Enhanced Fluorine-19 MRI Sensitivity using a Cryogenic Radiofrequency Probe: Technical Developments and Ex Vivo Demonstration in a Mouse Model of Neuroinflammation

Abstract

Neuroinflammation can be monitored using fluorine-19 (¹⁹F)-containing nanoparticles and ¹⁹F MRI. Previously we studied neuroinflammation in experimental autoimmune encephalomyelitis (EAE) using room temperature (RT) ¹⁹F radiofrequency (RF) coils and low spatial resolution ¹⁹F MRI to overcome constraints in signal-to-noise ratio (SNR). This yielded an approximate localization of inflammatory lesions. Here we used a new ¹⁹F transceive cryogenic quadrature RF probe ( ¹⁹ F-CRP) that provides the SNR necessary to acquire superior spatially-resolved ¹⁹F MRI. First we characterized the signal-transmission profile of the ¹⁹ F-CRP. The ¹⁹ F-CRP was then benchmarked against a RT ¹⁹F/¹H RF coil. For SNR comparison we used reference compounds including ¹⁹F-nanoparticles and ex vivo brains from EAE mice administered with ¹⁹F-nanoparticles. The transmit/receive profile of the ¹⁹ F-CRP diminished with increasing distance from the surface. This was counterbalanced by a substantial SNR gain compared to the RT coil. Intraparenchymal inflammation in the ex vivo EAE brains was more sharply defined when using 150 μm isotropic resolution with the ¹⁹ F-CRP, and reflected the known distribution of EAE histopathology. At this spatial resolution, most ¹⁹F signals were undetectable using the RT coil. The ¹⁹ F-CRP is a valuable tool that will allow us to study neuroinflammation with greater detail in future in vivo studies.

Figure 1

¹⁹F Cryogenic Radiofrequency Probe design and experimental setup. (A) Side view of the ¹⁹ F-CRP showing its geometry including external protective cylinder and an inner ceramic probe head that encloses the loop coil elements (not shown). The inner diameter dimension for the inner ceramic structure is shown in the cross-sectional view (right). (B) Three different experimental setups that were used to assess the ¹⁹ F-CRP quality. Shown are Setup 1 for the high concentration ¹⁹F phantom (upper panel), Setup 2 for the ¹⁹F nanoparticle phantoms (middle panel) and Setup 3 for the mouse brain phantom (lower panel). The dimension of the phantom setups are to scale with the dimensions of both ¹⁹ F-CRP and RT coil and an anatomic reference is shown on the right for comparison. The nanoparticles used in this study had the following physical characteristics: Z-average diameter = 164 nm, PdI = 0.06, z-Potential = 0.19 mV.

Figure 2

Transmission B ₁ ⁺ Field (B ₁ ⁺) for the ¹⁹ F-CRP. (A) Flip angle maps acquired in vertical and transversal orientation using a high concentration ¹⁹F phantom (Setup 1). (B) Profile plot of the FA along the vertical axis that depicts the change in FA with increasing distance to the CRP surface.

Figure 3

Comparison of SNR between the ¹⁹ F-CRP and ¹⁹ F/¹ H RT-coil. (A) Cross-sectional spin-echo ¹⁹F MR images of a TFE phantom acquired with the RT RF coil (left) and the CRP (right). The CRP showed a spatially varying sensitivity that is typical for transceive surface coils. (B) Plots of the SNR profile along the vertical axis at the center of the phantom. For the RT volume resonator (red curve) the SNR was very uniform within the phantom. In contrast, for the CRP the SNR drops rapidly with increasing distance to the RF coil. For this particular reference pulse power, SNR reached its maximum at 2.4 mm from the CRP surface, where it is 15-fold higher than the SNR of the RT coil. Beyond a distance of 8.1 mm the ¹⁹ F-CRP did not provide any SNR gain with regard to the ¹⁹ F/¹ H RT-coil.

Figure 4

Comparison of ¹⁹F signal sensitivity between ¹⁹ F-CRP and ¹⁹ F/¹ H RT-coil as a function of the number of ¹⁹F atoms. (A) Cross-sectional spin-echo ¹⁹F MR images of ¹⁹F nanoparticle phantoms acquired for both CRP (middle panel) and RT coil (lower panel). Each ¹⁹F MR image indicates an MR scan with a defined number of ¹⁹F atoms per voxel (upper panel) achieved with different concentrations of PFCE (ranging from 25 mM to 200 mM) and slice thicknesses varying from 0.4 to 2.0 mm. (B) Estimation of SNR gain provided by the ¹⁹ F-CRP compared to the ¹⁹ F/¹ H RT-coil using high PFCE concentrations (200 mM to 1200 mM) and slice thicknesses varying from 1.0 to 6.0 mm. Shown is a log-log plot of SNR versus ¹⁹F atoms per voxel including a linear fit for both CRP (y = 5e⁻¹⁶x) and RT coil (y = 4e⁻¹⁷x).

Figure 5

High spatial resolution ¹⁹F MR image of an ex vivo brain from an EAE mouse showing clinical disease. With both ¹⁹ F-CRP and ¹⁹ F/¹ H RT-coil, ¹⁹F MR images were acquired using a 3D-RARE sequence. ¹⁹F MR images (shown in red) were combined with ¹H MR images (shown in grayscale). ¹H MR images were acquired using a 3D-FLASH sequence and the ¹⁹ F/¹ H RT-coil. (A) Three exemplary slices from horizontal views of combined ¹⁹F/¹H MR images for both ¹⁹ F/¹ H RT-coil (upper panel) and ¹⁹ F-CRP (middle panel), in the lower panel a 300% zoom of the ¹⁹F/¹H MR images acquired with the CRP. (B) Three exemplary slices from coronal views of combined ¹⁹F/¹H MR images for both RT coil (upper panel) and CRP (middle panel). Registration of the Allen brain atlas to the ¹H image (lower panel) shows following labelled brain regions: rs: retrosplenial area; crn: cranial nerves; sc: superior colliculus (sensory related); pmv: posteromedial visual area; ps: postsubiculum; av: arbor vitae; cbn: cerebellar nuclei. (C) 3-D rendering of the combined ¹⁹F/¹H MR images for both ¹⁹ F/¹ H RT-coil (upper panel) and ¹⁹ F-CRP (lower panel).

Figure 6

High spatial resolution ¹⁹F MRI using acquisition times feasible for in vivo imaging. ¹⁹F MR images were acquired with the ¹⁹ F-CRP using acquisition times between 30 min and 11 h. The ¹⁹F images were scaled to units of SNR, thresholded at SNR = 4, and overlayed onto the ¹H MR images using a pseudocolor scale.