Table 1.
Non-invasive in vivo neuroimaging modalities as potential tools to detect adult human neurogenesis
| Method | Description | Primary strengths | Primary weaknesses |
|---|---|---|---|
| Positron emission tomography (PET) | Measures pairs of gamma rays generated indirectly by positrons emitted from an injected radiotracer | High chemical sensitivity (pico to nanomolar). PET probes potentially can label specific molecular adult neurogenesis targets | Requires injection of small amounts of short-lived radiotracers into bloodstream |
| Low-to-moderate temporal and spatial resolution (mm) | |||
| Limited use in repeated-measures studies within the same individual due to cumulative radiation exposure | |||
| Structural magnetic resonance imaging (MRI) | Measures resonance frequency of hydrogen atoms. Strong magnetic fields align protons of water, fat, proteinaceous fluid and solids, and changing radiofrequency pulse sequences alters the magnetization to create tissue contrast | High spatial resolution: sub-mm in 7-T magnets, permitting some delineation of hippocampal subregions. In animals, 9.4-T scanners can acquire nearly single-cell resolution (μm) in the hippocampus | Changes in hippocampal (dentate gyrus) morphometry do not necessarily reflect changes related to adult neurogenesis |
| Magnetic resonance spectroscopy (MRS) | Detects metabolites through their unique chemical shifts, typically proton (1H MRS). Area under the signal peak represents metabolite concentration | No contrast agent required High biochemical specificity. A putative biochemical peak specific to neural progenitor cell has been identified.122 | Low spatial resolution, as metabolite concentrations are usually 10−5- to 10−6-fold lower than water. Voxel size is substantially larger (cm3) than other MRI techniques |
| Blood-oxygenation level-dependent functional MRI (BOLD-fMRI) | An indirect measure of neural activity. An increase in neural activity elicits local increases in blood flow in nearby capillaries, altering the local magnetic field via concentration changes in deoxyhemoglobin and oxyhemoglobin | No contrast agent required Can detect functional effects of neurogenic-altering interventions/conditions | The ways in which adult neurogenesis influences hemodynamic responses in the dentate gyrus and downstream hippocampal regions are not known |
| Functional connectivity analyses can map intra-hippocampal and inter- hippocampal networks that are active during a behavioral task (indirectly relating the changes in adult neurogenesis to cognitive or affective networks) or at rest (thought to reflect structural connectivity) No contrast agent required | BOLD-fMRI reflects neural activity of multiple cell populations within the dentate gyrus (includes glutamatergic granule cells, GABAergic interneurons and astrocytes in addition to the adult-born granule cells) | ||
| Cerebral blood volume (CBV) | Measures change in signal intensity before and after injecting a contrast agent to calculate the amount of blood volume within a region-of- interest | Putative link between adult neurogenesis, angiogenesis and CBV shown.73 | Requires injection of contrast agent gadolinium into bloodstream |
| Higher spatial resolution compared with other functional imaging methods | The ways in which adult neurogenesis influences blood volume in the dentate gyrus and downstream hippocampal regions are not known | ||
| Cerebral blood flow (CBF) measured using arterial spin labeling functional MRI | Measures difference between signals from control image and ‘tagged’ image (tagging with a magnetic pulse perturbs arterial blood water magnetization before its entry into tissue) | No contrast agent required | The ways in which adult neurogenesis influences blood flow in the dentate gyrus and downstream hippocampal regions are not known |
MR and PET scanners are frequently used for clinical diagnosis and treatment monitoring. 1.5-T scanners are commonly used in clinical settings but hospitals are progressively upgrading to 3-T scanner facilities. 7-T and hybrid PET-MRI machines are increasingly available in research institutes. High-field MR scanners and spectrometers (4.7-, 9.4- and 14- T) and dedicated small animal PET scanners are used to image rodents. Functional neuroimaging methods such as BOLD-fMRI, CBV and CBF can be used to relate the putative adult neurogenesis-mediated changes in activity to behavior, in particular aspects of memory and emotion known to be altered by adult neurogenesis in animal models. Scans of several different MR-modalities can be acquired in the same scanner within the same session, offering complementary anatomical, physiological and metabolic data on putative adult hippocampal neurogenesis correlates. Repeated scans can be performed on the same individual, allowing us to assess the effects of pro- or anti-neurogenic interventions on the putative correlates over time. Large quantities of data can be acquired with these methods in a relatively short span of time, such as an hour or less.