Abstract:

Several treatment modalities for neuro-degenerative diseases or tumors of the central nervous system involve invasive delivery of large molecular weight drugs to the brain. Despite ample experimental efforts, accurate drug targeting for the human brain remains a challenge. Our interdisciplinary research aims at a systematic design process for the targeted delivery of therapeutic agents into specific regions of brain based on first principles mathematical equations of drug transport and pharmaco-kinetics in porous tissue. The proposed mathematical framework predicts achievable treatment volumes in the desired regions as a function of target anatomy and infusion catheter positioning. We tackle the three-dimensional optimal catheter placement problem to determine optimal infusion and catheter design parameters that maximize drug penetration and volumes of distribution in the target area, while minimizing toxicity in non-targeted regions. A novel computational approach for determining unknown transport properties of therapeutic agents from in-vivo imaging data will also be introduced. We expect for the near future that rigorous computational approaches like ours will enable physicians and scientists to design and optimize drug administration in a systematic fashion.