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MRS Reveals Chronic Inflammation in T2w MRI-Negative Perilesional Cortex - A 6-Months Multimodal Imaging Follow-Up Study.

ABSTRACT: Sustained inflammation in the injured cortex is a promising therapeutic target for disease-modification after traumatic brain injury (TBI). However, its extent and dynamics of expansion are incompletely understood which challenges the timing and placement of therapeutics to lesioned area. Our aim was to characterize the evolution of chronic inflammation during lesion expansion in lateral fluid-percussion injury (FPI) rat model with focus on the MRI-negative perilesional cortex. T2-weighted MR imaging (T2w MRI) and localized magnetic resonance spectroscopy (MRS) were performed at 1, 3, and 6 months post-injury. End-point histology, including Nissl for neuronal death, GFAP for astrogliosis, and Prussian Blue for iron were used to assess perilesional histopathology. An additional animal cohort was imaged with a positron emission tomography (PET) using translocator protein 18 kDa (TSPO) radiotracer [18F]-FEPPA. T2w MRI assessed lesion growth and detected chronic inflammation along the lesion border while rest of the ipsilateral cortex was MRI-negative (MRI-). Instead, myo-inositol that is an inflammatory MRS marker for gliosis, glutathione for oxidative stress, and choline for membrane turnover were elevated throughout the 6-months follow-up in the MRI- perilesional cortex (all p < 0.05). MRS markers revealed chronically sustained inflammation across the ipsilateral cortex but did not indicate the upcoming lesion expansion. Instead, the rostral expansion of the cortical lesion was systematically preceded by a hyperintense band in T2w images months earlier. Histologic analysis of the hyperintensity indicated scattered astrocytes, incomplete glial scar, and intracellularly packed and free iron. Yet, the band was negative in [18F]-FEPPA-PET. [18F]-FEPPA also showed no cortical TSPO expression within the MRS voxel in MRI- perilesional cortex or anywhere along glial scar when assessed at 2 months post-injury. However, [18F]-FEPPA showed a robust signal increase, indicating reactive microgliosis in the ipsilateral thalamus at 2 months post-TBI. We present evidence that MRS reveals chronic posttraumatic inflammation in MRI-negative perilesional cortex. The mismatch in MRS, MRI, and PET measures may allow non-invasive endophenotyping of beneficial and detrimental inflammatory processes to aid targeting and timing of anti-inflammatory therapeutics.

SUBMITTER: Yasmin A

PROVIDER: S-EPMC6707062 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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MRS Reveals Chronic Inflammation in T2w MRI-Negative Perilesional Cortex - A 6-Months Multimodal Imaging Follow-Up Study.

Yasmin Amna A Pitkänen Asla A Jokivarsi Kimmo K Poutiainen Pekka P Gröhn Olli O Immonen Riikka R

Frontiers in neuroscience 20190816

Sustained inflammation in the injured cortex is a promising therapeutic target for disease-modification after traumatic brain injury (TBI). However, its extent and dynamics of expansion are incompletely understood which challenges the timing and placement of therapeutics to lesioned area. Our aim was to characterize the evolution of chronic inflammation during lesion expansion in lateral fluid-percussion injury (FPI) rat model with focus on the MRI-negative perilesional cortex. T2-weighted MR im ...[more]

PMID: 31474824

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Project description:BackgroundLittle is known about the long-term success of non-drug therapies for treating dementia, especially whether the effects are sustained after therapy ends. Here, we examined the effects of a one-year multimodal therapy 10 months after patients completed the therapy.MethodsThis randomised, controlled, single-blind, longitudinal trial involved 61 patients (catamnesis: n = 52) with primary degenerative dementia in five nursing homes in Bavaria, Germany. The highly standardised intervention, MAKS, consisted of motor stimulation, practice of activities of daily living (ADLs), and cognitive stimulation. Each group of 10 patients was treated for 2 h, 6 days a week for 12 months. Control patients received standard nursing home care. At baseline, at the end of therapy (month 12), and 10 months thereafter (month 22), cognitive functioning was assessed using the cognitive subscale of the Alzheimer's Disease Assessment Scale, and the ability to perform ADLs was assessed using the Erlangen Test of Activities of Daily Living.ResultsDuring the therapy phase, the MAKS patients maintained their cognitive function and ability to carry out ADLs. After the end of therapy, both the control and the MAKS groups deteriorated in both their cognitive function (control, p = 0.02; MAKS, p < 0.001) and their ability to carry out ADLs (control, p < 0.001; MAKS, p = 0.001). However, in a confound-adjusted multiple regression model, the ability of the MAKS group to perform ADLs remained significantly higher than that of the control group even 10 months after the end of therapy (H0: βMAKS + βMAKS month 22 = 0; χ2 = 3.8568, p = 0.0496). Cohen's d for the difference between the two groups in ADLs and cognitive abilities 10 months after the end of therapy was 0.40 and 0.22, respectively.ConclusionsA multimodal non-drug therapy of dementia resulted in stabilisation of the ability to perform ADLs, even beyond the end of therapy. To prevent functional decline for as long as possible, therapy should be performed continuously until the benefit for the patient ends. Follow-up studies on larger numbers of patients are needed to definitively confirm these results.Trial registrationhttp://www.isrctn.com Identifier: ISRCTN87391496.

Dataset Information

MRS Reveals Chronic Inflammation in T2w MRI-Negative Perilesional Cortex - A 6-Months Multimodal Imaging Follow-Up Study.

Publications

MRS Reveals Chronic Inflammation in T2w MRI-Negative Perilesional Cortex - A 6-Months Multimodal Imaging Follow-Up Study.

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