Manganese concentration mapping in the rat brain with MRI, PET, and autoradiography

Topping, Geoffrey J.; Yung, Andrew; Schaffer, Paul; Hoehr, Cornelia; Kornelsen, Rick; Kozłowski, Piotr

doi:10.1002/mp.12300

Cited by 5 publications

(10 citation statements)

References 30 publications

(65 reference statements)

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“…In this study, we aimed to determine (1) when Mn 2+ flows into neurons, (2) when Mn 2+ in the extracellular space has been cleared while maintaining intracellular Mn 2+ , and (3) what is the appropriate interval required for repeated measurements. Although other studies have evaluated the distribution of Mn 2+ in the brain after systemic administration of MnCl 2 ( Takeda et al, 1995 ; Kuo et al, 2005 ; Tambalo et al, 2009 ; Chan et al, 2017 ; Topping et al, 2017 ), the above three time windows have not been previously clarified.…”

Section: Discussionmentioning

confidence: 99%

“…The distribution of parenchymal R1 was non-uniform ( Figures 1 , 4 ). It is not possible to determine by MRI whether these differences are due to differences in Mn 2+ accumulation or differences in biochemical environments that may affect the relaxivity of Mn 2+ ( Topping et al, 2017 ). Therefore, we cannot determine the distribution of neural activity in the brain by the R1 distribution pattern in a single subject.…”

Section: Discussionmentioning

confidence: 99%

“…Because R1 is proportional to [Mn 2+ ], R1 maps were calculated pixel-by-pixel by inverting T1 values of the T1 map to visualize [Mn 2+ ] distribution. [Note: As R1 is less sensitive to Mn 3+ , we treated R1 as reflecting Mn 2+ ( Topping et al, 2017 )].…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Manganese Dynamics in Mouse Brain After Systemic MnCl2 Administration for Activation-Induced Manganese-Enhanced MRI

Tanihira

Fujiwara

Kikuta

et al. 2021

Front. Neural Circuits

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Activation-induced manganese-enhanced MRI (AIM-MRI) is an attractive tool for non-invasively mapping whole brain activities. Manganese ions (Mn2+) enter and accumulate in active neurons via calcium channels. Mn2+ shortens the longitudinal relaxation time (T1) of H+, and the longitudinal relaxation rate R1 (1/T1) is proportional to Mn2+ concentration. Thus, AIM-MRI can map neural activities throughout the brain by assessing the R1 map. However, AIM-MRI is still not widely used, partially due to insufficient information regarding Mn2+ dynamics in the brain. To resolve this issue, we conducted a longitudinal study looking at manganese dynamics after systemic administration of MnCl2 by AIM-MRI with quantitative analysis. In the ventricle, Mn2+ increased rapidly within 1 h, remained high for 3 h, and returned to near control levels by 24 h after administration. Microdialysis showed that extracellular Mn returned to control levels by 4 h after administration, indicating a high concentration of extracellular Mn2+ lasts at least about 3 h after administration. In the brain parenchyma, Mn2+ increased slowly, peaked 24–48 h after administration, and returned to control level by 5 days after a single administration and by 2 weeks after a double administration with a 24-h interval. These time courses suggest that AIM-MRI records neural activity 1–3 h after MnCl2 administration, an appropriate timing of the MRI scan is in the range of 24–48 h following systemic administration, and at least an interval of 5 days or a couple of weeks for single or double administrations, respectively, is needed for a repeat AIM-MRI experiment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Manganese Dynamics in Mouse Brain After Systemic MnCl2 Administration for Activation-Induced Manganese-Enhanced MRI

Tanihira

Fujiwara

Kikuta

et al. 2021

Front. Neural Circuits

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“…In recent years, there has been a renewed interest in using radioactive manganese for PET imaging, in particular manganese-52 [32][33][34][35][36][37]. Mn-52 is a positron emitter with a long halflife of 5.6 days, which allows longitudinal biodistribution studies in the body and brain.…”

Section: Introductionmentioning

confidence: 99%

Anatomy, Functionality, and Neuronal Connectivity with Manganese Radiotracers for Positron Emission Tomography

et al. 2018

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The results were consistent with manganese-enhanced MRI studies, despite the much lower manganese concentration used for PET (100 mM Mn for MRI compared to ~ 0.05 mM for PET). This indicates that uptake and transport mechanisms are comparable even at low PET doses. This helps establish the use of manganese-based radiotracers in both preclinical and clinical studies to assess anatomy, function, and connectivity.

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“…Currently, techniques used to directly measure intracellular and tissue PO 2 , inlcude tumor vessel analysis, determination of tumor metabolism, determination of DNA damage in tumor cells, measurement of intra-tumor oxygen tension, detection of radioactive hypoxia markers or endogenous biological hypoxia markers, Oswald's magnetic resonance imaging (MRI) method, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) ( 19 ). However, all of these techniques have limitations, including invasiveness, narrow measurement range and low temporal and spatial resolution ( 20 ). The oxygen electrode method has previously been considered to be the ‘gold standard’ for the detection of tumor oxygen partial pressure ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

PO2‑based biodosimetry evaluation using an EPR technique acts as a sensitive index for chemotherapy

Cai

2018

Oncol Lett

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The partial pressure of oxygen (PO2) in the tumor microenvironment directly affects tumor sensitivity to chemotherapy. In the present study, a lithium phthalocyanine probe was implanted into MCF-7 human breast cancer cells, followed by transplant of the cells into nude mice. The present study used an electron paramagnetic resonance (EPR) oximetry measuring technique to dynamically monitor PO2 in the tumor microenvironment prior to and following chemotherapy, and aimed to determine the precise time window in which the microenvironmental PO2 peaked following chemotherapy. The results indicated that PO2 was significantly higher in breast cancer compared with control (P<0.05). Following four cycles of chemotherapy, the activity of NADH dehydrogenase, succinate-cytochrome c reductase and cytochrome c oxidase in the mitochondria of cells was significantly reduced when compared with their activity prior to chemotherapy (P<0.05). Regional blood flow in tumor tissues undergoing chemotherapy was significantly lower than that prior to chemotherapy (P<0.05). The rate of cellular apoptosis in the PO2 peak-based chemotherapy group was significantly greater than that in the conventional chemotherapy group after two and four cycles of chemotherapy (P<0.05). Tumor volume in the PO2 peak-based chemotherapy group was significantly reduced compared with that in the 0.9% NaCl solution control and the conventional chemotherapy groups after four cycles of chemotherapy (P<0.05). The tumor inhibitory rate of the experimental group was significantly higher than that of the conventional chemotherapy group (P<0.01). In conclusion, the present study may provide guidance for the development of effective strategies depending on tumor-maximal response to chemotherapy in an oxygen-rich environment. Additionally, the present study aimed to establish a foundation for a clinical noninvasive assessment intended to guide treatment and formulate individual regimens, in order to improve cancer therapeutics, sensitivity monitoring and curative effect estimation.

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Manganese concentration mapping in the rat brain with MRI, PET, and autoradiography

Cited by 5 publications

References 30 publications

Manganese Dynamics in Mouse Brain After Systemic MnCl2 Administration for Activation-Induced Manganese-Enhanced MRI

Manganese Dynamics in Mouse Brain After Systemic MnCl2 Administration for Activation-Induced Manganese-Enhanced MRI

Anatomy, Functionality, and Neuronal Connectivity with Manganese Radiotracers for Positron Emission Tomography

PO2‑based biodosimetry evaluation using an EPR technique acts as a sensitive index for chemotherapy

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