Editorial for “Detection of Neuroinflammation Induced by Typhoid Vaccine Using Quantitative Magnetization Transfer MR : A Randomized Crossover Study”

Normally with conventional MRI sequences we are able to sample the signal of those protons that are free in water, but there are protons bound to immobile macromolecules in tissue with very short T2 (≈10 μs)1 and, therefore, difficult to sample directly. However, their signal can be detected indirectly by exploiting its interactions with the free water pool via chemical and/or dipole exchange mechanisms generally referred to as the magnetization transfer (MT) effect. The quantitative magnetization transfer (qMT) approach can describe distinct tissue characteristics such as macromolecular pool size, MT exchange rate rather than the combined effect of multiple tissues. Despite evidence that qMT is sensitive to white matter pathology, the technique has yet to enter clinical practice. An important limitation is the duration of data acquisition, which, due to the coverage of the whole brain, can reach up to 45 minutes.2 Systemic inflammation is a condition in which mood, cognition, and behavior may be impaired. When inflammation or stress becomes chronic, its effects may become pathological and contribute to neuropsychiatric diseases, including depression.3 Its role in the etiology of common mental illnesses has only recently been recognized.4 Mediators of immune influence on the brain appear to be primarily attributable to proinflammatory cytokines, particularly interleukin-1, interleukin-6 (IL-6), and tumor necrosis factor-α. Cytokines are also released in response to both acute and chronic psychosocial stress,5 and elevated levels have also been found in people with depression.6, 7 Recently there has been a considerable interest in understanding the inflammatory responses within the brain. Due to the ultra-specialization of the disciplines, an academic scenario of the biomedical sciences has been created to consider the various physiological “sets” separately from each other. This was strongly more evident for the immune system. Currently, a major limitation of understanding neuroinflammation and psychiatric disorders is the inherent invasive methodology needed to study the phenomenon. Technologies that allow for the noninvasive characterization of neuroinflammation in humans may be PET scans with microglia-specific radiotracers8, 9 but it is associated with exposure to ionizing radiation, so its use is limited in vulnerable populations and in longitudinal studies, which require repeated use of PET over years, as occurs in the follow-up of neurodegenerative diseases. Magnetic resonance offers tools, such as metabolic approaches (Spectroscopy), blood–brain barrier integrity studies (CeMRI), and diffusion analysis techniques (DWI-DTI), which have been shown to describe well some “ultrastructural” aspects, without all those problems related to ionizing radiation. In this issue of JMRI, the article “Detection of neuroinflammation induced by typhoid vaccine using quantitative magnetization transfer: a randomized crossover study” proposes a low-level noninvasive neuroinflammation-sensitive technique to be used to establish the role of neuroinflammation in psychiatry and the pathophysiology of inflammation using qMT. As already mentioned in the limitations of this tool, the acquisition and analysis times are too long; however, the authors experimented with a scan time clinically compatible with normal patient compliance using a 3 T scanner (MAGNETOM Skyra 3 T MRI scanner in this case), which with a higher signal-to-noise ratio and with optimized acquisition to reduce the overall scan time improves patient tolerance. This could improve our ability to detect subtle inflammatory changes relative to 1.5 T.10 Despite the limitations related to the small size of the sample and to some technical “rigidities” (eg reduced FOV), the data obtained describe a tool with good sensitivity and the ability to obtain potentially useful biomarkers for understanding and classifying some steps that are subject to inflammatory processes, but further investigations will be necessary, as also stated by the authors. It will be interesting and curious to understand how this tool fits into a set of techniques already strongly involved in the processes of understanding the nature of neuroinflammation.