In this prospective, multicenter study of patients with acute spontaneous supratentorial Intracerebral Hemorrhage (ICH), each participant will have a standardized multimodal evaluation of neuroinflammation at 10 (±2) days after onset including translocator protein 18 kDa (TSPO) positron emission tomography (PET) using 18F-DPA-714 radioligand, BBB imaging using Dynamic contrast-enhanced (DCE)-MRI and a panel of pro-inflammatory and anti-inflammatory plasma biomarkers.
Intracerebral Hemorrhage (ICH) is the most devastating stroke subtype that affects \> 3 million people worldwide each year. Despite important efforts and the hope that minimally invasive surgical procedures may offer, there is currently no effective treatment. Perihematomal edema - a surrogate marker of neuroinflammation - has emerged as important contributors to poor functional outcome following acute ICH, and a potential treatment target. Innovative techniques have been developed to image and measure neuroimmune response (TSPO PET) and BBB integrity (DCE-MRI). These novel methods have been poorly studied in ICH. The effects of in vivo perihematomal neuroinflammation on the functional outcome of patients with acute ICH is widely unknown. The present study is a prospective, multicenter study of patients with acute spontaneous supratentorial ICH (within 48h after onset). Each participant will have a standardized multimodal evaluation of neuroinflammation at 10 days after onset including TSPO PET using 18F-DPA-714 radioligand, BBB imaging using DCE-MRI and a panel of pro-inflammatory and anti-inflammatory plasma biomarkers. In hospital follow up visit will occur at 14 days and end of follow up visit at 180 days. Functional outcome will be assessed by modified Rankin scale (mRS), which is a widely used and validated scale - ranging from 0 (no symptoms) to 6 (death) - to evaluate the functional outcome following ischemic or hemorrhagic strokes.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
TEP with 18F-DPA-714 injection
CHU de Bordeaux
Bordeaux, France
CHU de montpellier
Montpellier, France
CHU de Toulouse
Toulouse, France
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the functional outcome (poor versus favorable) at 6 months
* 18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR) within the perihematomal edema (PHE) using the mirror region of interest (ROI) in the contralateral hemisphere as reference. * The functional outcome at 6 months after ICH is quantified by the modified Rankin scale (which ranges from 0 \[no symptoms\] to 6 \[death\]). Poor functional outcome is defined as a modified Rankin scale score (mRs) ≥3
Time frame: o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o The functional outcome is measured at 6 months after ICH
Volume of brain tissue with increased 18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the functional outcome (poor versus favorable) at 6 months
* 18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR). Volume of brain tissue (mL) with increased 18F-DPA-714 binding is measured in the area around the hematoma. * The functional outcome at 6 months after ICH is quantified by the modified Rankin scale (which ranges from 0 \[no symptoms\] to 6 \[death\]). Poor functional outcome is defined as a modified Rankin scale score (mRs) ≥3
Time frame: o 18F-DPA-714 binding is measured at day 10 ±2 after ICH o The functional outcome is measured at 6 months after ICH
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the occurrence of neurological deterioration within 14 days after ICH onset
* 18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR) within the perihematomal edema (PHE) using the mirror region of interest (ROI) in the contralateral hemisphere as reference. * Neurological deterioration within 14 days after ICH onset is defined as a ≥4-point increase on the National Institutes of Health Stroke Scale (NIHSS) or ≥2-point decrease on the Glasgow Coma Scale (GCS) compared to baseline scores at the pre-inclusion visit
Time frame: o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o Neurological deterioration is assessed within 14 days after ICH onset
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18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the occurrence of early death
* 18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR) within the perihematomal edema (PHE) using the mirror region of interest (ROI) in the contralateral hemisphere as reference. * Early death is defined as death at day 30 after ICH onset.
Time frame: o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o Early death is assessed within 30 days after ICH onset.
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the clinical outcome at 6 months
* 18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR) within the perihematomal edema (PHE) using the mirror region of interest (ROI) in the contralateral hemisphere as reference. * Clinical outcome at 6 months is assessed by the distribution of modified Rankin scale scores
Time frame: o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o Clinical outcome is assessed et 6 months
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the mortality
* 18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR) within the perihematomal edema (PHE) using the mirror region of interest (ROI) in the contralateral hemisphere as reference. * Mortality is assessed at 6 months.
Time frame: o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o Mortality is assessed at 6 months.
Correlations of 18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH with MRI-derived measures of BBB breakdown and plasma levels of inflammatory biomarkers
* 18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR) within the perihematomal edema (PHE) using the mirror region of interest (ROI) in the contralateral hemisphere as reference. * BBB breakdown is quantified by MRI-derived quantitative measures based on maps of the contrast agent transfer coefficient (Ktrans) in the perihematomal area at day 10 ±2 after ICH; * Plasma levels of inflammatory biomarkers (including MMP9, TNF alpha, , IL-6 and -10, soluble TLR 2/4, Neutrophil Extracellular Traps (NETs) are measured at day 10 ±2 after ICH onset.
Time frame: PET, MRI and plasma inflammatory biomarkers measures are evaluated at day 10 ±2 after ICH onset
BBB breakdown at day 10 ±2 after ICH according to the functional outcome (poor versus favorable) at 6 months
* BBB breakdown is quantified by MRI-derived quantitative measures based on maps of the contrast agent transfer coefficient (Ktrans) in the perihematomal area at day 10 ±2 after ICH; * The functional outcome at 6 months after ICH is quantified by the modified Rankin scale (which ranges from 0 \[no symptoms\] to 6 \[death\]). Poor functional outcome is defined as a modified Rankin scale score (mRs) ≥3
Time frame: o MRI-derived quantitative measures of BBB breakdown are assessed at day 10 ±2 after ICH. o The functional outcome is measured at 6 months after ICH.
Plasma levels of inflammatory biomarkers at day 10 ±2 after ICH according to the functional outcome (poor versus favorable) at 6 months
* Plasma levels of inflammatory biomarkers (including MMP9, TNF alpha, , IL-6 and -10, soluble TLR 2/4, Neutrophil Extracellular Traps (NETs) are measured at day 10 ±2 after ICH onset; * The functional outcome at 6 months after ICH is quantified by the modified Rankin scale (which ranges from 0 \[no symptoms\] to 6 \[death\]). Poor functional outcome is defined as a modified Rankin scale score (mRs) ≥3
Time frame: o Plasma inflammatory biomarkers measures are assessed at day 10 ±2 after ICH. o The functional outcome is measured at 6 months after ICH.