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A Fast, Accurate Algorithm Enabling Efficient
Solution of a Drug Delivery Problem
Catherine E. Beni, Oscar P. Bruno
Applied and Computational Mathematics
California Institute of Technology
Introduction
The goal of magnetic drug delivery is to use magnetic fields to direct and
confine magnetically-responsive particles bound to therapeutic agents to
specific regions in a patient’s body-- thus allowing for focused treatment in an
area of interest.
Algorithm
Graded Mesh
D = .0001, vy = .0001, Ren = .01
Change of variable in the vessel to allow for resolution of the boundary layer
Tissue
To design a method leading to confinement of the magnetically-responsive
particles to a particular region of the body, a predictive capability must be
used to evaluate the effects of external magnetic forces on the convection and
diffusion of magnetic particles through the bloodstream and in membranes
and tissue.
The numerical solution of the Vessel-Membrane-Tissue (VMT) convection
diffusion problem proposed by Grief and Richardson is highly challenging:
Numerical Results
Membrane
COMSOL
VMT Solver
Speed
36 hours
< 5 minutes
Memory Requirements
32 GB
32.7 MB
→ 432 times faster.
→ 1000 times reduction in memory requirements.
Vessel
Alternating Directions Implicit (ADI)
Discretize in time:
Split into operators on Cn+1 and Cn
Greatly disparate time-scales
D = .00001, vy = .00001, Ren = .001
Extremely steep boundary layers
Occurrence of very small diffusion coefficients
and factor into differential operators in x and y
COMSOL
VMT Solver
Speed
N/A
< 8 minutes
Memory Requirements
> Available 32Gb
98.3 Mb
Framework
The VMT convection-diffusion problem:
The parameters D, vx, and vy vary in each layer
VMT geometry:
Solve the resulting scheme using Finite Difference methods
On-and-Off Fluid Freezing Methodology
Evolve algorithm until concentration in vessel reaches steady state
“Freeze” concentration in vessel by not applying solver in vessel region
Iterate twice using large time steps
Reduce time step, unfreeze vessel, and iterate until concentration in vessel
reaches steady state
Repeat
Change of Unknown
Conclusions
Developed a fast, efficient solver for a drug delivery problem
432 times faster than commercial package COMSOL Multiphysics
1000 times reduced memory requirements
Allows for solution of previously intractable problems
Use the following change of unknown
Future work
The VMT solver is based on a combination of
Use of a graded mesh to adequately resolve boundary layers
The Alternating Directions Implicit (ADI) method to overcome the
overwhelmingly restrictive CFL condition imposed by the fine spatial
discretization mentioned above
An on-and-off fluid-freezing methodology that allows for efficient treatment
of the multiple time-scales that coexist in the problem (whose equilibria arise
through a complex balance of fluid-flow, magnetic-pull and diffusion effects)
A change of unknown that enables evaluation of steady states in tissue and
membrane layers through a highly accelerated time-stepping procedure
to transform the differential operator in y in the membrane and tissue
regions into the Helmholtz equation to make use of a previously known fast
time-stepping method
Finite Difference methods restrict us to a rectangular geometry
Room for accuracy improvement
These two problems will be fixed by solving the ODEs present in the ADI method
with the new Fourier Continuation-Alternating Directions (FC-AD) methodology
See the talk by O.P. Bruno for more details
References
“The Behaviors of Ferro-Magnetic Nano-Particles in Blood Vessels under Applied
Magnetic Fields”, A. Nacev, C.E. Beni, O.P. Bruno, B. Shapiro (to be submitted)
A Noise-tolerant Fejér-based modified-FBP Reconstruction Algorithm (Fejér-mFBP)
for Positron Emission Tomography
C.E. Beni, O.P. Bruno
Applied and Computational Mathematics
California Institute of Technology
Introduction
Images can be reconstructed from Positron Emission Tomography (PET) scanners
via two methods: Iterative methods and Direct methods
Direct methods, such as the well-known Filtered Back Projection (FBP) algorithm
are fast, but reconstruct images that are low resolution.
Iterative methods, such as ML-EM (Maximum Likelihood-Expectation
Maximization) and OSEM (Ordered Subset Expectation Maximization), are much
slower (each iteration takes the same amount of time as a full reconstruction using a
direct method and approximately 20-30 iterations are required), but provide high
quality reconstructions.
Modified-FBP
Approximate the Radon transform with its Fourier series:
where ak and bk are the Fourier coefficients
MATLAB’s ‘iradon’
Combine with the derivative of the Hilbert transform
Shepp-Logan phantom
Fejér-mFBP
mFBP
Fejér-mFBP
Reconstructions using 711 values of ½ , 200 values of µ, and 200 Fourier modes
with 18.5% noise present → Realistic noise, unrealistically sensitive device
MATLAB’s ‘iradon’
Geometry
mFBP
Approximate CT and ST, the Hilbert transforms of cosine and sine respectively,
as follows:
Framework
Radon Transform:
MATLAB’s ‘iradon’
Reconstructions using 100 values of ½ , 200 values of µ, and 200 Fourier modes
→ Unrealistic noise, realistically sensitive device
Direct methods amplify noise and show a dramatic loss of information in the
reconstructed images
Goal: to design a fast, accurate reconstruction algorithm that does not
degrade substantially in the presence of noise
Reconstructions using 711 values of ½ , 200 values of µ, and 200 Fourier modes
→ Unrealistic noise, unrealistically sensitive device
Compute derivative of Hilbert transform:
Both methods suffer in the presence of noise:
Iterative algorithms are not guaranteed to converge
Reconstructed Images
mFBP
Fejér-mFBP
and integrate to obtain the modified-Filtered Back Projection (mFBP) algorithm
Fejér-mFBP
Fejér series of a given function:
Inverse Radon Transform:
Reconstructions using 100 values of ½ , 200 values of µ, and 200 Fourier modes
with 18.5% noise present → Realistic noise, realistically sensitive device
MATLAB’s ‘iradon’
h(½,µ) is the Hilbert transform of the Radon transform
mFBP
Fejér-mFBP
By approximating the Radon transform with a Fejér series instead, we obtain
the Fejér-mFBP algorithm:
Original FBP
Compute the Hilbert transform and its derivative as follows:
Numerical Results
Conclusions
Both algorithms were implemented in C++
Integrate to obtain the inverse Radon transform
Each reconstruction requires ~3.6 seconds, the same amount of time used by
MATLAB’s built-in ‘iradon’ function
All reconstructions shown here are of the well-known Shepp-Logan phantom
generated using MATLAB’s built-in ‘phantom’ command
Developed a new reconstruction algorithm that, in presence of noise, yields
iterative-solver-like quality at FBP computational costs.
References
“A Noise-Tolerant Fejér-based modified-FBP Reconstruction Algorithm (Fejér-mFBP)
for Positron Emission Tomography”, C.E. Beni, O.P. Bruno (to be submitted)