From 1bcc4be1f45e82822099029df64a3947d832e4ad Mon Sep 17 00:00:00 2001
From: Vesa Oikonen <vesoik@utu.fi>
Date: Sat, 18 Mar 2023 14:49:29 +0200
Subject: [PATCH] simulation on cavity contamination

---
 content/model_mtrap.html          |  67 ++-
 content/pic/mtrap_f05_bcon.svg    | 694 ++++++++++++++++++++++++++++++
 content/pic/mtrap_f05_cavbias.svg | 183 ++++++++
 content/pic/mtrap_f10_bcon.svg    | 694 ++++++++++++++++++++++++++++++
 content/pic/mtrap_f10_cavbias.svg | 183 ++++++++
 content/pic/mtrap_f20_bcon.svg    | 694 ++++++++++++++++++++++++++++++
 content/pic/mtrap_f20_cavbias.svg | 183 ++++++++
 7 files changed, 2696 insertions(+), 2 deletions(-)
 create mode 100644 content/pic/mtrap_f05_bcon.svg
 create mode 100644 content/pic/mtrap_f05_cavbias.svg
 create mode 100644 content/pic/mtrap_f10_bcon.svg
 create mode 100644 content/pic/mtrap_f10_cavbias.svg
 create mode 100644 content/pic/mtrap_f20_bcon.svg
 create mode 100644 content/pic/mtrap_f20_cavbias.svg

diff --git a/content/model_mtrap.html b/content/model_mtrap.html
index 9ececf4f..3595a256 100644
--- a/content/model_mtrap.html
+++ b/content/model_mtrap.html
@@ -1,7 +1,7 @@
 ---
 title: MPI with chemical microspheres
 author: Vesa Oikonen
-updated_at: 2023-03-16
+updated_at: 2023-03-18
 created_at: 2023-02-27
 tags:
   - Perfusion
@@ -500,8 +500,71 @@ images.
 
 
 
+<h3><a name="contamination">The effect of spillover on LV cavity</a></h3>
 
-<p>Script and data used to make these simulations are available in
+<p>In the present model and previous simulations the assumption is that true arterial blood curve
+can be extracted from a small ROI drawn in the middle of the LV cavity.
+In practise, the blood curve may be contaminated by myocardial muscle curve because of spillover
+and partial volume effects. 
+In this simulation, the cavity curves were simulated with &beta; values 100%, 95%, 90%, and 85%, 
+meaning contamination of 0%, 5%, 10%, and 15% from myocardium, respectively. 
+Since the level of tissue curve is dependent on perfusion, the simulation is
+performed with three different K<sub>1</sub> values, 0.5, 1.0, and 2.0.
+The simulated data were then fitted using <a href="./tpcclib/doc/fitmtrap.html">fitmtrap</a>
+according to <a href="#eq_9">Eq 9</a>. The model fitted the simulated curves perfectly (not shown).
+The simulated cavity curves and myocardial curve, and the bias induced to the estimated model
+parameters, are shown in <a href="#fig_10">Fig 10</a>.
+The simulations suggest that tissue-contaminated blood curve leads to overestimation of all model
+parameters. The bias in both K<sub>1</sub> and V<sub>B</sub> is similar to the contamination-% of 
+the cavity curve. While the higher perfusion leads to higher overestimation of cavity curve,
+this does not influence the bias in estimated K<sub>1</sub> values, which seems to be overestimated
+by about the same percentage in all perfusion levels. 
+Most of the bias seems to be absorbed by the parameter k<sub>2</sub>.</p>
+
+
+<p><a name="fig_10"></a></p>
+<figure style="border: 1px solid #000; width: 98%;">
+
+<a href="./pic/mtrap_f05_bcon.svg"><img src="./pic/mtrap_f05_bcon.svg" 
+style="margin: 1em; width: 45%;" 
+alt="Effect of spillover and partial volume effect on LV cavity curve when K1=0.5"></a>
+<a href="./pic/mtrap_f05_cavbias.svg"><img src="./pic/mtrap_f05_cavbias.svg" 
+style="margin: 1em; width: 45%;" 
+alt="Effect on estimated model parameters when K1=0.5"></a>
+
+<a href="./pic/mtrap_f10_bcon.svg"><img src="./pic/mtrap_f10_bcon.svg" 
+style="margin: 1em; width: 45%;" 
+alt="Effect of spillover and partial volume effect on LV cavity curve when K1=1.0"></a>
+<a href="./pic/mtrap_f10_cavbias.svg"><img src="./pic/mtrap_f10_cavbias.svg" 
+style="margin: 1em; width: 45%;" 
+alt="Effect on estimated model parameters when K1=1.0"></a>
+
+<a href="./pic/mtrap_f20_bcon.svg"><img src="./pic/mtrap_f20_bcon.svg" 
+style="margin: 1em; width: 45%;" 
+alt="Effect of spillover and partial volume effect on LV cavity curve when K1=2.0"></a>
+<a href="./pic/mtrap_f20_cavbias.svg"><img src="./pic/mtrap_f20_cavbias.svg" 
+style="margin: 1em; width: 45%;" 
+alt="Effect on estimated model parameters when K1=2.0"></a>
+
+<figcaption style="margin: 1em;"><b>Figure 10.</b> 
+The effect of spillover and partial volume effects on the blood curves extracted from the LV cavity
+(left side), and the induced bias on estimated model parameter (right side), with three different
+perfusion levels (K<sub>1</sub> 0.5, 1.0, and 2.0). 
+In this simulation the V<sub>B</sub> in myocardial regions is 0.25 and k<sub>2</sub>=0.24.
+The biases in K<sub>1</sub> and V<sub>B</sub> estimates are similar, causing the curves to overlap.
+</figcaption>
+</figure>
+
+<p>Overall, the results of this simulation suggest that the possible contamination of LV cavity
+curve by myocardial muscle causes overestimation of K<sub>1</sub>, the bias remains at acceptable
+level. On the other hand, the nuisance parameter k<sub>2</sub> is severely biased, suggesting that
+k<sub>2</sub> should not be constrained if contamination of LV cavity curve is suspected.</p>
+
+
+
+
+
+<p><br><br>Script and data used to make these simulations are available in
 <a href="https://gitlab.utu.fi/vesoik/simulations/">https://gitlab.utu.fi/vesoik/simulations/</a>.
 </p>
 
diff --git a/content/pic/mtrap_f05_bcon.svg b/content/pic/mtrap_f05_bcon.svg
new file mode 100644
index 00000000..5d987903
--- /dev/null
+++ b/content/pic/mtrap_f05_bcon.svg
@@ -0,0 +1,694 @@
+<?xml version="1.0" encoding="utf-8"?>
+<svg version="1.1" baseProfile="full"
+     xmlns="http://www.w3.org/2000/svg"
+     xmlns:xlink="http://www.w3.org/1999/xlink"
+     xmlns:ev="http://www.w3.org/2001/xml-events"
+    viewBox="0 0 10000 10000"
+    preserveAspectRatio="xMinYMin meet">
+  <title>mtrap_f05_bcon.svg</title>
+  <defs>
+    <symbol id="sym-rect" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points="13 13, 13 107, 107 107, 107 13" />
+    </symbol>
+    <symbol id="sym-circ" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <circle cx="60" cy="60" r="46" />
+    </symbol>
+    <symbol id="sym-uptr" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points=" 14 14, 106 14, 60 106 " />
+    </symbol>
+    <symbol id="sym-dotr" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points=" 14 106, 106 106, 60 14 " />
+    </symbol>
+    <symbol id="sym-letr" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points=" 106 14, 106 106, 14 60 " />
+    </symbol>
+    <symbol id="sym-ritr" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points=" 14 14, 14 106, 106 60 " />
+    </symbol>
+    <symbol id="sym-diam" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points=" 60 14, 106 60, 60 106, 14 60 " />
+    </symbol>
+  </defs>
+
+  <title>K1=0.5</title>
+
+  <!-- Main title viewport -->
+  <svg x="0px" y="0px" width="10000px" height="833"
+      viewBox="0 0 10000 833"
+      preserveAspectRatio="xMidYMid meet">
+    <text x="5000" y="624.75"
+        font-family="Sans-serif" text-anchor="middle" font-size="416" fill="black">
+      K1=0.5
+    </text>
+    <text x="5000" y="833"
+        font-family="Sans-serif" text-anchor="middle" font-size="277" fill="black">
+      
+    </text>
+  </svg>
+
+  <!-- Y axis title viewport -->
+  <svg x="0px" y="833px" width="555px" height="8612"
+      viewBox="0 0 555 8612"
+      preserveAspectRatio="xMidYMid meet">
+    <text x="416.25" y="4306"
+        font-family="Sans-serif" text-anchor="middle" font-size="388" fill="black" transform="rotate(270,416.25,4306)">
+      g/mL
+    </text>
+  </svg>
+
+  <!-- X axis title viewport -->
+  <svg x="0px" y="9445px" width="10000px" height="555"
+      viewBox="0 0 10000 555"
+      preserveAspectRatio="xMidYMid meet">
+    <text x="5000" y="416.25"
+        font-family="Sans-serif" text-anchor="middle" font-size="388" fill="black">
+      Time (min)
+    </text>
+  </svg>
+
+  <!-- Plot area viewport -->
+  <svg x="555px" y="833px" width="6945px" height="8612"
+      viewBox="0 0 6945 8612"
+      preserveAspectRatio="xMidYMid meet">
+
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+    <polyline fill="none" stroke="black" stroke-width="20"
+      points="10,10 10,8171 6439,8171 6439,10 10,10" />
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+    <!-- plot_0 : Myoc -->
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+      <title>Myoc</title>
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+    <!-- plot_1 : Blood 100 -->
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+    </g>
+
+    <!-- plot_2 : Blood 95 -->
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+    </g>
+
+    <!-- plot_3 : Blood 90 -->
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+      <title>Blood 90</title>
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+    </g>
+
+    <!-- plot_4 : Blood 85 -->
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+      <text x="456.32" y="4606.27">15</text>
+      <text x="456.32" y="3378.96">20</text>
+      <text x="456.32" y="2151.65">25</text>
+      <text x="456.32" y="924.343">30</text>
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+  <svg x="7500px" y="833px" width="2500px" height="8612"
+      viewBox="0 0 2500 8612"
+      preserveAspectRatio="xMidYMid meet">
+    <g font-family="Sans-serif" text-anchor="Start" font-size="266" fill="black">
+      <text x="500" y="399">Myoc</text>
+      <text x="500" y="753">Blood 100</text>
+      <text x="500" y="1107">Blood 95</text>
+      <text x="500" y="1461">Blood 90</text>
+      <text x="500" y="1815">Blood 85</text>
+    </g>
+    <g stroke="black" fill="black" fill-opacity="0.92" stroke-width="25">
+      <line x1="62.5" y1="332.5" x2="437.5" y2="332.5" />
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+    <g stroke="red" fill="red" fill-opacity="0.92" stroke-width="25">
+      <line x1="62.5" y1="686.5" x2="437.5" y2="686.5" />
+    </g>
+    <g stroke="blue" fill="blue" fill-opacity="0.92" stroke-width="25">
+      <line x1="62.5" y1="1040.5" x2="437.5" y2="1040.5" />
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+    <g stroke="green" fill="green" fill-opacity="0.92" stroke-width="25">
+      <line x1="62.5" y1="1394.5" x2="437.5" y2="1394.5" />
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+    <g stroke="purple" fill="purple" fill-opacity="0.92" stroke-width="25">
+      <line x1="62.5" y1="1748.5" x2="437.5" y2="1748.5" />
+    </g>
+  </svg>
+</svg>
diff --git a/content/pic/mtrap_f05_cavbias.svg b/content/pic/mtrap_f05_cavbias.svg
new file mode 100644
index 00000000..acd1258e
--- /dev/null
+++ b/content/pic/mtrap_f05_cavbias.svg
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+      <polygon points=" 60 14, 106 60, 60 106, 14 60 " />
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+  <title>K1=0.5</title>
+
+  <!-- Main title viewport -->
+  <svg x="0px" y="0px" width="10000px" height="833"
+      viewBox="0 0 10000 833"
+      preserveAspectRatio="xMidYMid meet">
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+    <text x="5000" y="833"
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+  <!-- Y axis title viewport -->
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+      preserveAspectRatio="xMidYMid meet">
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+  <!-- X axis title viewport -->
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+      preserveAspectRatio="xMidYMid meet">
+    <text x="5000" y="416.25"
+        font-family="Sans-serif" text-anchor="middle" font-size="388" fill="black">
+      Contamination of BTAC (%)
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+  <!-- Plot area viewport -->
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+      <use xlink:href="#sym-rect" x="6271" y="4392.75" width="100" height="100" />
+    </g>
+
+    <!-- plot_1 : K1 -->
+    <g stroke="blue" stroke-width="25" fill="blue" fill-opacity="0.92">
+      <title>K1</title>
+      <path fill="none" d="
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+      <use xlink:href="#sym-circ" x="-60" y="8086.87" width="120" height="120" />
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+      <use xlink:href="#sym-circ" x="6261" y="4345.15" width="120" height="120" />
+    </g>
+
+    <!-- plot_2 : k2 -->
+    <g stroke="green" stroke-width="25" fill="green" fill-opacity="0.92">
+      <title>k2</title>
+      <path fill="none" d="
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+      <use xlink:href="#sym-uptr" x="-70" y="8052.17" width="140" height="140" />
+      <use xlink:href="#sym-uptr" x="2037" y="5727.28" width="140" height="140" />
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+      <use xlink:href="#sym-uptr" x="6251" y="257" width="140" height="140" />
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+  </svg>
+
+
+    <!-- X axis ticks inside plot area -->
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+  <!-- Legends viewport -->
+  <svg x="7500px" y="833px" width="2500px" height="8612"
+      viewBox="0 0 2500 8612"
+      preserveAspectRatio="xMidYMid meet">
+    <g font-family="Sans-serif" text-anchor="Start" font-size="344" fill="black">
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+      <text x="500" y="974">K1</text>
+      <text x="500" y="1432">k2</text>
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+    <g stroke="red" fill="red" fill-opacity="0.92" stroke-width="25">
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+    <g stroke="blue" fill="blue" fill-opacity="0.92" stroke-width="25">
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+    <g stroke="green" fill="green" fill-opacity="0.92" stroke-width="25">
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+  </svg>
+</svg>
diff --git a/content/pic/mtrap_f10_bcon.svg b/content/pic/mtrap_f10_bcon.svg
new file mode 100644
index 00000000..d19f8e79
--- /dev/null
+++ b/content/pic/mtrap_f10_bcon.svg
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+<?xml version="1.0" encoding="utf-8"?>
+<svg version="1.1" baseProfile="full"
+     xmlns="http://www.w3.org/2000/svg"
+     xmlns:xlink="http://www.w3.org/1999/xlink"
+     xmlns:ev="http://www.w3.org/2001/xml-events"
+    viewBox="0 0 10000 10000"
+    preserveAspectRatio="xMinYMin meet">
+  <title>mtrap_f10_bcon.svg</title>
+  <defs>
+    <symbol id="sym-rect" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points="13 13, 13 107, 107 107, 107 13" />
+    </symbol>
+    <symbol id="sym-circ" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <circle cx="60" cy="60" r="46" />
+    </symbol>
+    <symbol id="sym-uptr" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
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+    <symbol id="sym-dotr" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
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+    </symbol>
+    <symbol id="sym-letr" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points=" 106 14, 106 106, 14 60 " />
+    </symbol>
+    <symbol id="sym-ritr" viewBox="0 0 120 120" preserveAspectRatio="xMinYMin meet" >
+      <polygon points=" 14 14, 14 106, 106 60 " />
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+      <polygon points=" 60 14, 106 60, 60 106, 14 60 " />
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+  </defs>
+
+  <title>K1=1.0</title>
+
+  <!-- Main title viewport -->
+  <svg x="0px" y="0px" width="10000px" height="833"
+      viewBox="0 0 10000 833"
+      preserveAspectRatio="xMidYMid meet">
+    <text x="5000" y="624.75"
+        font-family="Sans-serif" text-anchor="middle" font-size="416" fill="black">
+      K1=1.0
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+    <text x="5000" y="833"
+        font-family="Sans-serif" text-anchor="middle" font-size="277" fill="black">
+      
+    </text>
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+
+  <!-- Y axis title viewport -->
+  <svg x="0px" y="833px" width="555px" height="8612"
+      viewBox="0 0 555 8612"
+      preserveAspectRatio="xMidYMid meet">
+    <text x="416.25" y="4306"
+        font-family="Sans-serif" text-anchor="middle" font-size="388" fill="black" transform="rotate(270,416.25,4306)">
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+  </svg>
+
+  <!-- X axis title viewport -->
+  <svg x="0px" y="9445px" width="10000px" height="555"
+      viewBox="0 0 10000 555"
+      preserveAspectRatio="xMidYMid meet">
+    <text x="5000" y="416.25"
+        font-family="Sans-serif" text-anchor="middle" font-size="388" fill="black">
+      Time (min)
+    </text>
+  </svg>
+
+  <!-- Plot area viewport -->
+  <svg x="555px" y="833px" width="6945px" height="8612"
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+  <!-- Coordinate area viewport -->
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+       6245 5538 6258 5538 6270 5538 6283 5538 6296 5538
+       6308 5538 6321 5538" />
+    </g>
+
+    <!-- plot_1 : Blood 100 -->
+    <g stroke="red" stroke-width="25" fill="red" fill-opacity="0.92">
+      <title>Blood 100</title>
+      <path fill="none" d="
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+       6308 7398 6321 7398" />
+    </g>
+
+    <!-- plot_2 : Blood 95 -->
+    <g stroke="blue" stroke-width="25" fill="blue" fill-opacity="0.92">
+      <title>Blood 95</title>
+      <path fill="none" d="
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+       6245 7274 6258 7274 6270 7274 6283 7274 6296 7274
+       6308 7274 6321 7274" />
+    </g>
+
+    <!-- plot_3 : Blood 90 -->
+    <g stroke="green" stroke-width="25" fill="green" fill-opacity="0.92">
+      <title>Blood 90</title>
+      <path fill="none" d="
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+       6245 7150 6258 7150 6270 7150 6283 7150 6296 7150
+       6308 7150 6321 7150" />
+    </g>
+
+    <!-- plot_4 : Blood 85 -->
+    <g stroke="purple" stroke-width="25" fill="purple" fill-opacity="0.92">
+      <title>Blood 85</title>
+      <path fill="none" d="
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+        font-family="Sans-serif" text-anchor="middle" font-size="388" fill="black" transform="rotate(270,416.25,4306)">
+      g/mL
+    </text>
+  </svg>
+
+  <!-- X axis title viewport -->
+  <svg x="0px" y="9445px" width="10000px" height="555"
+      viewBox="0 0 10000 555"
+      preserveAspectRatio="xMidYMid meet">
+    <text x="5000" y="416.25"
+        font-family="Sans-serif" text-anchor="middle" font-size="388" fill="black">
+      Time (min)
+    </text>
+  </svg>
+
+  <!-- Plot area viewport -->
+  <svg x="555px" y="833px" width="6945px" height="8612"
+      viewBox="0 0 6945 8612"
+      preserveAspectRatio="xMidYMid meet">
+
+  <!-- Coordinate area viewport -->
+  <svg x="496px" y="0px" width="6449px" height="8181"
+      viewBox="0 0 6449 8181"
+      preserveAspectRatio="xMidYMid meet">
+    <polyline fill="none" stroke="black" stroke-width="20"
+      points="10,10 10,8171 6439,8171 6439,10 10,10" />
+
+    <!-- plot_0 : Myoc -->
+    <g stroke="black" stroke-width="25" fill="black" fill-opacity="0.92">
+      <title>Myoc</title>
+      <path fill="none" d="
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+       6308 3090 6321 3090" />
+    </g>
+
+    <!-- plot_1 : Blood 100 -->
+    <g stroke="red" stroke-width="25" fill="red" fill-opacity="0.92">
+      <title>Blood 100</title>
+      <path fill="none" d="
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+       6308 7398 6321 7398" />
+    </g>
+
+    <!-- plot_2 : Blood 95 -->
+    <g stroke="blue" stroke-width="25" fill="blue" fill-opacity="0.92">
+      <title>Blood 95</title>
+      <path fill="none" d="
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+       6308 7110 6321 7110" />
+    </g>
+
+    <!-- plot_3 : Blood 90 -->
+    <g stroke="green" stroke-width="25" fill="green" fill-opacity="0.92">
+      <title>Blood 90</title>
+      <path fill="none" d="
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diff --git a/content/pic/mtrap_f20_cavbias.svg b/content/pic/mtrap_f20_cavbias.svg
new file mode 100644
index 00000000..87a66c57
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+    viewBox="0 0 10000 10000"
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+  <title>K1=2.0</title>
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+        font-family="Sans-serif" text-anchor="middle" font-size="388" fill="black" transform="rotate(270,416.25,4306)">
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-- 
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