What Does the Future Hold for Brain Imaging and Radiotherapy?

Are we going to see radiotherapy machines largely gathering dust in the future? The shift to individualized cancer care has already begun and looks like a pill or infusion that specifically targets a biological marker for a particular tumor cell type. CAR-T cell therapy is one such treatment, which involves extraction of a patient’s own T-cells, modification to recognize a specific cancer cell antigen and subsequent reintroduction to the patient, in essence using his or her own immune system to destroy the cancer.

However, the number of tumor cell types that can be treated with these immunotherapies is still limited. For other health conditions, such as arteriovenous malformations in the brain – where physical structures need to be altered near extremely critical and vulnerable tissue – a radiotherapy intervention remains one of the top treatment options. This is also the case for particular types of epilepsy that cannot be treated with medications or surgery.

Radiotherapy is here to stay, at least for some time and for some conditions. Accordingly, let us take a look at several recent improvements in brain cancer diagnostics, new adaptive treatment methods and further opportunities to enhance equipment and patient treatment quality assurance (QA).

Regardless of where radiotherapy is targeted and for what clinical indication, the preservation of healthy tissue is of the utmost importance. This is essential when it comes to sparing organs which are particularly sensitive to radiation or where loss of function may occur.

Primary brain tumors originate in the brain and grow from a specific point, giving a well-defined target area for the administration of radiation and a well-specified remaining area for dose minimization. Secondary brain tumors originate from outside the brain, typically from a few common cancer types, such as lung and breast cancers. The cancer cells migrate through the body and pass through the blood-brain barrier and can cause multiple brain metastasis. In this case, whole brain irradiation may be advised in order to ensure small metastasis not visible from the magnetic resonance imaging (MRI) or computed tomography (CT) scan are captured by the therapy.

Here one can see a myQA.SRS active area superimposed over a sagittal view of the brain with multiple targets. Based on a solid-state detector, the my QA.SRS dosimeter combines the accuracy and resolution of film quality assurance (QA) with the efficiency of digital workflow and is compatible with existing linacs. (Image courtesy of IBA Dosimetry.)

Whereas the beginnings of cancer treatment started with ensuring the cancer was fully treated, more recent research has looked at dose de-escalation to mitigate side effects and secondary tumor risk. This has transformed whole brain irradiation to include sparing of the hippocampal region, cochlea and hypothalamus/pituitary gland, respectively preserving memory and hearing, and reducing hormonal deficiencies.¹

With so many advancements in X-ray radiotherapy treatment, there is an emphasis on making it better, reducing the dose to sensitive areas and giving thoughtful consideration to the patient who is experiencing these treatments.

Key Advances in Diagnostic Imaging of Tumors

Here are just some of the latest advancements in imaging for seeking out the smallest tumors and giving the best delineation between healthy and cancerous tissue.

• Advanced MRI techniques for improved targeting. Using advanced MRI techniques like perfusion- and diffusion-weighted imaging and MR spectroscopy as standalone diagnostic tools provides notable benefits compared with conventional MRI methods in assessing tumor extent, grade and treatment response. The integration of these techniques with positron emission tomography (PET) imaging demonstrates promising improvements in tumor diagnosis and patient outcomes.²
• Intraoperative gamma cameras. Intraoperative gamma cameras are being used in combination with radiopharmaceuticals that are taken up by specific tissue types. They offer a two-dimensional (2D) field of view, enabling good coverage of the surgical area showing cancerous tissue with a single measurement compared with the previous one-dimensional (1D) gamma probes. The resulting imaging is a more intuitive aid for decision-making during tumor resection surgery, mitigating against tumor cells being left behind.³
• Hyperpolarized 13C magnetic resonance spectroscopy (MRS). Specialized techniques are used to increase the nuclear spin of13C, which is bound to compounds designed to be taken up by certain cell types. The hyperpolarized 13C-labeled compound is injected and the patient rapidly imaged. It can provide higher sensitivity metabolic imaging in comparison to conventional MRI. For example, an increase in a certain metabolic process (glycolytic activity) is a characteristic of certain brain tumors.⁴

Emerging Pathways with Adaptive Radiotherapy

Although imaging techniques can be used alone as input into the radiotherapy treatment plan, there is a move toward combining imaging and treatment, creating therapies that are being adapted in real time.

Here are some of the highlights in adaptive radiotherapy:

1. SCINTIX – biology-guided radiotherapy:In this treatment, radiopharmaceuticals (currently approved for ¹⁸F-Fludeoxyglucose) are injected into the patient to perform PET imaging. The tumor locations determined from combined PET and CT imaging are used to define and alter the treatment plan in real time.⁵
2. MRI-guided radiotherapy. This modality integrates real-time MRI imaging into radiation therapy, offering superior soft tissue visualization and allowing for adaptive treatment planning. It enables continuous monitoring during treatment, enhancing precision, reducing safety margins and potentially enabling dose escalation to the tumor. This approach is particularly beneficial for tumors in complex anatomical locations, such as the brain.⁶
3. Artificial Intelligence (AI) techniques for image analysis. Artificial intelligence is not only providing automated tumor delineation, but it can also provide information on the aggressiveness, genetic makeup and potential response of the tumor to treatment. Artificial intelligence-driven systems are now capable of dynamically adapting the targeting of radiation doses in real time during treatment, considering changes in anatomy and the response of the tumor.⁷

Although there are obvious benefits from the aforementioned adaptive radiotherapy techniques, they also come with a much higher price tag than conventional radiotherapy linear accelerators (linac) and gamma knife treatment facilities. Low- and middle-income countries will struggle to build their oncology services with these much more expensive treatment options while many hospitals in industrialized countries already have numerous radiotherapy linacs in their oncology centers. In this case, auxiliary devices offer a lower-cost method for delivering the most accurate treatment possible from existing equipment by ensuring the treatment beam is targeted accurately.

From Treatment to Quality Assurance: Keys to Achieving Improved Precision with Dosimetry

Regular calibration and testing of the treatment beam, multi-leaf collimator positions and dose delivered according to the agreed treatment plans are fundamental to successfully operating a radiotherapy linac. The method and plan are only as good as the equipment set up for delivering them.

One notable improvement here is the myQA SRS dosimeter, a solution for stereotactic radiosurgery (SRS) offered by IBA Dosimetry that enables more precise QA delivered in less time.⁸ The dosimeter, based on a solid-state detector, combines the accuracy and resolution of film QA with the efficiency of digital workflow and is compatible with existing linacs. With the adoption of new technology, both the accuracy of patient QA and workflow have been improved, providing the confidence to deliver patient treatment plans with the accuracy intended.

Looking to the future, and to achieve ultimate treatment accuracy and patient comfort, several challenges still need to be addressed.

• How can we ensure patients are positioned comfortably in line with a known reference to the radiotherapy treatment beam without the need for a head frame?

• How can one work around inevitable patient movement during treatment in the absence of a head frame?

• How can we monitor the beam’s accuracy during the treatment itself rather than pre-treatment?

In the future, we could see a new form of digital dosimeter with high resolution, low beam absorption as well as thin and flexible construction. Such a dosimeter could be positioned on the linac head with minimal interference to the treatment beam, and feed back live data to the treatment planning tool for comparison or, even better, feed the information back to the linac itself, which could compensate for minor errors versus the original plan in real time. If such a dosimeter was flexible, it could even be positioned onto the patient, imaged pre-treatment for referencing against a known index and used to adapt the beam target. Such technology is not such a leap away from reality, when considering the advances in AI processing and thin film detector technology.

As a first step toward this ambitious vision, a personalized skull cap with an embedded printed radiation detector on it could accurately monitor the position of the treatment beam in real time. If the resolution cannot be achieved, a new type of flexible X-ray dosimeter could be immediately transferable to a wider set of radiotherapy applications to improve the verification of treatments to other parts of the body. This would be a perfect extension of the single dose-point ionization chambers that are currently used for open field irradiations. Live, accurate and 3D dose mapping will enable better treatment plans to be formed with improved patient outcomes.

In Conclusion

As individualized patient treatment plans become the norm throughout different medical fields, radiotherapy will be no exception. New diagnostic imaging techniques will enable us to see more detail, new treatment modalities will enhance our ability to improve success rates and flexible X-ray dosimeters will be used as on-patient monitors, molding themselves to each unique patient and providing a 2D map of the delivered dose upon entry to the body. The future of radiotherapy is only just beginning to get interesting.

Dr. Beck is a medical applications engineer at Silveray, an X-ray imaging detector developer, based in Greater Manchester, United Kingdom.

Mr. Cathie is co-founder and CEO of Silveray.

References

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2. Overcast WB, Davis KM, Ho CY, et al. Advanced imaging techniques for neuro-oncologic tumor diagnosis with an emphasis on PET-MRI imaging of malignant brain tumors. Curr Oncol Rep. 2021;23(3):34.

3. Farnworth AL, Bugby SL. Intraoperative gamma cameras: a review of development in the last decade and future outlook. J Imaging. 2023;9(5):102.

4. Miskovsky M, Gusyatiner O, Lanz B, et al. Hyperpolarized 13C-glucose magnetic resonance highlights reduced aerobic glycolysis in vivo in infiltrative glioblastoma. Sci Rep. 2021;11(1):5771.

5. Vitzhum LK, Surucu M, Gensheimer MF, et al. BIOGUIDE-X: a first in-human study of the performance of positron emission tomography-guided radiation therapy. Int J Radiat Oncol Biol Phys. 2024;118(5):1172-1180.

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8. IBA Dosimetry. Radiation therapy. Available at: https://www.iba-dosimetry.com/radiation-therapy . Accessed April 18, 2024.