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1 Microengineering Improves MR Sensitivity

       Neil MacKinnon, Jan G. Korvink, and Mazin Jouda

       Institute of Microstructure Technology, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany

      1.1 Introduction

Thirty years have passed since 1991 when Paul Callaghan published his book on magnetic resonance microscopy [1], and many works have subsequently appeared that have made numerous advances in this exciting field possible. Our goal for this chapter is to (informally) revisit some of Callaghan’s analysis, to reflect on it, and then take account of some of the advances and insights that have been reported since then.

      1.1.1 Comparative Electromagnetic Radiation Imaging

      Paul Callaghan’s book [1] is perhaps the first publication to consider magnetic resonance imaging (MRI) in the same light as optical microscopy. This will also be our starting point.

      Until the advent of super-resolution microscopy, refractive optical microscopy was essentially a radiation scattering method, in which a beam of photons from an independent light source was sent on its way to scatter off objects, followed by traversal of the beam through a focusing objective on its way back to a detector, to thereby reveal the structure and composition of the scattering object. The limitations of this approach, in terms of resolution, is known as the Abbe limit δ = λ/(2 n sin θ), where n is the refractive index, θ the half-angle of the spot subtended by the lens, and λ the radiation wavelength.

Using radio waves taken for convenience at 300 MHz, a thus interpreted refractive MRI system would have a resolution of ~500 mm, which is a dire prospect for applications of MRI. In a seminal paper, Mansfield et al. [2] reported on a form of nuclear magnetic resonance (NMR) diffraction, in which they considered a solid-state periodic lattice of spins in a macroscopically sized lattice, revealing diffraction patterns on the order of the lattice. As a follow-up to this idea, Blümler et al. [3] and Bernhard Blümich [4] reported (the latter in a paper dedicated to Paul Callaghan) on an interesting intertwining of concepts of the k -space vector of refractive MRI and the spatial periodicity of a lattice-like diffractive structure, further exploring diffractive imaging. Blümich’s paper contains a few more gems worth discussing, but would distract us too far from the optical viewpoint we are considering here.

Near-field effects can be further exploited to increase the resolution of an imaging system. At optical wavelengths, one is hardly able to extend beyond 200 nm of resolution with currently available light sources. “The diffraction limit of light is 100 times the size of structures that cell biologists study as they characterise events in organelles or membranes,” Hari Schroff (NIH/NIBIB) is quoted to say in [5], yet below 200 nm “is where most cellular action is,” the author notes. The alternative is to avoid scattering as an imaging paradigm, instead, to image photon sources (also known as quantum emitters).

      Interestingly, deep space astronomy always worked this way around by observing photon emitters, so that astronomers only consider objects that were once themselves sources of radiation, such as stars and their predecessors and descendants. In astronomy, the limit of resolution is therefore not dominated by the wavelength of the radiation, which can be very small when compared to the size and distance of the astronomical objects, but rather by the measuring instrument’s principle of operation, its detection sensitivity, and in particular, its effective aperture.

      When imaging radiation sources, such as single photon emitters in molecules, we now know that we can greatly improve on the Abbe limit, by about a factor of 10, especially when combined with techniques of stimulated emission and depletion, and one of the numerous variations based on fluorophore emission dynamics. These techniques, which have revolutionized cellular biology and won its inventor Stefan Hell the Nobel Prize in 2014, are of course not accessible to astronomers, who would have to wait too long for excitation signals to pass from observer to object and back again. But for cell biology this is not problematic. Although at currently ~30 nm, the resolution is still far from the desired 1 nm limit, advances in image processing present a feasible route to achieve further improvements. But the technique also raises some questions. Sample preparation is very difficult, and imaging is indirect as fluorophores have to be invasively attached to interesting molecules, almost certainly modifying their behavior.

Magnetic resonance microimaging is a noninvasive technique that is clearly more closely related to stimulated emission depletion (STED) microscopy than to conventional scattering light microscopy. A localized atomic nucleus’ spin is a quantum absorber/emitter. By localizing the excitation field spatially or by frequency, a sub-selection of the spins in a sample can be prepared to absorb radiation. Further localization can ensure that emission of radiation energy is again sub-selected, for example along the geometrical intersection of two orthogonal manifold slices, the one for excitation, the other for emission. A range of further techniques, such as available through relaxation contrast, or phase accumulation, can again further sub-select spins before readout, thereby improving resolution in direct analogy to the techniques of fluorophore emission dynamics. Noninvasive Faraday-detected

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