Use of spatial frequency domain imaging (SFDI) to quantify drug

delivery

Colorado state UniversitySchool of Biomedical engineering

BIOM 590 /ECE 581A – BiophotonicsStudent: Minh Anh Nguyen

Motivation• The objective of this presentation is to discuss

some of the optical imaging methods which were applied in the article on spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging

Background• Biological tissues are made of molecules that

absorb light of characteristic wavelengths• The wavelength of the light determines how it

interacts with a material through absorption, scattering and emission

• Most tissue is cloudy so it is difficult to measure the absorption and scattering of the light in it. Optical imaging is an ideal tool to study these tissue properties

• Optical imaging techniques do, however, have limitations such as difficulties in estimating tissue absorption and scattering properties

Drug diffusion within the brain is limited• The brain is a delicate organ and is protected in

many ways• After injection of a drug into the ventricular

section, there is minimal distribution of the drug into the brain

• The reason for limited drug diffusion into the brain from the ventricles is that the ability of diffusion decreases with the square of the distance

• T = x2/4*D– T is the time for drug diffusion through a distance (x)– diffusion coefficient (D) in water

Problem Statement

• Brain tumors are still a difficult challenge in diagnosis and treatment due to their fast development and poor prediction

• Brain tumors have many distinctive characteristics relative to tumors growing in peripheral tissues; medical imaging could be a valuable tool in their study

• Another challenge is an understanding of drug delivery to the brain and an ability to measure drug concentrations in brain tissues in real time

Spatial frequency domain imaging (SFDI)• Allows calculation of optical properties of biological tissues– Absorption coefficient ua -> how much light is absorbed in the

tissue• ua can be used to calculate pathophysiological parameters:

-Hemoglobin volume fraction, water content, etc.– Reduced scattering coefficient us ‘ -> how much light is scattered

in the tissues

• ua =∑ Ci*εi, where Ci is molar concentration, εi is the extinction spectrum of tissue i.

• Assume: optical drugs oxygenated hemoglobin (HbO) and dexoxygenated hemoglobin (HbR) are the dominant drugs in the tissue

• ua = CHbO *εHbO + CHb*εHb +Cdrug*εDrug

Principle of SFDI• The images captured by the camera carry

information on the tissue characteristics• DC and AC components indicate how much light is

absorbed and scattered in the tissueMac,fx = [(2*(I1, fx -I2, fx)2 + (I2, fx -I3, fx)2 + (I3, fx -I1, fx)2)1/2]/3

fx= 0 mm-1, Mdc = 1/3 *(I1, fx+ I2, fx+ I3, fx)

D

Two spatial frequency projections Nguyen, Thu T.A et al., (2012)

• These components are used to calculate optical properties (ua, us’) through a diffusion equation.

Applications of SFDI

• SFDI was used to determine total hemoglobin content of tumor tissue versus normal brain tissue as well as their light scattering and absorption parameters

Diffuse Reflectance Spectroscopy (DRS)• Optical pharmacokinetic (OP) method• Diffuse reflectance spectroscopy with a specific

geometry; uses a noninvasive real-time measurement of drug concentrations

• Determines drug concentrations by measuring the change of the wavelength-dependent total absorption coefficient of the tissue

• Used to measure changes in the absorption coefficient of the scattering due to the arrival and diffusion of the drug

• A method for monitoring local drug delivery to tissues in vivo, and to validate a model of drug delivery

Optical pharmacokinetic (OP) method

Diagram of the optical pharmacokinetics system

Optical pharmacokinetic (OP) method

• The change in tissue absorption coefficient Δua, is -ln (R2/R1) = B+Δua L (ua); where L (ua) is the path length. R1 and R2 are the diffuse reflectance spectra of tissue taken after and before injection of the optical drug

• B is a baseline shift due to the changes in the scattering parameters between two measurements, R1 and R2.

• B = co(t) +c1(t)λ + c2(t)λ2, where co(t), c1(t), c2(t) are baseline coefficient and λ is wavelength.

Optical pharmacokinetic (OP) method (cont.)

• The equation to calculate the path length, which dependents on the total absorption is, L (ua) = Xo +X1*e(-X2

Δua

). X0, X1, and X2 are path length coefficients based on the probe fiber geometry

• ua = [Δ(CHbO(t)+ CHbO(to))] *εHbO (λ) + [Δ (CHb(t)+ CHb(t0)]εHb (λ) +CDrug*εDrug(λ);

• Δua = Δ(CHbO εHbO + CHbεHb +CDrugεDrug)

• The equation that can be used to calculate the difference in drug concentration between two diffuse reflectance measurements is -ln (R2/R1) = B+Δ(CHbO *εHbO + CHb*εHb +Cdrug*εDrug)*[Xo +X1*e(-X2 Δ(CHbO *εHbO + CHb *εHb +CDrug *εDrug))].

Thank You

References

1. Bin, Yang. "Optical and Structural Property Mapping of Soft Tissues Using Spatial Frequency Domain Imaging." Optical and Structural Property Mapping of Soft Tissues Using Spatial Frequency Domain Imaging. 8 Aug. 2015. Web. 11 Dec. 2015. <https://repositories.lib.utexas.edu/handle/2152/31345>.

2. Erickson, Tim A., Amaan Mazhar, David Cuccia, Anthony J. Durkin, and James W. Tunnell. "Lookup-table Method for Imaging Optical Properties with Structured Illumination beyond the Diffusion Theory Regime." J. Biomed. Opt. Journal of Biomedical Optics: 036013.

3. Ergin, Aysegul, Mei Wang, Jane Zhang, Irving Bigio, and Shailendra Joshi. "Noninvasive in Vivo Optical Assessment of Blood Brain Barrier Permeability and Brain Tissue Drug Deposition in Rabbits." J. Biomed. Opt. Journal of Biomedical Optics: 057008.

4. Laughney, Ashley M, Venkataramanan Krishnaswamy, Elizabeth J Rizzo, Mary C Schwab, Richard J Barth, David J Cuccia, Bruce J Tromberg, Keith D Paulsen, Brian W Pogue, and Wendy A Wells. "Spectral Discrimination of Breast Pathologies in Situ Using Spatial Frequency Domain Imaging." Breast Cancer Research Breast Cancer Res.

5. "Introduction to Hyperspectral Image Analysis." Introduction to Hyperspectral Image Analysis. Web. 12 Dec. 2015. <http://spacejournal.ohio.edu/pdf/shippert.pdf>.

6. Singh-Moon, Rajinder P., Darren M. Roblyer, Irving J. Bigio, and Shailendra Joshi. "Spatial Mapping of Drug Delivery to Brain Tissue Using Hyperspectral Spatial Frequency-domain Imaging." J. Biomed. Opt Journal of Biomedical Optics (2014): 096003.

7. Weber, Jessie R., David J. Cuccia, William R. Johnson, Gregory H. Bearman, Anthony J. Durkin, Mike Hsu, Alexander Lin, Devin K. Binder, Dan Wilson, and Bruce J. Tromberg. "Multispectral Imaging of Tissue Absorption and Scattering Using Spatial Frequency Domain Imaging and a Computed-tomography Imaging Spectrometer." J. Biomed. Opt. Journal of Biomedical Optics: 011015.

8. Wei, Xiaoli, Xishan Chen, Man Ying, and Weiyue Lu. "Brain Tumor-targeted Drug Delivery Strategies." Brain Tumor-targeted Drug Delivery Strategies. Web. 12 Dec. 2015.

9. Nguyen, Thu T.A, and Jessica C. Ramella-Roman. "The Novel Application of a Spatial Frequency Domain Imaging to Determine Signature Spectra Differences between Infected and Non-infected Burn Wounds." The Burn Center, Washington Hospital, Medstar Health Institute. 1 Apr. 2012. Lecture.