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SAKESpectral Analysis for Kinetic Estimation

User manual

Informations about the document

File name user_manual.2.0.2.pdf

Version 2.0.2Creation date 11/03/2012

Last change date 22/11/2012Document state Formal

Usage ExternalAuthor Andrea Scaboro

Approved by Riccardo TesselliChecked by Stefano TomboliniSupervisors Prof. Tullio Vardanega,

Prof. Riccardo CardinProject Managers Gaia Rizzo,

Mattia Veronese


Contents

1 Introduction 1

1.1 Goal of the document . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2 Contacts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3 Content of the package . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.4 System Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2 Product 1

2.1 Description of the product . . . . . . . . . . . . . . . . . . . . . . . . . . 12.2 Typical user . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.3 Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.4 License . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

3 User's guide 3

3.1 Install . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33.1.1 Install on Windows . . . . . . . . . . . . . . . . . . . . . . . . . . 33.1.2 Install on Linux and Mac . . . . . . . . . . . . . . . . . . . . . . 5

3.2 Home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63.3 Menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63.4 Echo Window . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73.5 Wizard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83.6 Help . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93.7 Preprocessing Choice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103.8 Preprocessing Arterial . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

3.8.1 Preprocessing Arterial Function . . . . . . . . . . . . . . . . . . . 123.8.2 Model Arterial . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123.8.3 Delay Correction . . . . . . . . . . . . . . . . . . . . . . . . . . . 133.8.4 Decay Correction Arterial . . . . . . . . . . . . . . . . . . . . . . 133.8.5 Save File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

3.9 Preprocessing Region . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143.9.1 Decay Correction ROI . . . . . . . . . . . . . . . . . . . . . . . . 153.9.2 Save File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

3.10 Preprocessing Image . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163.10.1 Preprocessing Image Function . . . . . . . . . . . . . . . . . . . . 173.10.2 Decay Correction Image . . . . . . . . . . . . . . . . . . . . . . . 183.10.3 Summed PET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183.10.4 Save File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

3.11 SA Quanti�cation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193.12 Apply SA Quanti�cation . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

3.12.1 Computational time . . . . . . . . . . . . . . . . . . . . . . . . . 233.13 Results Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

3.13.1 Results Analysis with data at region level . . . . . . . . . . . . . 243.13.2 Results Analysis with data at image level . . . . . . . . . . . . . 253.13.3 Export . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263.13.4 Info File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

3.14 Input and Output �le management . . . . . . . . . . . . . . . . . . . . . 273.14.1 Input Files . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273.14.2 Output Files . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

3.15 Graphs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

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3.15.1 Interaction between graphs . . . . . . . . . . . . . . . . . . . . . 293.15.2 Graphs Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . 293.15.3 Insert a Curve . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303.15.4 Legend . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303.15.5 Set Scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303.15.6 Zoom & Unzoom . . . . . . . . . . . . . . . . . . . . . . . . . . . 313.15.7 Point Info . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

3.16 Images . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323.17 Keyboard Shortcut . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

4 Frequently Asked Questions 34

5 Glossary 35

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List of Tables

1 Keyboard Shortcut . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

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List of Figures

1 Install - STEP 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Install - STEP 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Install - STEP 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Install - STEP 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Install - STEP 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Install - STEP 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Home window . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 SAKE Menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Echo Window . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 710 Wizard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 811 Help of the Program (F1) . . . . . . . . . . . . . . . . . . . . . . . . . . 912 Data selection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1013 Preprocessing at the arterial level . . . . . . . . . . . . . . . . . . . . . . 1114 Choice of the function to perform at arterial level. . . . . . . . . . . . . 1215 Model Arterial Input. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1216 Delay Correction Input. . . . . . . . . . . . . . . . . . . . . . . . . . . . 1317 Decay Correction Arterial Input. . . . . . . . . . . . . . . . . . . . . . . 1318 Save Arterial File. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1419 Preprocessing at region level . . . . . . . . . . . . . . . . . . . . . . . . . 1420 Decay Correction ROI Input. . . . . . . . . . . . . . . . . . . . . . . . . 1521 Save Exam File. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1622 Preprocessing at image level . . . . . . . . . . . . . . . . . . . . . . . . . 1623 Choice of the function to perform at image level. . . . . . . . . . . . . . 1724 Decay Correction Image Input. . . . . . . . . . . . . . . . . . . . . . . . 1825 Save Summed PET Output. . . . . . . . . . . . . . . . . . . . . . . . . . 1826 Save Image File. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1927 Selection of the type of SA Quanti�cation . . . . . . . . . . . . . . . . . 1928 SA variables insertion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2029 Select type of kinetic tracer . . . . . . . . . . . . . . . . . . . . . . . . . 2130 Insert Signal to Noise Ratio . . . . . . . . . . . . . . . . . . . . . . . . . 2131 Insert Passband . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2232 Insert pre�x name of the output �les . . . . . . . . . . . . . . . . . . . . 2233 Example of SA Quanti�cation execution and remaining time. . . . . . . 2234 Con�rm to stop the SA Quanti�cation. . . . . . . . . . . . . . . . . . . . 2235 End of the quanti�cation . . . . . . . . . . . . . . . . . . . . . . . . . . 2336 Results Analysis with data at region level . . . . . . . . . . . . . . . . . 2437 Results Analysis with data at image level . . . . . . . . . . . . . . . . . 2538 Export SAKE �le. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2639 Info SAKE �le. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2640 Graphs Description. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2941 Graphs Legend. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3042 Graphs Set Scale. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3043 Zoom Area. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3144 Point Info. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3145 Images Description. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

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1 Introduction

1.1 Goal of the document

The purpose of this document is to lead the user through the setup of the program andto show how to use it.

1.2 Contacts

Every problem regarding this application can be reported to: [email protected].

1.3 Content of the package

The package contains:documentation:

• a README.txt �le with the instruction for the setup.

• a LICENSE.txt �le with the license.

• a manual.pdf this manual.

program:

• installers for Windows, Ubuntu and Mac in three separate folders.

1.4 System Requirements

• Operating System:

� Windows 7/Vista/Microsoft Windows XP Service Pack 2+;

� MAC OS X Snow Leopard 10.6.6+;

� Linux (K)Ubuntu 10.04+.

• hardware: ~1 GB of disk usage, 512 MB RAM

• the resolution of the screen must greater than 1024x768 pixel.

2 Product

2.1 Description of the product

SAKE is a program created to process PET (Positron Emission Tomography) examsdata. The user will be able to visualize the data, to apply several functions and to viewthe results, all included in a unique pipeline.

2.2 Typical user

This tool has been built to be as much user friendly as possible in order to be fullyusable for people with a limited computer knowledge (e.g.: doctors, biologists, chemists,clinicians,...) but with high interest in Spectral Analysis (SA).

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2.3 Support

The software has been developed with the support of the Bioengineering group of theDepartment of Information Engineering (University of Padova) and the PET method-ology group of Hammersmith Hospital (Imperial College of London).

2.4 License

The product is an open-source software released under the Attribution-NonCommercial-ShareAlike 3.0 Unported license (CC BY-NC-SA 3.0). Further information can be foundhere: http://creativecommons.org/licenses/by-nc-sa/3.0/

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3 User's guide

In this section are described the main functionalities of the program.

3.1 Install

3.1.1 Install on Windows

STEP 1: Launch the �le �Sake.exe�.

STEP 2: Click Next to continue.

Figure 1: Install - STEP 2

STEP 3: Accept the terms of the agreement.


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STEP 4: Choose the folder in which you want to install Sake 1.0.


STEP 5: If Matlab Compiler Runtime is not already installed, the user has to installit. To setup, follow the program guide.


STEP 6: If Microsoft MSVC2010 is not already installed, the user has to install it. Tosetup, follow the program guide.


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STEP 7: End.


3.1.2 Install on Linux and Mac

The SAKE version for Linux and Mac will be released in December 2012. For moreinformation, please contact [email protected].

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3.2 Home

Figure 7: Home window

This is the home page. Here the user can choose among these options:

• Perform Preprocessing activities (box 1, Figure 7);

• Perform Spectral Analysis Quanti�cation (box 2, Figure 7);

• Results Analysis (box 3, Figure 7).

To choose, click in the corresponding area.

The Echo Window (box 4, Figure 7) will display the information regarding the functionsworking within the program. For further information about the Echo Window, pleaserefer to �Echo Window� (3.4).

3.3 Menu

Figure 8: SAKE Menu

Every window has the following menu:

File: Contains only the Exit option to quit the program.

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Action: Contains the options Undo and Redo to cancel and restore the changes appliedby the processing functions.

Visualize: Contains the options Echo Window and Lock Echo Window. The �rst oneallows the user to enable or disable the Echo Window. The second one insteadallows the user to lock o resize the Echo Window.

Help: Contains the options Context Help that displays the help, Wizard that displaysthe wizard, About and About Qt that show some information about the programitself and the framework used.

3.4 Echo Window

Figure 9: Echo Window

This is a window where the system will show the information messages. The messagesare divided in three di�erent types and colors (see box 1, Figure 9):

• Informative: green;

• Warning: orange;

• Error: red;

• Hints: black.

It is possible to drag the Echo Window to another part of the program or detach it,moving it out of the window. The user can do this easily using the Drag&Drop, clickingon the upper part of the Echo Window (see box 2, Figure 9) and dragging it.In the upper right part of the Echo Window she will �nd the buttons for �detaching�(see box 3, Figure 9) and �closing�(see box 4, Figure 9) the echo window.

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3.5 Wizard

Figure 10: Wizard

When running the program the �rst time, the user is presented the Wizard that willdescribe the main functionalities of the program. The actions the user is able to do are:

• Read the information (see box 1, Figure 10);

• Disable it at the next start of the program (see box 2, Figure 10);

• Move through wizard's pages (see box 3, Figure 10).

• Close the window (see box 4, Figure 10).

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3.6 Help

Figure 11: Help of the Program (F1)

The user can at any time press the F1 button or click on the help menu to view theHelp. It will help the user to �nd out what she needs.On the top (see box 1, Figure 11) the user can search one or more terms in the Helppages.

On the left part (see box 2, Figure 11) the user can see the list of contents in the Help.

On the right part (see box 3, Figure 11) the user can see the description of the contentselected.

The Help can be closed through the �Close� button, on the lower right (see box 4,Figure 11).

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3.7 Preprocessing Choice

Figure 12: Data selection.

This is the screen that is shown if the user chooses the pre-processing in the homewindow. The user has to choose the data she wants to analyze, among:

• Arterial Input Function data (box 1, Figure 12);

• PET at region level data (box 2, Figure 12);

• PET at voxel level data (box 3, Figure 12).

To proceed, click in the corresponding area.

It is possible to return to the SAKE Home page pressing the �Back � button, down onthe left (see box 4, Figure 12).

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3.8 Preprocessing Arterial

Figure 13: Preprocessing at the arterial level

In this window the user is able to apply the preprocessing of arterial data. The userhas to load the arterial �le clicking the �Load File� icon (see box 2, Figure 13). Thearterial data will be presented in various graphs (see box 1, Figure 13).

In the toolbar on the left the user is able to:

• Load File (box 2, Fig. 13): load a new arterial �le;

• Function (box 3, Fig. 13): choose a function to preprocess the �le;

• Save File (box 4, Fig. 13): save the current �le after having elaboration;

• Undo (box 5, Fig. 13): undo the last action;

• Redo (box 6, Fig. 13): revert the e�ects of the undo action;

• Home (box 7, Fig. 13): go back to the SAKE Home.

In the right part of the window the user:

• can add a new graph in the graph section (box 8, Fig. 13);

• has the list of curves that can be dragged in a graph (box 9, Fig. 13).

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3.8.1 Preprocessing Arterial Function

Figure 14: Choice of the function to perform at arterial level.

This is the window that will open when the user presses the �Function� icon. The usercan choose among:

• Model Arterial (box 1, Figure 14);

• Decay Correction Arterial (box 2, Figure 14);

• Delay Correction (box 3, Figure 14).


The user can go back to the pre processing window to presses �Cancel � (see box 4,Figure 14).

3.8.2 Model Arterial

Figure 15: Model Arterial Input.

The user can perform arterial modeling, �tting the arterial data to the sum of expo-nential functions (up to three exponential terms). Applying the �Model Arterial �, awindow will open where the user will be prompted to insert up to six input parameters(A1, A2, A3, B1, B2, B3) (see box 1, Figure 15). It is possible to apply a simpler model(e.g., modeling to the sum of two exponential functions), setting some of the parametersequal to zero. The user can choose SOLVE or FIT (see box 2, Figure 15), visualizing

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the model time curve solved with the parameters inserted or the model �t of the datarespectively. To con�rm press �Apply� (see box 3, Figure 15), to cancel press �Cancel �(see box 4, Figure 15).

3.8.3 Delay Correction

Figure 16: Delay Correction Input.

Applying the �Delay Correction�, a window will open where the value of the delayvariable must be inserted (see box 1, Figure 16). To con�rm press �Apply� (see box 2,Figure 16), to cancel press �Cancel � (see box 3, Figure 16).

3.8.4 Decay Correction Arterial

Figure 17: Decay Correction Arterial Input.

Applying the �Decay Correction Arterial �, a window will open where the type of correc-tion to be applied to the arterial data must be chosen, between �Isotope 18F �, �Isotope11C � and �Isotope 15O� (see box 1, Figure 17). To con�rm press �Apply� (see box 2,Figure 17), to cancel press �Cancel � (see box 3, Figure 17).

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3.8.5 Save File

Figure 18: Save Arterial File.

When the user saves the new arterial �le, a window will prompt him to select thedirectory in which save the output �le (see box 1, Figure 18). The user has to enterthe �lename to save the �le (see box 2, Figure 18). To con�rm press �Save� (see box 3,Figure 18), to cancel press �Cancel � (see box 4, Figure 18).

3.9 Preprocessing Region

Figure 19: Preprocessing at region level

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In this window the user is able to apply the preprocessing at region level. At �rst theuser has to load the �le with the PET regional data through the �Load File� icon (seebox 2, Figure 19). The window will then load the information in various graphs (seebox 1, Figure 19).In the toolbar on the left the user is able to:

• Load File (box 2, Fig. 19): load a new exam �le;

• DecayCorr (box 3, Fig. 19): apply the �Decay Correction ROI � processingfunction;

• Save File (box 4, Fig. 19): save the current �le after having elaboration;


• Redo (box 6, Fig. 19): reverts the e�ects of the undo action;



• can add a new graph in the graphs section (box 8, Fig. 19);


3.9.1 Decay Correction ROI

Figure 20: Decay Correction ROI Input.

At preprocessing region level, only one function can be applied, �Decay Correction

ROI �. Applying the �DecayCorr �, a window will open where the type of correction tobe applied to the PET data must be chosen, between �Isotope 18F �, �Isotope 11C � and�Isotope 15O� (see box 1, Figure 20). To con�rm press �Apply� (see box 2, Figure 20),to cancel press �Cancel � (see box 3, Figure 20)

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3.9.2 Save File

Figure 21: Save Exam File.

When the user saves the new region �le, a window will prompt to select the directoryin which save the output �le (see box 1, Figure 21). The user has to enter the �lenameto save the �le (see box 2, Figure 21). To con�rm press �Save� (see box 3, Figure 21),to cancel press �Cancel � (see box 4, Figure 21).

3.10 Preprocessing Image

Figure 22: Preprocessing at image level

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In this window the user is able to apply the preprocessing at voxel level. At �rst theuser has to load a valid image �le, through the �Load Image� icon (see box 3, Figure22). The window will then load the information in various images and graphs (see box1, Figure 22). In addition, it is possible to upload an exam �le which contains theinformation about the scanning schedule and an image mask pressing the �Load File�(see box 2, Figure 22) and �Load Mask � (see box 4, , Figure 22) icon. In both cases awindow will appear where the user can choose the �le to load. These �les are necessaryto perform a processing function. After that the user has uploaded the exam �le, theinformation contained within it will be presented in various graphs.

In the toolbar on the left the user is able to:

• Load File (box 2, Fig. 22): load a new exam �le;

• Load Image (box 3, Fig. 22): load a new image to preprocess;

• Load Mask (box 4, Fig. 22): load a new mask for the analysis;

• Function (box 5, Fig. 22): choose a function to preprocess the �le;

• Save File (box 6, Fig. 22): save the current �le after elaboration;


• Redo (box 8, Fig. 22): revert the e�ects of the undo action;




• has the list of curves that can be dragged in a graph (box 11, Fig. 22);

• can manage image con�guration (box 12, Fig. 22) (�Images� (3.16)).

3.10.1 Preprocessing Image Function

Figure 23: Choice of the function to perform at image level.

This is the window that will open when the user presses the �Function� icon. The usercan choose among:

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• Decay Correction Image (box 1, Figure 23);

• Summed PET (box 2, Figure 23).


The user can go back to the pre processing window pressing �Cancel � (see box 3, Figure23).

3.10.2 Decay Correction Image

Figure 24: Decay Correction Image Input.

Applying the �Decay Correction Image�, a window will open where the type of correctionto be applied to the PET data must be chosen, between �Isotope 18F �, �Isotope 11C �and �Isotope 15O� (see box 1, Figure 24). To con�rm press �Apply� (see box 2, Figure24), to cancel press �Cancel � (see box 3, Figure 24)

3.10.3 Summed PET

Figure 25: Save Summed PET Output.

When the user applies the �Summed PET �, a window will ask to enter the output�le name (see box 1, Figure 25), select the directory in which the user wants to savethe output �le (see box 2, Figure 25) and select the �le format between �.nii� or�.img/.hdr� (see box 3, Figure 25). To con�rm press �Save� (see box 4, Figure 25), tocancel press �Cancel � (see box 5, Figure 25).

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3.10.4 Save File

Figure 26: Save Image File.

When the user saves the new image �le, a window will ask to select the directory inwhich save the output �le (see box 1, Figure 26). The user has to enter the �lename tosave the �le (see box 2, Figure 26) and select the �le format between �.nii� or �.img/.hdr�(see box 3, Figure 26). To con�rm press �Save� (see box 3, Figure 26), to cancel press�Cancel � (see box 4, Figure 26).

3.11 SA Quanti�cation

Figure 27: Selection of the type of SA Quanti�cation

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In this window the user has to select the SA Quanti�cation type to apply. Both themethod (see box 1, Figure 27) and the kind of data (region or voxel level), (see box 2,Figure 27).The user can select these methods:

• Standard SA: Standard Spectral Analysis technique;

• SA Rank Shaping: Spectral Analysis optimized for tracer with Reversible Ki-

netic;

• SA With Iterative Filtering: Spectral Analysis optimized for tracer with Ir-

reversible Kinetic.

Two level of analysis can be employed:

• Region level: Region of interest (ROI) analysis;

• Voxel level: Voxel-wise analysis.

Once the user has chosen the method and level options, it is possible to continue to thenext step by pressing the �Next� button (see box 3, Figure 27).

The user can go back to the SAKE Home pressing the �Back � button (see box 4, Figure27).

3.12 Apply SA Quanti�cation

Figure 28: SA variables insertion

Figure 28 shows the window which is obtained selecting the Standard Spectral Analysis.

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In the �rst part (see box 1, Figure 28) the user has to select the �les for the SAQuanti�cation, which will be the same for all type of SA Quanti�cation selected butwill vary depending on the level of analysis chosen.The �les are:

• Arterial File: The �le containing the arterial data;

• Exam �le: The �le containing the PET data at region level.

• Image �le: Image �le with the PET data at image level (required for analysis atthe voxel level).

• Mask �le: The corresponding mask �le containing a binary mask of the cerebralvoxels (required for analysis at the voxel level).

To upload the corresponding �le the user has to press the �Load � button or �click to

load..�.

Every SA Quanti�cation method requests the same three variables (see box 2, Figure28):

• Number of Components: It is suggested a value greater than/equal to 20.

• Beta Min: Beta grid of components, Lower Limit.

• Beta Max: Beta grid of components, Upper Limit. It has to be greater than/equalto BetaMin*100.

In addition, a fourth variable will be requested according to the method chosen (seebox 3, Figure 28):

• Type: In case of Standard SA Quanti�cation. It is the type of the kinetic tracer.It is possible to choose among Reversible, Irreversible, Unknown.

Figure 29: Select type of kinetic tracer

• SNR: In case of Rank Shaping SA. It stands for �Signal to Noise Ratio�. Thetwo values has to be between BetaMin and BetaMax. The default values are:[Betamin*10, BetaMax].

Figure 30: Insert Signal to Noise Ratio

• passband: In case of SA with Iterative Filtering. It is the Filter passband. Thetwo values has to be between BetaMin and BetaMax. The default values are:[Betamin*10, BetaMax/2].

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Figure 31: Insert Passband

The user can go back to the SAKE Home pressing the �Cancel � button (see box 4,Figure 28).

Once that all the �les have been uploaded and the variables added, the user can continuepressing the �Apply� button (see box 5, Figure 28).A window will appear where the user will be able to select the directory in which savethe output �les. Then another window will appear, where the user will be prompted toselect the pre�x to be added to the �les to save (see box 1, Figure 32).

Figure 32: Insert pre�x name of the output �les

At both stages the user can go back to the screen where new �les and variables can beloaded, pressing �Cancel � (see box 2, Figure 32).The quanti�cation will start as soon as the user presses the �OK � button (see box 3,Figure 32). The �les will be saved automatically.

While quanti�cation is performed, a window indicating the progress status and remain-ing time appears (Figure 33).

Figure 33: Example of SA Quanti�cation execution and remaining time.

The user can stop the SA Quanti�cation by closing this window, in this case the pro-gram will be closed as well. It will be requested another con�rm, to continue the SAQuanti�cation press �Cancel � (see box 1, Figure 34), to stop and exit press �OK � (seebox 2, Figure 34).

Figure 34: Con�rm to stop the SA Quanti�cation.

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When the quanti�cation ends, a window will appear where is possible to choose between�Go To Results Analysis� (see box 1, Figure 35) or �Go To Home� (see box 2, Figure35).

Figure 35: End of the quanti�cation

3.12.1 Computational time

The di�erent type of Spectral Analysis approaches take a variable amount of time tobe completed. Here we report the average time on a PC with 4 Gb of RAM and a 3.17GHz processor.Spectral Analysis: It takes < 5 min for region-wise analysis and 15 min for a voxelbased analysis.

Rank-shaping Spectral Analysis: It is the most computational demanding method.It takes < 15 min for region-wise analysis and 2 hrs for a voxel based analysis.

Spectral Analysis with Iterative Filter: The computational time is comparablewith standard Spectral Analysis. It takes < 5 min for region-wise analysis and 20 minfor a voxel based analysis.

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3.13 Results Analysis

In this screen the user can view the results. The user has to load a proprietary format�le containing the quanti�cation results. The program can recognize automatically ifthe analyzed data are region or voxel data, and according to that it shows the resultsin the proper way.

3.13.1 Results Analysis with data at region level

When the user loads a proprietary format �le at region level, a window like the followingone will appear:

Figure 36: Results Analysis with data at region level

Only for the Results Analysis with data at region level there is the �Parameters� button(see box 5, Figure 36). When the user clicks on it, a table will appear with the estimatesobtained in the quanti�cation block for the ROIs.In the toolbar on the left the user can:

• Load File (box 1, Fig. 36): load a proprietary format �le;

• Export (box 2, Fig. 36): export the data in a standard �le format PDF �Export�

(3.13.3);

• Info File (box 3, Fig. 36): view the information of the loaded �le �Info File�

(3.13.4).





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3.13.2 Results Analysis with data at image level

When the user loads a proprietary format �le at image level, a window like the followingone will appear:

Figure 37: Results Analysis with data at image level

In the toolbar on the left the user can:

• Load File (box 1, Fig. 37): load a proprietary format �le;

• Load Source (box 2, Fig. 37): load the source image containing the raw PETdata to compare the values;

• Export (box 3, Fig. 37): export the data in a standard �le format PDF �Export�

(3.13.3);

• Info File (box 4, Fig. 37): view the information on the loaded �le �Info File�

(3.13.4).



• can choose the parametric map to be shown between MapVtQuant, MapKiQuant,MapVbQuant and MapOrderQuant (box 6, Fig. 37);

• can manage images con�gurations (box 7, Fig. 37) (�Images� (3.16)).

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3.13.3 Export

Figure 38: Export SAKE �le.

When the user chooses to export the data in a standard �le format PDF, a window willappear asking to select the directory in which the output �le must be saved (see box 1,Figure 38). The user has to enter the �lename to save the �le (see box 2, Figure 38).To con�rm, press �Save� (see box 3, Figure 38), to cancel the operation press �Cancel �(see box 4, Figure 38).A copy of what the user is viewing will be generated, including the information regardingthe analysis and the general data.

3.13.4 Info File

Figure 39: Info SAKE �le.

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Clicking �Info�, a window will appear with the list of �les used for the quanti�cation(see box 1, Figure 39), the method of spectral analysis applied (see box 2, Figure 39)and the values of variables used for quanti�cation (see box 3, Figure 39).Press �OK � (see box 4, Figure 39) to close the window.

3.14 Input and Output �le management

3.14.1 Input Files

Arterial Files Arterial �les must be .txt �les, constituted by three columns with tabseparator, i.e. arterial time, tracer concentration in plasma and in blood respectively.The �rst line can contain the columns labels.Each column must contain the same number of elements, and each element must bereal-valued. There are no constraints on the values that the arterial data can have.The arterial time course must be increasing and its unit can be either minutes or seconds.

Region Files PET region data �les must be .txt �les with tab separator. The �rstline can contain the columns labels. The input �le can contain from one to an unde�nednumber of regions. The �le must be structured as follow: 1st column: mid-scan time

values; 2nd column: vector containing the frame length values; 3rd Noise Standard

Deviation; from 4th to end: raw region PET data. Consequently the number of columnsmust be equal or greater than 4.Each column must contain the same number of elements, and each element must bereal-valued. There are no constraints on the values that the PET data can have.The region time course must be increasing and its unit can be either minutes or seconds.

Image Files The voxel-wise analysis requires three di�erent �les to be loaded, i.e. a.txt �le containing the information about the PET exam, a 4-dimensional �le containinga dynamic PET image for a single subject and the corresponding 3-dimensional binarymask image of the subject.The image �les can be in NifTi format (.nii) or Analyze format (.hdr/.img). The formatof the .txt �le of the PET exam is the same standard of the input �le for the regionlevel analysis. In particular, it can be used the same �le.There must be coherence between the concentration units of the exam and the image�les.

3.14.2 Output Files

Arterial Files Elaborated arterial data can be saved in .txt �les, using the sameformat as the input �les, i.e. three columns with tab separator.

Region Files Elaborated region PET data can be saved in .txt �les, using the sameformat as the input �les, i.e. at least four columns with tab separator.

Image Files Elaborated image PET data can be saved in the same format of thedata loaded by the user, maintaining its characteristics (i.e., origin and/or voxel size).When present, the summed PET will be saved in the same format of the 3-dimensionalmask image, maintaining its characteristics (i.e., origin and/or voxel size).

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Quanti�cation results The results are automatically saved after any type of quan-ti�cation. All variables estimated must be saved in a proprietary �le (.sake), that canbe upload in the results analysis block.A diary �le is also saved, containing all the information about the quanti�cation em-ployed (type of analysis, original data, etc.).In addition to the creation of these �les, the following �les are created:Region analysis: A �_�t.txt' �le with the estimated �t of the region data. The �lehas the same format of the input �le, containing in the �rst line the columns labelsloaded by the exam �le (e.g., �time�, �ROI1�, ... �ROIn�), in the �rst column the timevector and in the following columns the region �ts.A second �le �_par.txt� is created, with the estimated parameters. The �rst line con-tains the columns labels, as loaded by the exam �le, the �rst column contains the labelof the parameters saved, i.e. Weighted Residual Sum of Squares (WRSS), Residual Sumof Squares (RSS), Volume of Distribution (Vt), its precision as Coe�cient of Variation(CV), the Irreversible Uptake Rate constant (Ki) and its precision (CV Ki), the BloodVolume (Vb) and its precision (CV Vb), the Model Order (number of non-zero compo-nents estimated) and the Trapping (equal to 1 if present). For each column the valueof every variable is reported for all the regions. The value �-1� indicates that a variablewas not estimated (e.g., Ki is not estimated in a rank-shaping SA approach).Image analysis: The parametric maps of voxel �t (4-dimensional), Vt, Ki, Vb andModel Order (all 3-dimensional) are saved individually in NifTi or Analyze format (.niior .hdr/.img), according to the input mask �le format.For both level of analysis a Matlab �le for expert users is also stored, containing theelaborated results.In particular, for region-wise analysis, it contains the raw region PET data (�ROI�), thetime course (�time_PET�), the NSD, the �t matrix (with the same size of ROI), thematrix containing all the estimated parameters (�parameter�, with the same format asreported in the output �_par.txt� �le), and also the �Alfa� and �Beta� matrix, with theestimated spectra.Warning: Rank-shaping SA do not return information about Ki, CV Ki (set = 1), orthe estimated spectra (i.e., Alfa and Beta are both = −1).For voxel-wise analysis, it contains the raw voxel data, organized in a 2-dimensionalmatrix �TACs� (time x nr of voxels). In �indTAC� are reported the indices in the maskof the analyzed voxels. The time PET course and ��t� (containing all the voxel �t,it is a matrix with the same size of �TACs�) are stored as well. In �Alfa�, �Beta� and�parameter� the estimated spectra and parameters are reported, with the same formatas the region level analysis.When applying SA with Iterative Filter at the voxel level, a variable �setup� is storedwith the information about the quanti�cation analysis (the original PET time scan,plasma and blood (�Cp� and �Cb�) interpolated in a virtual grid (�tv�), the logarithmicgrid of beta used for the analysis, the transfer matrix �M� and the passband values.

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3.15 Graphs

Figure 40: Graphs Description.

Figure 40 shows an example of visualization of PET data at the ROI level.

3.15.1 Interaction between graphs

If two or more graphs are present, the user can move them into the designated areathrough Drag&Drop action, by clicking on the upper part of the graph (see box 1,Figure 40). Dragging it while pressing the button, once reached the desired position,the graph is moved just releasing the button. The user can switch two graphs positionsbetween them, or place a graph on the right or left side of another graph, by releasingthe button in the corresponding �Drop Here� areas (see box 6, Figure 40).

3.15.2 Graphs Activities

The main actions that an user can do are:

• Close (box 2, Fig. 40): Close the graph pressing the �Close graph� button.

• Legend (box 3, Fig. 40): View the curves legend.

• Set Scale (box 4, Fig. 40): Set the minimum and maximum value for the graph.

• Insert a Curve (box 5, Fig. 40): Drag a curve from the curve list onto thegraph.

• Zoom: Zooming the graph.

• Unzoom: Unzoom the graphic.

• Info: Visualize the information of a point.

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3.15.3 Insert a Curve

When the user insert a curve in the graph, it will be shown in the graph if it is notalready present in the window, otherwise the message �Curve already in graph.� willappear.

3.15.4 Legend

Figure 41: Graphs Legend.

When the user click on the �Legend � icon the list of curves in the corresponding graphwill be shown. Here the user can delete a curve pressing the red X or drag it in anothergraph.

3.15.5 Set Scale

Figure 42: Graphs Set Scale.

If the user want to see only a part of the graph, it is possible to outline the axis limitsby clicking the icon �Set Scale�. A window will open where to set the chosen values (seebox 2, Figure 42), to modify the visualization press �Con�rm� button (see box 3, Figure42), to cancel press �Close� button (see box 4, Figure 42). The user can otherwise letthe program to set the limits automatically, by choosing �auto� (see box 1, Figure 42).

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3.15.6 Zoom & Unzoom

Figure 43: Zoom Area.

The user zoom an area of the graph selecting it with the left button of the mouse. Togo back to the previous zoom level it is possible to press the right button inside thegraph.

3.15.7 Point Info

Figure 44: Point Info.

The user can view the value of a point, dragging the cursor over the point itself.

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3.16 Images

Figure 45: Images Description.

In the image visualization, the image is presented in the three planes, i.e. coronal (seebox 1, Figure 45), sagittal (see box 2, Figure 45) and axial (see box 3, Figure 45).When the user clicks on a point of the image, the graph on the right bottom will beupdated, showing the data time course in the selected point (see box 4, Figure 45).

It is possible to zoom or unzoom an image with the �Zoom In� (see box 5, Figure 45)and �Zoom Out� (see box 6, Figure 45) buttons or through the scroll wheel, when thecursor is over the image.

With the slider or spinbox (see box 7, Figure 45), it is possible to change the coordinatesof the image.

It is possible to improve the quality of data by choosing the �Smoothing� function (seebox 8, Figure 45).

The user will be able to choose the color scale through the list (see box 9, Figure 45).The possible scales are:

• Grey;

• Jet.

In addition, the user can choose the value range of the color scale (see box 10, Figure 45).

The user can choose the time frame of the 4D image visualized with the slider or spinbox(see box 11, Figure 45).

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3.17 Keyboard Shortcut

Action Keyboard Shortcut

Exit from the program CTRL+Q

Undo CTRL+Z

Redo CTRL+R

Enable/Disable Echo Window CTRL+O

Open Wizard CTRL+W

Open About window CTRL+A

Save processed �le CTRL+S

Open Context Help F1

Table 1: Keyboard Shortcut

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4 Frequently Asked Questions

The following are the F.A.Q. related to the Sake program.

• � Question: What is the content of the package downloaded from the linkgiven?

� Answer: The package contains the installer of the program, a readme.txtwith simple instructions to setup the program, the license.txt �le with thelicense and this manual.

• � Q: How can I re-activate the guided tour once that I have closed it?

� A: You can easily do it through the Help menu and click on the Wizard

option.

• � Q: Where can I download the latest version of the software?

� A: You can download it from: http://bio.dei.unipd.it/sake

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http://bio.dei.unipd.it/sake



5 Glossary

Drag&Drop: In computer graphical user interfaces, Drag&Drop is the action of se-lecting a virtual object by �grabbing� it and dragging it to a di�erent location or ontoanother virtual object.

PET: Positron Emission Tomography is a nuclear imaging technique which allows thein vivo estimation of important physiological parameters, such as blood �ow, glucosemetabolism and neuroreceptor binding. In PET, radioactive tracers which decay bypositron emission are injected into the patient/animal being studied. The subject isthen positioned into a scanner where special scintillator crystals are employed to detectthe photon emissions. The �nal outcome of these measurements is the distribution ofthe tracer over time in the area of interest (e.g. the brain).

Redo: The opposite of undo. The redo command reverses the undo or advances thebu�er to a more current state.

SA: Spectral Analysis.

Undo: Undo is a command in many computer programs. It erases the last change doneto the �le reverting it to an older state.

Wizard: A software wizard is a user interface type that presents a user a sequence ofdialog boxes that lead the user through a series of well-de�ned steps that show how touse the program.

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