**1. Introduction**

Brain-machine interfaces (BMIs) have made great progress as prostheses (e.g., for visionimpaired individuals). Those patients were willing to undergo major surgery, expense, and to have centimeter-scale electrical devices implanted in their nervous systems. The scope of influence of BMI of the future is clearly large, potentially including cognitive enhancement and memory storage, and quite likely with ramifications beyond anybody's present imagination [1, 2]. To fully exploit the power of BMI, some big steps need to be taken. For wide and long-term public use, the invasiveness of the implant procedure and toxicity of the implant materials need to be eliminated. The number of neuronal channels an implanted device must address needs to be increased by many orders of magnitude, and the entire nervous system must be accessible. The spatial resolution should be smaller or equal to the diameter of small groups of neurons (i.e., micron-sized), and the temporal resolution should be faster than or comparable to neurons in the native brain (i.e., sub-millisecond response time).

**2. Brain access**

consumer) applications.

under magnetic gradient.

in size with age, with an overall area of 6 mm2

To date, developers of the smart-dust [8] concept have constructed millimeter-sized particles using wafer-based lithographic methods typically employed for electronic circuitry (e.g., CMOS). Traditional electronic particles below a millimeter in size are difficult to power without a tether to the outside world, because of poor electromagnetic coupling to small antennas. In order to implant or remove electronic particles of these sizes, practitioners need millimetersized holes, requiring either surgery or interventional procedures to go through the vessels or subarachnoid spaces. Because of the potential for damage to eloquent nervous structures, such procedures carry risks and expensive and are therefore inappropriate for wide (e.g.,

As will be discussed below, we and others have formulated contrast solutions containing high concentrations of nano-sized particles with magnetic properties (e.g., spintronic, magnetoelectric) that do not need to rely on traditional approaches to enter or interact with the brain. As in drug delivery, we have shown that nanoscale particles can be delivered intranasally, which is considered a noninvasive administration mode in the clinical literature [9, 10]. The cribriform plate separates the nasal from the cranial cavities, with foramina that decline slightly

and others have demonstrated that magnetic particles with diameters of up to 250 nm readily enter the cranium with the assistance of a 20-mT magnetic gradient, with no appreciable intracranial entry in the absence of an imposed magnetic field (**Figure 1**). Minimally invasive routes other than intranasal are possible, for example, via lumbar puncture or via intravenous administration. However, both of these routes require overcoming countervailing current flows (of

Once in the intracranial cavity, magnetic particles can be manipulated using magnetic gradients for delivery to specific brain foci. The tracks that such particles make are micron-sized, unlike the millimeter scale holes made during conventional deep-brain stimulation surgery. Magnetic particle manipulation is difficult with a conventional MRI, since it is very hard to create magnetic gradients that can overcome the static MRI field strength. However, our group and others have constructed MRI systems where the static field can be temporarily

**Figure 1.** Transport into brain. Rat olfactory bulb before (left) and after (right) intra-nasal administration of particles

cerebrospinal fluid and blood, respectively) that make them less attractive.

at age 25 and 4 mm2

Image-guided Placement of Magnetic Neuroparticles as a Potential High-Resolution...

http://dx.doi.org/10.5772/intechopen.75522

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at age 66 [11]. Our group

Most medical researchers attempt to translate therapeutic approaches from animal models to human use. Unfortunately, there are significant barriers to taking this approach to BMI. Optical dyes that are the mainstay of animal research do not work for animals larger than a few centimeters because of light scattering and the photon-stopping power of tissue. The multi-decade-long history of failure to bring optical mammography into clinical practice suggests that light scatter is not a problem that is easily solved [3]. Implanted tethered electrodes and high-intensity-focused ultrasound can only address one section of the nervous system at a time. Genetic manipulation of brain circuitry (e.g., with optogenetic or sonogenetic techniques) has significantly increased our understanding of preclinical neurosciences, but would still require invasive focal delivery of gene vectors, optical fibers, or ultrasonic transducers that would limit wide use in humans [4, 5].

Oscillating magnetic fields do not interact much with tissue, especially below several gigahertz in frequency, and therefore penetrate the human head readily. Magnetic resonance imaging methods that examine blood oxygen-level dependency (BOLD) rely on vascular changes that have a poor spatial and temporal resolution. Magnetic resonance imaging (MRI) pulse sequences that read out electrical current (e.g., from Lorentz forces causing neuronal displacement) can detect micro-amp levels (far from the nanoampere currents generated from individual or small neuronal bundles) although technical improvements such as fast magnetic gradients may improve performance in the future [6]. Imaging of electrical currents (magnetoencephalography) is limited to millimeter spatial resolution due to the variable impedance of the brain and the detector resolution [7].

In this chapter, we summarize contrast-enhancement approaches to BMI that could yield readout and writing of the entire brain with high spatial and temporal resolution. Contrast enhancement from radioactive and other materials has been used in radiology practices for the past century to explore and diagnose diseases of the nervous system. The contrast materials that appear the most promising are based on magnetic nanoparticles, which we attempt to describe more fully in this chapter.
