pet-mri tools (v.0707)

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PET-MRI Tools: A program package for the analysis of dynamic PET studies registered to anatomical images University of Debrecen, Medical and Health Science Centre Department of Nuclear Medicine József Varga July 2007

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Slide presentation of the medical image processing package "PET-MRI Tools", developed for research purposes.

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Page 1: PET-MRI Tools (V.0707)

PET-MRI Tools: A program package

for the analysis of dynamic PET studies

registered to anatomical images

University of Debrecen,

Medical and Health Science Centre

Department of Nuclear Medicine

József Varga

July 2007

Page 2: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 2

Purposes:

• Originally: PARTIAL VOLUME CORRECTION

in the calculation of quantitative parameters derived from (static

and dynamic) PET studies of the:

- brain (serotonine receptors)

- kidneys (angiotensine receptors)

Other aims:

• General processing with anatomical VOIs

(volumes of interest)

• Kinetic analysis (curves and parametric images)

• Use of some brain atlas for automatic region definitions

• 3D statistics (with SPM)

Page 3: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 3

Requirements:

• Easy integration of GPL (public) programs

and earlier packages of our own

– C/C++ source codes

– MatLab modules

– Executables

• Handling multiple medical file formats

• Easy development and testing of new and adapted

algorithms

– Must support both scripting and C/C++

• Convenient interface for non-programmers

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PET-MRI Tools - July 2007 J. Varga 4

Principles of PET-MRI Tools

• Platform: primarily PC with Windows

• Bilingual environment

(C++ and MatLab)

• Modular structure, with MINC

files as connection points

• Flexible

• Simple user interface

generally available

fast development + fast execution

exchangable moduls

to support development

for physician users

Page 5: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 5

PROGRAMMING ENVIRONMENT

Operating system: MS Windows 9X/NT/2000/XP

Hardware: PC

MatL

ab

MS

Vis

ual

Stu

dio

Standalone executables

C/C++ modules

MatLab modules

Matlab programs

MEX files (dll-s)

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PET-MRI Tools - July 2007 J. Varga 6

USER INTERFACE / 1:

Interface generator for functions

function [lh,tacs]=tac( image_file, voi_file, tac_file, makeplot,...

voilevel, weighted )

% Generates time-activity curves, and saves them to file

%#!1:Image file;infile;*.mnc

%#!2:VOI file;infile;*.voi

%#3:New TAC file name;outfile;*.tac

%#4:Show graphs?;check;1

%#5:Threshold if using VOI masks;num;0.005;1;0.5

%#6:Weight with probabilities?;check;1

%#>2

if ( nargin<2 )

[lh,tacs]=runfn('tac');

return;

end

function [lh,tacs]=tac( image_file, voi_file, tac_file, makeplot,...

voilevel, weighted )

% Generates time-activity curves, and saves them to file

Page 7: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 7

USER INTERFACE / 2:

Menu

% Menu structure for curve processing

% Jozsef Varga, Cyric, Sendai, 2001

Curve processing

>&Conversion

>>Conversion &planner,convplan

>>&Set to MINC,set2minc

>>&Analyze to MINC,anal2minc

>>&InterFile to MINC,dynif2minc

>>S&um dynamic series,start_volsum

>&Display

>>&Show series,minc_show_caller

...

>&Curves

>>&TAC creation,tac_caller

>>Create from &C/S,cs_tac_caller

>>&Read from any file,loadcurves_caller

>>Read from TAC &file,readcurves_caller

Page 8: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 8

USER INTERFACE / 3:

Procedure Control

% lungtu.proc

%#!1:SPECT file name in DIAG;infile;*.kv*

%#!2:New file name;outfile;m:\tudo\*.mnc

%#>0

1:Convert;diag2minc;#0,1#;#0,2#;1;0

2:Create coronal;reslice_minc;#0,2#;coronal;[changeext('#0,2#','C.mnc')];3;;

3:Draw VOI;drawvoi_call;#2,3#;;[changeext('#0,2#','C.voi')]

4:Create isocount VOI;autiso_rel_cs;#0,2#;#3,3#;;[changeext('#0,2#','_tu.voi')]

5:Check VOI;drawvoi_call;#0,2#;;#4,4#;#4,4#

6:Quantitate;tuq;#0,2#;#4,4#

Page 9: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 9

USER INTERFACE / 4:

Batch processing

• Repeated calling of the same procedure for a

list of studies

• Automatic mode of procedure control:

Steps labeled as non-essential are skipped

(e.g. visual inspection and possibility for manual

corrections)

Page 10: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 10

ELEMENTS:

Conversion from scanner (PET, MRI) formats

to MINC

GE4096 GEAdv InterFile DICOM Signa4 Signa5

(SPECT) (CT)

Functional MINC

Structural MINC

A single MINC file contains all the information about a study

Shimadzu3

(DIAG)

Micro-CT Micro-PET

Page 11: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 11

ELEMENTS: Image display modes

• Multi-image

(„montage”)

• Fused

• 2 image sets

+ VOIs

x

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PET-MRI Tools - July 2007 J. Varga 12

ELEMENTS: 3D browser modes

• From single file

• From fused files

Page 13: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 13

ELEMENTS for processing MRI

Automatic brain extraction,

Segmentation (3 methods),

Tissue labeling

Gray segment in PET geometry

Tissue labels

Page 14: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 14

Membership functions (0 P 1)

CSF gray white

AFCM

CUA

Page 15: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 15

Segments: slice #33

AFCM CUA 3D

More gray in the cerebellum

Original MRI

Both label sets fused

Page 16: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 16

Gray segment in

the PET geometry,

before and after

convolution with

PET PSF

Page 17: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 17

Comparison of MRI brain segmentation

methods for the PVC of coregistered PET

• Simulated MRI images

• Four combinations of added noise and inhomogeneities

• Three theoretically different segmentation methods:

– CUA: Gaussian components, ML

(Wang, Y., 1995)

– AFCM: „Adaptive Fuzzy C-means”

(Pham D. L., Prince J. L., 1999)

– SPM segmentation: template+affine transformation

(Ashburner J, Friston KJ, 1997)

• Comparison in PET geometry

Varga J., Pham D.L., Wang Y. & al.: Comparison of MRI brain segmentation methods for the

partial volume correction of coregistered PET. Eur. J. Nucl. Med. 29: S157, 2002.

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PET-MRI Tools - July 2007 J. Varga 18

Conclusions:

• Fuzzy segmentation should be preferred

• The local accuracy of the applied template-

based method was questionable, making it less

appropriate for PVC of the brain cortex.

• AFCM performs better at low noise, but is more

sensitive to noise than the CUA method

• Our method of comparing convolved rather than

high-resolution segments is more realistic when

the application of routine (suboptimal) MRI for

the PVC of emission tomograms is considered.

Page 19: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 19

Elements for processing PET Brain extraction,

3D volumes of interest

Time-activity curves

Graphical analysis

Page 20: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 20

„Graphical” analysis

Input data?

Arterial curve Reference area

Irreversible:

Patlak

Reversible:

Logan

Linear: Logan

Bilinear: Ichise

Non-linear: SRTM,

Lammertsma-Hume

Page 21: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 21

Elements: Coregistration and fusion

(baboon study shown)

PET-MRI fusion (AIR)

SERT distribution volume (Logan) parametric image fused with MRI

Page 22: PET-MRI Tools (V.0707)

Control

Suppressed

MDMA

Page 23: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 23

Elements: Volume operation tools,

including partial volume correction

Raw image

Corrected image (3 comp.)

([C-11] McN study of Parkinson-dis. patient)

Page 24: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 24

4D PET MINC

MRI MINC

Coregistration (minc_air) Volume drawing

(polygon <-> mask)

Curves

Quant.

Kinetic anal. Graphical anal. (Patlak, Logan, Ichise)

3D

4D

Param. image (Logan)

PVC (pvc3; pvc_r)

Summation (vol_sum)

Page 25: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 25

What is partial volume effect?

original

degraded

Hot objects of size

smaller than or close

to system resolution

seem to be less

active.

Page 26: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 26

PVE and spillover

• Partial volume effect: a hot object is smaller than the

resolution volume

it seems less active

• Spillover: warm environment increases the counts of

a small colder object

Page 27: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 27

Mathematical formulation

FOV

o rdrrPSFrIrI ),()()(

where: Io observed image

I (true) activity distribution

PSF point spread function

PSFIIo

Short notation (convolution):

Page 28: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 28

Voxel-by-voxel PVC method implemented

(3 compartments):

PET:

Summation (vol_sum)

MRI:

Brain extraction (bet)

Segmentation Coregistration (minc_air)

PVC3 (corr_spillover)

Spreading (PETconvolve)

Reslice segments (tissue_masks)

Page 29: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 29

Example: Partial volume correction of

serotonine transporter PET

Uncorrected

Corrected

(2 tissue compartments)

Page 30: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 30

General model (Rousset):

N

kD

k

N

kD

k

k

k

k

k

r)drPSF(r,TI(r)

r)dr)PSF(r,r(TI(r)

T

D

1

kk

1

:Dover constant is Teach if

: ionsconcentratactivity with true

, domains :components tissueN Supposing

(Rousset O.G. et al., J Nucl Med, 1998)

Page 31: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 31

Calculation for VOI-s

i k

i k

VOI Dpix

ik

N

k

kik

N

kVOI D

k

ipix

ii

drr)drPSF(r,n

wTw

drrdrrPSFTn

tVOI

1 with t

:separation

),(1

t

:in conc. observedmean with

regions, tonsobservatio gRestrictin

1

i

1;

i

geometric transfer matrix

Page 32: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 32

Conditions of the general model:

• Each domain is homogeneous

(true activity concentration is constant inside)

• The domains cover the volumes of interest (VOIs)

AND their neighborhood

Page 33: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 33

MIXED MODEL, Stage 1: Automatic segmentation combined with

manual VOIs

• Automatic segmentation

G (gray), W (white) and CSF

(together they cover the whole brain)

• Manual VOIs on transversal, coronal and/or sagittal

slice sets

• Using the rest of the tissue compartments (outside all

manual VOIs) as additional domains for the

calculations

Page 34: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 34

Stage 1: Steps of the calculations

• Calculating the representations of the coronal and sagittal VOIs

in the transversal slices

• Subtracting the union of the manual VOIs from the tissue

segments

G0, W0, CSF0 (rest of the segments)

• Application of the general model to the manual VOIs

AND G0, W0, CSF0

(together they cover the whole brain)

Page 35: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 35

Stage 2: Template-based VOIs

• Two associated templates are necessary:

– An „atlas”: set of VOI templates

– An MRI slice set that the „atlas” refers to

• E.g.: ICBM template

Page 36: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 36

Stage 2: Steps of the procedure

• Registration (calculation of the spatial transformation) of the MRI

template to the patient’s MRI

E.g.: AIR5, warping with 5th order polynomials

• Application of the transformation to the VOI templates (so that they

fit to the patient’s MRI)

• Coregistration of the patient’s MRI to PET

AIR, linear

• Transformation of the VOIs to the PET geometry

• Application of the template-based OR mixed PVC model.

Page 37: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 37

Patient’s

MRI MRI template

MRIICBM registration: 1. step: affine (12 pm.)

2. step: 5th order nonlin. (168 pm.)

Patient’s

4D PET Labels

Labels / VOIs in

PET geometry

Automatic processing of brain PET studies:

Summed

(3D) PET

Rigid

coregistration

ICBM

Combined PETICBM

transform

Extracted

brain

Parametric

images

Regional

parameters

Time-act.

curves

PV-corrected

4D PET

PV-corrected

param. images

PV-corrected

curves

Page 38: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 38

Patient’s

MRI MRI template

Registration:

1. step: affine (12 pm.)

2. step: 5th order nonlin. (168 pm.)

Patient’s

4D PET Labels

PET / param. images

in ICBM geometry SPM

3D comparison of brain PET studies:

Summed

(3D) PET

Rigid

coregistration

ICBM

Combined PETICBM

transform

Extracted

brain

Parametric

images

Page 39: PET-MRI Tools (V.0707)

PET-MRI Tools - July 2007 J. Varga 39

Patient’s

SPECT

SPECT

template

Coregistration: 1. step: scaled rigid (7 pm.)

2. step: affine (12 pm.)

Patient’s

dynamic planar

Hemispherical CBF (from Patlak plot)

Normalisation

Labels

Brain in standard

geometry Averaging (whole brain)

SPM

3D comparison of brain SPECT studies: