MRI Imaging of the Lungs with Hyperpolarized Gases: Current and SUNDAY Session IV: Update in Thoracic Imaging MRI Imaging of the Lungs with Hyperpolarized Gases: Current and Session IV: Update in Thoracic Imaging No Disclosure STR Annual Meeting & Postgraduate Course San Antonio, Texas, March 16-19, 2014 Duke University Medical Center STR Annual Meeting & Postgraduate Course San Antonio, Texas, March 16-19, 2014 Duke University Medical Center Outline Adding Function to Structure: Making Inert Gases Visible by MRI 1 H SSFP MRI Hyperpolarized MRI Source: H 2O 1 H density: ~100 Mol/liter Source: gas density ~0.01 Mol/liter +3ħ = Un-polarized nuclei Polarized nuclei +1ħ Optical Pumping 1. A. Kastler, Journal de Physique et le Radium 11, 255 (1950). S Spin Exchange I 2. M. A. Bouchiat Phys Rev Lett 5, 373 (1960). or Hyperpolarize Dispense QA Administer and polarization 10 5 increased T 1 = 2-3hrs once dispensed T 1 20s upon inhalation (O 2 ) 8s breath-hold fast GRE 171
The Challenge of MRI MRI circa late 1990 s MRI circa mid 2000 s Historical price $ 130/liter Current price $ 600/liter MacFall et al., Radiology 200: 553 (1996) Patz et al. Eur J Rad 64:334-344(2007). Saftey and Tolerability 1. Inhaltion of causes no change in vital signs, ECG, Lab tests 2. Inhalation of 1 liter causes transient symptoms in 91% pts - dizziness (50%), paresthesia (30%), hypoesthesia (30%), euphoria (30%) 3. Inhalation of caused no hypoxia 3 He Healthy Asthma COPD Virgincar, et al., NMR in Biomed. 2012 4. Resolution of symptoms in 1.6 +/- 0.9 min Driehuys, et al., Radiology. 2012 Asthma 39.5m (12.9%) Respiratory Infections 200,000 Interstitial lung disease 200,000 COPD 19.3m (6.3%) Lung Cancer 375,000 Pulmonary embolism 600,000 Centers for Disease Control and Prevention (CDC) 2011 100 yr old test Insensitive Highly variable Effort-dependent Black box Small Airways: the Silent Zone PFT: Pulmonary Function Testing conducting zone transitional & respiratory zones trachea bronchi terminal respiratory alveolar ducts alveolar sacs # 0 1.8 12 1 2.5 1 1.2 4.8 2 2.3 2 0.8 1.9 4 2.1 3 0.6 0.8 8 2.0 4 0.45 1.3 16 2.5 5 0.35 1.07 32 3.1 16 0.06 0.17 6x10 4 180 17 19 0.05 0.10 5x10 5 10 3 20 22 23 0.04 0.05 8x10 6 10 5 cm cm cm 2 Weibel, 1989 172
COPD Before Therapy: FEV 1 = 28% Asthma: Baseline Defect % = 30% 15 min After Salbutamol: FEV 1 = 30% Post Albuterol Defect % = 19.3% Kirby et al. Radiology, 2011, 261, p. 283-92 COPD Functional MR Phenotypes? Free diffusion D 0=2cm 2 /s Lung structure restricts diffusion D=0.2 cm 2 /s S.S. Kaushik et al., Magn. Reson. Med. New Drug Development is Not the Whole Story (Sick) (Feeling Good) D LCO : 44% D LCO : 92% IPF 74% ventilated 65 yr old normal Blood Gas Barrier Impairment 173
Dissolving Dissolving RBC gas space Moderate Solubility in Tissues 10-20% Large In Vivo Chemical Shift >200 ppm Dissolved-Phase Cleveland et al., Plos ONE 2010 Dissolving IPF Quantitative 3D -Transfer Maps Gas-Transfer gradient: -0.45% cm -1 IPF Mean Gradient in Normals: 2.00 ± 0.74% cm -1 normal S. Kaushik et al, J. Appl. Physiol. 2013 IPF Dermatomyositis ILD IPF Subject in in Transfer to RBCs - 28% of normals - DLCO 44% Spectroscopy 174
Gas Transfer Gas Transfer -RBC CT Direct visualization of airspaces Summary Unique strategies for evaluating pulmonary structure and function Visualization and quantification of therapy response Diffusion Weighted Imaging contrast Imaging of airspace enlargement, e.g. emphysema imaging is replacing MRI Dissolving in lung tissue and blood Imaging gas exchange and uptake Zack Cleveland Gary Cofer Mike Foster Shiv Kaushik Yi Qi Monica Kraft Matt Freeman L. Hedlund Justus Roos Rohan Virgincar John Nouls Tamara Branca Scott Robertson Al Johnson Simone Degan The Team Mu He Page McAdams Cecil Charles Warren Warren Sean Fain, Jan Wolber Harald Möller, U. Wisconsin GE Healthcare Max Planck Bastiaan Driehuys 175