Emerging Electromagnetic Technologies for Brain Diseases Diagnostics, Monitoring and Therapy

Although the human brain comprises only 2% of the body weight, it receives 15–20% of the cardiac output and accounts for 20% of the total body oxygen consumption. Since the brain has almost no energy reserves, adequate cerebral blood flow is essential to prevent brain damage. Under normal circumstances the brain has an intrinsic ability to regulate its blood supply. This cerebral autoregulation may be impaired after traumatic brain injury or other cerebral insults (e.g. subarachnoid haemorrhage). For the treating neurointensivist, it is one of the main therapeutic needs to maintain adequate cerebral perfusion in these patients to prevent secondary brain insults, which ultimately result in further cerebral damages. Up to now, there are only few monitoring tools available to achieve this goal. All of them have limitations (e.g. focal methods with a sampling error, exposure to radiation, no 24 h availability, high staff resources, high costs). This chapter will give an overview about the current monitoring strategies and the requirements new techniques have to fulfil.

This chapter provides an introduction to the physical principles underlying the adoption of microwave technology as a biomedical imaging modality for diagnosis and follow-up of neurological diseases and injuries (e.g., stroke, haematoma). In particular, a theoretical analysis, supported by numerical simulations and experiments, will be given to describe the physical constraints that arise in this kind of application and the relevant limitations. In addition, we discuss the main aspects to be faced when implementing microwave imaging technology in a clinical scenario, by exploiting a design procedure to determine the number of antennas needed to capture, in a non-redundant way, the largest part of the available data.

Continuous monitoring of a patient’s brain who is admitted to intensive care with a diagnosis of hemorrhagic stroke poses a great technological challenge. Existing medical imaging modalities such as CT and MRI that are extensively used for brain imaging are practically not suitable for these purposes. Nevertheless, microwave imaging as an emerging medical imaging technique can provide a safer and cost-effective alternative for continuous monitoring of the brain. In this context, differential microwave imaging with qualitative inverse scattering methods such as linear sampling method and factorization method is considered to determine evolution of intracranial hemorrhage without generating anatomical images. Through sequential S-parameters measurements performed on a brain phantom with a prototype microwave imaging system that cylindrically rotates two transceiver antennas around, feasibility of continuous monitoring of hemorrhagic strokes via microwave imaging is experimentally evaluated.

ElectroMagnetic Tomography (EMT) is an emerging biomedical imaging modality with great potential for non-invasive assessment of acute and chronic functional and pathological conditions of brain tissue. The mission of EMTensor GmbH is to bring this innovative technology into practical diagnostics of brain, including detection of stroke and traumatic brain injuries, followed by 24/7 monitoring of functional viability of tissue and an assessment of efficacy of treatment. The goal is to create a unique infrastructure based on compact-sized devices, information processing systems and services, which will lead to a breakthrough in brain diagnostics. The idea is to shift the paradigm from a reactive approach, where treatment follows a delayed diagnosis, to a proactive and preventive approach, where early diagnosis leads to successive treatment. The topics of this chapter include a brief introduction of the imaging procedures used at EMTensor GmbH. Furthermore, recent improvements of our image reconstruction algorithms will be discussed briefly, followed by a virtual study to explore the spectrum of potential applications of EMT technology for brain diagnostics. In a next step, the EMTensor BRain IMaging scanner Generation 1 (BRIM G1) will be described. In particular, attention will be given to the imaging results obtained with this scanner in clinical trials. Finally, recent improvements on imaging hardware and chamber topology will be discussed, which have been considered in our second generation brain imaging scanner (BRIM G2).

Microwave radiometry is a passive and noninvasive technique that is able to measure deep tissue temperature and track changes in thermal profiles in tissue up to 5 cm below the surface over several hours. These characteristics make microwave radiometry a suitable technique to monitor brain temperature during extended hypothermic surgeries, and thus avoid potential complications that result from poorly controlled low temperature levels and return to normothermia. This chapter addresses all development stages of a radiometric brain thermometer including: radiometer electronics; antenna design and fabrication; power to temperature calibration algorithm; multilayer head phantom model with variable temperature compartments; experimental validation of sensor performance; and initial clinical implementation. In particular, a radiometric antenna is described based on a log-spiral design optimized in silico to receive energy from deep brain. The prototype is tested using a realistic head phantom that consists of an anatomical human skull with separate brain and scalp compartments in which tissue-equivalent fluid phantoms circulate at independent temperatures (32 °C for scalp and 37 °C for brain). Experimental data shows that the calculated radiometric brain temperature tracks within 0.4 °C the measured brain phantom temperature over a 4.6 h experiment, when the brain phantom is lowered 10 °C and then returned to original temperature. A clinical case confirms the ability to noninvasively monitor temperature in deep brain using microwave radiometry, with radiometric measurements that closely track changes in core temperature as measured in the nasopharynx. Both simulated and experimental results demonstrate that a 1.1–1.6 GHz radiometric sensor with 2.5 cm diameter is an appropriate tool for noninvasive monitoring of deep brain temperature.

The synergic exploitation of electromagnetic fields and nano-components has led, in the last two decades, to the definition of new therapeutic tools for the treatment of cancer. One of these tools is the Magnetic Nanoparticle Hyperthermia, an emerging hyperthermic treatment where the tumor heating is achieved by accumulating into it magnetic nanoparticles and applying a low frequency magnetic field. Magnetic Nanoparticle Hyperthermia is very attractive thanks to the biocompatibility and low toxicity of the employed magnetic nanoparticles and the possibility of their selective accumulation into the tumor by means of minimally invasive administration routes. Moreover, they exhibit high dissipation capability and the transparency of the human tissues to low frequency magnetic fields allows treating tumors deeply located in the body. For these reasons, Magnetic Nanoparticle Hyperthermia has been extensively investigated, and clinical trials on human patients have been performed since 2003, with encouraging results and reduced side effects, especially concerning brain tumors. In this framework, an important topic is the characterization, both theoretical and experimental, of the properties, particularly the losses, of magnetic nanoparticles. The aim is to identify the nanoparticle parameters (size and shape) and the exposure conditions (magnetic field amplitude and frequency) that maximize the dissipation capability of the magnetic nanoparticles, in order to minimize their concentration in the tumor. However, maximizing the magnetic losses is only one face of the coin: one must also avoid overheating of the healthy tissue surrounding the tumor, due to the eddy currents induced by the applied field. Therefore, one should actually face a more complex constrained optimization problem. This explains in part why the setting of the operative parameters is still based on empirical, possibly over-restrictive, criteria, although the individuation of the actual optimal working conditions is a key point to extend its clinical effectiveness. In this chapter we will prevalently address this last aspect of Magnetic Nanoparticle Hyperthermia. We will begin with an overview of the main biological and physiological effects that are at the basis of the use of heating as an oncological treatment and of the main hyperthermia modalities. Next, we will introduce and discuss Magnetic Nanoparticle Hyperthermia, reporting the main results of its feasibility assessment and of the clinical trials performed up to now. Then, after revising the state of the art and current issues concerning the optimization of the magnetic nanoparticle losses, we will present a recently proposed criterion for the optimal choice of the working conditions in Magnetic Nanoparticle Hyperthermia, critically discussing the reliability of the analytical models on which it is based. Numerical results relative to the challenging and clinically relevant case of brain tumors, obtained by exploiting a 3D realistic model of the human head, will be presented, discussing their significance and practical relevance. Then, exploiting these results, the limits of clinical applicability of Magnetic Nanoparticle Hyperthermia for the treatment of brain tumors in adult patients will be estimated. A discussion on the possible future developments will conclude the chapter.

Since the half of the past century, attempts to locally treat intracranial neoplasms have grown. From pioneering interstitial seeds of various materials (radioactive, non-radioactive) with or without the application of ElectroMagnetic Field (EMF), recently new interest was elicited by the possibilities offered by the nanotechnologies. The blocking activity of the Blood-Brain Barrier (BBB) represents main problem for every treatment of brain neoplasms. Shortly, here we summarize some aspects of the blood-brain barrier problem in the perspective of more efficient therapeutic approaches, like the use of nanoparticle and their theranostic possibilities.

As the boundary between biology, medicine, and engineering remains indistinct, electromagnetics engineering applications are expanding to encapsulate a variety of public health issues. Medical applications of microwaves are a very rapidly developing research and application field, especially for intracranial applications. Currently, in order to acquire the most valuable complementary data in terms of quality and quantity, benefiting from the advantages of the various techniques, combination of two or more techniques is pursued both in diagnostics and therapy. The so-called multimodal approach may be achieved either by post-session analysis of data or via simultaneous use of techniques in order to reveal the multifactorial interplay of the underlying mechanisms during brain activation, disease and therapy. This chapter will review the progress in diagnostic, therapeutic and theranostic multi-modal multispectral methods, with specific attention to cerebrovascular diseases and monitoring of the brain activity.