Ion Cyclotron Resonance Therapy
Under the influence of an externally generated low-frequency magnetic field and external low-frequency MF source, ions’ paths become bent into an orbit known as the cyclotron orbital.
Cyclotrons produce continuous beams for rapid scanning and feature an efficient energy switching time. Furthermore, these machines support respiratory gating to manage motion during treatment sessions.
Treatment Options
Cyclotron resonance therapy offers an alternative to conventional particle therapy methods that use electrons and protons, by employing ion beams instead. These beams can be tailored specifically to cancerous cells while sparing surrounding healthy tissues from damage; as a result, this technique has less severe side effects and could potentially extend survival for those living with advanced diseases.
There are two primary accelerators used in clinical applications to accelerate charged particles: cyclotrons and synchrotrons. Cyclotrons such as those used in FLASH proton therapy systems like IBA Proteus 235 and Varian ProBeam employ magnetic and electric fields to accelerate ions. A cyclotron can extract beam current of up to 800nA with maximum energy outputs up to 250 MeV in mere milliseconds; its intensity can also be varied for intensity-modulated proton therapy (IMPT).
Superconducting cyclotrons like the one at MIT have much smaller footprints and weight 60% less than conventional ones; yet due to technical challenges they haven’t yet been adopted for carbon ion therapy use.
Cyclotron resonance can be used to detect ion spectra in complex mixtures of natural organic matter. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is a molecular characterization technique that employs electric and magnetic fields to detect ions within Penning traps; fixed detectors detect image current produced by passing ions over time and produce signals with frequencies related to each individual ion’s mass-to-charge ratio.
This data can be used to determine the formulas of ions present in a sample and deconvolve its signal using FT-ICR-MS. Additionally, mass spectrum confirmation can also be done with this technique.
One theory behind ion cyclotron resonance’s effectiveness is its capacity to increase the coherent water fraction found within our bodies’ water molecules, formed from molecules with quantum oscillations in phase, creating stronger electromagnetic interactions among them and making them more stable – an effect similar to acupuncture’s therapeutic benefits.
Safety
A cyclotron system uses superconducting magnets and electric fields of such magnitude that ions are captured and precessed, producing a small image current which can be detected by pairs of detector plates, with this signal measured as the ratio between mass and charge; when coupled with its frequency and mass/charge value it gives us information that enables Fourier transform mass spectrometry (FTMS).
Cyclotron resonance therapy utilizes similar technology to produce multiple beams of protons that allow clinicians to deliver high dose rates while sparing healthy tissue, known as FLASH proton therapy and becoming increasingly common across clinics.
Cyclotron resonance therapy does pose some safety concerns; one major one being its inability to extract a steady current (constant current) of energy for various beam sizes and energies, making it less suitable for three-dimensional dose delivery such as in IMPT which requires precise dose delivery around targets. Furthermore, its energy selection system uses an energy degrader which may alter beam intensity; this can cause activation near it which necessitates additional shielding measures as well as radiation protection for proton engineers working nearby.
Cyclotron resonance therapy could produce a magnetic field that alters the body’s normal electrical properties, potentially leading to reduced resistance or an increase in reactance at specific sites of a patient’s body, similar to what might happen with acupuncture treatments. This effect could result in reduction or an increase in resistance, similarly mimicking what would occur with traditional Chinese acupuncture sessions.
To mitigate this potential issue, MED CRI has designed an innovative device that neutralizes the vertical component of Earth’s magnetic field in treatment bed zones by using Helmholtz coils to zero out vector component south-north of magnetic fields parallel to powered alternating magnetic fields. This can maximize superficial geomagnetic flux which in turn will decrease interference with cyclotron electromagnetic fields.
Regulatory Considerations
Ion cyclotron resonance therapy can be an extremely effective option for treating tumors while sparing normal tissue. Furthermore, its radiation intensity is much lower than proton beam therapy – making it less likely to cause side effects in sensitive organs. Unfortunately, operating cyclotrons and synchrotrons requires significant investments in equipment and infrastructure – to minimise risks effectively the ion source must remain in top working condition with appropriate maintenance conducted regularly to maintain it properly.
Cyclotrons use accelerators to produce ion beams, with their intensity easily modulable for proper dosing for each patient. Meanwhile, synchrotrons utilize superconducting magnetic fields to accelerate electrons. This technology provides for more precise energy modulation resulting in improved dose delivery and precision.
Cyclotrons and synchrotrons both produce high-energy ions of various energies, but only cyclotrons offer continuous beams suited for treating static targets more efficiently than pencil beam scanning techniques employed by most proton beam therapy systems. Cyclotrons also boast greater efficiency as they can extract more current from their isocenter than some higher energy synchrotron systems available today.
Ion cyclotron resonance mass spectrometry (ICRMS) is an invaluable diagnostic tool for identifying cancerous cells and other pathologic entities. The process begins by injecting packets of ions into a Penning trap (a static electric/magnetic ion trap), measuring electrical current between detection plates, and tracking their frequency of rotation to their mass-to-charge ratio; Fourier transform analysis can then be applied on image current values to provide further details of an ion’s mass/charge value (frequency is directly proportional to its mass/charge ratio; Fourier transform analysis on image current will allow identifying individual ions).
Researchers have explored the effects of ion cyclotron resonance (ICR) on cell differentiation. For instance, in one experiment ex vivo expanded hematopoietic stem cells were exposed to 7Hz calcium ICR; as a result of ICR’s effect on them significantly altered their lineage with cardiogenic differentiation occurring while inhibiting angiogenic differentiation.
Although Ion Cyclotron Resonance Therapy can be useful in various applications, some regulatory considerations must be addressed prior to its approval for clinical use. A key concern with ICR therapy is that it could disrupt lipid membrane conductivity and lead to increases in permeability and resistance – leading to FDA proposed stricter safety standards for this form of therapy as a solution.
Cost
Ion Cyclotron Resonance (ICCR) technology has quickly become the go-to method for producing beams for particle therapy due to its compact size and ability to produce clinically relevant, high intensity ions with great speed and consistency. Utilizing superconducting magnets and electric fields to capture and precess ions like its counterpart the Fourier Transform Ion Cyclotron Resonance Mass Spectrometer used in NMR protein molecular analysis (see image below), ICCR uses superconducting magnets and electric fields in tandem to capture and precess them, similar to how Fourier Transformed Ion Cyclotron Resonance Mass Spectrometric Analysis does the same way (see image below).
Cyclotrons offer a constant low-energy beam that is easy to adjust on a millisecond scale and maintains intensity stability within 5%, providing for efficient FLASH PT treatments. Cyclotrons also boast faster switching times than synchrotrons, which is essential when treating patients for motion management during treatment.
Both isochronous cyclotrons and synchrocyclotrons can accelerate carbon ions for cancer therapy, with isochronous cyclotrons generally providing lower construction and operating costs; for instance, Varian ProBeam utilizes one.
However, its more complex operation and extensive maintenance requirements make it a more costly choice.
Cyclotron therapy holds an edge over synchrotrons for proton therapy because its rotating accelerating stage facilitates quick scanning. Furthermore, its much quicker switching time between energy levels allows better control of ion velocity during circulation which is essential in providing effective treatment of tumors.
Cyclotrons that accelerate protons require an expansive cyclotron sextupole with steering magnets at the extraction point to achieve higher turn separation, increasing both their complexity and cost. Furthermore, isochronous cyclotrons use fixed radio frequencies (RFs) during acceleration to achieve isochronism and vertical focus, while synchrocyclotrons utilize variable frequencies, an azimuthally variable magnetic field and variable energy circulation – further complicating operations and driving up costs.