Here, we give a brief overview of neuroimaging methods relevant for KLS research and explain the structural, neurovascular and metabolic sources they measure.

MRI

MRI is the state-of-the-art method when it comes to high-resolution structural imaging of the brain. As MRI is sensitive to the interaction between protons, predominantly found in water, and different tissue compartments it gives images with excellent contrast between white and grey matter and cerebrospinal fluid, without adding external contrast agents. By adjusting MRI scanner settings, it is possible to enhance certain tissue contrasts. For example, T2-weighted (T2W) and diffusion-weighted (DWI) is often used for pathology visualisation. Diffusion tensor imaging (DTI), or tractography, is used for visualisation of white matter tracts through the enhanced diffusion of water along axons.

fMRI

By fMRI, it is possible to visualise the brain at work. When neurons are active, they induce release of vasoactive substances in predominantly astrocytes that triggers cerebral blood flow increase, which leads to transportation of oxygenated blood into the active area. Since the fMRI signal is sensitive to blood oxygenation through the BOLD response, fMRI provides indirect images of brain activation. fMRI is applied in two modes: (1) task-based fMRI which show brain areas that are activated by a specific task, e.g., working memory tasks that have been applied in KLS research and (2) resting-state (rs) fMRI which show brain areas that are functionally connected to each other during rest, i.e., functional connectivity. By similar methods, functional connectivity can also be studied during task performance. When referring to fMRI studies in this review, we use the term BOLD response for task-based fMRI results and functional connectivity for rs-fMRI results.

Magnetic resonance spectroscopy (MRS)

MRS is most commonly focused on proton containing substances other than water and fat (1H-MRS) but also other magnetic nuclei, for example phosphorus (31P-MRS), are possible to capture. 1H-MRS gives information of brain metabolites in the form of a spectrum where the spectral peaks are related to concentrations of different metabolites, such as n-acetylaspartate (NAA), and the neurotransmitters glutamate and GABA. MRS is mostly applied using a single voxel technique, where a spectrum is captured in one selected region of the brain.

SPECT

SPECT is a nuclear medicine imaging method that uses gamma-ray emitting radionuclides to estimate tissue function. The most common radionuclide for brain imaging is a metastable isotope of technetium, 99mTc. When 99mTc is bound to a certain ligand and injected to the blood stream, it passes the blood-brain barrier. When the gamma rays are captured in the scanner, they give information about cerebral perfusion.

PET

PET is another nuclear medicine imaging method that captures information from pairs of gamma rays derived from protons emitted from certain radionuclides, so-called tracers. Several PET tracers have been developed to gain information about specific neuroreceptors. However, the most common method is FDG-PET where the measured concentration of the distributed tracer corresponds to regional glucose metabolism.