Electron Paramagnetic Resonance (Electron Spin Resonance) and its contributions to MRI

 

 

ESR

 

Magnetic resonance imaging (MRI) is essentially “proton resonance imaging” as it uses the magnetic resonance of the hydrogen nucleus i.e. the proton. A similar technique termed electron spin resonance (ESR) or electron paramagnetic imaging (EPR) uses the magnetic resonance of the electron. 


It has been suggested by Holder D.S (19851987) that ESR could be most appropriate for the detection of brain electric activity. Holder is also cited in U.S. patent 4719425 https://www.google.com/patents/US4719425) for detection of brain activity with NMR and ESR. Due to the decreased abundance in biological systems of unpaired electrons (detected by the technique) and the short half-lives of related species such as free radicals, ESR is generally conducted with introduction of a paramagnetic substance which acts as a reporter. Also, given that the gyromagnetic ratio for the electron is 28 GHz/T, this means that for a scanner of 1 Tesla, the electromagnetic radiation required to achieve magnetic resonance is 28 GHz which is in the range of microwaves. This is problematic due to the fact that water, the main component of the human body, absorbs microwaves.

 

 

Reading notes from Danhier P. and Gallez B. (2014)

 

Magnetic resonance imaging (MRI) is essentially “proton resonance imaging” as it uses the magnetic resonance of the hydrogen nucleus i.e. the proton. A similar technique termed electron spin resonance (ESR) or electron paramagnetic imaging (EPR) uses the magnetic resonance of the electron. The gyromagnetic ratio of the proton is 42.5 MHz/T, while that of of the electron is 28 GHz/T, which means that for a scanner of 1 Tesla, the electromagnetic radiation required to achieve magnetic resonance is 42.5 MHz for the proton and 28 GHz for the electron. The fact that the ESR-required radiation is in the microwave range is problematic, because tissues contain a very important percentage of water which absorbs microwaves - this water property is used in microwave ovens for heating. For living organisms, the concentration of protons is very significant, as it is in the order of 100 M, while that of unpaired electrons which are found in paramagnetic chemical species (cf. free radicals) is extremely low. Additionally, free radicals (e.g. nitric oxide, superoxide, hydroxyl radicals) have a very short half-life. These can only be detected using spin-trapping strategies which generate stable spin adducts following interaction with a nitrone. Due to the above, ESR is generally conducted with introduction into the living system of a paramagnetic substance which acts as a reporter.

 

 


Combination of MRI and ESR: Proton Electron Double Resonance Imaging (PEDRI) or Overhauser Magnetic Resonance Imaging (OMRI) 

 

A powerful imaging application is represented by the combination of MRI and ESR which is known as Proton Electron Double Resonance Imaging (PEDRI) or Overhauser Magnetic Resonance Imaging (OMRI). The Overhauser effect is a prominent mechanism of dynamic nuclear polarization (DNP) (cf. hyperpolarization)  which consists of the transfer of the polarization of electrons to nuclei (including protons) resulting in the polarization of the latter. Practically, instead of irradiating the nuclei, one irradiates or excites the electrons and thereby mediates nuclei polarization. On a technical aspect, samples are irradiated at the resonance frequency of the electrons while the magnetic field strength is kept low and then the magnetic field is increased rapidly to obtain the nuclear magnetic resonance signal. To avoid tissue overheating by the ESR pulse, the technique field‐cycled PEDRI was developed. 

 

Patent US4719425A entitled “NMR imaging method and apparatus” https://patents.google.com/patent/US4719425A/en presents a technique for measuring the electrical activity of the brain using NMR and ESR based as mentioned on “measuring the broadening of the width of NMR spectral lines”. Its principle appears to be similar to that presented for MRCDI. Quoting the patent, “a discharging neuron in the brain introduces an inhomogeneity in the magnetic field which reveals itself as a broadening of resonance lines which can be measured to determine the neuron discharge current flux”. The said inhomogeneity is equivalent to the perturbation mentioned in the MRCDI section. This leads to dephasing and thereby different precession frequencies resulting in spectroscopic line broadening. Also, the Fourier transform providing a Lorentzian (similar to the bell-curve distribution Gaussian distribution) due to different frequencies has an increased linewidth. By measuring the phase change by can determine the magnetic field of the brain.

 

 

 

 

Reading notes from Danhier P. and Gallez B. (2014)

 

Magnetic resonance imaging uses the magnetic resonance of the hydrogen nucleus i.e. the proton, while electron spin resonance (ESR) imaging uses that of the electron. The gyromagnetic ratio of the proton is 42.5 MHz/T, while that of of the electron is 28 GHz/T, which means that for a scanner of 1 Tesla, the electromagnetic radiation required to achieve magnetic resonance is 42.5 MHz for the proton and 28 GHz for the electron. The fact that the ESR-required radiation is in the microwave range is problematic, because tissues contain a very important percentage of water which absorbs microwaves - this water property is used in microwave ovens for heating. Due to the bulk microwave absorption by water, ESR will be less sensitive and will create the risk of tissue overheating which is an important concern (it is noted that SAR tests on mobile phones examine this risk). The most usual commercial EPR spectrometers used for instance for pharmacokinetics, operate at 9 GHz (X-band) for a magnetic field around 0.34 T. However, for animals, there is a requirement for much lower frequencies e.g. 1 GHz (L-band). It is noted that at 1 GHz the depth of penetration is of about 1 cm but with a reduced sensitivity.

 

The proton spin has a relaxation time of 0.1 to 1 second, while the electron spin returns to equilibrium following excitation much more rapidly (ns to µs). Due to this, ESR is conducted with continuous wave irradiation using a lower power microwave field, while the magnetic field strength is increased gradually to obtain resonance. This creates complicated issues requiring extended technical expertise.

 

For living organisms, the concentration of protons is very significant, as it is in the order of 100 M, while that of unpaired electrons which are found in paramagnetic chemical species (cf. free radicals) is extremely low. Additionally, free radicals (e.g. nitric oxide, superoxide, hydroxyl radicals) have a very short half-life. These can only be detected using spin-trapping strategies which generate stable spin adducts following interaction with a nitrone. An exception of a paramagnetic substance which can be easily detected is melanin.

 

Due to the above, in ESR generally, a paramagnetic substance has to be introduced into the living system to act as a reporter for different indices such as oxygenation, redox status, pH and microviscosity.

 

For oximetry studies, a small quantity of a paramagnetic probe such as charcoal particles is injected and the pO2 can be measured non-invasively with low frequency EPR. Oxygen which is paramagnetic, interacts with the paramagnetic centers of the probe and induces a shortening of the T2 electronic relaxation time. This results in the broadening of the EPR spectroscopy line of the oxygen-sensitive probe. ERP has been used to validate or invalidate oximetry results from BOLD-MRI (fMRI) and MRI (with probes) or other techniques.

 

ERP can similarly provide valuable information to MRI performed with contrast agents as most of these contain species with unpaired electrons. It is noted that the interaction of the electron spin with the proton spin influences the relaxation of the proton spin. It is suggested that by using ESR with MRI contrast agents such as gadolinium, manganese, nitroxides and iron oxide particles it is possible to quantify the signal and qualitatively characterize it. This can also be performed with melanin.

 

The best example for combining ERP and MRI consists of the Overhauser Magnetic Resonance Imaging (OMRI) or Proton Electron Double Resonance Imaging (PEDRI). This technique uses dynamic nuclear polarization or the Overhauser effect for the detection of free radicals. Samples are irradiated at the resonance frequency of the electrons i.e. the free radicals, while the magnetic field strength is kept low and then the magnetic field is increased rapidly to obtain the nuclear magnetic resonance signal. A long T2 electronic relaxation or a narrow ERP line is preferred. To avoid tissue overheating by the ERP pulse, the technique field‐cycled PEDRI was developed. Most studies have addressed the detection of nitroxides and triaryl methyl or trityl radicals.