculature around them in these individuals, employing quantifiable measures such as vascular density and diameter. Additionally, we performed scans on an HHT patient who had undergone anti-angiogenic therapy, allowing us to observe changes in vasculature before and after treatment.

Results

The results from this pilot study demonstrate the feasibility of evaluating the HHT lesion using this novel methodology and suggest the potential of OCTA to noninvasively track HHT lesions over time. The average percentage change in density between HHT patients' lesions and control was 37%. The percentage increase in vessel diameter between lesion and control vessels in HHT patients was 23.21%.

Conclusion

In this study, we demonstrated that OCTA, as a functional extension of OCT, can non-invasively scan HHT lesions in vivo. We scanned five subjects with HHT lesions in various areas (lip, ear, finger, and palm) and quantified vascular density and diameter in both the lesions and adjacent healthy tissue. This non-invasive method will permit a more comprehensive examination of HHT lesions.

Significance

This method of non-invasive imaging could offer new insights into the physiology, management, and therapeutics of HHT-associated lesion development and bleeding.

Cover page of Impact of Tissue Handling and Size Modification on Septal Chondrocyte Viability

Impact of Tissue Handling and Size Modification on Septal Chondrocyte Viability

(2024)

Introduction

The physical modification of cartilage grafts during rhinoplasty risks chondrocyte death at the margins where the tissue is cut. This study compares chondrocyte viability between diced, scaled, and pate samples in human models, and further computes percent chondrocyte viability as a function of sequential dicing size in a computational model.

Methods

Septal cartilage from 11 individuals was prepared as follows: diced (1 mm cubic), scaled (shaved to <1 mm thickness ~ translucent), pate (0.02 g of scraped cartilage surface), positive control (2 × 2 mm diced), and negative control (2 × 2 mm diced soaked in 70% EtOH). Viability analysis was performed using Live/Dead assay™ and confocal microscopy. Numerical simulation of cartilage dicing in 0.05 mm increments was performed using MATLAB assuming 250 chondrocytes/mm3 with each average chondrocyte size of 65 μm2.

Results

Chondrocyte viability was similar between 1 mm diced cartilage, scaled cartilage, and positive control samples (p > 0.05). Conversely, pate samples had significantly less viability compared to positive controls, diced samples, and scaled samples (all p < 0.01 after Bonferroni correction). Pate samples had similar chondrocyte viability compared to negative controls (p = 0.36). On computational modeling, cartilage viability decreased to 50% as the diced sample was cut from 1 mm edge length to 0.7-0.8 mm. Similarly, cartilage viability decreased to 26% at 0.55-0.65 mm, 11% at 0.4-0.5 mm, and <5% at <0.4 mm edge length.

Conclusion

Modifying septal cartilage grafts into 1 mm diced or scaled samples maintains ideal chondrocyte viability whereas pate preparations result in significant chondrocyte death. According to computational analysis, chondrocyte viability sharply decreases as the cartilage is diced below 0.7-0.8 mm.

Level of evidence

N/A Laryngoscope, 134:4259-4265, 2024.

An Optical System for Cellular Mechanostimulation in 3D Hydrogels

(2024)

We introduce a method utilizing single laser-generated cavitation bubbles to stimulate cellular mechanotransduction in dermal fibroblasts embedded within 3D hydrogels. We demonstrate that fibroblasts embedded in either amorphous or fibrillar hydrogels engage in Ca2+ signaling following exposure to an impulsive mechanical stimulus provided by a single 250 µm diameter laser-generated cavitation bubble. We find that the spatial extent of the cellular signaling is larger for cells embedded within a fibrous collagen hydrogel as compared to those embedded within an amorphous polyvinyl alcohol polymer (SLO-PVA) hydrogel. Additionally, for fibroblasts embedded in collagen, we find an increased range of cellular mechanosensitivity for cells that are polarized relative to the radial axis as compared to the circumferential axis. By contrast, fibroblasts embedded within SLO-PVA did not display orientation-dependent mechanosensitivity. Fibroblasts embedded in hydrogels and cultured in calcium-free media did not show cavitation-induced mechanotransduction; implicating calcium signaling based on transmembrane Ca2+ transport. This study demonstrates the utility of single laser-generated cavitation bubbles to provide local non-invasive impulsive mechanical stimuli within 3D hydrogel tissue models with concurrent imaging using optical microscopy. STATEMENT OF SIGNIFICANCE: Currently, there are limited methods for the non-invasive real-time assessment of cellular sensitivity to mechanical stimuli within 3D tissue scaffolds. We describe an original approach that utilizes a pulsed laser microbeam within a standard laser scanning microscope system to generate single cavitation bubbles to provide impulsive mechanostimulation to cells within 3D fibrillar and amorphous hydrogels. Using this technique, we measure the cellular mechanosensitivity of primary human dermal fibroblasts embedded in amorphous and fibrillar hydrogels, thereby providing a useful method to examine cellular mechanotransduction in 3D biomaterials. Moreover, the implementation of our method within a standard optical microscope makes it suitable for broad adoption by cellular mechanotransduction researchers and opens the possibility of high-throughput evaluation of biomaterials with respect to cellular mechanosignaling.

Cover page of Effect of a Novel Ergonomic Sheath on Dental Device-Related Muscle Work, Fatigue and Comfort-A Pilot Clinical Study.

Effect of a Novel Ergonomic Sheath on Dental Device-Related Muscle Work, Fatigue and Comfort-A Pilot Clinical Study.

(2024)

Background: Dental instrumentation with hand-held devices is associated with discomfort, fatigue and musculoskeletal diseases or repetitive stress injuries. The goal of this in vivo study was to determine the effect of an ergonomic handle sheath on muscle work, comfort and fatigue associated with (a) piezoelectric scaling by hygienists with and without musculoskeletal disorders (MSDs), and (b) dental cavity preparation by healthy dentists using a dental micromotor. Materials and Methods: Two groups of ten hygienists each tested the piezoelectric scaler. Hygienists in Group 1 had no MSDs, while those in Group 2 had been diagnosed with MSDs. Additionally, ten dentists with no MSDs used a dental micromotor to prepare four standardized cavities. Time-based work in four muscles, comfort and fatigue were recorded in the presence and absence of an add-on soft, insulating handle sheath. Data were analyzed using a repeated measures analysis of variance model with Tukeys post-hoc test. Results: Comfort, fatigue and muscle work were significantly better for both devices when the sheath was used. While hygienists with MSDs used more muscle work to complete the set scaling task, and the sheath-related reduction in work was somewhat greater, these MSD-related differences did not quite reach significance. Conclusions: The results of this pilot study show that the ergonomic performance of an ultrasonic scaler and a dental micromotor may be improved by the use of an ergonomic handle sheath.