Quantitative MRI Integration with Cerebrospinal Fluid Testing to Improve Encephalitis Diagnosis

Abstract

Differentiating bacterial from viral encephalitis remains a persistent diagnostic challenge. MRI provides rapid structural, metabolic, and perfusion insights, whereas cerebrospinal fluid (CSF) analysis using PCR and culture delivers pathogen-specific confirmation. Each modality, however, carries critical limitations when used in isolation. In this prospective single-center diagnostic-accuracy study conducted in accordance with STARD 2015 guidelines, seventy-six consecutive patients fulfilling the International Encephalitis Consortium criteria underwent standardized MRI protocols (DWI, FLAIR, SWI, ASL, and MRS) alongside comprehensive CSF microbiological testing (multiplex PCR and culture). Quantitative MRI biomarkers apparent diffusion coefficient (ADC), FLAIR intensity ratios, SWI microhemorrhage burden, MRS lactate/Cr and NAA/Cho ratios, and ASL cerebral blood flow were analyzed against a composite diagnostic reference. MRI alone achieved an area under the curve (AUC) of 0.87, CSF microbiology alone 0.90, and integrated MRI–PCR interpretation 0.96, with statistical superiority confirmed by DeLong testing (p = 0.01 vs MRI; p = 0.04 vs PCR). Quantitative thresholds improved reproducibility (ADC < 0.8 × 10⁻³ mm²/s and lactate/Cr > 0.25 indicating bacterial disease; FLAIR ratio > 1.4 and ASL hyperperfusion suggesting viral etiology), while inter-reader agreement was excellent (κ = 0.82; ICC = 0.87). Pathogen-level analysis demonstrated that MRI performed best for HSV and Streptococcus pneumoniae, whereas PCR remained essential for enterovirus and EBV. Decision-curve analysis confirmed that integration provided the highest net clinical benefit, reducing overtreatment and delays, shortening time to targeted therapy (10 h vs 24 h), and improving 90-day functional outcomes. Integrated MRI-PCR interpretation thus represents a superior, reproducible, and clinically meaningful framework that redefines the diagnostic standard of care for encephalitis.