Biomedical applications of magnetic Biomedical applications of - PowerPoint PPT Presentation

“Biomedical applications of magnetic Biomedical applications of magnetic “ nanoparticles: nanoparticles: I: Drug delivery” ” I: Drug delivery M.R. Ibarra 1,2 1,2 , R. Fern Pacheco 1 1 , C. Marquina , C. Marquina 2 2 and J.G , R. Ferná ández ndez- -Pacheco and J.G M.R. Ibarra 1 Valdivia 1 Valdivia II: Electromagnetic radiation” ” II: Electromagnetic radiation G. F. Goya 1 1 , V. Graz ú 1 1 , C. Marquina , C. Marquina 2 2 , M. R. Ibarra , M. R. Ibarra 1,2 1,2 , V. Grazú G. F. Goya 1 1 Instituto de Nanociencia de Instituto de Nanociencia de Arag Aragó ón n, , 2 2 Instituto de Instituto de Ciencia Ciencia de de Materiales Materiales de de Arag Aragó ón n http//:ina.unizar.es Zaragoza (Spain) (Spain) Zaragoza

OUTLINE OF THE TALK OUTLINE OF THE TALK Biomedical applications of magnetic nanoparticles II: Biomedical applications of magnetic nanoparticles II: Electromagnetic radiation Electromagnetic radiation -Introduction -Therapy based in magnetic hiperthermia -Diagnostic based in nuclear magnetic resonance effect: MRI

Marcelo Knobel y Gerardo F. Goya , Scientific American. 31, DIC. 2004

OUTLINE OF THE TALK OUTLINE OF THE TALK Biomedical applications of magnetic nanoparticles II: Biomedical applications of magnetic nanoparticles II: Electromagnetic radiation Electromagnetic radiation -Introduction -Therapy based in magnetic hiperthermia -Diagnostic based in nuclear magnetic resonance effect: MRI

What is hyperthermia? Hyperthermia (thermal therapy or thermotherapy) is a type of cancer treatment in which body tissue is exposed to high temperatures (up to 45 ° C ). Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues. By killing INA - INA cancer cells and damaging proteins and structures within Aragon Institute of Nanoscience - cells, hyperthermia may shrink tumors. Aragon Institute of Nanoscience National Cancer Institute, USA

• Loss separation The formulation is the same for an alternating and rotating field = + P P P core hysteresis eddy • Hysteresis loss Rate of change of energy used to affect magnetic domain wall motion • Eddy-current loss (classical eddy currents) Due to induced currents flowing in closed paths within magnetic material

1. In NPs suspensions (@ RT), the Brownian relaxation in viscous media is η τ = 3 V H B k T B 2. Néel relaxation is R.E. Rosensweig, JMMM 252 (2002) 370. τ = τ   K V M   exp N 0   k T  B  So the total (parallel) relaxation is = + 1 1 1 τ τ B τ N

The “Bio-Heat Equation” ∂ ρ ⋅ ⋅ = ⋅ ∇ T c k T ∂ t t t t ρ t = tissue density c t = tissue specific heat capacity k t = thermal conductivity,

Pennes’ equation estimates the temperature field T( x,y,z,t ) at nearby tissues ∂ { } = ∇ − − + T 1 2 k T w c ( T T ) Q ∂ ρ t b b a t c t t ρ t = tissue density C t = tissue specific heat capacity Q = density of heat production rate, T a = temperature at infinite distances w b , = perfusion rate It relates to the functional definition of c b = blood specific heat capacity Specific Absorption Rate (SAR): amount of energy converted in energy per time and mass ∆ =   = C T Q S SAR  m  ∆ ρ FF m  t  Fe t

SETUP SETUP LPT T = 46 º C HYS TMP DW B FG 250 kHz 700 V PP L IN IN H RGC 123 kW G. F. Goya, V. Grazú and M.R. Ibarra, Current Nanoscience, 2007.

MAGNETIC CELLS 4 DCs 3 2 DCs + FeC M S =40.3 emu/g Difference 40 CDs FeC 2 -3 emu) 1 1 20 -3 emu) M (emu/g) 0 0 M (x10 0 M (x10 H C =244 Oe -1 -20 -2 -1 -3 -40 -4 -2 -10 -8 -6 -4 -2 0 2 4 6 8 10 -10 -8 -6 -4 -2 0 2 4 6 8 10 -12 -9 -6 -3 0 3 6 9 12 H (kOe) H (kOe) H (kOe) G.F. Goya et al. J.Exp.Med, submitted

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OUTLINE OF THE TALK OUTLINE OF THE TALK Biomedical applications of magnetic nanoparticles II: Biomedical applications of magnetic nanoparticles II: Electromagnetic radiation Electromagnetic radiation -Introduction -Therapy based in magnetic hiperthermia -Diagnostic based in nuclear magnetic resonance effect: MRI

Magnetic Resonance Imaging • Non-invasive medical imaging method, like ultrasound and X-ray. • Clinically used in a wide variety of specialties. Abdomen Spine Heart / Coronary

Magnetic Resonance Imaging Advantages: – Excellent / flexible contrast – Non-invasive – No ionizing radiation – Arbitrary scan plane Challenges: – New contrast mechanisms – Faster imaging

MRI Systems At $2 million, the most expensive equipment in the hospital…

Magnetic Resonance Imaging (MRI) -Based on the magnetic relaxation of hydrogen water protons in tissues -Resonance phenomena have different relaxation time depending of the active tissue under a radiofrequency signal. The radiation emited due to the relaxation can be detected and espatially localized within the body giving rise to contrast imaging -The constrast is enhanced by paramagnetic or superparamagnetic nanovectors

Magnetic Resonance • Certain atomic nuclei including 1 H exhibit nuclear magnetic resonance. • Nuclear “spins” are like magnetic dipoles. 1 H

Polarization • Spins are normally oriented randomly. • In an applied magnetic field, the spins align with the applied field in their equilibrium state. • Excess along B 0 results in net magnetization. No Applied Field Applied Field B 0

Precession • Spins precess about applied magnetic field, B 0 , that is along z axis. • The frequency of this precession is proportional to the applied field: ω = γ B

Excitation • “Excite” spins out of their equilibrium state. Transverse RF field (B 1 ) rotates at γ B 0 about z-axis. • Magnetization B 0 B 1 Rotating Frame

RELAXATION (Pankhurst et al. J. Phys. D: Appl. Phys 36 (2003) R167)

Relaxation • Magnetization returns exponentially to equilibrium: – Longitudinal recovery time constant is T 1 (spin-lattice) – Transverse decay time constant is T 2 (spin-spin) • Relaxation and precession are independent. Precession Decay Recovery

Signal Reception • Precessing spins cause a change in flux ( Φ ) in a transverse receive coil. • Flux change induces a voltage across the coil. z B 0 Φ y Signal x

Spin Echoes • 180 ° RF tip can reverse the dephasing effects of off-resonance. • Spins realign at some time to form a spin echo

MR Image Formation • Gradient coils provide a linear variation in B z with position. • Result is a resonant frequency variation with position. B z Position

Gradient Coils z z z y y y x x x X gradient Y gradient Z gradient Gradient coils generate spatially varying magnetic field so that spins at different location precess at frequencies unique to their location, allowing us to reconstruct 2D or 3D images.

Selective Excitation 1 Position Slope = γ G Frequency (a) (b) Magnitude Frequency (c)

Image Acquisition • Gradient causes resonant frequency to vary with position. • Receive sum of signals from each spin. Frequency Position

Magnetic Gradients • Gradient adds to B0, so field depends on position • Precessional frequency varies with position! • “Pulse sequence” modulates size of gradient Spins at each position sing at different frequency • RF coil hears all of the spins at once • Differentiate material at a given position by selectively listening to that frequency Fast High field precession B 0 Slow Low field precession

Simple “imaging” experiment (1D) increasing field

Simple “imaging” experiment (1D) Signal Fourier transform “Image” position Fourier Transform: determines amount of material at a given location by selectively “listening” to the corresponding frequency

2D Imaging via 2D Fourier Transform 1DFT 1D Signal 1D “Image” 2DFT k y y k x x 2D Signal 2D Image

Resolution • Image resolution increases as higher spatial frequencies are acquired. 1 mm 2 mm 4 mm k y k y k y k x k x k x

Contrast • Contrast is the difference in appearance of different tissues in an image. X-ray contrast is based on transmission.

Contrast in MRI • Hydrogen (water) density results in contrast between tissues. • Many other mechanisms, some based on relaxation.

T 2 Contrast Short Echo-Time Long Echo-Time CSF (cerebrospinal fluid) Signal White/Gray Matter Time

T 1 Contrast Short Repetition Long Repetition White/Gray Matter Signal Signal Time CSF Time

Knee Imaging - Menisci • MRI is the best non-invasive method of diagnosing meniscal tears FSE DEFT

Enhance MRI contrast by molecular recognition Magnetic core Antibody detector tumor of cancer biomarker tumor CONTRAST AGENT tumor Núcleo magnético anticuerpo reconocedor carcasa de de tumores sílice tamaño controlado

Dendritic cells as MRI contrast agent G. Goya et al. INA (2006)