draft 2

.gitignore

@@ -2,6 +2,8 @@
 notes
 main.pdf
 texmf
+.vscode
+feedback
 
 ## Core latex/pdflatex auxiliary files:
 *.aux

ANN/hhg.tex

@@ -0,0 +1,16 @@
+\section{Higher harmonic generation microscopy}
+Higher harmonic generation is a nonlinear scattering process resulting from femtosecond pulse lasers interacting with tissue.
+Photons from the incident laser beam combine into one photon via a virtual state, preserving the energy.
+In this study, two higher harmonic generation variants are used: second (SHG) and third harmonic generation (THG).
+THG happens at structural interfaces, making it useful to image \eg cells and their nuclei or axons.
+SHG is generated by non-centrosymmetric structures, such as collagen.
+Sometimes, photons combine into a photon with a slightly lower energy than the combination of incidence photons.
+This is autofluorescence.
+\Cref{fig:hhg-jablonski} shows a Jablonski diagram for THG, SHG and 2PEF.
+
+\begin{figure}[hb]
+    \centering
+    \includegraphics[width=\linewidth]{ANN/images/hhg-jablonski.png}
+    \caption[HHG Jablonski diagram]{Jablonski diagram for third (THG) and second harmonic generation (SHG), and two-photon excitation fluorescence (2PEF).}
+    \label{fig:hhg-jablonski}
+\end{figure}

frontbackmatter/appendix-sclicom.tex

@@ -0,0 +1,17 @@
+\section{Flow of images to splits}\label{app:folds-splits-viz}
+The splits are created as described in \cref{subsubsec:slicom-folds}.
+The process is visualized in \cref{fig:folds-splits-viz}.
+
+\begin{figure*}
+    \centering
+    \includegraphics[height=0.55\paperheight]{pediatric-brain-tumours/images/folds-splits-viz.pdf}
+    \caption[Flow of images to splits]{
+        The flow of images to splits.
+        Top row shows available cases.
+        Every block is one case.
+        Middle row shows available images and is linked to the cases.
+        Bottom row shows training, validation and test splits.
+        Colors show flow within one fold.
+    }
+    \label{fig:folds-splits-viz}
+\end{figure*}

frontbackmatter/appendix-skin.tex

@@ -1,9 +1,136 @@
+\section{Fits to stress-strain curves}
+PCA and logistic curve fits to the skin stress-strain curves are shown in \cref{fig:pca_fits, fig:logistic_fits}, respectively.
+
+\begin{figure*}
+    \ContinuedFloat
+    \centering
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_6.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_7.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_8.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_9.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_10.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_11.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_12.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_13.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_14.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_15.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_16.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_17.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_18.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_19.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_20.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_21.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_22.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_23.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_24.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_25.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_26.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_27.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_28.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_29.pdf}
+    \raggedleft Continued on next page.
+\end{figure*}
+
+\begin{figure*}
+    \centering
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_30.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_31.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_32.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_33.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_34.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_45.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_46.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_47.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_48.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_49.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_50.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_51.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_52.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_53.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_54.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_55.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_56.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_57.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_58.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_59.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_60.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/pca-fits/sample_61.pdf}
+    \caption[PCA fits]{
+        PCA fits for every truncated and interpolated strain-stress curve.
+        The interpolated measurements (blue) are estimated by the PCA curve (red) along with their $R^2$.
+        PCA is done on all available thigh data.
+        Note that the vertical axes are not equal.
+    }
+    \label{fig:pca_fits}
+\end{figure*}
+
+\begin{figure*}
+    \ContinuedFloat
+    \centering
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_6}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_7.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_8.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_9.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_10.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_11.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_12.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_13.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_14.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_15.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_16.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_17.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_18.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_19.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_20.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_21.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_22.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_23.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_24.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_25.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_26.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_27.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_28.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_29.pdf}
+    \raggedleft Continued on next page.
+\end{figure*}
+
+\begin{figure*}
+    \centering
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_30.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_31.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_32.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_33.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_34.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_45.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_46.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_47.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_48.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_49.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_50.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_51.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_52.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_53.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_54.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_55.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_56.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_57.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_58.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_59.pdf} \\
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_60.pdf}
+    \includegraphics[width=0.24\linewidth]{skinstression/images/logistic-fits/sample_61.pdf}
+    \caption[Logistic fits]{
+        Logistic fits (red) and their $R^2$ for every strain-stress curve (black).
+        Note that the vertical axes are not equal.
+    }
+    \label{fig:logistic_fits}
+\end{figure*}
+
 \section{Configuration spaces}\label{app:skin_conf_search_spaces}
-The configuration search space for \textsc{Skinstression} is summarized in \cref{tab:conf_skin}.
+The configuration search space for Skinstression is summarized in \cref{tab:conf_skin}.
 
 \begin{table}
     \centering
-    \caption[\textsc{Skinstression} configuration search space]{\textsc{Skinstression} configuration search space.}
+    \caption[Skinstression configuration search space]{Skinstression configuration search space.}
     \label{tab:conf_skin}
     \begin{tabular}{cccccc}
         \toprule                                                             \\
@@ -31,10 +158,10 @@ \section{Software diagrams}\label{app:skin_c4}
 \begin{figure*}
     \centering
     \includesvg[pretex=\small, width=\linewidth]{images/skinstression_system_context_diagram.svg}
-    \caption[\textsc{Skinstression} system context diagram]{
-        System context diagram of \textsc{Skinstression}.
+    \caption[Skinstression system context diagram]{
+        System context diagram of Skinstression.
         An experimentalist images collagen in skin tissue using an SHG microscope.
-        The microscope output serves as input to \textsc{Skinstression} which trains a convolutional neural network to find the strain-stress curve of the imaged tissue.
+        The microscope output serves as input to Skinstression which trains a convolutional neural network to find the strain-stress curve of the imaged tissue.
         The trained model can serve as a substitution to the SHG microscope, or provide new insights in why tissue has particular stretch properties.
     }
 \end{figure*}
@@ -43,9 +170,9 @@ \section{Software diagrams}\label{app:skin_c4}
 \begin{figure*}
     \centering
     \includesvg[pretex=\tiny, angle=90, width=0.9\textheight,height=\linewidth,keepaspectratio]{images/skinstression_container_diagram.svg}
-    \caption[\textsc{Skinstression} container diagram]{
-        Container diagram of \textsc{Skinstression}.
-        The bounding box shows internal communications of \textsc{Skinstression}.
+    \caption[Skinstression container diagram]{
+        Container diagram of Skinstression.
+        The bounding box shows internal communications of Skinstression.
         Images generated with the SHG microscope get stored and can be read by PyimageQualityRanking (PyIQ).
         PyIQ sorts the images by quality, such that they can be read in order by notebooks and the main application.
         The main application reads locally stored configurations using Hydra.

general_discussion_and_conclusion.tex

@@ -0,0 +1 @@
+TODO

general_introduction.tex

@@ -1,9 +1,31 @@
 \section{Deep learning for higher harmonic microscopy}
-Insert some text relating the two projects to each other and introduce the overall challenges.
+Visualizing living tissue and cells is of vital importance in life sciences and health care.
+Standard, non-invasive techniques such as magnetic resonance imaging, ultrasound imaging, and computed tomography fail to image structures at resolutions high enough to distinguish structures as individual cells or connective tissue.
+These structures are interesting for pathologists or skin stretch experts.
+Higher harmonic generation (HHG) microscopy can image cells and tissue at resolutions of \qty{0.2}{\micro\meter} per pixel (mpp) in seconds.
+These high resolution images %can be large (sometimes \num{3e8} 24-bit pixels) and
+can contain complex structures and features.
+
+Interesting features are collagen and elastin fibers oriented in all directions when determining stretch properties of skin tissue.
+Mechanically stretching the tissue to get stress-strain curves is time-expensive and could break the tissue.
+Tissue images may have all information needed to determine stretch properties such as Young's modulus or maximum stress.
+\Cref{ch:skinstression} studies the possibility of acquiring stress-strain curves from second harmonic generation (SHG) images alone.
+This may be a step forward to find out skin properties \emph{in vivo} with an endoscope to aid plastic surgery.
+
+Other interesting features are disease patterns in the study of pathology.
+Current clinical practice includes analysis of histopathological data.
+However, making this data takes a long time, mainly caused by tissue processing.
+HHG imaging can do this in seconds, allowing for intraoperative feedback.
+Feedback can \eg include amount of resected tumor tissue or tumor type.
+This would still require intraoperative image analysis, while time is scarce.
+\Cref{ch:sclicom} studies the possibility to classify two pediatric brain tumors, medulloblastoma or pilocytic astrocytoma, from HHG images and explaining which regions were important for the classifications.
+
+The experiments are preceded by an introduction on HHG imaging and deep learning concepts used by the two projects in \cref{ch:theory}.
+\Cref{ch:general_discussion_and_conclusion} discusses overarching challenges and gives recommendations for advancing AI for HHG imaging.
 
 \section{Reporting of clinical artificial intelligence}
-The prediction models described here may aid health care providers in estimating the probability of risk that an outcome is present.
-The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed guidelines to report on such diagnostic models \cite{Collins2015, Moons2015}.
+The prediction models described in this work may eventually aid health care providers in acquiring clinically relevant parameters or estimating the probability of risk that an outcome is present.
+The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed guidelines to report on such diagnostic models \cite{Collins2015, Moons2015, Heus2020}.
 Recent advances in artificial intelligence (AI) apply AI as black box predictive models in health care, often not sufficiently well reported.
 Transparent reporting on these black box models builds confidence in using and further developing the models.
 This is especially important in health care, where there is a need for automation while trust in AI is yet to be earned.
@@ -14,6 +36,3 @@ \section{Reporting of clinical artificial intelligence}
 A clinician should then be explained how the model came to its conclusion, along with its confidence.
 To account for these challenges, an extension for the TRIPOD statement, TRIPOD-AI is currently being developed \cite{Collins2021,Collins2020}.
 Reports on the diagnostic models developed in this study aim to adhere to TRIPOD-AI as well as possible\footnote{The reader is invited to use the TRIPOD-AI accompanying PROBAST-AI \cite{Wolff2019a, Wolff2019b, Collins2021} checklist to assess the risk of bias of the predictive models.}.
-
-\section{Structure}
-Quick explanation of thesis structure.