The identification of neural stem and progenitor cells (NPCs) by in vivo brain imaging could have important implications for diagnostic, prognostic, and therapeutic purposes. We describe a metabolic biomarker for the detection and quantification of NPCs in the human brain in vivo. We used proton nuclear magnetic resonance spectroscopy to identify and characterize a biomarker in which NPCs are enriched and demonstrated its use as a reference for monitoring neurogenesis. To detect low concentrations of NPCs in vivo, we developed a signal processing method that enabled the use of magnetic resonance spectroscopy for the analysis of the NPC biomarker in both the rodent brain and the hippocampus of live humans. Our findings thus open the possibility of investigating the role of NPCs and neurogenesis in a wide variety of human brain disorders.

Development of noninvasive techniques to discover new biomarkers in the live brain is important to further understand the underlying metabolic pathways of significance for processes such as anesthesia-induced apoptosis and cognitive dysfunction observed in the undeveloped brain. We used in vivo proton magnetic resonance spectroscopy and two different signal processing approaches to test the hypothesis that volatile (isoflurane) and intravenous (propofol) anesthetics at equipotent doses produce distinct metabolomic profiles in the hippocampus and parietal cortex of the live rodent. For both brain regions, prolonged isoflurane anesthesia was characterized by higher levels of lactate (Lac) and glutamate compared with long-lasting propofol. In contrast, propofol anesthesia was characterized by very low concentrations of Lac ([lac]) as well as glucose. Quantitative analysis revealed that the [lac] was fivefold higher with isoflurane compared with propofol anesthesia and independent of [lac] in blood. The metabolomic profiling further demonstrated that for both brain regions, Lac was the most important metabolite for the observed differences, suggesting activation of distinct metabolic pathways that may impact mechanisms of action, background cellular functions, and possible agent-specific neurotoxicity.

We developed a non-magnetic positron-emission tomography (PET) device based on the rat conscious animal PET that operates in a small-animal magnetic resonance imaging (MRI) scanner, thereby enabling us to carry out simultaneous PET/MRI studies. The PET detector comprises 12 detector blocks, each being a 4 × 8 array of lutetium oxyorthosilicate crystals (2.22 × 2.22 × 5 mm(3)) coupled to a matching non-magnetic avalanche photodiode array. The detector blocks, housed in a plastic case, form a 38 mm inner diameter ring with an 18 mm axial extent. Custom-built MRI coils fit inside the positron-emission tomography (PET) device, operating in transceiver mode. The PET insert is integrated with a Bruker 9.4 T 210 mm clear-bore diameter MRI scanner. We acquired simultaneous PET/MR images of phantoms, of in vivo rat brain, and of cardiac-gated mouse heart using [(11)C]raclopride and 2-deoxy-2-[(18)F]fluoro-D-glucose PET radiotracers. There was minor interference between the PET electronics and the MRI during simultaneous operation, and small effects on the signal-to-noise ratio in the MR images in the presence of the PET, but no noticeable visual artifacts. Gradient echo and high-duty-cycle spin echo radio frequency (RF) pulses resulted in a 7% and a 28% loss in PET counts, respectively, due to high PET counts during the RF pulses that had to be gated out. The calibration of the activity concentration of PET data during MR pulsing is reproducible within less than 6%. Our initial results demonstrate the feasibility of performing simultaneous PET and MRI studies in adult rats and mice using the same PET insert in a small-bore 9.4 T MRI.