Some Aspects in Medical Imaging

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Some Aspects in Medical Imaging
Debasis Mitra Computer Science Florida Institute
of Technology Acknowledgement Grant T.
Gullberg Radiotracer Department Life Sciences
Division Lawrence Berkeley National Lab Unknown
sources from the Web
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Co-ordinates

• Why this talk?
• Where am I now?
• What does this lab do?

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Lawrence Berkeley National Lab
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Center for Functional Imaging
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Biomedical Imaging is the Engineering behind
Radiology

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Types of Imaging Instruments

• Computer Tomography (X-ray)
• Magnetic Resonance Imaging (MRI)
• Single Photon Emission Computed Tomography
  (SPECT) gamma ray of 100-few hundred kev
• Positron Emission Tomography (PET) gamma ray
  from in situ positron annihilation, 500 kev
• Ultra Sound
• Optical or Laser Tomography (Infrared)
• Fluoroscopy, Opto-acoustic, Electron,
  Atomic-force, Radio-frequency,

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CT
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GE VG3 Millennium Hawkeye SPECT/CT
collimators
?-ray detectors
x,y
Acquisition system
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Scintillation Camera and Collimator
Patient
Collimator localizes events in object and
determines sensitivity and spatial resolution of
the camera
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Collimator
converging
parallel hole
pinhole
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Positron Emission Tomography Does Not Need a
Collimator

• Positron annihilates with electron ? two gamma
  photons each at 511 keV leave under 180?
• Coincidence detection (electronic collimation)

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PET
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MRI
Epilepsy MRI, PET-time 1, 2
Brain tumor
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Fiber Tracking of DTMRI Data
Rohmer D, Sitek A, Gullberg GT Reconstruction
and visualization of fiber and laminar structure
in the normal human heart from ex vivo DTMRI
data. Investigative Radiology, 42777-789, 2007.
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Ultrasound
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CardiARC
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Clinical FeasibilityResults
Conventional
Spectrum Dynamics
1.45 Mcounts total (heart 10, backgnd 90) Pixel
size 6.91 mm 6.91 mm Iterative
reconstruction Total acquisition time 17.5 min
0.8 Mcounts total (heart 60, backgnd 40) Pixel
size 2.46 mm 6.91 mm 6.91 mm Iterative
reconstruction Total acquisition time 2.2 min
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Radiopharmaceuticals forCardiac Imaging

• 201Tl
• 99mTc-sestamibi (2-Meth0xy-2-methylpropyl
  isonitrile)
• 99mTc-tetrafosmin
• 99mTc-teboroxime
• 123I-iodorotenone
• 123I-BMIPP (fatty acid)
• 123I-IPPA (fatty acid)

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Targets of Study

• Heart,
• Lungs, liver, other organs in torso
• Brain Alzheimers Disease Neuroimaging
  Initiative (ADNI)
• Breast
• Tumor

Breast Cancer
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Physics behind Models

• Emission tomography SPECT, PET, MRI
• Transmission tomography X-ray, Optical
• Reflection Ultra Sound, Total Internal
• Reflection Fluoroscopy (TIRF for single cell
• visualization)
• Scattering Muon tomography?

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Mathematical Problem Formulation

• Forward Problem (modeling) How the data would
  look like
• given probe and the model
• D F(M) Forward project
• An implementation is a Simulation software
• Inverse Problem (tomography) What the model
  would be
• given the probe and data
• M F (D) back-project
• An implementation is a Reconstruction software
• Noise in data makes it a hard statistical
  problem
• Data volumemay be additional computational
• challenge
• http//en.wikipedia.org/wiki/Inverse_problem

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Reconstruction Algorithms

• Analytic-inverse E.g., Radon transformation for
  
• emission/absorption (mostly useless except for
  theoretical
• purpose)
• Algebraic Reconstruction voxel by voxel
  reconstruct the model
• Iterative Reconstruction using Expectation
  Maximization
• Ordered Set EM
• Maximum A Posteriori (MAP-EM)
• Penalized Least Square (PLS) 1.5 iteration!

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Dynamic Imaging

• Problem Objects move during data gathering
• Question How to reconstruct (1) Object, (2)
  Motion
• A successful approach Level Set
• For blood concentration change in tissues
• Temporal B-spline
• Tensor imaging with MRI

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Fit the 123I-BMIPP Data to a Compartment Model

• Need to estimate an input function.
• Time activity curves have to be estimated
  directly from the projections.
• A methyl group on the ? position of the carbon
  chain limits the oxidation of 123I-BMIPP.
• Differs from 123IPPA which is
• completely metabolized to
• benzoic acid.

TG
IPPA
Model of IPPA Metabolism
Benzoic acid
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Spatiotemporal Modeling Using A Small Number of
Splines to Represent Realistic Physiological
Curves

• Quadratic B-Spline Temporal Basis Functions

• Zero Order (voxels) B-Spline Spatial Bases

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Slow-Rotation Dynamic Pinhole SPECT
Blood Time Activity Curve Estimated from
Projections Using Factor Analysis
1 sec frames, 180 rotation of one
head Recirculation time is 6-8 seconds
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Results Dynamic Early Data
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Image Spatial Representations
Pixels / voxels Blobs Linear B-splines Cubic
B-splines Custom-made shapes Irregular meshes
. . . . . . . . . . . . . .
regular
sparse
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Metabolic Rate of BMIPP
Normal
Ki0.40 min-1
SHR
Ki0.15 min-1
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Metabolic Rate FDG vs BMIPP
BMIPP
FDG
Ki0.40 min-1
Ki0.15 min-1
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SHR hypertensive rat model (genetically modified)
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WKY normal rat
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Flow rate changesSHR Hypertensive, WKY normal
SHR SHR WKY WKY
Age (months) A (min-1) B (min-1) A (min-1) B (min-1)
7 0.94 1.44
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21 0.22 0.60
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Temporal Comparison of 1st Principal Strain for
SHR and WKY
anterior wall
septum
SHR
1st PS
WKY
FS
Veress A et al. Regional changes in the
diastolic deformation of the left ventricle for
SHR and WKY rats using 18FDG based microPET
technology and hyperelastic warping. Annals of
Biomedical Engineering 3611041117, 2008.
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Parametric Imaging
Summed Images (between 2 and 12 min)
Parametric Images of k21
Sitek A, Di Bella EVR, Gullberg GT,
Huesman RH Removal of liver activity
contamination in teboroxime dynamic cardiac SPECT
imaging using factor analysis. J Nucl Cardiology
9197-205, 2002.
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SUMMARY

• The SHR shows increased glucose metabolism and
  reduced fatty acid metabolism.
• The reverse is true for the nomotensive WKY rat.
• The SHR model is used to develop techniques for
  analysis of imaging data of heart failure related
  to metabolism.
• Molecular Insight Pharmaceuticals is now
  evaluating 123I-BMIPP in clinical trials.
• These results of fatty acid metabolism correlate
  with those in humans with hypertensive left
  ventricular hypertrophy. (de las Fuentes et al. J
  Nucl Cardiol 13369, 2006)

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COMMENTS

• The SHR has a defective gene (CD36) on chromosome
  4.
• The defect is associated with compromised
  long-chain FA transport across the cell membrane.
• The defect causes insulin resistance, alteration
  in basal glucose metabolism.
• Short-chain FA diet decreases glucose uptake,
  alleviates hypertrophy, but hypertension is not
  improved.
• Proposed research will compare 123I-BMIPP with
  18FTHA.

Hajri T et al. Defective fatty acid uptake in
the spontaneously hypertensive rat is a primary
determinant of altered glucose metabolism,
hyperinsulinemia, and myocardial hypertrophy. J
Biological Chem 27623661-23666, 2001.
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MRI is way advanced in Dynamic Imaging
Diffusion Tensor Imaging
A high-resolution diffusion tensor imaging scan
reveals differences between healthy tracts of
axons, at left and in the lower enlargement, and
tracts of injured axons, at right and in the top
enlargement, in a person who sustained a
moderate to severe traumatic brain injury. Such
damage has been shown to correlate with
cognitive impairment. (Image courtesy of Dr.
Deborah Little)
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Diffusion Tensor
Diffusion within a single voxel. (a) Diagram
shows the 3D diffusion probability density
function in a voxel that contains spherical cells
(top left) or randomly oriented tubular
structures that intersect, such as axons (bottom
left). This 3D displacement distribution, which
is roughly bell shaped, results in a symmetric
image (center), as there is no preferential
direction of diffusion. The distribution is
similar to that in unrestricted diffusion but
narrower because there are barriers that hinder
molecular displacement. The center of the image
(origin of the r vector) codes for the proportion
of molecules that were not displaced during the
diffusion time interval.
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Sheet Tracking of DTMRI Data
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Fiber Tracking of Right and Left Ventricle
Cardiac Band Hypothesis The four chamber heart
is built from a single continuous band of muscle.
Torrent-Guasp F, Kocicab MJ, Cornoc AF,
et al. Towards new understanding of the heart
structure and function. Eur J Cardiothorac Surg.
200527191-201.
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Advancement of Data Acquisition Technology

• List mode acquire data for recording time for
  each
• track and reconstruct with it a computational
  challenge
• Time-of-flight Acquire event versus data
  collecting
• time new type of detectors needed
• Compton gamma camera provides some measure of
• angle of a track
• Newer Technology Opto-acoustic, Fluorescence,
• Target-specific detectors e.g., Cardiac-Spect,
  faster
• and cleaner data with higher resolution

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Molecular Imaging

• Medical imaging is primarily at organ-level
• With more genetic information available today it
  is
• usual to think in terms of metabolism behind
  images,
• and target cellular-level processes
• Current focus is to develop ligands that are
• tagged with imaging agents, (2) binds to some
• protein or metabolite that we want to visualize
  with imaging
• Understanding dynamic organ-level images from
• metabolic point of view is another new area

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Total Internal Reflection Imaging
TIRF imaging of actin networks and their
reorganization in the cortex of Dictyostelium
cells.
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Auto-diagnosis/prognosisMachine learning

• Images are still used by radiologists for
• diagnosis/prognosis, or by biologist for doing
  science
• technology targets exclusively to improve
• image quality, and nothing more
• It is quite possible to use machine learning
  algorithms
• to help the process
• image is input, zones of interest with
  annotations are output

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Thanks!

• Debasis Mitra
• dmitra_at_cs.fit.edu