BME 501 Advanced Topics in Biomedical Systems Spring 2014 Dr. Kay 1BME 501 Lecture Notes – Apr 30 BME Applications for Cardiovascular Pathologies • Diagnosing CV Pathologies • NanotechnologyDiagnosing CV Pathologies: • Heart poses unique challenges for imaging • Need high temporal resolution to accurately image heart perpetually in motion • Need high spatial resolution to accurately image small structures of heartDiagnosing CV Pathologies: Radiography • Uses X-rays to view non-uniformly composed material • Beam of X-rays projected toward object • Density and composition of each region determine how much of beam absorbed • X-rays that pass all the way through object are captured on other side by detector • Detector gives 2D representation of all structures superimposed on one anotherDiagnosing CV Pathologies: Ultrafast Computed Tomography Indications • Diagnosis of suspected coronary artery disease • Follow-up for coronary artery bypass graft (CABG) • Evaluation of valvular abnormalities and cardiac masses Contraindications • Pregnancy • Allergy to/inability to handle iodine in contrast agent • Arrhythmias, tachycardia, coronary artery stentsDiagnosing CV Pathologies: Ultrafast Computed Tomography Procedure • Patient injected with intravenous contrast agent (iodine-based) • Patient lies on motorized table and moved through short, circular chamber • Multiple X-rays taken as X-ray source rotates around patient • X-ray sensors move to remain positioned opposite the X-ray source • One full rotation usually consists of 20-30 imaging eventsDiagnosing CV Pathologies: Ultrafast Computed Tomography Procedure • Data processed to construct cross-sectional or 3D images • Multiple rows of detectors allow for multiple cross-sections to be captured simultaneously • Sub-second rotation combined with multi-slice capture provide high temporal and spatial resolution • EKG-gating allows correlation of CT data with phases of cardiac cycleDiagnosing CV Pathologies: CV Magnetic Resonance Imaging Indications • Initial evaluation and follow-up of congenital heart disease – Assessment of shunt size – Evaluation of abnormal structures of heart • Diagnosis and follow-up of acquired heart disease – Planning stenting of aortic aneurysm – Assessment of vasculature of heart – Assessment of ventricular function and mass – Detection of coronary artery disease – Detection/assessment of MI & myocardial viabilityDiagnosing CV Pathologies: CV Magnetic Resonance Imaging • Non-invasive • Uses radio waves, magnets, and computer processer • Does not use ionizing radiation, does not carry risk of causing cancer • Creates both still and moving pictures of heart and major blood vesselsDiagnosing CV Pathologies: CV Magnetic Resonance Imaging Procedure • Patient placed within long tube of MRI scanner • Strong, stable magnetic field generated around area to be imaged • Three gradient magnets produce lower strength, variable fields for specific regions • Multiple radiofrequency coils transmit radio waves into specific regions of patient’s bodyDiagnosing CV Pathologies: CV Magnetic Resonance Imaging Procedure • Hydrogen atoms are abundant in the human body • When strong magnetic field applied, hydrogen atoms line up in direction of the field • Hydrogen protons line up pointing at patient’s feet or head (about 50:50) • Hydrogen-specific radiofrequency (RF) pulse is directed toward body-region of interestDiagnosing CV Pathologies: CV Magnetic Resonance Imaging Procedure • Unmatched hydrogen protons absorb energy from RF pulse and spin in different direction • The RF pulse forces them to spin at particular frequency, in particular direction • The three gradient magnets turn on and off rapidly to alter main magnetic field on local level • When RF pulse turned off, hydrogen protons return to resting state by releasing energy that is picked up by detection coils of machine With targeted contrast, areas of infarction appear bright white (fat around heart also appears white)2.1 nm 7.5 nm Diagnosing CV Pathologies: Quantum Dots • Nanocrystals made of semiconductor material on order of 1-10 nm • So small that certain quantum phenomena become dominant • Act like artificial atoms – Can have a few electrons or several thousand – Energy levels are quantized due to confinement of electronsDiagnosing CV Pathologies: Quantum Dots Properties • Quantum confinement allows only for discrete energy levels • Energy levels depend on size of quantum dotsDiagnosing CV Pathologies: Quantum Dots Fabrication • Self-assembly: quantum dots nucleate spontaneously when material is grown on a substrate not lattice matched • Viral assembly: genetically engineered bacteriophage viruses direct construction of quantum dots • Electrochemical assembly: ionic reaction at an electrolyte-metal interface results in spontaneous assembly of nanostructures • Laser production: laser directed at solid object generates quantum dotsDiagnosing CV Pathologies: Quantum Dots Bio-Imaging Applications • Tagging of biomolecules allows for – Tracing drug-delivery – Locating tumors/abnormal tissues – Identifying metabolic abnormalities – Tracking movements of molecules in live cells • Advantages vs. organic dyes – Longer life (minimal degradation) – Can emit whole spectrum – Brighter – Useful at multiple scalesNanotechnology: • Engineered functional systems at the molecular scale • Altering scale alters properties of material • Risks – Nanoparticles readily absorbed into body – Reactivity increased – Toxicity unknownNanotechnology: Detecting Cardiac Necrosis I • Dying cardiac cells release specific proteins into blood • Nano-particles coated with antibodies bind to different, specific proteins • Bound proteins can be separated out and measured/quantified Nanoparticle Bio-Barcode TechnologyNanotechnology: Detecting Cardiac Necrosis II • Nanoscale cantilever array can be used to measure proteins in blood • Top of each cantilever coated with different antibodies for independent protein measurement • Bound proteins on top of specific cantilever causes downward deflection • Additional cantilevers used for thermo-mechanical and chemical calibrationNanotechnology: Promoting Cardiac Cell Growth • Nanoscale “scaffolding” made via self-assembling Peptide Amphiphiles (PAs) • PAs can be designed to be attracted