Identifying in vivo inflammation using magnetic nanoparticle spectra

Abstract

We are developing magnetic nanoparticle (NP) methods to characterize inflammation and infection in vivo. Peritoneal infection in C57BL/6 mice was used as a biological model. An intraperitoneal NP injection was followed by measurement of magnetic nanoparticle spectroscopy of Brownian rotation (MSB) spectra taken over time. MSB measures the magnetization of NPs in a low frequency alternating magnetic field. Two groups of three mice were studied; each group had two infected mice and one control with no infection. The raw MSB signal was compared with two derived metrics: the NP relaxation time and number of NPs present in the sensitive volume of the receive coil. A four compartment dynamic model was used to relate those physical properties to the relevant biological processes including phagocytic activity and migration. The relaxation time increased over time for all of the mice as the NPs were absorbed. The NP number decreased over time as the NPs were cleared from the sensitive volume of the receive coil. The composite p-values for all three rate constants were significant: raw signal, 0.0002, relaxation, <10−16 and local NP clearance, <10−16. However, not all the individual mice had significant changes: Only half the infected mice had significantly different rate constants for raw signal reduction. All infected mice had significantly smaller relaxation time constants. All but one of the infected mice had significantly lower rate constants for local clearance. Relaxation is affected by both phagocytic activity, edema and temperature changes and it should be possible to better isolate those effects to more completely characterize inflammation using more advanced MSB methods. The MSB NP signal can be used to identify inflammation in vivo because it has the unique ability to monitor phagocytic absorption through relaxation measurements.

Simultaneous temperature and viscosity estimation capability via magnetic nanoparticle relaxation

“…Alternatively, if the goal is to estimate the temperature alone, a single measurement can be performed at a medium-to-high amplitude drive field at frequencies above 3 kHz, where the signal is largely desensitized to the viscosity effect but is highly sensitive to temperature. The temperature and viscosity metrics in Equations (10) (11) were defined using the slopes of the linear fits to τ versus temperature and τ versus viscosity curves. According to Equations (5) (6), while 𝜏 B linearly depends on viscosity, neither 𝜏 B nor 𝜏 N has linear dependence with respect to temperature.…”

“…This procedure is repeated at all operating points, and the sensitivity metrics are computed using the slopes of the linear fits 0.36%/(mPa⋅s) at 25 • C. Next, in Figure 6, the estimated sensitivities for temperature and viscosity for all operating points are given as color maps. Figure 6a shows temperature sensitivities at different operating points in units of %/ • C, computed using Equation (10). Here, each subplot displays the temperature sensitivities at distinct viscosity levels from 0.9 mPa⋅s to 3.6 mPa⋅s.…”

“…In reality, due to the relaxation effects, the magnetic moments of MNPs cannot align with the drive field instantaneously, and this delayed response causes a loss of signal‐to‐noise ratio (SNR) and a blurring of the MPI image. Although the relaxation behavior can deteriorate image quality, it also provides functional imaging capability to MPI for applications such as temperature mapping, 3–5 viscosity mapping, 6–9 and identifying inflammation 10,11 . While the theoretical aspects of relaxation mechanisms under AC fields need further investigation, their effects on the MPI signal have been studied via experimental procedures.…”

“…Although the relaxation behavior can deteriorate image quality, it also provides functional imaging capability to MPI for applications such as temperature mapping, [3][4][5] viscosity mapping, [6][7][8][9] and identifying inflammation. 10,11 While the theoretical aspects of relaxation mechanisms under AC fields need further investigation, their effects on the MPI signal have been studied via experimental procedures.…”

The biological effects of geomagnetic field exhibit an important potential for cancer and vascular diseases

“…More importantly, the biological effects of geomagnetic field have great significance for the diagnosis and treatment of human diseases. For instance, the magnetic nanoparticle (NP) method being developed has the unique ability to monitor phantom absorption through relaxation measurements and can also be used to identify inflammation in vivo (Weaver et al, 2020). At the same time, magnetic particle spectrometers can assess the maturity of a thrombus, predict its age and the nature of the clot, thereby providing an earlier, more accurate, and noninvasive diagnosis of thrombotic diseases including stroke, myocardial infarction, and deep vein thrombosis (Khurshid et al, 2018).…”