Early detection of elevated lactate levels in a mitochondrial disease model using chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) at 7T-MRI

Saito, Shigeyoshi; Takahashi, Yusuke; Ohki, Akiko; Shintani, Yasunori; Higuchi, Takahiro

doi:10.1007/s12194-018-0490-1

Cited by 41 publications

(25 citation statements)

References 41 publications

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“…To assess brain metabolites, we performed 1 H-magnetic resonance spectroscopy (MRS) at 2 days after cell administration. 26 Additionally on day 2, positron emission tomography (PET) using [ 18 F] mitochondrial peripheral benzodiazepine receptor (PBR) ligands visualized the distribution of microglia activation. 27 To evaluate the cerebral blood flow (CBF), we conducted magnetic resonance imaging (MRI) -arterial spin labelling (ASL) at 2 days (acute phase) and 4 weeks (sub-acute phase) after administration.…”

Section: Methodsmentioning

confidence: 99%

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy

Suzuki

Sato

Kushida

et al. 2020

J Cereb Blood Flow Metab

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Perinatal hypoxic ischemic encephalopathy (HIE) results in serious neurological dysfunction and mortality. Clinical trials of multilineage-differentiating stress enduring cells (Muse cells) have commenced in stroke using intravenous delivery of donor-derived Muse cells. Here, we investigated the therapeutic effects of human Muse cells in an HIE model. Seven-day-old rats underwent ligation of the left carotid artery then were exposed to 8% oxygen for 60 min, and 72 hours later intravenously transplanted with 1 × 104 of human-Muse and -non-Muse cells, collected from bone marrow-mesenchymal stem cells as stage-specific embryonic antigen-3 (SSEA-3)+ and −, respectively, or saline (vehicle) without immunosuppression. Human-specific probe revealed Muse cells distributed mainly to the injured brain at 2 and 4 weeks, and expressed neuronal and glial markers until 6 months. In contrast, non-Muse cells lodged in the lung at 2 weeks, but undetectable by 4 weeks. Magnetic resonance spectroscopy and positron emission tomography demonstrated that Muse cells dampened excitotoxic brain glutamatergic metabolites and suppressed microglial activation. Muse cell-treated group exhibited significant improvements in motor and cognitive functions at 4 weeks and 5 months. Intravenously transplanted Muse cells afforded functional benefits in experimental HIE possibly via regulation of glutamate metabolism and reduction of microglial activation.

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Section: Methodsmentioning

confidence: 99%

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy

Suzuki

Sato

Kushida

et al. 2020

J Cereb Blood Flow Metab

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“…Rectal temperature was continuously monitored and maintained at 36.5 ± 0.5°C throughout all experiments. During the MRI scan, the rats were held in place fixed by a handmade ear bar and anesthetized through a facemask with 2% isoflurane (Saito et al, 2018). Transaxial 3-dimensional (3D) T 1 -weighted MR images (T 1 WIs) parameters were as follows: TR/TE = 400/9.57 ms, matrix = 256 × 224 × 45, field of view = 25.6 × 22.4 × 9.0 mm, average = 4, and spatial resolution = 100 × 100 × 200 μm.…”

Section: Methodsmentioning

confidence: 99%

Prenatal Irradiation-Induced Hippocampal Abnormalities in Rats Evaluated Using Manganese-Enhanced MRI

Saito

Sawada

Aoki

2018

Front. Neural Circuits

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The aim of this study was to characterize hippocampal abnormalities in rats after prenatal x-ray irradiation using manganese-enhanced MRI (MEMRI). All radiation-exposed rat brains showed a reduced volume with prominent dilatation of lateral ventricles. Moreover, MEMRI-enhanced areas within the hippocampus were reduced in volumes by approximately 25% of controls, although the entire volume of hippocampus was decreased by approximately 50% of controls. MEMRI signals were enhanced strongly in the hilus and granular layer of the dentate gyrus (DG) and the pyramidal layer and infrapyramidal region of the CA3 region, and moderately along the CA1/2 pyramidal cell layer in the control rats. In radiation-exposed rats, MEMRI signals in the CA1/2 regions disappeared due to disrupting their laminar organization, although strong MEMRI signals were sustained in the DG and CA3 regions. Histopathological examinations in radiation-exposed rats revealed disorganizations of the DG granule cell layer and the CA3 pyramidal cell layer with reducing the cell density. The CA1/2 pyramidal cell layer was disrupted by invading ectopic cell mass. Neural cell adhesion molecule (NCAM)-positive fiber bundles were sustained in radiation-exposed rats, although they distributed aberrantly in the suprapyramidal CA3 region with a slight reduction of NCAM staining. Furthermore, glial components consisted largely by astrocytes and minor by microglia were densely distributed in the DG rather than in other hippocampal regions, and their density radiation-exposed rats. In conclusion, MEMRI signal enhancements could delineate different neuronal and/or glial components among hippocampal regions. We characterized microstructures of the deformed hippocampus as well as its macrostructures in a prenatally radiation-exposed rat model using in vivo MEMRI. The present findings provide advantageous information for detecting nondestructively hippocampal deformations in neurodevelopmental disorders.

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“…The chemical shift of the hydroxylic proton of the lactate is very close to the water signal and renders quite difficult to directly detect lactate in vivo by CEST imaging. However, correlation of the signal arising from lactate between CEST and MR spectroscopy has been performed in a lymphoma murine tumor upon lactate infusion (130) or in a mitochondrial disease model (131). Other approaches exploited lactate-responsive PARACEST contrast agents for taking advantage of the larger chemical shift difference of these molecules and the CEST contrast dependence with lactate concentration (132,133).…”

Section: Imaging Lactatementioning

confidence: 99%

Non-invasive Investigation of Tumor Metabolism and Acidosis by MRI-CEST Imaging

Consolino¹,

Anemone²,

Capozza³

et al. 2020

Front. Oncol.

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Altered metabolism is considered a core hallmark of cancer. By monitoring in vivo metabolites changes or characterizing the tumor microenvironment, non-invasive imaging approaches play a fundamental role in elucidating several aspects of tumor biology. Within the magnetic resonance imaging (MRI) modality, the chemical exchange saturation transfer (CEST) approach has emerged as a new technique that provides high spatial resolution and sensitivity for in vivo imaging of tumor metabolism and acidosis. This mini-review describes CEST-based methods to non-invasively investigate tumor metabolism and important metabolites involved, such as glucose and lactate, as well as measurement of tumor acidosis. Approaches that have been exploited to assess response to anticancer therapies will also be reported for each specific technique.

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Early detection of elevated lactate levels in a mitochondrial disease model using chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) at 7T-MRI

Cited by 41 publications

References 41 publications

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy

Prenatal Irradiation-Induced Hippocampal Abnormalities in Rats Evaluated Using Manganese-Enhanced MRI

Non-invasive Investigation of Tumor Metabolism and Acidosis by MRI-CEST Imaging

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