Researchers from Singapore and China have developed a swallowable X-ray dosimeter the size of a large pill capsule that can monitor gastrointestinal radiotherapy in real time. In proof-of-concept tests on irradiated rabbits, their prototype proved approximately five times more accurate than current standard measures for monitoring the delivered dose.
The ability to precisely monitor radiotherapy in real time during treatment would allow evaluation of the in situ absorbed radiation dose in dose-limiting organs such as the stomach, liver, kidneys and spinal cord. This could make radiation treatments safer and more effective, potentially reducing the severity of side effects. Measuring the delivered and absorbed dose during radiotherapy of gastrointestinal tumours, however, is a difficult task.
The new dosimeter, described in Nature Biomedical Engineering, could change this. The 18 x 7 mm capsule contains a flexible optical fibre embedded with lanthanide-doped persistent nanoscintillators. The ingestible device also incorporates a pH-responsive polyaniline film, a fluidic module for dynamic gastric fluid sampling, dose and pH sensors, an onboard microcontroller and a silver oxide battery to power the capsule.
First authors Bo Hou and Luying Yi of the National University of Singapore and co-researchers explain that the nanoscintillators generate radioluminescence in the presence of X-ray radiation, which propagates to the ends of the fibre via total internal reflection. The dose sensor measures this light signal to determine the radiation delivered to the targeted area.
As well as X-ray dosimetry, the capsule also measures physiological changes in pH and temperature during treatment. The polyalinine film changes colour according to the pH of gastric fluid in the fluidic module; the pH is then measured by the colour contrast ratio of the pH sensor, which analyses light after it passes through the film. Additionally, the afterglow of the nanoscintillators after irradiation can be used as a self-sustaining light source to continuously monitor dynamic pH changes for several hours without the need for external excitation. The researchers point out that this capability is not yet available with existing pH capsules.
The photoelectric signals from the two sensors are processed by an integrated detection circuit that wirelessly transmits information to a mobile phone app. Once activated, the app can receive data from the capsule in real time via Bluetooth transmission. Data such as the absorbed radiation dose, and the temperature and pH of the tissues, can be displayed graphically, stored locally or uploaded to cloud servers for permanent storage and data dissemination.
Prior to in vivo testing, the researchers assessed the dose response of the nanoscintillators. They used a neural network-based regression model to estimate the radiation dose from the radioluminescence, afterglow and temperature data. They developed the model using over 3000 data points recorded while exposing the capsule to X-rays at dose rates from 1 to 16.68 mGy/min, and temperatures of 32 to 46℃.
The team found that both radioluminescence and afterglow intensities are directly proportional to dose variations, suggesting that combining the two will lead to more precise estimates of absorbed dose.
Next, the researchers validated the dosimeter’s performance in three anaesthetized adult rabbits. Following surgical insertion of a capsule in the stomach of each animal, they performed CT scans to identify the capsule’s precise position and angle. They then irradiated each animal multiple times over a 10 hr time period using a progressive X-ray dose rate.
“Our wireless dosimeter accurately determined the dose of radiation in the stomach, as well as minute changes in pH and temperature, in real time,” the team reports. “The capsule inserted in the gastrointestinal cavity was capable of rapidly detecting changes in pH and temperature near irradiated organs.”
Tiny ingestible capsule helps treat gastrointestinal disorders
Before the dosimeter capsule can be clinically tested, a positioning system needs to be developed to place and anchor it at the target site after being swallowed. Better and more accurate calibration of the conversion from optical signal into absorbed dose is also needed prior to clinical evaluation.
The potential of the new dosimeter extends beyond gastrointestinal applications. The researchers envision its use for dose monitoring of prostate cancer brachytherapy, for example, using a capsule anchored in the rectum. Real-time measurements of absorbed dose in nasopharyngeal or brain tumours may also be feasible if a smaller sized capsule can be placed in the upper nasal cavity.
