Magnetic Resonance Microscopy. Группа авторов

High Resolution From Enhanced Sensitivity

      1.2.1 Coil Miniaturization

In Equation 1.2, d represents the sensitivity of the NMR detector, which has been proven to increase with decreasing d [18]. Numerous reports have been published on how to improve the NMR detection sensitivity by miniaturizing the detection coil [19–22]. The vast majority of those papers targeted NMR spectroscopy applications, and far fewer talked about microscopy [23–25]. One of the papers that targeted both applications though is the work reported by [26]. In this paper a novel high-resolution NMR/MRI Helmholtz microcoil was introduced (Figure 1.1). The coil that was manufactured using a combination of standard and home-developed micro fabrication technologies featured an extremely user-friendly sample-handling approach that allows easy loading/unloading of the sample.

      Figure 1.1 A micro Helmholtz coil manufactured using a mixture of standard and home-developed micro-manufacturing technologies. [26] N. Spengler et al. (2014), figure 04 [p.05]/with permission from IOP Publishing Ltd.

      The coil was manufactured by stacking three layers, the top and the bottom of which are made of glass, each featuring a wire-bonded 1.5-winding coil using a 25-µm diameter copper wire. The coils were encapsulated in SU-8 epoxy-based photoresist. The glass layers also contained copper traces for the feed and return paths of the current. These layers were spaced by a poly(methyl methacrylate) (PMMA) layer, which was U-shaped to allow the sample-handling microfluidic chip to slide in the sensor. The Helmholtz microcoil was designed and optimized to achieve an extremely uniform B₁ field (92% ratio of signal intensity at flip angles of 810/90) while maintaining the high B₀ homogeneity (1.79 Hz achieved linewidth of a water sample).

The exceptional performance of the microcoil in terms of B₁ uniformity and local field homogeneity allowed high-resolution microimaging. Figure 1.2 shows the optical (left) and MR (right) microimages of a deionized water sample of 154 nl volume. The sample contains 50-µm diameter polymer beads to show some contrast. The MR image that is a sum of 80 acquisition was recorded over a total scan time of 11 h, 22 min, and 40 s. With a matrix size of 256 × 256 and covering a 2.5 × 2.5 mm field of view (FoV), the MR image exhibited an in-plane resolution of 10 × 10 µm for a slice with a 100-µm thickness.

      Figure 1.2 MR microimaging of a 154-nl deionized water sample with 50-µm diameter polymer beads. (left) Optical micrograph. (right) MR image. [26] N. Spengler et al. (2014), figure 10 [p.07]/with permission from IOP Publishing Ltd.

      1.2.2 The Lenz Lens: A Tool to Boost Sensitivity

The quest for higher coil sensitivity, SNRcoil ∝ B1/(iR), made researchers invest huge efforts in the design and optimization of the NMR detector. These efforts resulted in numerous publications covering a wide diversity of coil geometries and applications. Nevertheless, none of these efforts went beyond two major pathways: (i) optimizing the coil geometry to better confine the sample and thus achieve a higher filling factor, which, in turn, results in a higher B₁ per unit current seen by the sample; and (ii) reducing coil resistance, R, and thus its noise contribution either by a careful selection of coil materials, or by cooling the coil windings. In certain cases, however, these strategies might not be applicable as, for example, if one wants to study the inner body parts. For this particular case, implantable inductively coupled inductor-capacitor (LC) resonators have been shown to enhance the imaging SNR remarkably [27–32]. Nevertheless, despite their advantages, LC resonators suffer from limited frequency accessibility due to their narrow-band nature, which originates from the resonance phenomena, and the difficulty in tunability due to their sensitivity to both the sample and the pick-up coil [33].

An alternative to the LC resonator is the Lenz lens (LL) shown in Figure 1.3. The LL consists of two electrically connected loops: the inner and outer loop, where the outer loop collects the magnetic flux of the pick-up coil and converts it to a current. As this current passes through the inner loop of the LL, it generates a larger magnetic field in the sample than the field that would otherwise be produced by the pick-up coil only. The LL, though less powerful in terms of field amplification compared with the LC resonator, is superior to it in terms of tunability and wide frequency accessibility [33]. Figure 1.4 depicts a simulated comparison of the SNR as the coil geometry increases with respect to the sample volume of a single-loop planar wired coil (blue), a single-loop planar coil with a LL (red), and a single-loop planar coil with an LC resonator (green).

      Figure 1.3 The Lenz lens (LL) collects the magnetic flux of the pick-up coil and focuses it into the sample region resulting in an enhanced sensitivity of the measurement.

      Figure 1.4 A comparison of the LL performance versus the LC resonator for a planar single-loop pick-up coil. The first point of the blue curve is the optimum situation where the coil geometry perfectly matches the sample volume (coil-to-sample diameter ratio = 1). As the coil geometry increases in comparison with the sample volume the SNR decreases. In this suboptimal situation, the SNR can be improved by using either an LC resonator (green curve) or a LL (red curve). In this figure, La,S is the inductance of the small pick-up coil, La,B is the inductance of a big pick-up coil, Lb is the inductance of the outer loop of the LL, Lc is the inductance of the inner loop of the LL, and M is the mutual inductance.

The concept of LL was applied by Spengler et al. [34] to his previously reported NMR micro Helmholtz detector. Figure 1.5 shows an LL with 1 mm outer diameter and 0.2 mm inner diameter inserted inside the micro Helmholtz LL2 coil. In the paper, four different lenses were tested, namely plate lenses LL1 and LL2 with inner diameters of 0.2 mm and 0.4 mm, respectively, and wire lenses LL3 and LL4 with inner diameters of 0.2 mm and 0.4 mm, respectively. The performance of the lenses was evaluated via a series of MRI spin echo imaging experiments on a deionized water sample. All experiments were preceded by flip angle adjustment routines to ensure that all the measurements are conducted at the same flip angle, namely 90°. Figure 1.6 calculates the SNR enhancement due to the various lenses (LL1–LL4) and compares it with the reference SNR of the micro Helmholtz coil without lenses (the red curve). According to the results, exploiting LLs can significantly enhance the coil sensitivity and thus the achievable imaging resolution. The SNR enhancement varies largely with the inner diameter of the lens (increases as the inner diameter decreases) but changes slightly with the topology used (plate/wire). The maximum SNR enhancement reported in the paper was 2.8, which would allow reducing the voxel volume by 64% (reducing the voxel length by 29%) while maintaining the acquisition time and the SNR per voxel unchanged. A system that combines the concepts of both the LL and the LC resonator has been introduced by Kamberger et al. [35]. The so-called resonant LL benefits from the field-focusing feature of the LL and the signal amplification advantage due to resonance. The resonant LL was integrated with an MR-compatible incubation platform designed to cultivate organotypic hippocampal slice cultures (OHSCs), to perform in vitro MR microscopy of brain tissues. The wireless LL was purposely employed to avoid the direct connections of wired RF coils, thereby giving the incubation platform more flexibility and freedom. Moreover and more importantly, avoiding wired coils reduces the number of different-materials interfaces, which consequently diminishes the susceptibility-mismatch-based imaging artifacts. In fact, the latter issue is an extremely important aspect when considering microscopy. For this reason, the LL introduced in [35] was carefully