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Lower Back Pain (LBP) is the second most common neurological ailment in the United States after the headache. It costs over $100 billion annually in treatment and related rehabilitation costs including worker compensation. In fact, it is the most common reason for lost wages and missed work days. Degenerative Disc Disease (DDD) is the major abnormality that causes LBP. Moreover, Magnetic Resonance Imaging (MRI) test is the main clinically approved non-invasive imaging modality for the diagnosis of DDD. However, there is over 50 % inter- and intra-observer variability in the MRI interpretation that urges the need for standardized mechanisms in MRI interpretation. In this chapter, we propose a Computer Aided Diagnosis (CAD) System for Disc Degenerative Disease detection from clinical Magnetic Resonance Imaging (MRI). This CAD produces a reproducible and clinically accurate diagnosis of the …