1. Introduction
Shortening the time from onset to treatment is critical for improving the prognosis of acute ischemic strokes. In the era of reperfusion therapy for acute ischemic strokes, the capability of quick detection of cerebral infarct and a prompt referral from a busy emergency room to a neurology specialist for thrombolysis or thrombectomy is important [
1].
The computed tomography (CT) has been the first-line diagnostic modality for patients who are suspected to have an acute stroke [
2]. Among all strokes, approximately 87% are ischemic and the rest are hemorrhagic [
3]. On CT images, the presence of intracranial hemorrhage can be easily detected. However, detecting cerebral infarct due to ischemic stroke has not been easy. It is because lesion boundaries of ischemic strokes in CT images are not clearly defined [
4]. Both CT and magnetic resonance imaging (MRI) can be used for delineation of brain stroke lesions [
5,
6]. In the recent two decades, researchers have been devising automated cerebral infarct delineation methods to allow for operator-independence, reproducibility, and a considerable saving of detection time [
5,
7,
8]. Due to the relatively lower image contrast [
9], accurate delineation with CT poses more challenges than with MRI.
The traditional algorithms for automated infarct delineation were devised on the basis of a set of feature extraction rules defined by the algorithm developers after a careful and profound investigation on a set of clinical data [
6]. It is difficult to achieve perfection, because some features are hidden and hard to discern. This factor undermined the performance of traditional automated cerebral infarct delineation algorithms. In contrast to traditional automated methods, artificial intelligence methods based on deep neural networks can learn image features from the training data [
10]. They can potentially facilitate the cerebral infarct modeling and alleviate the limiting factor of traditional non-deep learning methods [
11]. In particular, the convolutional neural networks (CNN), a class of artificial neural network, use convolution kernels to extract specific image features. They have been successfully applied in different image classification problems [
12].
Motivated by the need for improving the prognosis and treatment of acute ischemic strokes, this research developed a CNN-based automated method to facilitate a facile and quick cerebral infarct detection on brain CT images. Image preprocessing, statistical analysis-based detection, and data augmentation were used to enhance the detection performance of the developed CNN.
3. Results
Shown in
Figure 3 are some intermediate images produced during the preprocessing steps. The images in the top row are, from left to right, an original control CT image, the result of the spatial normalization (Step C3), and the result of intensity transformation (Step C4). The images in the central row are, from left to right, the average CT map of all control CT (Step C10), the standard deviation CT map of all control CT (Step C10), and a patient CT image after normalization to our own CT template (Step P3). The images in the bottom row are, from left to right, the result of spatial smoothing by the kernel with a 5-mm FWHM (Step P6), the t-score map (Step P7), and the ischemic infarct area drawn by the clinician.
The result of training and testing the proposed CNN is shown in the confusion matrices in
Table 1. The performance of the CNN is evaluated in terms of the accuracy rate, defined as:
where TP, TN, FP, and FN stand for true positive, true negative, false positive, and false negative, respectively.
Table 1 indicates that the proposed CNN attained a good accuracy rate of 94.4% in the training set. The accuracy rate in the test set was 93.9%.
The output of cerebral infarct detection with the proposed CNN is exemplified in
Figure 4. The detected infarcted patches on a CT slice are marked by red squares on the t-score map of the CT slice in
Figure 4a, whereas, in
Figure 4b, they are marked by red squares on the intensity-transformed brain parenchyma image, i.e., the CT image after Step P5. Shown in
Figure 4c is the corresponding MRI slice on which the red area represents the detected infarct delineated by the experienced neurologist mentioned above (Chen YW) [
13] with a semi-automated method.
Using the coordinates of the detected infarcted patches on the t-score map, we can identify the corresponding brain areas on Brodmann areas or Eve Atlas. For example,
Figure 5a shows a detected infarcted patch on the t-score map. This detected infarct corresponded to an acute infarction in the right middle cerebral artery (MCA) territory delineated by the experienced neurologist.
Figure 5b shows that this detected infarcted patch covered a portion of area 48 (Retrosubicular area) of the Brodmann areas, which is a small part of the medial surface of the temporal lobe.
Figure 5c shows that it involved areas EA25 (INSULAR), EA47 (External_capsule_left), EA60 (PUTAMEN_left), and EA62 (GLOBUS_PALLIDUS_left) on the Eve Atlas. Note that the patient CT images were spatially normalized to MNI space in Step P3 and the Brodmann areas and EVE Atlas had also been normalized to the MNI space. A detected infarcted patch had the same coordinates on the patient’s CT image, the Brodmann areas, and the EVE Atlas. Hence, mapping a detected infarcted patch to the Brodmann areas or EVE Atlas was conducted simply by using the same coordinates and required no image processing.
The proposed method was implemented with MATLAB programming. The MATLAB program takes about 5 min per patient from reading the image files until finishing the infarct detection. The program ran under Microsoft Windows 10 in a desktop computer with an Intel Core i7 CPU and an 8-gigabyte RAM, without a GPU (graphics processing unit).
4. Discussion
The performance of the automated cerebral infarct delineation on MRI has been proved to render accurate results due to the high contrast of MRI [
8]. However, MRI is normally not readily available immediately following the stroke onset. On the contrary, CT is a more convenient modality that can be utilized short after the stroke onset. The result of this research shows that by incorporating the power of deep learning with CNN, the accuracy of the automated cerebral infarct detection on CT could attain an acceptable level (93.9% in the test set). Hence, the automated cerebral infarct detection on CT can potentially be good enough for a frontline detection of cerebral infarction, despite the lower contrast of CT images.
In this research, the patch size was selected after considering the accuracy rate, detection time, and even network training time. Training time was quite tolerable in this research, because our simple network did not require a long training time. The most important factor to consider would be the accuracy rate. Among the 32 × 32, 16 × 16, and 8 × 8 patch sizes, the 16 × 16 patch size led to 93.9% accuracy rate and the 8 × 8 patch size is on par with it, whereas the 32 × 32 patch size only led to an accuracy rate over 80%. The detection time affects the end user’s working efficiency and convenience and is, hence, also important. We first supposed that it would be the fastest with the 8 × 8 patch size. However, in fact, the fastest was with the 16 × 16 patch size, which was about 50% faster than with the 8 × 8 patch size. The reason was because the patch number extracted from a patient’s CT images with the 8 × 8 patch size was four times that with the 16 × 16 patch size. Thus, the 16 × 16 patch size was a better selection than the other two sizes.
With the proposed method, a large infarct shown as the red area in
Figure 4c was faithfully detected as a mosaic of 15 contiguous tesserae (patches) shown in
Figure 4a,b. The shapes of the true infarct in the individual tesserae were versatile, as can be seen in
Figure 4a. In the scope of some patches, the infarct took the whole patch area, whereas in some others patches, the infarct took a small area. The infarct shapes in different patches were different. This detection result has demonstrated the capability of the proposed CNN in detecting infarcts of various morphologies. This result has also confirmed that the 16 × 16 patch size was truly an adequate selection for the proposed CNN. Moreover, this result has also corroborated the sufficiency of the training data by data augmentation fulfilled with only the shifting operation, without using other operations, such as rotation, flipping, cropping, padding, or intensity transforms.
As stated in
Section 2.1.1, infarcted images of 16 recruited subjects and non-infarcted images of 38 recruited subjects were used for the training of the proposed CNN. One may question whether the number of subjects were too small and, hence, whether the proposed network could be insufficiently trained. In fact, the training and the infarct detection of the proposed CNN was patch-wise instead of slice-wise or subject-wise. After data augmentation on the original patches, there were totally 4176 patches for the training of the proposed CNN. Thus, the amount of the training dataset was sufficiently large, as has been evidenced by the high accuracy rate of our trained CNN.
The pixel intensity transformation carried out in Step C4, Step C7, and Step P4 changed the HU of every pixel. It was an important image preprocessing function. The performance of our method would not have been satisfactory without this effort. The approximate HUs of air and bone are −1000 and 1000, respectively. The pixels in the intracranial tissues have HUs near 0. For example, the HU of CSF = 0, white matter = 25, gray matter = 35, and blood = 60 [
14]. In Steps C4, C7, and P4, the distance between two consecutive HUs in the range −99 to 100 was enlarged by 11 times. Thus, the contrast of different tissues in the brain were enhanced. On the other hand, the HUs from −1000 to −100 and from 101 to 1000 only received a constant raise without a contrast enhancement. Another effort of the image preprocessing that contributed to the high accuracy rate was the elimination of the CSF, carried out in Step C8 and P5. CSF could have intensities close to those of the cerebral infarcts and might lead to false positive results. For instance, in the CT image shown in
Figure 6, the intensity in the CST was close to that in the infarct region. The CST would be falsely detected as infarcted if it was not eliminated.
There is a possible change with time in the boundary line of an infarcted region in the brain past stroke onset, so the radiological images taken at different times after stroke may have different detectable cerebral infarct boundaries. For example, the manifestation of an infarcted cerebral region on the DWI becomes brighter in the first several days after the onset, and it gradually turns darker in the following several days. In this retrospective research, there was a delay of 3.8 ± 1.5 (mean ± standard deviation) days between a recruited subject took CT and MRI scans. In this research, in order to use supervised learning to train the proposed CNN for detecting cerebral infarcts from CT images, the results of the semi-automated MRI infarct delineation by the experience neurologist mentioned above were taken as the correct output for the network training. Due to the time delay of taking an MRI scan after taking a CT scan, there was a discrepancy between the detected cerebral infarct boundary on the MRI and the real cerebral infarct boundary at the time of CT scan. This discrepancy became a source of error for network training and a limit to the accuracy rate of the proposed CNN.
Brain atrophy can happen with ageing in forms of general or focal shrinkage of brain structure [
16]. However, it is usually not easy to attain age matching of the control group and the patient group. As described in
Section 2.2 (Step P7), the t-score of each pixel of the patients was obtained by using the probability distribution of all the control CTs as the reference. Hence, the accuracy of the cerebral infarct detection might be affected by the ageing effect. In other words, the false detection (false positive or false negative) might be due to the unmatched ages between the patient group and the control group. Shown in
Figure 7 is an example of the result of cerebral infarct detection with our method on the CT of an elderly patient from the test set. In
Figure 7a, the red square on the right hemisphere encompassed a darker area that was actually the image of a sulcus formed due to ageing and filled with fluid. As shown in
Figure 7b, this sulcus location of the patient got high t-scores when its intensities were compared with the average intensities at the corresponding location of the control group, where there was no sulcus. This caused the patch to be falsely detected as an infarcted patch. To alleviate this problem, it is important to implement an age match between the control group and the patient group. Provided enough subjects can be recruited, a better strategy is to form several control groups of different age ranges and establish different average CT maps and standard deviation CT maps (in Step C10) for patients of different age groups.
Physicians have been applying grading systems as a basis for decision making after stroke onset. ASPECTS is a widely used means for evaluating early ischemic changes in acute strokes [
17]. The scoring is based on non-contrast CT scans. To compute the ASPECTS, 1 point is subtracted from 10 for any evidence of early ischemic change in any of the 10 defined regions. In fact, ASPECTS evaluation does not cover all the cerebral areas and sometimes the physicians may want to know the cerebral infarct location in terms of a more precise brain map.
Figure 5 exemplifies mapping the detected cerebral infarct patches to two popular brain maps with finer brain parcellation. The Brodmann’s map, as shown in
Figure 5b, is the most popular cortical map. In this map, the human cerebral cortex is divided into 52 areas on the basis of the observations of the cytoarchitecture. Each area is assigned a number [
18]. The JHU-MNI-ss atlas, also called the Eve atlas, as shown in
Figure 5c, from Johns Hopkins University, emphasizes the parcellation of the white matter, while also containing the grey matter. It is a single-subject female brain with an isotropic resolution of 1 mm
3 in the standard MNI coordinates [
19].
It was found that the infarct volume has a correlation with the National Institutes of Health Stroke Scale (NIHSS) [
20]. Hence, including NIHSS in the training data could possibly enhance the network training effectiveness and raise the detection accuracy. NIHSS is used to evaluate the level of neurological deficits due to acute cerebral infarction. It is scored by rating the patient’s ability in answering questions and performing activities. A trained observer requires less than 10 min to complete the rating of the 15-item neurologic examination of NIHSS. Considering the short rating time and the possibly higher detection accuracy, it seems worthwhile to conduct NIHSS rating and incorporate NIHSS in the network training.
A literature review has found few papers similar to this work that applied deep learning with CNN for cerebral infarct detection on brain CT. Tuladhar et al. [
21] developed a CNN-based infarct segmentation method and attained a Dice similarity coefficient (DSC) of 0.45%. The generalization of their model was strengthened by using independent multi-center datasets for training, test and validation, as well as using ground truth segmentations by multiple expert observers. Sales Barros et al. [
22] utilized a three-CNN approach for cerebral infarct segmentation and attained a 0.57 average DSC of voxel-wise accuracy and a 0.88 intraclass correlation coefficient (ICC) of infarct volume. The three CNNs were developed for the delineation of subtle, intermediate, and severe infarcts, respectively. Gautam et al. [
23] used CNN to classify brain CT into hemorrhagic stroke, ischemic stroke, or normal and attained a 92.22% classification accuracy.
The most valuable application of the automated CT cerebral infarct detection will be for the prompt detection of cerebral infarction using the CT taken in the emergency room. As the phrase “time is brain” emphasizes, the brain nerves quickly lose function when a stroke occurs. Incorporating the proposed CNN for the accurate real-time CT-based cerebral infarct detection can help save brain function in time and enhance the efficiency of stroke care.