Kinematic Characterization of Left Ventricular Chamber Stiffness and Relaxation

Heart failure is the most common cause of hospitalization today, and diastolic heart failure accounts for 40-50% of cases. Therefore, it is critical to identify diastolic dysfunction at a subclinical stage so that appropriate therapy can be administered before ventricular function is further, and perhaps irreversibly impaired. Basic concepts in physics such as kinematic modeling provide a unique method with which to characterize cardiovascular physiology, specifically diastolic function (DF). The advantage of an approach that is standard in physics, such as the kinematic modeling is its causal formulation that functions in contrast to correlative approaches traditionally utilized in the life sciences. Our research group has pioneered theoretical and experimental quantitative analysis of DF in humans, using both non-invasive (echocardiography, cardiac MRI) and invasive (simultaneous catheterization-echocardiography) methods. Our group developed and validated the Parametrized Diastolic Filling (PDF) formalism which is motivated by basic physiologic principles (LV is a mechanical suction pump at the mitral valve opening) that obey Newton\u27s Laws. PDF formalism is a kinematic model of filling employing an equation of motion, the solution of which accurately predicts all E-wave contours in accordance with the rules of damped harmonic oscillatory motion. The equation\u27s lumped parameters--ventricular stiffness, ventricular viscoelasticity/relaxation and ventricular load--are obtained by solving the `inverse problem\u27. The parameters\u27 physiologic significance and clinical utility have been repeatedly demonstrated in multiple clinical settings. In this work we apply our kinematic modeling approach to better understand how the heart works as it fills in order to advance the relationship between physiology and mathematical modeling. Through the use of this modeling, we thereby define and validate novel, causal indexes of diastolic function such as early rapid filling energy, diastatic stiffness, and relaxation and stiffness components of E-wave deceleration time

Plasma Electrolytic Oxidation (PEO) Coating on γ-TiAl Alloy: Investigation of Bioactivity and Corrosion Behavior in Simulated Body Fluid

The effect of applied voltage (400, 450, and 500 V) on the microstructure, bioactivity, and corrosion rate of plasma electrolytic oxidation (PEO) coatings on γ-TiAl alloy was investigated. The microstructure and chemical composition of the achieved coatings were studied, along with their corrosion and bioactivity behaviors in simulated body fluid (SBF). The results demonstrated that the higher the coating′s surface pore, the greater the number of suitable sites for the formation of hydroxyapatite with a spherical structure. The coatings applied utilizing 400, 450, and 500 V displayed 59.4, 96.6, and 145 Ω.cm2 as their inner layer electrical resistances, respectively. The findings of the biological examination revealed that Mesenchymal stem cells (MSCs) displayed more cytocompatibility and had a higher capacity for cell attachment in the PEO-coated sample than in γ-TiAl, as a result of better initial cell attachment made possible by the topography of the 500 V PEO coatings. The latter has significant potential to be employed in orthopedic applications

Multi-institutional consensus on machine QA for isochronous cyclotron-based systems delivering ultra-high dose rate (FLASH) pencil beam scanning proton therapy in transmission mode

BackgroundThe first clinical trials to assess the feasibility of FLASH radiotherapy in humans have started (FAST-01, FAST-02) and more trials are foreseen. To increase comparability between trials it is important to assure treatment quality and therefore establish a standard for machine quality assurance (QA). Currently, the AAPM TG-224 report is considered as the standard on machine QA for proton therapy, however, it was not intended to be used for ultra-high dose rate (UHDR) proton beams, which have gained interest due to the observation of the FLASH effect.PurposeThe aim of this study is to find consensus on practical guidelines on machine QA for UHDR proton beams in transmission mode in terms of which QA is required, how they should be done, which detectors are suitable for UHDR machine QA, and what tolerance limits should be applied.MethodsA risk assessment to determine the gaps in the current standard for machine QA was performed by an international group of medical physicists. Based on that, practical guidelines on how to perform machine QA for UHDR proton beams were proposed.ResultsThe risk assessment clearly identified the need for additional guidance on temporal dosimetry, addressing dose rate (constancy), dose spillage, and scanning speed. In addition, several minor changes from AAPM TG-224 were identified; define required dose rate levels, the use of clinically relevant dose levels, and the use of adapted beam settings to minimize activation of detector and phantom materials or to avoid saturation effects of specific detectors. The final report was created based on discussions and consensus.ConclusionsConsensus was reached on what QA is required for UHDR scanning proton beams in transmission mode for isochronous cyclotron-based systems and how they should be performed. However, the group discussions also showed that there is a lack of high temporal resolution detectors and sufficient QA data to set appropriate limits for some of the proposed QA procedures

Dramatic Response of a Large Sacral Chordoma to Intensity Modulated Proton Beam Therapy

Sacral chordomas are slow-growing, indolent, and locally invasive tumors that typically present with pain and neurologic dysfunction. Wide en-bloc surgical excision is the primary treatment, but achieving adequate margins is difficult and surgery is often associated with significant morbidity. Adjuvant radiation therapy (RT) is utilized to decrease the risk of local recurrence or as definitive treatment for nonsurgical candidates. Although chordomas are considered to be relatively radioresistant tumors, several studies have demonstrated tumor response to high-dose proton therapy. Here, we present a patient with a large sacral chordoma who underwent definitive treatment with intensity-modulated proton therapy (IMPT)

Radiation shielding and safety implications following linac conversion to an electron FLASH‐RT unit

Purpose Due to their finite range, electrons are typically ignored when calculating shielding requirements in megavoltage energy linear accelerator vaults. However, the assumption that 16 MeV electrons need not be considered does not hold when operated at FLASH-RT dose rates (~200× clinical dose rate), where dose rate from bremsstrahlung photons is an order of magnitude higher than that from an 18 MV beam for which shielding was designed. We investigate the shielding and radiation protection impact of converting a Varian 21EX linac to FLASH-RT dose rates. Methods We performed a radiation survey in all occupied areas using a Fluke Biomedical Inovision 451P survey meter and a Wide Energy Neutron Detection Instrument (Wendi)-2 FHT 762 neutron detector. The dose rate from activated linac components following a 1.8-min FLASH-RT delivery was also measured. Results When operated at a gantry angle of 180° such as during biology experiments, the 16 MeV FLASH-RT electrons deliver ~10 µSv/h in the controlled areas and 780 µSv/h in the uncontrolled areas, which is above the 20 µSv in any 1-h USNRC limit. However, to exceed 20 µSv, the unit must be operated continuously for 92 s, which corresponds in this bunker and FLASH-RT beam to a 3180 Gy workload at isocenter, which would be unfeasible to deliver within that timeframe due to experimental logistics. While beam steering and dosimetry activities can require workloads of that magnitude, during these activities, the gantry is positioned at 0° and the dose rate in the uncontrolled area becomes undetectable. Likewise, neutron activation of linac components can reach 25 µSv/h near the isocenter following FLASH-RT delivery, but dissipates within minutes, and total doses within an hour are below 20 µSv. Conclusion Bremsstrahlung photons created by a 16 MeV FLASH-RT electron beam resulted in consequential dose rates in controlled and uncontrolled areas, and from activated linac components in the vault. While our linac vault shielding proved sufficient, other investigators would be prudent to confirm the adequacy of their radiation safety program, particularly if operating in vaults designed for 6 MV