BACKGROUND AND PURPOSE: Studies in animal models suggest that inflammation is a major contributor to secondary injury after intracerebral hemorrhage (ICH). Direct, noninvasive monitoring of inflammation in the human brain after ICH will facilitate early-phase development of anti-inflammatory treatments. We sought to investigate the feasibility of multimodality brain imaging in subacute ICH. METHODS: Acute ICH patients were recruited to undergo multiparametric MRI (including dynamic contrast-enhanced measurement of blood-brain barrier transfer constant (Ktrans ) and PET with [11 C]-(R)-PK11195). [11 C]-(R)-PK11195 binds to the translocator protein 18 kDa (TSPO), which is rapidly upregulated in activated microglia. Circulating inflammatory markers were measured at the time of PET. RESULTS: Five patients were recruited to this feasibility study with imaging between 5 and 16 days after onset. Etiologies included hypertension-related small vessel disease, cerebral amyloid angiopathy (CAA), cavernoma, and arteriovenous malformation (AVM). [11 C]-(R)-PK11195 binding was low in all hematomas and 2 (patient 2 [probable CAA] and 4 [AVM]) cases showed widespread increase in binding in the perihematomal region versus contralateral. All had increased Ktrans in the perihematomal region (mean difference = 2.2 × 10-3 minute-1 ; SD = 1.6 × 10-3 minute-1 ) versus contralateral. Two cases (patients 1 [cavernoma] and 4 [AVM]) had delayed surgery (3 and 12 months post-onset, respectively) with biopsies showing intense microglial activation in perilesional tissue. CONCLUSIONS: Our study demonstrates for the first time the feasibility of performing complex multimodality brain imaging for noninvasive monitoring of neuroinflammation for this severe stroke subtype.
BACKGROUND AND PURPOSE: Studies in animal models suggest that inflammation is a major contributor to secondary injury after intracerebral hemorrhage (ICH). Direct, noninvasive monitoring of inflammation in the human brain after ICH will facilitate early-phase development of anti-inflammatory treatments. We sought to investigate the feasibility of multimodality brain imaging in subacute ICH. METHODS: Acute ICHpatients were recruited to undergo multiparametric MRI (including dynamic contrast-enhanced measurement of blood-brain barrier transfer constant (Ktrans ) and PET with [11 C]-(R)-PK11195). [11 C]-(R)-PK11195 binds to the translocator protein 18 kDa (TSPO), which is rapidly upregulated in activated microglia. Circulating inflammatory markers were measured at the time of PET. RESULTS: Five patients were recruited to this feasibility study with imaging between 5 and 16 days after onset. Etiologies included hypertension-related small vessel disease, cerebral amyloid angiopathy (CAA), cavernoma, and arteriovenous malformation (AVM). [11 C]-(R)-PK11195 binding was low in all hematomas and 2 (patient 2 [probable CAA] and 4 [AVM]) cases showed widespread increase in binding in the perihematomal region versus contralateral. All had increased Ktrans in the perihematomal region (mean difference = 2.2 × 10-3 minute-1 ; SD = 1.6 × 10-3 minute-1 ) versus contralateral. Two cases (patients 1 [cavernoma] and 4 [AVM]) had delayed surgery (3 and 12 months post-onset, respectively) with biopsies showing intense microglial activation in perilesional tissue. CONCLUSIONS: Our study demonstrates for the first time the feasibility of performing complex multimodality brain imaging for noninvasive monitoring of neuroinflammation for this severe stroke subtype.
Authors: Zahraa S Al-Ahmady; Ben R Dickie; Isabelle Aldred; Dhifaf A Jasim; Jack Barrington; Michael Haley; Eloise Lemarchand; Graham Coutts; Satinderdeep Kaur; Jessica Bates; Sarah Curran; Ruth Goddard; Megan Walker; Adrian Parry-Jones; Kostas Kostarelos; Stuart M Allan Journal: Theranostics Date: 2022-05-26 Impact factor: 11.600
Authors: William C Kreisl; Min-Jeong Kim; Jennifer M Coughlin; Ioline D Henter; David R Owen; Robert B Innis Journal: Lancet Neurol Date: 2020-11 Impact factor: 44.182
Authors: Frederick Bonsack; Catherine A Foss; Ali S Arbab; Cargill H Alleyne; Martin G Pomper; Sangeetha Sukumari-Ramesh Journal: Front Neurosci Date: 2018-02-22 Impact factor: 4.677
Authors: Mark G MacAskill; Agne Stadulyte; Lewis Williams; Timaeus E F Morgan; Nikki L Sloan; Carlos J Alcaide-Corral; Tashfeen Walton; Catriona Wimberley; Chris-Anne McKenzie; Nick Spath; William Mungall; Ralph BouHaidar; Marc R Dweck; Gillian A Gray; David E Newby; Christophe Lucatelli; Andrew Sutherland; Sally L Pimlott; Adriana A S Tavares Journal: J Nucl Med Date: 2020-08-28 Impact factor: 11.082
Authors: Mark G MacAskill; Catriona Wimberley; Timaeus E F Morgan; Carlos J Alcaide-Corral; David E Newby; Christophe Lucatelli; Andrew Sutherland; Sally L Pimlott; Adriana A S Tavares Journal: Eur J Nucl Med Mol Imaging Date: 2021-08-02 Impact factor: 9.236