Department of Radiology. University of Virginia. Wilson Miller SPIN October 7

Transcription

1 Medical Imaging of Hyperpolarized Gases Wilson Miller University of Virginia Department of Radiology October 7 SPIN 2008

2 p Nuclear Magnetic Resonance Net alignment Excitation RF pulse p p p p B p p Magnetization vector

3 p Nuclear Magnetic Resonance Precesses at Net alignment resonance frequency ω = γb p p p p B θ p p Magnetization vector

4 Nuclear Magnetic Resonance RF coil Precesses at resonance frequency ω = γb NMR Signal T = 2π/ω

5 Nuclear Magnetic Resonance Boltzmann distribution Pthermal = = tanh N N + γhb 4π kt N N B e p 1 H Large magnetic field (1.5 ~ 3.0 Tesla)

6 Nuclear Magnetic Resonance Boltzmann distribution B Thermal polarization: ~ % at 1.5 T (5 parts per million) Large magnetic field (1.5 ~ 3.0 Tesla)

7 Magnetic Resonance Imaging Frequency encoding: Gradient maps spatial location to frequency x ω B Signal is Fourier transform: s ( t ) = x e i ω ( x ) t ( ) dx ρ Magnetic field gradient: B = (B 0 +xg x )z

8 Magnetic Resonance Imaging 2003 Nobel Prize in medicine! Frequency encoding: Gradient maps spatial location to frequency x ω B Signal is Fourier transform: s ( t ) = x e i ω ( x ) t ( ) dx ρ Magnetic field gradient: B = (B 0 +xg x )z

9 Hyperpolarized Noble-Gas MRI Spin-exchange optical pumping (SEOP) Polarization: ~0.0005% 50% Stable spin-1/2 noble gases: 3 He, 129 Xe

10 MITI Polarizer 129 Xe: 500 ml ~10% (1 hour) 3 He: 1 L, 30~40% (15 hours)

11 Polarization Cell

12 Polarize overnight Current polarizer: 30-40% polarization 1 liter 3 He per day New polarizer: 40-?% polarization 3 liters 3 He per day Dispense into bag

13 Siemens Avanto (1.5 Tesla) Vest-shaped shaped RF coil (48.5 MHz for 3 He) Inhale gas from bag

14 Hyperpolarized Noble-Gas MRI Contrast agent? Directly image the inhaled gas Conventional Axial 1 H MRI Axial 3 He MRI EE de Lange EE et al. Evaluation of asthma with hyperpolarized helium-3 MRI: Correlation with clinical severity and spirometry. Chest 130: (2006).

15 Static Ventilation Imaging Healthy Subject Asthmatic EE de Lange et al. Lung air spaces: MR imaging evaluation with hyperpolarized 3 He gas. Radiology 1999; 210:

16 Static Ventilation Imaging Severe-persistent asthmatic Pre Albuterol Post Albuterol TA Altes et al. Hyperpolarized 3He MR Lung Ventilation Imaging in Asthmatics Preliminary Findings. JMRI 2001;13:378-84

17 Static Ventilation Imaging Mild-intermittent asthmatic Pre Methacholine Post Methacholine EE de Lange et al. The regional variability of airflow obstruction within the lungs of asthmatics: Assessment with hyperpolarized 3 He MRI. J Allergy Clin Immunol 119: (2007).

18 Unusual Subject Chest radiograph 3 He MRI Pneumatocele

19 3D Static Ventilation Imaging Coronal Sagittal Axial Isotropic 3mm resolution GW Miller et al. Improving the quality of 3D hyperpolarized gas images using feedback-controlled flip controlled flip-angle evolution. ISMRM 12:1681 (Kyoto, 2004).

20 3D Static Ventilation Imaging

21 Ventilation Imaging Applications Asthma Chronic obstructive pulmonary disease (COPD) Cystic Fibrosis Lung transplant / rejection

22 MR Grid Tagging Tag the magnetization End-inspiration End-expiration Displacement

23 2-Phase Grid Tagging Slice 1 Slice 2 Slice 3 Slice 4 Temporal resolution of displacement vectors achieved via linear interpolation J Cai et al. MR Grid-Tagging Using Hyperpolarized Helium-3 for Regional Quantitative Assessment of Pulmonary Biomechanics and Ventilation. Magn Reson Med 58: (2007).

24 Dynamic Grid Tagging Slice 1 Slice 2 Slice 3 Slice 4 Slice 5 Pulse sequence parameters: Tag spacing 22 mm 5 coronal slices (TH 25 mm), flip angle 4 50% angular density, heavily interleaved TR / TE = 3.4 / 1.2 ms 870 ms per full image set Temporal pseudo-resolution 50 ms

25 Dynamic Grid Tagging 0.0s 0.7s 1.4s 2.1s Raw 3 He images Differential displacement GW Miller et al. Regional quantification of pulmonary biomechanics using dynamic MRI of grid-tagged hyperpolarized 3 He. ISMRM 15:945 (Berlin, 2007).

26 Tagging Applications Pulmonary Biomechanics Chronic obstructive pulmonary disease (COPD) Radiation Therapy

27 P 0 T1-Weighted Contrast Hyperpolarized nuclei T1 in bag is tens of minutes T1 in lung is ~20 seconds, due to O 2 T1-weighted 3 He imaging provides P A O 2 contrast Thermally polarized nuclei T1 time Polarization

28 Quantitative PO 2 Mapping Phantom experiments 15% O po2 [atm] 3 He image

29 P A O 2 Mapping in Human Lungs Healthy volunteer inhaled 3 He plus room air 3 He image PA O 2 map Coronal projection mm Hg cm slice

30 P A O 2 Mapping in Human Lungs Healthy volunteer 2 different inhalations 3 He + room air 3 He + O mm Hg Mean = 101 mm Hg Mean = 227 mm Hg GW Miller et al. Short-breath breath-hold hold lung po 2 mapping with hyperpolarized 3 He MRI. ESMRMB 22 (Basle, 2005).

31 P A O 2 Mapping in Human Lungs Female, age 65, left-lung transplant 1 H image 3 He image PA O 2 map GW Miller et al. Short-breath breath-hold hold po 2 imaging with 3 He: Initial experience in lung disease. ISMRM 14:1289 (Seattle, 2006). mm Hg

32 P A O 2 Applications Pulmonary embolus Sickle Cell disease High-Altitude Pulmonary Edema

33 Lung Structure vs. Imaging Resolution 3 He image of rabbit lung Pixel resolution ~ 3 mm

34 Lung Structure vs. Imaging Resolution acinus ~3 mm Alveoli ~200 µm Fine lung structure

35 Diffusion as a Probe of Microstructure Apparent Diffusion Coefficient (ADC) Normal Alveolar Sac Emphysematous Alveolar Sac 200 µm small, healthy airspaces enlarged, diseased airspaces Low 3 He ADC High 3 He ADC

36 Diffusion-Weighted Contrast How do we measure diffusion using NMR? Use magnetic-field gradients to encode displacement

37 B x Diffusion-Weighted Pulse Sequence G x time x Precessing spins in lab frame Vector sum in rotating frame

38 B x Diffusion-Weighted Pulse Sequence G x time x Precessing spins in lab frame Vector sum in rotating frame

39 B x Diffusion-Weighted Pulse Sequence G x time x Precessing spins in lab frame Vector sum in rotating frame

40 B x Diffusion-Weighted Pulse Sequence G x time x Precessing spins in lab frame Vector sum in rotating frame

41 B x Diffusion-Weighted Pulse Sequence G x time x Precessing spins in lab frame Vector sum in rotating frame

42 B x Diffusion-Weighted Pulse Sequence G x time x Precessing spins in lab frame Vector sum in rotating frame

43 B x Diffusion-Weighted Pulse Sequence G x time x Precessing spins in lab frame Vector sum in rotating frame

44 Diffusion-Weighted Pulse Sequence G x time S 1 = S 0 e b ADC Use this equation to extract ADC So-called b value can be calculated from gradient waveform (free diffusion) S 0 S 1 Vector sum in rotating frame

45 3 He ADC: Lung Transplant CT scan ADC map Native Transplant Native Transplant ~0.8 cm 2 /s ~0.2 cm 2 /s 3 He free diffusion coefficient: ~0.9 cm 2 /s in air cm 2 /s

46 Time-Dependent Diffusivity Normal Lung Emphysema Histology is gold standard for characterizing microstructure

47 Time-Dependent Diffusivity Simulated Brownian motion Emphysema Normal D 0 free diffusion D(t) restricted diffusion very restricted diffusion t

48 Time vs. Length Scales v r j ( t ) D ( t ) ~ 2 2 d v r j (0) x D t 2 t j time GW Miller et al. Simulations of short-time time diffusivity in lung airspaces and implications for S/V measurements using hyperpolarized-gas MRI. 26: (2007). gas MRI. IEEE Trans Med Imag G x t

49 Time vs. Length Scales x ~ 2 D t Diffusion time Max. diffusion distance ( 3 He in air) Structural sensitivity determined by diffusion time

50 Diffusion Applications Structural information! Emphysema Lung development Asthma? Smoking-related lung disease

51 Second-Hand Smoking Low Exposure High Exposure Smoker Short time scale (~1 ms) Long time scale (~1 s) C Wang et al. Detection of the Changes in the Lungs of People who had High Exposure to Secondhand Cigarette Smoke Using Long-time Diffusion MRI. RSNA 93 (Chicago, 2007). time-scale Global 3 He

52 What about 129 Xe? Cons Intrinsically lower MR signal Absorbed into tissues and blood Pros Naturally abundant Absorbed into tissues and blood

53 Dissolved-Phase Imaging Solubility ~1% Xe in airspaces (flip < 1 ) Resonance frequency in dissolved phase is different by ~200 ppm (chemical shift) Xe in tissue (flip ~90 ) Blood, tissue frequencies slightly different Tissue / blood Alveoli ppm

54 Chemical-Shift Imaging (CSI) Image both gas and dissolved phases, separate based on frequency Rabbit with pulmonary embolus Control Left Pulmonary Artery Occluded Dissolved Xe Xe Gas Dissolved Xe Xe Gas J Mata et al. High-resolution Chemical Shift Imaging of the lungs with Xe-129 during a single 6 second breath-hold: hold: Results from a rabbit model of pulmonary embolism. ISMRM 16:2679 (Toronto, 2008).

55 Dixon-based CSI Separately image both dissolved-phase resonances Blood Rat with pulmonary fibrosis Normal Fibrosis Barrier

56 Dixon-Based CSI Airspaces Barrier (tissue) Red Blood Cells Control X-ray DSA Left lung treated with Bleomycin (day 11 post) Normal Fibrosis B Driehuys et al. Imaging alveolar capillary gas transfer using hyperpolarized 129 Xe MRI. PNAS 2006; 103:

57 Indirect Imaging of Gas Exchange Xenon Transfer Contrast (XTC) Dynamic equilibrium among compartments Repeated, selective destruction of non-equilibrium dissolved magnetization Dynamic Equilibrium Dynamic Equilibrium Exploit large gas-phase magnetization as an amplifier for weak dissolved-phase signals K Ruppert et al. Probing Lung Physiology With Xenon Polarization Transfer Contrast (XTC). Magn Reson Med 2000; 44:

58 Effects of Exchange on Gas Signal Gas Peak: Exchange Gas Peak: Control Xe in tissue Xe in airspaces

59 Applications of 129 Xe Transfer Opens up lots of new possibilities Direct window into gas exchange Tissue density Surface-to-Volume ratio (S/V) Fibrosis Pulmonary edema Radiation injury

60 Medical Significance of Hyperpolarized-Gas MRI New insight into lung function and disease Earlier detection of lung disease Regional assessment of microstructure Regional maps of gas exchange Efficacy of therapy drug development Minimally invasive Safely repeated

61 UVa Hyperpolarized Gas Research Group Radiology Tally Altes, MD Jim Brookeman, PhD Jing Cai, PhD Yulin Chang, PhD John Christopher, MTE Eduard de Lange, MD Joanne Gersbach, RN Klaus Hagspiel, MD Doris Harding, RN Jaime Mata, PhD John Mugler, PhD Kun Qing Kai Ruppert, PhD Chengbo Wang, PhD Physics Michael Carl, PhD Gordon Cates, PhD Peter Dolph Karen Mooney Vladimir Nelyubin, PhD Jaideep Singh Al Tobias, PhD Biomedical Engineering Craig Meyer, PhD