Mass spectrometry imaging (MSI) is well-known for the non-labeling visualization of analytes, including drugs and their metabolites in biological samples. In this study, we applied three different tools of MSI, desorption electrospray ionization (DESI)-MSI, matrix-assisted laser desorption ionization (MALDI)-MSI, and a newly developed atmospheric pressure (AP)-MALDI-MSI known as iMScopeTM QT for rapid mapping of imipramine, chloroquine, and their metabolites in C57BL/6 male wild-type mice. Among three MSI tools, better detection capability for targeted drugs at higher speed (up to 32 pixels/s) was observed in iMScope QT. It revealed that imipramine and its metabolites were significantly accumulated in the renal cortex of mice, but chloroquine and its metabolites were highly accumulated in the renal pelvis and renal medulla of mice. Additionally, a higher accumulation of imipramine was noted in the thalamus, hypothalamus, septum, and hindbrain of mice brains. However, chloroquine and its metabolites showed notable accumulation in the lateral ventricle, fourth ventricle, and fornix of the mice brains. These findings of our study can be helpful in understanding clinically relevant properties, efficacy, and potential side effects of these drugs. Our study also showed the potentiality of iMScope QT for rapid mapping of small drugs and their metabolites in biological samples.

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, has significant health benefits. Previous studies reported decreased levels of DHA and DHA-containing phosphatidylcholines in the brain of animals suffering from Alzheimer’s disease, the most common type of dementia; furthermore, DHA supplementation has been found to improve brain DHA levels and memory efficiency in dementia. Oil extracted from the seeds of Plukenetia volubilis (green nut oil; GNO) is also expected to have DHA like effects as it contains approximately 50% α-linolenic acid, a precursor of DHA. Despite this, changes in the spatial distribution of DHA in the brain of animals with dementia following GNO or DHA supplementation remain unexplored. In this study, desorption electrospray ionization imaging mass spectrometry (DESI-IMS) was applied to observe the effects of GNO or DHA supplementation upon the distribution of DHA in the brain of male senescence-accelerated mouse-prone 8 (SAMP8) mice, a mouse model of dementia. DESI-IMS revealed that brain DHA distribution increased 1.85-fold and 3.67-fold in GNO-fed and DHA-fed SAMP8 mice, respectively, compared to corn oil-fed SAMP8 mice. Memory efficiency in SAMP8 mice was also improved by GNO or DHA supplementation. In summary, this study suggests the possibility of GNO or DHA supplementation for the prevention of dementia.

Dementia is a major public health concern nowadays. Reduced levels of brain docosahexaenoic acid (DHA) and DHA-phosphatidylcholines (DHA-PCs) in dementia patients were reported previously. Recently, we have reported that supplementation of green nut oil (GNO) or DHA improves memory function and distribution levels of brain DHA in senescence accelerated mice P8 (SAMP8). GNO is extracted from Plukenetia volubilis seeds, and SAMP8 is a well-known model mouse of dementia. In this current study, we examined the results of GNO or DHA supplementation in the distribution levels of brain DHA-PCs in same model mouse of dementia using desorption electrospray ionization (DESI) mass spectrometry imaging (MSI). We observed significantly decreased distribution of brain DHA-PCs, PC (16:0_22:6), and PC (18:0_22:6) in SAMP8 mice compared to wild type mice, and GNO or DHA treatment restored the decreased distribution levels of PC (16:0_22:6) and PC (18:0_22:6) in the brain of SAMP8 mice. These results indicate that GNO or DHA supplementation can ameliorate the decreased distribution of brain DHA-PCs in dementia, and could be potentially used for the prevention and treatment of dementia.

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Ligamentum flavum hypertrophy (HLF) is the most important component of lumbar spinal canal stenosis (LSCS). Analysis of hypertrophied ligamentum flavum (HLF) samples from patients with LSCS can be an important que. The current study analyzed the surgical samples of HLF samples in patients with LCSC using quantitative and qualitative high performance-liquid chromatography and mass spectrometry. We collected ligamentum flavum (LF) tissue from twelve patients with LSCS and from four patients with lumbar disk herniation (LDH). We defined LF from LSCS patients as HLF and that from LDH patients as non-hypertrophied ligamentum flavum (NHLF). Total lipids were extracted from the LF samples and evaluated for quantity and quality using liquid chromatography and mass spectrometry. The total lipid amount of the HLF group was 3.6 times higher than that of the NHLF group. Phosphatidylcholines (PCs), ceramides (Cers), O-acyl-ω-hydroxy fatty acids (OAHFAs), and triglycerides (TGs) in the HLF group were more than 32 times higher than those of the NHLF group. PC(26:0)+H+, PC(25:0)+H+, and PC(23:0)+H+ increased in all patients in the HLF group compared to the NHLF group. The thickness of the LF correlated significantly with PC(26:0)+H+ in HLF. We identified the enriched specific PCs, Cers, OAHFAs, and TGs in HLF.