Medical Application of Spin-Polarized Noble Gases: Emphysema Index Based on Polarized He-3 and Xe-129 Diffusion in the Lung Sina Tafti , William J Garrison,

Medical Application of Spin-Polarized Noble Gases: Emphysema Index Based on Polarized He-3 and Xe-129 Diffusion in the Lung Sina Tafti , William J Garrison, John P Mugler, Y Michael Shim, Talissa A Altes, Jaime F Mata, Nicholas J Tustison, Kun Qing, Eduard E de Lange, Gordon D Cates, and G Wilson Miller University of Virginia 23rd International Spin Symposium September CT Proton MRI He-3 Gas Image on Proton MRI ADC Map on Proton MRI

B B Origin of the MR Signal Classical picture
Imagine a spin initially aligned with the static magnetic field If the spin is tipped away from the B axis The spin and its magnetic field precesses about the axis with frequency 𝑓= γ𝐵 Radiofrequency (RF) coil in the transverse plane Precessing spin induces a changing voltage in the coil which is the MR signal B RF coil B MR Signal

4 MRI Terminology Flip Angle θ After application of RF pulse that tips the magnetization away from the static field axis: Longitudinal Magnetization 𝑴 𝒛 Longitudinal signal exponential grows back to its initial amplitude with time constant 𝑇 1 𝑀 0 𝑴 𝒛 𝑇 1 Transverse magnetization decays with effective time constant 𝑇 2 ∗ Transverse Magnetization 𝑴 ⊥ 𝑴 ⊥ 𝑇 2 ∗ time

Spatial Encoding using Magnetic Field Gradients
5 MRI Theory Spatial Encoding using Magnetic Field Gradients A gradient is a linear variation in the strength of the scanner’s magnetic field along a particular direction. The gradient creates a linear mapping between position and resonant frequency: Z gradient X gradient ΔB ΔB = 𝑮 𝒙 ∙𝒙 𝟎 B x 𝒙 𝟎 𝒇= 𝜸 𝟐𝝅 ( 𝑩 𝟎 +ΔB )= 𝜸 𝟐𝝅 ( 𝑮 𝒙 ∙𝒙+ΔB )

Spatial Encoding using Magnetic Field Gradients
6 MRI Theory Spatial Encoding using Magnetic Field Gradients Apply gradients in all three dimensions to have a 3D mapping between position and frequency. 𝑮 𝒙𝒚𝒛= 𝑮 𝒙 𝒙 + 𝑮 𝒚 𝒚 + 𝑮 𝒛 𝒛 = 𝝏 𝑩 𝒛 𝝏𝒙 𝒙 + 𝝏 𝑩 𝒛 𝝏𝒚 𝒚 + 𝝏 𝑩 𝒛 𝝏𝒛 𝒛 Define k-space: 𝒌(𝒕) ≡ γ 𝟐π 𝒕 𝟎 𝒕 𝑮 𝒙𝒚𝒛 𝒕 ′ 𝒅 𝒕 ′ k-space is Fourier conjugate of image space. Each location in k-space corresponds to a different spatial frequency in image space.

MRI Theory Image Reconstruction 𝜌 ( 𝒓 ) ∝ 𝑆( 𝒌 ) 𝑒 2𝜋𝑖 𝒌 ∙ 𝒓
7 MRI Theory Image Reconstruction k-space Image space There is a Fourier relationship between spin density 𝜌 ( 𝒓 ) and k-space signal intensity 𝑆( 𝒌 ): 𝜌 ( 𝒓 ) ∝ 𝑆( 𝒌 ) 𝑒 2𝜋𝑖 𝒌 ∙ 𝒓 Fourier transform properties: All k-space pixels contribute to every image space pixel intensity Central k-space pixels contribute the most K y y With conventional MRI acquisition, impossible to obtain resolution that resolves microstructure of the lungs Kx x

Motion of Gas Molecules in the Lungs
8 Motion of Gas Molecules in the Lungs Free diffusion: Brownian motion of the gas molecules. Only obstacles to motion are other freely diffusing particles Restricted diffusion: Pseudo-random walk in the presence of rigid barriers Apparent diffusion coefficient (ADC) Difference between ADC and 𝐷 0 reflects degree of restriction imposed by confining structures 𝐷 0 ≡ 𝛿 2 2Δ𝑡 ε 𝑛 =−1 ε 𝑛 =+1 𝑥 𝑖 𝑁Δ𝑡 − 𝑥 𝑖 𝑖 = 𝑛=1 𝑁 𝛿ε 𝑛 =𝑁 𝛿 2 =2 𝐷 0 𝑡 For i-th gas molecule 𝐴𝐷𝐶 ≡ 𝑥 𝑖 𝑡 − 𝑥 𝑖 𝑖 2𝑡 𝐷 0 𝐴𝐷𝐶 𝑥 𝑖 𝑡 − 𝑥 𝑖 𝑖 t

Diffusion-Weighted MRI
9 Diffusion-Weighted MRI time Gx Bx x Way this works is as follows: Consider collection of spins in a uniform magnetic field, all in phase and precessing at the same rate. Coherent, yields large signal in our pickup coil Apply linearly varying magnetic field, they begin precessing at different rates. Signal in our pickup coil goes to zero as they dephase. Reverse the gradient, apply it for the same amount of time, spins rewind back into coherence. If spins are stationary, get the same signal back that you started with. If on the other hand, the spins move between the gradients, don’t get complete refocusing, and the macroscopic signal (vector sum) is less than you started with. Referred to as diffusion attenuation. Vector sum in rotating frame Precessing spins in lab frame

10 Diffusion-Weighted MRI time Gx Bx x Vector sum in rotating frame Precessing spins in lab frame

MRI Diffusion Measurement
17 MRI Diffusion Measurement Magnetic field gradient causes displacement-dependent phase accrual φ(𝑡) = 𝑛=1 𝑁 γ𝐺 𝑥 𝑛 Δ𝑡 = γ𝐵=ω Mean squared phase accumulated during application of a magnetic field gradient is φ(𝑡) 2 = γ 2 𝐺 2 (𝐴𝐷𝐶) 𝑡 3 MR signal has the following relationship with diffusion-dependent phase accrual 𝑆∝ 𝑒 − φ(𝑡) 2 2 𝑆∝ 𝑒 − 1 3 γ 2 𝐺 2 (𝐴𝐷𝐶) 𝑡 3 MR signal attenuation is given by: 𝑏= γ 2 𝐺 2 𝑡 3 𝑆 𝑏 = 𝑆 0 𝑒 −𝑏∙𝐴𝐷𝐶 where

Diffusion Weighted MRI (DW-MRI) of Polarized Noble Gases
18 𝑆 𝑏 = 𝑆 0 𝑒 −𝑏∙𝐴𝐷𝐶 𝑐𝑚 2 /s

Our 3He Polarizer Spin Exchange Optical Pumping Hybrid alkali
19 Our 3He Polarizer Spin Exchange Optical Pumping Rb + K + 3He Temperature Controllers and Laser Drivers Hybrid alkali Polarize 3He to ~ 60% 5 orders of magnitude higher polarization than thermal equilibrium at body temperature @ 1.5 T Our polarizer produces ~ 2.5L of polarized gas per batch Optics Helmholtz Coils for Static Field Oven (cell inside) 3He Gas Pluming Electronics supplying static field and NMR measurement

Commercial 129Xe Polarizers
20 Commercial 129Xe Polarizers Xemed xenon polarizer Plarean xenon polarizer Both produce ~ 30% polarized 129Xe

3 mm in-plane resolution
21 Imaging Healthy volunteers Patients with varying chronic obstructive pulmonary disease Vest-shaped RF coil (Clinical MR Solutions) tuned to He-3 or Xe-129 resonant frequency 1.5 T whole-body scanner (Siemens Avanto) 4 cm CT Scan Siemens SOMATOM Definition Flash 0.9 ×0.9 ×0.7 𝑚𝑚 voxel resolution Inhale same volume of gas ( 𝑁 2 ) Imaging Parameters: 3 mm in-plane resolution Matrix size = 36 × 64 COPD: chronic obstructive pulmonary disease

Gas images superimposed on 1H (conventional) MRI
22 Imaging Inhale 0.4L of He-3 or 1L of Xe-129 Gas images superimposed on 1H (conventional) MRI

23 ADC Maps

Emphysema Emphysema: destruction of alveolar walls
24 Emphysema Emphysema: destruction of alveolar walls Gas molecules in emphysematous acinus travel farther compared to those in healthy airspaces CT CT Healthy COPD

Applications of ADC Maps for Emphysema Characterization
25 ADC maps can be used to detect tissue destruction due to emphysema Emphysematous regions are associated with high ADC values due to destroyed alveolar walls Healthy lungs have homogenous, low ADC values 𝑐𝑚 2 /s 𝑐𝑚 2 /s 3He Mean ADC = 0.204 3He Mean ADC = 0.512 CT CT 3He Mean ADC = 0.207 3He Mean ADC = 0.654 CT CT

Emphysema Index (EI) Definition
26 Emphysema Index (EI) Definition CT Based on CT Hounsfield unit (HU): CT-EI is defined as the percentage of the lung below the attenuation threshold of −950 HU*. We propose an alternative formulation of EI based on ADC values: Fraction of voxels with He-3 ADC values greater than 𝑐𝑚 2 𝑠 Fraction of voxels with Xe-129 ADC values greater than 𝑐𝑚 2 𝑠 95th percentile of all voxels from healthy subjects 𝑐𝑚 2 𝑠 95th percentile of all voxels from healthy subjects 𝑐𝑚 2 𝑠 *Bae K. et al, Medicine (2016) 95(48).

27 Results

28 Results

29 Results Excellent correlation between He-3 and Xe-129 ADC

31 In this study, ADC-EI appears to be more sensitive to early stages of emphysema than CT-EI. 2 1 CT EI: 38 % false negative Xe-129 ADC EI: 14 % false negative 3 4

Results 32 CT Xe-129 ADC He-3 ADC ADC EI CT EI 3He: 0.03 0.01
cm2/s cm2/s 3He: 0.93 129Xe: 0.84 0.23 cm2/s cm2/s 3He: 0.60 129Xe: 0.65 0.01 cm2/s cm2/s

Results 33 * 𝑝 < 0.05 ** 𝑝 < 0.005 *** 𝑝 < 0.0005 * ** ** *

Summary and Conclusions
34 Summary and Conclusions Use apparent diffusion coefficient obtained from diffusion-weighted MRI of spin polarized noble gases to propose an alternative formulation of emphysema index He-3 and Xe-129 ADC EI offer remarkably similar results, suggesting that ADC EI is a robust method of quantifying emphysema severity In our study, both He-3 and Xe-129 ADC appear to be more sensitive tools for detecting early stages of emphysema than CT

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Medical Application of Spin-Polarized Noble Gases: Emphysema Index Based on Polarized He-3 and Xe-129 Diffusion in the Lung Sina Tafti , William J Garrison,

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Medical Application of Spin-Polarized Noble Gases: Emphysema Index Based on Polarized He-3 and Xe-129 Diffusion in the Lung Sina Tafti , William J Garrison,

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Presentation on theme: "Medical Application of Spin-Polarized Noble Gases: Emphysema Index Based on Polarized He-3 and Xe-129 Diffusion in the Lung Sina Tafti , William J Garrison,"— Presentation transcript:

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