Stanford University
Department of Radiation Oncology

Presenter of 1 Presentation

REAL-TIME OPTICAL OXIMETRY UNDER IRRADIATION

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
18:00 - 19:00
Room
Room 2.15
Lecture Time
19:00 - 19:10

Abstract

Background and Aims

Transient changes in oxygen tension in tissues taking place during FLASH radiotherapy may explain its biological effects. However, because the kinetics of oxygen depletion and recovery occur on a very short timescale, it is challenging to measure these effects in vivo using existing methods. Here we developed a real-time optical oximetry system with millisecond temporal resolution to elucidate early radiochemistry under irradiation.

Methods

Oxygen measurements were performed in vitro using the phosphorescence quenching method and a water-soluble molecular nanoprobe (Fig. 1). An epifluorescence fiber-coupled system was designed and built. The system was validated using a standard dissolved oxygen meter. The changes in oxygen per unit dose (G-value) were quantified in response to irradiation by 320 kVp x-ray and 16 MeV electron beam at dose rates ranging from 0.04 Gy/s to 100 Gy/s.

mainfig_signal decay.png

Results

Transient oxygen depletion of phosphate buffer solution under standard kV X-ray irradiation was continuously measured every millisecond (Fig. 2). The samples at normoxia with oxygen concentration of 150–240 µM had constant G-value of 0.54 uM/Gy, however hypoxic samples (15 µM and below) had significantly lower G-values (Fig. 3).

contmeas-xray1.png

oxygen depletion (μm_gy) michaelismenten.png

Conclusions

Our observations suggest that oxygen depletion rate decreases under hypoxia, with the measured data being a good fit to Michaelis-Menten kinetics. Future works will measure oxygen depletion kinetics of biomimetic lipid emulsions and in vivo mice under irradiation. We anticipate that the proposed method will capture crucial millisecond-order oxygen change after individual e-beam pulses.

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Author Of 3 Presentations

FLASH-ENABLED PROTON SBRT/SRS WITH IMPROVED HIGH-DOSE SPARING VIA SIMULTANEOUS DOSE AND DOSE RATE OPTIMIZATION (SDDRO)

Session Type
FLASH in the Clinic Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
10:20 - 11:30
Room
Hall C
Lecture Time
11:10 - 11:20

Abstract

Background and Aims

To investigate the clinical potential of FLASH-RT for improving high-dose sparing of OAR, to enable SBRT/SRS that could otherwise fail to meet dose constraints with CONV-RT.

Methods

CONV-RT (via Bragg peaks (BP)) and FLASH-RT (via transmission beams (TB)) are compared with PBS proton therapy, i.e., CONV-RT planned with IMPT-BP, and FLASH-RT planned respectively with IMPT and SDDRO of TB. While IMPT only optimizes the dose distribution, SDDRO also optimizes the FLASH effect, i.e., to maximize the normal tissue volume receiving dose rate and dose thresholds pertinent to the FLASH effect, which was set to be 40Gy/s and 8Gy. The plan evaluation is based on the effective dose (de), i.e., the product of the physical dose (d) and FLASH dose modifying factor, which was set to be 0.7 when normal tissues meet both dose rate and dose thresholds.

Results

CONV-RT (IMPT-BP) was compared with FLASH-RT (IMPT and SDDRO). In terms of effective dose, (1) conformal index (CI) values show that SDDRO had the best target dose conformality; (2) mean doses at PTV-10mm (10mm expansion of PTV) suggest that SDDRO had the fastest high-dose falloff for normal tissues adjacent to the target.

table.jpg

lung.jpg

Conclusions

Compared to CONV-RT (IMPT-BP), FLASH-RT via SDDRO improved high-dose sparing of OAR, which can potentially enable proton SBRT/SRS that could otherwise fail to meet dose constraints, e.g., the reduction of V12Gy from 44cc to 14cc to meet V12Gy≤15cc for this case to be eligible for brain SRS.

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REAL-TIME OPTICAL OXIMETRY UNDER IRRADIATION

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Wed, 01.12.2021
Session Time
18:00 - 19:00
Room
Room 2.15
Lecture Time
19:00 - 19:10

Abstract

Background and Aims

Transient changes in oxygen tension in tissues taking place during FLASH radiotherapy may explain its biological effects. However, because the kinetics of oxygen depletion and recovery occur on a very short timescale, it is challenging to measure these effects in vivo using existing methods. Here we developed a real-time optical oximetry system with millisecond temporal resolution to elucidate early radiochemistry under irradiation.

Methods

Oxygen measurements were performed in vitro using the phosphorescence quenching method and a water-soluble molecular nanoprobe (Fig. 1). An epifluorescence fiber-coupled system was designed and built. The system was validated using a standard dissolved oxygen meter. The changes in oxygen per unit dose (G-value) were quantified in response to irradiation by 320 kVp x-ray and 16 MeV electron beam at dose rates ranging from 0.04 Gy/s to 100 Gy/s.

mainfig_signal decay.png

Results

Transient oxygen depletion of phosphate buffer solution under standard kV X-ray irradiation was continuously measured every millisecond (Fig. 2). The samples at normoxia with oxygen concentration of 150–240 µM had constant G-value of 0.54 uM/Gy, however hypoxic samples (15 µM and below) had significantly lower G-values (Fig. 3).

contmeas-xray1.png

oxygen depletion (μm_gy) michaelismenten.png

Conclusions

Our observations suggest that oxygen depletion rate decreases under hypoxia, with the measured data being a good fit to Michaelis-Menten kinetics. Future works will measure oxygen depletion kinetics of biomimetic lipid emulsions and in vivo mice under irradiation. We anticipate that the proposed method will capture crucial millisecond-order oxygen change after individual e-beam pulses.

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TEMPORAL RESOLUTION REQUIREMENTS FOR MEASURING THE KINETICS OF OXYGEN DEPLETION DURING FLASH RADIOTHERAPY, BASED ON A 3D COMPUTATIONAL MODEL OF BRAIN VASCULATURE

Session Type
FLASH Mechanisms Track (Oral Presentations)
Date
Fri, 03.12.2021
Session Time
10:50 - 11:50
Room
Room 2.15
Lecture Time
11:20 - 11:30

Abstract

Background and Aims

FLASH has been shown to improve the therapeutic ratio of RT. The mechanism behind this effect has been partially explained by the ROD hypothesis. However, to better understand the contribution of oxygen, it is necessary to measure O2 in-vivo during FLASH irradiation. This study’s goal is to determine the temporal resolution required to accurately measure the rapidly changing oxygen concentration in FLASH RT.

Methods

We conducted a computational simulation of oxygen dynamics using a real vascular model constructed from a public fluorescence microscopy dataset. The dynamic distribution of oxygen tension (po2) was modeled by a PDE considering oxygen diffusion, metabolism, and ROD. The underestimation of ROD due to oxygen recovery was evaluated assuming either complete or partial depletion and a range of parameters such as oxygen diffusion, consumption, vascular po2, and vessel density.

Results

The O2 concentration recovers rapidly after FLASH RT. Assuming a temporal resolution of 0.5s, the estimated ROD is only 50.7% and 36.7% of its actual value in cases of partial and complete depletion. Additionally, the underestimation of ROD strongly depends on the vascular density. To estimate ROD rate with 90% accuracy, temporal resolution on the order of milliseconds is required considering the uncertainty in parameters involved.

Conclusions

The rapid recovery of O2 poses a great challenge for in-vivo ROD measurements in FLASH RT. Temporal resolution on the order of milliseconds is recommended for ROD measurements in the normal tissue. Further work is warranted to investigate whether the same requirements apply to ROD measurements in tumors, given their irregular vasculature.

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