Use of spatial frequency domain imaging (sfdi) to quantify drug delivery

1. Use of spatial frequency domain
imaging (SFDI) to quantify drug
delivery
Colorado state University
School of Biomedical engineering
BIOM 590 /ECE 581A – Biophotonics
Student: Minh Anh Nguyen

2. 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

3. 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

4. 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

5. 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

6. 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
extinctionspectrum 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

7. 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 tissue
Mac,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 =
1
3∗(𝑢𝑠′+𝑢𝑎)
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.

8. 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

9. 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

10. Optical pharmacokinetic (OP) method
Diagram of the optical pharmacokinetics system

11. 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.

12. 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 Δu
a
). 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(C
HbO
*ε
HbO
+
C
Hb
*ε
Hb
+C
Drug
*ε
Drug
))].

13. Thank You

14. 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>.
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<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
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Devin K. Binder, Dan Wilson, and Bruce J. Tromberg. "Multispectral Imaging of Tissue Absorption and Scattering Using
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8. Wei, Xiaoli, Xishan Chen, Man Ying, and Weiyue Lu. "Brain Tumor-targeted Drug Delivery Strategies." Brain Tumor-
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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.