Tongue Tumor Detection in Hyperspectral Images Using Deep Learning Semantic Segmentation
Tongue Tumor Detection in Hyperspectral Images Using Deep Learning Semantic Segmentation
4, APRIL 2021
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TRAJANOVSKI et al.: TONGUE TUMOR DETECTION IN HYPERSPECTRAL IMAGES USING DEEP LEARNING SEMANTIC SEGMENTATION 1331
Previous studies have mostly focused on tumor classification and second for correctly segmenting the tumor tissue
tasks [10]–[13] in HSI images. Fei et al. [11] have evaluated the in some cases, although VIS channels remain the most
use of HSI (450–900 nm) on specimen from patients with head significant ones for the performance on average.
and neck cancer. They achieved an area under the ROC-curve r We have proposed a novel channel selection/reduction
(AUC) of 0.94 for tumor classification with a linear discriminant technique, rather than standard reduction techniques that
analysis on a data set of 16 patients in which 10 were verified to eliminate pure channel information (e.g., PCA), and we
have squamous cell carcinoma (SCCa). However, their testing have demonstrated that there is a selected set of number
was done on specimens from the same patient as the classifier of channels that leads to optimal performance; meaning
was trained on. Lu et al. [14] and Halicek et al. [12] acquired that with smaller number of channels part of the signal
multiple specimen from 50 head and neck cancer patients with is lost and higher number of channels brings extra noise,
26 having squamous cell carcinoma (SCCa) in the same visual both contributing to reduced performance.
spectral range 450-900 nm. They [12] did a classification task The remainder of the paper is organized as follows. Details
with deep convolutional neural networks on 25 × 25 patches of the clinical dataset are given in Section II. The proposed
with leaving-one-patient-out cross-validation and reported ac- methods and the obtained results are provided in Section III
curacy of 77% for the SCCa group. Animal study on mice [15] and Section IV, respectively. We conclude in Section V.
with induced tumors was conducted by Ma et al. [10], achieving
an accuracy of 91.36% with convolutional neural networks in
a leave-one-out cross-validation also for a classification task. A II. CLINICAL DATASET
similar animal study on prostate cancer and on head and neck The clinical data was collected at the Netherlands Cancer
cancer in mice were conducted in [16] and [17]. Ravì et al. [18] Institute (NKI) - Antoni van Leeuwenhoek Hospital in Amster-
use random forest-based approaches on hyperspectral images for dam, the Netherlands. Hyperspectral images of specimens from
brain tumor segmentation. Other machine learning techniques, 14 patients undergoing surgery for the removal of squamous cell
minimum spanning trees [19], support vector machines [13], carcinoma of the tongue were acquired. All ethical guidelines
[20], k-nearest neighbors algorithm [21], [22], naïve [22] Bayes, required for ex vivo human studies were followed.
gaussian mixture models [23] and well-performing deep learn- Directly after resection, the specimen was brought to the
ing architectures [24] (e.g., inception [25]), have also be used pathology department, where the resection margins were inked
for hyperspectral images, mostly for classification tasks. In order according to the routine clinical workflow. The pathologist
to simplify and reduce the large number of channels, standard localized the tumor by palpation and subsequently cut the spec-
techniques such as tensor decomposition [26] or principal com- imen through the middle of the tumor. First, a RGB image
ponent analysis (PCA) [27] are applied. In all mentioned studies was taken from the cut surface with a regular photo camera.
the focus lies entirely on spectral information in the visible range Immediately after and without touching the specimen, the cut
around 450–900 nm. surface of the specimen was imaged with two hyperspectral
All of the above research works: (i) have utilize only the cameras (Spectral Imaging Ltd., Oulu, Finland), one operating
visible part of the spectra; (ii) have focused mainly on animal in the visible wavelength range (VIS) and the other in the
cases; (iii) have mostly utilize PCA or other well-established near-infrared wavelength range (NIR). The instrumentation with
techniques for channels/dimensionality reduction; or (iv) have the hyperspectral cameras and the supporting equipment for data
mostly focused on classification task as a global malignancy as- acquisition are shown in Fig. 1. After HSI imaging, the specimen
sessment per patient. However, the need of real-time and precise was subjected to further routine pathological processing, and the
intraoperative feedback requires accurate segmentation between pathologist annotated different tissue types on the histopathol-
the tumor and non-tumor in human tissues. In this work, we have ogy slide. Additional details on the data acquisition can be found
examined several structural, spectral and semantic segmentation in [32].
deep learning models (such as U-Net [28] variants) taking Both HSI cameras are push broom line scan system. The VIS
patches of images with all or predefined channels selection, camera captures 384 wavelengths in the 400 nm-1000 nm range
but assessing the global performance on a per patient/specimen with 1312 samples per line, for 612 lines. The NIR camera
base. Compared to the previous work, we have used much captures 256 wavelengths in the 900 nm-1700 nm range with
broader spectra utilizing both the visible (VIS) and near-infrared 320 samples per line, for 191 lines.
(NIR) spectral ranges [29] that has been rarely employed [30], In order to label the HSI data, a histopathological slide is taken
[31], especially in the context of deep learning methods. The from the surface that has been scanned. The slide is digitized and
contributions of the paper are the following: delineated to mark the tumor (red), healthy muscle (green) and
r With the best semantic segmentation method, we have epithelium & non-tumor tissue (blue). This is the first step shown
achieved competitive performance of average dice coef- in Fig. 2(a). From the delineation a mask is created. During
ficient and area under the ROC-curve of 0.891 ± 0.053 histopathological processing the specimen was deformed and to
and 0.924 ± 0.036, respectively, in the leave-patients-out correct this, a non-rigid registration algorithm is used. Obvious
cross-validation with on a clinical data set of 14 patients. matching points in the histopathological and RGB images were
r We have demonstrated that the (often omitted) near- visually selected. Using these points, the mask is transformed to
infrared spectra are crucial: first for spotting/classifying; match the RGB picture. This is depicted in Fig. 2(a) in middle
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1332 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 68, NO. 4, APRIL 2021
III. METHODS
Having the annotation masks along with the hyper-cube al-
lows for supervised machine learning. With the annotated data
at hand, we consider two types of methods: 1) pixel-wise classi-
fication: spectral, structural, hybrid, 2) semantic segmentation;
and compare their performance. It is also important to stress that
we have a prediction for two classes: healthy1 and tumor tissues.
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TRAJANOVSKI et al.: TONGUE TUMOR DETECTION IN HYPERSPECTRAL IMAGES USING DEEP LEARNING SEMANTIC SEGMENTATION 1333
Fig. 2. (a) Annotation and registration of the hyperspectral data: tumor (red), healthy tongue muscle (green), and healthy epithelium or other
non-tumor tissue (blue). (b) Reflectance of the acquired data for VIS and NIR. (Blue curves, labeled as “unknown,” represent epithelium or other
non-tumor tissue and it has been used with term “non-tumor,” interchangeably.)
TABLE I
THE NUMBER OF PIXELS PER PATIENT IN THE SPECIM-VIS DATASET. PATIENT 30 WAS THE ONLY PATIENT WITHOUT NON-TUMOR TISSUE IN THE
ANNOTATION. THE TERM NON-TUMOR REFERS TO EPITHELIUM OR OTHER ORDINARY NON-TUMOR TISSUE
TABLE II
THE NUMBER OF PIXELS PER PATIENT FOR THE SPECIM-NIR DATASET
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Fig. 3. (a) Depth-wise convolutions outcome. (b) Behavior for the channel selection loss function.
only two units. The hidden layers in between had 320, 160 and is designed, using a 1 × 1 patch that covers all wavelengths to
80 units, and those layers were followed by batch normalization incorporate spectral features and a bigger patch with selected
to stabilize the training process. The neural network is visualized channels for the structural information. The network is visu-
in Fig. 4(a). Alternatively, instead of fully connected layers, alized in Fig. 4(c). A spectral patch is selected from the data
convolutional neural networks [36] (i.e. shareable weights and volume, and fed into four fully connected layers. The first of
translation-invariant filters) have been also explored, but these those layers has the same number of units as the amount of
resulted in slightly worse or comparable performance. The next wavelengths in the spectral sample. The following hidden layers
thing worth considering is expanding to the spatial context of have 256, 128 and 64 units respectively. Additionally, a structural
the data cube. However, taking more pixels in a combination patch is selected from the data using the channel ranking as
to having all channels is becoming computationally challenging discussed in the channel selection section. The patch is flattened
(e.g., significantly slower or memory demanding) and it also and followed by four hidden dense layers with 512, 256, 126
brings extra redundancy and possible conflicting context in some and 64 units. After concatenation of the spectral and structural
of the channels with the annotation. Some channel importance branches, four additional dense layers follow with 64, 32, 16 and
prioritization and filtering are in order as elaborated in the 2 output units. After every layer, batch normalization is applied
following sections. to stabilize the training process.
3) Structural Neural Network Architectures: By increas-
ing the patch size, morphological features in the HSI data can
be used to classify the tissue. With the most important channels B. Semantic Segmentation Based on U-Net Neural
known either reduced by the channels selection (as described Network Variants
earlier) or alternatively a principle component analysis (PCA), a Based on the hyper-cubes and corresponding annotations,
model that focuses on structure can be trained. Data with a high we create HSI input and annotation patches with wider spatial
resolution will benefit the most from this approach, as it will context. The reason of using patches, with a fixed size per
contain more structural information compared to low resolution experiment, is two-fold: (i) we have a limited data from 14
data. With 45 VIS channels selected and spatial patch of 21 × 21, patients and in this way, we create a train and validation cohort of
input data cubes are defined. The number of VIS channels used patches that can lead to reasonable results and (ii) in the semantic
have been selected empirically. We conducted experiments with segmentation, the spatial dimensions (length and width) of the
different number of channels, and found that (i) initially the HSI data cubes are different, thus some patching is needed in
performance improved when more channels were included; (ii) order to have a unique input data shape for any neural network.
the performance did not get any better when using more than Moreover, having convolutional layers at the initial layer still
45 VIS channels [37, Page 19, Figure 16]. This is followed by allows to examine the test performance on the full spatial size
flattening which results in 19,845 input units. The network is for different patients with one predict forward pass in the neural
similar to the spectral model, with fully connected hidden layers network without changing it at all. We use leave-patients-out
and it is shown in Fig. 4(b). The difference lies in the input cross validation, thus there are never patches from the same
shape and the first fully connected layer. Instead of matching patient in both train and validation sets.
the number of units of the flattened channel-filtered input, 1024 In our approach, we use 100 random patches of size 256 × 256
units are used. This is done to reduce the number of parameters for each patient with the central pixels being 50/50 tumor
in the model. As in the spectral neural networks, convolutional and healthy classes and appropriate channel selection of the
neural blocks are also tried, but these result in worse or similar most significant channels as explained in Section III-A1. This
performance over the fully connected layers. means that we do 7-fold cross-validation with 1200 patches
4) Hybrid Spectral & Structural Neural Network Archi- (12 patients) of size 256 × 256× #channels for training and
tectures: To utilize both spectral and structural contexts, we 200 patches (2 patients) for validation. (We have conducted
derive a dual-stream spectral and structural model. The model additional experiments having standard train/validation/hold out
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TRAJANOVSKI et al.: TONGUE TUMOR DETECTION IN HYPERSPECTRAL IMAGES USING DEEP LEARNING SEMANTIC SEGMENTATION 1335
Fig. 4. Benchmark neural networks, visualized using [34]. (a) Spectral neural network. (b) Structural neural network with channels filtering.
(c) Dual-stream spectral and structural neural network.
set data partition or having nested cross-validation – thus leaving Although, this loss could be promising, it also brings two addi-
less patients for reporting results, but the results are similar tional parameters that have to be tuned. With these input patches
to those with this partition scheme.) Each patch contains both and annotations (size 256 × 256 × 2 tumor/no tumor), we train
tumor and healthy tissue and in fact, covers most of the spatial a U-Net neural network [28] variant with batch normalization.
part of each HSI cube. It depends on the tissue, but in each The architecture is visualized in Fig. 5(a).
patch for training both healthy and tumor tissues are decently In order to separately examine the contribution of the VIS and
represented. To achieve better generalization, we apply standard NIR parts of the data cube, we derive dual-stream U-Net based
data-augmentation techniques such as rotation and flipping of neural network. As visualized in Fig. 5(b), there is a separate
the patches. As a loss function dice coefficient is used for for stream/branch of the VIS and NIR accepting the corresponding
training and validation that compares the overlap of the full-size parts of the data cube, followed by appropriate averaging or
prediction map with the annotation map. Additionally, we have maximization for the final prediction.
experimented with alternative losses like the focal loss, but 1) Details on the Training Process: We have experi-
comparable (or worse) and less stable results were obtained. mented with different batch size and, as expected, reasonable
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1336 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 68, NO. 4, APRIL 2021
Fig. 5. U-Net based neural network architectures for HSI data. The visualization is drawn using PlotNeuralNet software [34] (https://github.
com/HarisIqbal88/PlotNeuralNethttps://github.com/HarisIqbal88/PlotNeuralNet). (a) Singe-stream U-Net for stacked (VIS and NIR) patches. (b)
Dual-stream U-Net based with separate VIS and NIR streams.
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TRAJANOVSKI et al.: TONGUE TUMOR DETECTION IN HYPERSPECTRAL IMAGES USING DEEP LEARNING SEMANTIC SEGMENTATION 1337
TABLE III
RESULTS OF THE EXPERIMENTS WITH DIFFERENT DEEP NEURAL NETWORKS
selection band for a single patient and the conclusion on which NIR) are stacked in a cube, channel importance selection algorithm is applied and
the X most significant are selected; (ii) “HSI U-Net Stacked X + Y ch central”
channels are more important is made based on all patients thus means the central X VIS channels are selected (from 384 in total), the central
those having recognized as the most important in the majority Y NIR channels are selected (from 256) and then they are stacked together in a
of the patients being ranked higher as a cumulative contribution HSI cube; (iii) “HSI U-Net Stacked X + Y ch most important” means channel
importance is separately applied for VIS and NIR, such that the most important
across all patients. This is the only (i) fair and general approach, X VIS channels are selected, the most important Y NIR channels are selected
(ii) it is important if we bring additional data from a new patient and then they are stacked together in a HSI cube.
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Fig. 8. Validation performance represented per patient by the dice coefficient, AUC, accuracy, sensitivity and specificity. On the x-axis are the
patient ID. (The ID values are not of particular meaning or importance.)
Fig. 9. A VIS (1st column) and NIR (2nd column) HSI bands, the RGB representations (3rd column), ground truth (4th column; green is for healthy,
red is for tumor tissue) and hard predictions of our method (5th column; predicted pixels are green for values smaller than 0.5, or red for values at
least 0.5) for 4 patients. (For the two HSI slices (first two columns), standard viridis color map has been used, see e.g., [40].)
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TRAJANOVSKI et al.: TONGUE TUMOR DETECTION IN HYPERSPECTRAL IMAGES USING DEEP LEARNING SEMANTIC SEGMENTATION 1339
Fig. 10. An exceptional case. Ground truth (green for healthy, red for tumor) and hard predictions (threshold 0.5) by VIS and NIR U-Net.
aspects has the best performance (in bold). It is important to In this figure, for this particular patient, we can see that by using
stress that by both using less and more than 128 channels NIR channels, the algorithm captures the tumor tissue, while
the performance is degraded (Table III) as either some tumor this is not a case by using VIS channels only. Although there
information is ignored or some noisy channels dominate in the are such cases as in Fig. 10, which highlights the importance of
decision, respectively. It is also interesting to mention that the the NIR channels, in the majority of the cases VIS channels are
proposed HSI U-Net variant still works well, although starting those contributing the most in spotting the tumor tissue.
with less initial filters compared to the input channels, opposite
to standard U-Net for RGB images (where 3 channels are sig- V. CONCLUSION
nificantly less than the initial number of filters), thus realizing
Real-time tumor segmentation during surgery is an impor-
an immediate pooling/selection effect. With the best performing
tant and challenging task. On the other hand, recent hyper-
HSI U-Net, we achieve a mean dice coefficient and AUC vali-
spectral camera developments offer additional possibility for
dation scores of 0.891 ± 0.053 and 0.924 ± 0.036, respectively.
better quality and more insights that can lead to more accurate
In Fig. 8, the performance on a per-patient base is shown,
segmentation. Several techniques have been proposed in the
demonstrating the algorithm works well (with some reasonable
past, mostly based on standard machine learning and pixel-wise
variance) in all cases. In addition, it is interesting to mention
approaches. To the best of our knowledge, this is the first work
U-Net experiments with RGB patches show significantly worse
using deep learning U-Net [28] semantic segmentation for tumor
performance (around 0.8 for both dice and AUC) than those with
detection and trainable channels selection for both NIR and
multiple HSI channels, which suggests that the HSI channels
VIS HSI spectra. The proposed semantic segmentation shows
richness is important for improved precision. On the other hand,
superior performance over the other alternatives (average dice
Halicek et al. [41] conducted research focusing on this aspect
coefficient and area under the ROC-curve of 0.891 ± 0.053 and
and found HSI did not provide significant advantages over the
0.924 ± 0.036, respectively). We also demonstrate that channel
identification of tumor margins in ex-vivo tissue compared to
selection and filtering is beneficial over the full spectra for
RGB imagery. Therefore, we admit more in-depth research is
achieving better performance, that both VIS and NIR channels
needed in this direction. To better illustrate the accuracy of the
are important and very good performance can be achieved even
prediction compared to the ground truth labels, we depicted the
with a limited amount of data. Moreover, we have shown that
hard prediction map and the ground truth maps for 4 patients in
the often omitted near-infrared (NIR) spectra is crucial for
Fig. 9. It is also important to mention that although the network
detecting the tumor in some cases. The hyperspectral cameras
is trained on fixed patches, the reported test results are based on
have been demonstrated to be powerful tools in many fields;
the original HSI dimension (that is different for each HSI image)
and the technology, augmented with accurate algorithms, has a
directly using the obtained model, because the convolutional
huge potential in biomedical engineering and medicine and with
kernels of the initial layers can take arbitrary input size with a
promising results available could be a doctors’ supportive tool
single pass. We have done experiments with U-Net networks of
for real-time surgeries and an alternative to digital pathology.
different number of layers, different units per layer, different
dropout values or other regularizers, but the performance is
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