Detection of blood‐brain barrier dysfunction using advanced imaging methods to predict seizures in dogs with meningoencephalitis of unknown origin

Abstract

Background The blood‐brain barrier (BBB), which separates the intravascular and neuropil compartments, characterizes the vascular bed of the brain and is essential for its proper function. Recent advances in imaging techniques have driven the development of methods for quantitative assessment of BBB permeability. Hypothesis/Objectives Permeability of the BBB can be assessed quantitatively in dogs with meningoencephalitis of unknown origin (MUO) and its status is associated with the occurrence of seizures. Animals Forty dogs with MUO and 12 dogs without MUO. Methods Retrospective, prospective cohort study. Both dynamic contrast enhancement (DCE) and subtraction enhancement analysis (SEA) methods were used to evaluate of BBB permeability in affected (DCE, n = 8; SEA, n = 32) and control dogs (DCE, n = 6; SEA, n = 6). Association between BBB dysfunction (BBBD) score and clinical characteristics was examined. In brain regions where BBBD was identified by DCE or SEA magnetic resonance imaging (MRI) analysis, immunofluorescent staining for albumin, glial fibrillary acidic protein, ionized calcium binding adaptor molecule, and phosphorylated mothers against decapentaplegic homolog 2 were performed to detect albumin extravasation, reactive astrocytes, activated microglia, and transforming growth factor beta signaling, respectively. Results Dogs with BBBD had significantly higher seizure prevalence (72% vs 19%; P = .01) when compared to MUO dogs with no BBBD. The addition of SEA to routine MRI evaluation increased the identification rate of brain pathology in dogs with MUO from 50% to 72%. Conclusions and Clinical Importance Imaging‐based assessment of BBB integrity has the potential to predict risk of seizures in dogs with MUO.

New insights into the treatment of meningoencephalomyelitis of unknown origin since 2009: A review of 671 cases

“…Magnetic resonance imaging also remains imperfect with some studies finding that as many as 40% of lesion are not detected and there are large variations in lesion appearance [reviewed by ( 46 )]. An interesting approach to use MRI for more precise diagnosis is to determine the permeability of the blood-brain barrier in dogs with MUO ( 102 ).…”

Quantitative analysis of magnetic resonance images for characterization of blood‐brain barrier dysfunction in dogs with brain tumors

“…Using HR, BBBD was detected in dogs with rather robust leakage, such as in cases of hypervascularization, blood vessel abnormalities, and congestion, 35 even when the overall number of positive voxels was small. The LR, on the other hand, limits the values of positive voxels to the range between the mean PID of the temporal muscle and the mean plus 1 SD and, hence, detects only voxels with mild enhancement.…”

“… 34 In dogs, DCE‐MRI enables the identification and quantification of brain areas with BBBD in naturally occurring brain diseases. 25 A less demanding semiquantitative method that was suggested for detecting BBBD is subtraction enhancement analysis (SEA), 35 which compares enhancement in each brain voxel in MR images obtained before and after intravenous contrast administration.…”