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Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.

ABSTRACT: Purpose To investigate the sustained-attention and memory-enhancing neural correlates of the oral administration of methylene blue in the healthy human brain. Materials and Methods The institutional review board approved this prospective, HIPAA-compliant, randomized, double-blinded, placebo-controlled clinical trial, and all patients provided informed consent. Twenty-six subjects (age range, 22-62 years) were enrolled. Functional magnetic resonance (MR) imaging was performed with a psychomotor vigilance task (sustained attention) and delayed match-to-sample tasks (short-term memory) before and 1 hour after administration of low-dose methylene blue or a placebo. Cerebrovascular reactivity effects were also measured with the carbon dioxide challenge, in which a 2 × 2 repeated-measures analysis of variance was performed with a drug (methylene blue vs placebo) and time (before vs after administration of the drug) as factors to assess drug × time between group interactions. Multiple comparison correction was applied, with cluster-corrected P < .05 indicating a significant difference. Results Administration of methylene blue increased response in the bilateral insular cortex during a psychomotor vigilance task (Z = 2.9-3.4, P = .01-.008) and functional MR imaging response during a short-term memory task involving the prefrontal, parietal, and occipital cortex (Z = 2.9-4.2, P = .03-.0003). Methylene blue was also associated with a 7% increase in correct responses during memory retrieval (P = .01). Conclusion Low-dose methylene blue can increase functional MR imaging activity during sustained attention and short-term memory tasks and enhance memory retrieval. © RSNA, 2016 Online supplemental material is available for this article.

SUBMITTER: Rodriguez P

PROVIDER: S-EPMC5084971 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.

Rodriguez Pavel P Zhou Wei W Barrett Douglas W DW Altmeyer Wilson W Gutierrez Juan E JE Li Jinqi J Lancaster Jack L JL Gonzalez-Lima Francisco F Duong Timothy Q TQ

Radiology 20160628 2

Purpose To investigate the sustained-attention and memory-enhancing neural correlates of the oral administration of methylene blue in the healthy human brain. Materials and Methods The institutional review board approved this prospective, HIPAA-compliant, randomized, double-blinded, placebo-controlled clinical trial, and all patients provided informed consent. Twenty-six subjects (age range, 22-62 years) were enrolled. Functional magnetic resonance (MR) imaging was performed with a psychomotor v ...[more]

PMID: 27351678

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Project description:Breast-conserving surgery is facing the challenge of objective tumor margin identification intraoperatively. Near-infrared fluorescence imaging would be an ideal approach to visualize tumor margins during surgeries. In this preliminary study, the feasibility of methylene blue-based near-infrared fluorescence imaging technique for breast cancer detection was assessed in resected human breast specimens after breast cancer surgeries. Thirty patients with breast cancer scheduled for surgical treatment were enrolled, including 10 patients with preoperative chemotherapy and 20 patients without. Each of them received an injection of 1 mg/kg methylene blue intravenously 3 hours before the surgery. Then, a home-developed methylene blue-specific near-infrared fluorescence imaging system was employed to image the resected breast tissues and identify the tumor by the fluorescence contrast. Specimens were taken for pathological examinations as the reference. There were no severe adverse events attributable to methylene blue. Of 20 patients, who did not receive preoperative chemotherapy, 16 exhibited fluorescent contrast on their resected tissues (signal-to-background ratio: 1.94 ± 0.71). In contrast, tumors were identified in 3 of 10 specimens from patients who underwent preoperative chemotherapy (signal-to-background ratio: 1.63 ± 0.38). A total of 35 tissues were sampled from 30 specimens. Besides 30 tumor samples, 5 more suspicious samples with fluorescence signal were confirmed to be benign hemorrhagic tissues. Therefore, a sensitivity of 0.63 and a positive predictive value of 0.79 were achieved by the methylene blue fluorescence imaging strategy. Here, we demonstrate the feasibility of using methylene blue fluorescence imaging to identify breast cancer. Preoperative chemotherapy had an impact on imaging effect, which may reduce the detection rate. After all, methylene blue fluorescence imaging has great potential to be used into breast-conserving surgery for tumor-positive margins detection, but further clinical trial study is needed ( http://www.chictr.org.cn/ Clinical Trial Registry ID: ChiCTR1800015400, Near-infrared fluorescence imaging applied in breast cancer identification with methylene blue).

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Project description:Purpose To evaluate the effects of histologic features and anatomic magnetic resonance (MR) imaging characteristics of brain tumors on the functional MR imaging signal in the primary motor cortex (PMC), as false-negative blood oxygen level-dependent (BOLD) functional MR imaging activation can limit the accurate localization of eloquent cortices. Materials and Methods Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant retrospective study. It comprised 63 patients referred between 2006 and 2014 for preoperative functional MR imaging localization of the Rolandic cortex. The patients had glioblastoma multiforme (GBM) (n = 20), metastasis (n = 21), or meningioma (n = 22). The volumes of functional MR imaging activation were measured during performance of a bilateral hand motor task. Ratios of functional MR imaging activation were normalized to PMC volume. Statistical analysis was performed for the following: (a) differences between hemispheres within each histologic tumor type (paired Wilcoxon test), (b) differences across tumor types (Kruskal-Wallis and Fisher tests), (c) pairwise tests between tumor types (Mann-Whitney U test), (d) relationships between fast fluid-attenuated inversion recovery (FLAIR) data and enhancement volume with activation (Spearman rank correlation coefficient), and (e) differences in activation volumes by tumor location (Mann-Whitney U test). Results A significant interhemispheric difference was found between the activation volumes in GBMs (mean, 511.43 voxels ± 307.73 [standard deviation] and 330.78 voxels ± 278.95; P < .01) but not in metastases (504.68 voxels ± 220.98 and 460.22 voxels ± 276.83; P = .15) or meningiomas (424.07 voxels ± 247.58 and 415.18 voxels ± 222.36; P = .85). GBMs showed significantly lower activation ratios (median, 0.49; range, 0.04-1.15) than metastases (median, 0.79; range, 0.28-1.66; P = .043) and meningiomas (median, 0.91; range, 0.52-2.05; P < .01). There was a moderate correlation with the volumes of FLAIR abnormality in metastases (ρ = -0.50) and meningiomas (ρ = -0.55). Enhancement volume (ρ = -0.11) and tumor distance from the PMC (median, 0.73 and range, 0.04-2.05 for near and median, 0.82 and range, 0.39-1.66 for far; P = .14) did not influence activation. Conclusion BOLD functional MR imaging activation in the ipsilateral PMC is influenced by tumor type and is significantly reduced in GBMs. FLAIR abnormality correlates moderately with the activation ratios in metastases and meningiomas. © RSNA, 2016 Online supplemental material is available for this article.

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Dataset Information

Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.

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Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain.

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