Flattening filter free beam energy selection and its impact in multitarget intracranial stereotactic radiosurgery treatments.

Extensive work has been done on the characteristics, dosimetry, and efficacy of flattening filter free (FFF) beams in radiosurgery. However, no study has addressed the dosimetric impact of FFF beam energy selection on treatment plan quality. This study aims to present a systematic dosimetric comparison of plan quality between 10 FFF vs 6 FFF beams in intracranial stereotactic radiosurgery (SRS) treatments using volumetric modulated arc therapy (VMAT). The dosimetric evaluation is based on radiation therapy oncology group (RTOG) dose conformity (CIRTOG) and gradient (GIRTOG) indices, and irradiated normal brain tissue volume. Thirty-five VMAT-based intracranial SRS treatments to multiple brain metastases using a 2.5 mm multileaf collimator (MLC) and 10 MV FFF beam were replanned with a 6 MV FFF and same MLC. The replans incorporated the same arc arrangement, planning target volume (PTV) and organs at risk structures, PTV coverage and prescription isodose normalization. The 6 MV FFF had a sharper dose fall-off compared to the 10 MV FFF (GIRTOG-10 FFF = 4.70, GIRTOG-6 FFF = 4.56; p < 0.05) and comparable conformity index (CIRTOG-10 FFF = 1.11, CIRTOG-6 FFF = 1.10; p = 0.9). On average, the irradiated normal brain tissue volume was 11% lower with 6 MV FFF compared to 10 MV FFF (p < 0.05). However, this difference was diminished for large target volumes and increased number of targets treated. The main dosimetric improvement of a 6 MV FFF over a 10 MV FFF beam is the sharper dose fall-off which directly correlates with less normal brain tissue volume irradiation.

Acceleration Sensitivity in Bulk-Extensional Mode, Silicon-Based MEMS Oscillators.

Acceleration sensitivity in silicon bulk-extensional mode oscillators is studied in this work, and a correlation between the resonator alignment to different crystalline planes of silicon and the observed acceleration sensitivity is established. It is shown that the oscillator sensitivity to the applied vibration is significantly lower when the silicon-based lateral-extensional mode resonator is aligned to the <110> plane compared to when the same resonator is aligned to <100>. A finite element model is developed that is capable of predicting the resonance frequency variation when a distributed load (i.e., acceleration) is applied to the resonator. Using this model, the orientation-dependent nature of acceleration sensitivity is confirmed, and the effect of material nonlinearity on the acceleration sensitivity is also verified. A thin-film piezoelectric-on-substrate platform is chosen for the implementation of resonators. Approximately, one order of magnitude higher acceleration sensitivity is measured for oscillators built with a resonator aligned to the <100> plane versus those with a resonator aligned to the <110> plane (an average of ~5.66 × 10-8 (1/g) vs. ~3.66 × 10-9 (1/g), respectively, for resonators on a degenerately n-type doped silicon layer).

Focused ultrasound-mediated sonochemical internalization: an alternative to light-based therapies.

Activation of sonosensitizers via focused ultrasound (FUS), i.e., sonodynamic therapy has been proposed as an extension to light-activated photodynamic therapy for the treatment of brain as well as other tumors. The use of FUS, as opposed to light, allows treatment to tumor sites buried deep within tissues as well as through the intact skull. We have examined ultrasonic activation of sonosensitizers together with the anticancer agent bleomycin (BLM), i.e., sonochemical internalization (SCI). SCI is a technique that utilizes FUS for the enhanced delivery of endo-lysosomal trapped macromolecules into the cell cytoplasm in a similar manner to light-based photochemical internalization. The released agent can, therefore, exert its full biological activity, in contrast to being degraded by lysosomal hydrolases. Our results indicate that, compared to drug or FUS treatment alone, FUS activation of the sonosensitizer AlPcS2a together with BLM significantly inhibits the ability of treated glioma cells to grow as three-dimensional tumor spheroids in vitro.

Synergistic chemotherapy by combined moderate hyperthermia and photochemical internalization.

Combination therapies of photochemical internalization (PCI) and moderate hyperthermia (MHT) were investigated in an in vitro system consisting of human and rat glioma spheroids. PCI using the amphiphilic photosensitizer, AlPcS2a and two anti cancer agents BLM or 5-FU were used. Spheroids were irradiated with λ = 670 nm laser light in an incubator at temperatures ranging from 37 to 44°C. For each temperature investigated, spheroids were divided into 4 groups: control, drug-only, photodynamic therapy (PDT), and PCI. PDT and PCI spheroids were exposed to radiant exposures ranging from 0.3 to 2.5 J cm(-2) using an irradiance of 5 mW cm(-2). Toxicity was evaluated from spheroid growth kinetics. The combination of PCI and MHT resulted in significant increases in BLM efficacy at 44°C for both cell line derived spheroids compared to controls at 37°C over the range of radiant exposures examined. 5-FU PCI was ineffective for the human cell line at both 37 and 44°C.

Comparing the Effects of Light- or Sonic-Activated Drug Delivery: Photochemical/Sonochemical Internalization.

Photochemical internalization (PCI) is a technique that uses the photochemical properties of photodynamic therapy (PDT) for the enhanced delivery of endolysosomal-trapped macromolecules into the cell cytoplasm. The released agent can therefore exert its full biological activity, in contrast to being degraded by lysosomal hydrolases. Activation of photosensitizers via ultrasound (US), called sonodynamic therapy (SDT), has been proposed as an alternative to light-activated PDT for the treatment of cancerous tumors. The use of focused US (FUS) to activate photosensitizers allows treatment at tumor sites buried deep within tissues, overcoming one of the main limitations of PDT/PCI. We have examined ultrasonic activation of photosensitizers together with the anticancer agent bleomycin (BLM) using sonochemical internalization (SCI), as an alternative to light-activated PCI. Our results indicate that, compared to drug or US treatment alone, US activation of the photosensitizer AlPcS2a together with BLM significantly inhibits the ability of treated glioma cells to form clonogenic colonies.