Level set segmentation using non-negative matrix factorization with application to brain MRI

We address the problem of image segmentation using a new deformable model based on the level set method (LSM) and non-negative matrix factorization (NMF). We describe the use of NMF to reduce the dimension of large images from thousands of pixels to a handful of metapixels or regions. In addition, the exact number of regions is discovered using the nuclear norm of the NMF factors. The proposed NMF-LSM characterizes the histogram of the image, calculated over the image blocks, as nonnegative combinations of basic histograms computed using NMF (V ~ W H). The matrix W represents the histograms of the image regions, whereas the matrix H provides the spatial clustering of the regions. NMF-LSM takes into account the bias field present particularly in medical images. We define two local clustering criteria in terms of the NMF factors. The first criterion defines a local intensity clustering property based on the matrix W by computing the average intensity and standard deviation of every region. The second criterion defines a local spatial clustering using the matrix H. The local clustering is then summed over all regions to give a global criterion of image segmentation. In LSM, these criteria define an energy minimized w.r.t. LSFs and the bias field to achieve the segmentation. The proposed method is validated on synthetic binary and gray-scale images, and then applied to real brain MRI images. NMF-LSM provides a general approach for robust region discovery and segmentation in heterogeneous images

A Survey of Brain Tumour Segmentation Methods- A Review

Brain tumor segmentation aims to separate the different tumor tissues such as active cells, necrotic core, and edema from normal brain tissues of White Matter (WM), Gray Matter (GM), and Cerebrospinal Fluid (CSF). MRI based brain tumor segmentation studies are attracting more and more attention in recent years due to non-invasive imaging and good soft tissue contrast of Magnetic Resonance Imaging (MRI) images. With the development of almost two decades, the innovative approaches applying computer-aided techniques for segmenting brain tumo rare becoming more and more mature and coming closer to routine clinical applications. The purpose of this paper is to provide a comprehensive overview of MRI-based brain tumor segmentation methods

Cancer diagnosis using deep learning: A bibliographic review

In this paper, we first describe the basics of the field of cancer diagnosis, which includes steps of cancer diagnosis followed by the typical classification methods used by doctors, providing a historical idea of cancer classification techniques to the readers. These methods include Asymmetry, Border, Color and Diameter (ABCD) method, seven-point detection method, Menzies method, and pattern analysis. They are used regularly by doctors for cancer diagnosis, although they are not considered very efficient for obtaining better performance. Moreover, considering all types of audience, the basic evaluation criteria are also discussed. The criteria include the receiver operating characteristic curve (ROC curve), Area under the ROC curve (AUC), F1 score, accuracy, specificity, sensitivity, precision, dice-coefficient, average accuracy, and Jaccard index. Previously used methods are considered inefficient, asking for better and smarter methods for cancer diagnosis. Artificial intelligence and cancer diagnosis are gaining attention as a way to define better diagnostic tools. In particular, deep neural networks can be successfully used for intelligent image analysis. The basic framework of how this machine learning works on medical imaging is provided in this study, i.e., pre-processing, image segmentation and post-processing. The second part of this manuscript describes the different deep learning techniques, such as convolutional neural networks (CNNs), generative adversarial models (GANs), deep autoencoders (DANs), restricted Boltzmann’s machine (RBM), stacked autoencoders (SAE), convolutional autoencoders (CAE), recurrent neural networks (RNNs), long short-term memory (LTSM), multi-scale convolutional neural network (M-CNN), multi-instance learning convolutional neural network (MIL-CNN). For each technique, we provide Python codes, to allow interested readers to experiment with the cited algorithms on their own diagnostic problems. The third part of this manuscript compiles the successfully applied deep learning models for different types of cancers. Considering the length of the manuscript, we restrict ourselves to the discussion of breast cancer, lung cancer, brain cancer, and skin cancer. The purpose of this bibliographic review is to provide researchers opting to work in implementing deep learning and artificial neural networks for cancer diagnosis a knowledge from scratch of the state-of-the-art achievements

Deep Convolutional Neural Networks Model-based Brain Tumor Detection in Brain MRI Images

Diagnosing Brain Tumor with the aid of Magnetic Resonance Imaging (MRI) has gained enormous prominence over the years, primarily in the field of medical science. Detection and/or partitioning of brain tumors solely with the aid of MR imaging is achieved at the cost of immense time and effort and demands a lot of expertise from engaged personnel. This substantiates the necessity of fabricating an autonomous model brain tumor diagnosis. Our work involves implementing a deep convolutional neural network (DCNN) for diagnosing brain tumors from MR images. The dataset used in this paper consists of 253 brain MR images where 155 images are reported to have tumors. Our model can single out the MR images with tumors with an overall accuracy of 96%. The model outperformed the existing conventional methods for the diagnosis of brain tumor in the test dataset (Precision = 0.93, Sensitivity = 1.00, and F1-score = 0.97). Moreover, the proposed model's average precision-recall score is 0.93, Cohen's Kappa 0.91, and AUC 0.95. Therefore, the proposed model can help clinical experts verify whether the patient has a brain tumor and, consequently, accelerate the treatment procedure.Comment: 4th International conference on I-SMAC (IoT in Social, Mobile, Analytics and Cloud) (I-SMAC 2020), IEEE, 7-9 October 2020, TamilNadu, INDI

Karakterizacija predkliničnega tumorskega ksenograftnega modela z uporabo multiparametrične MR

Introduction: In small animal studies multiple imaging modalities can be combined to complement each other in providing information on anatomical structure and function. Non-invasive imaging studies on animal models are used to monitor progressive tumor development. This helps to better understand the efficacy of new medicines and prediction of the clinical outcome. The aim was to construct a framework based on longitudinal multi-modal parametric in vivo imaging approach to perform tumor tissue characterization in mice. Materials and Methods: Multi-parametric in vivo MRI dataset consisted of T1-, T2-, diffusion and perfusion weighted images. Image set of mice (n=3) imaged weekly for 6 weeks was used. Multimodal image registration was performed based on maximizing mutual information. Tumor region of interested was delineated in weeks 2 to 6. These regions were stacked together, and all modalities combined were used in unsupervised segmentation. Clustering methods, such as K-means and Fuzzy C-means together with blind source separation technique of non-negative matrix factorization were tested. Results were visually compared with histopathological findings. Results: Clusters obtained with K-means and Fuzzy C-means algorithm coincided with T2 and ADC maps per levels of intensity observed. Fuzzy C-means clusters and NMF abundance maps reported most promising results compared to histological findings and seem as a complementary way to asses tumor microenvironment. Conclusions: A workflow for multimodal MR parametric map generation, image registration and unsupervised tumor segmentation was constructed. Good segmentation results were achieved, but need further extensive histological validation.Uvod Eden izmed pomembnih stebrov znanstvenih raziskav v medicinski diagnostiki predstavljajo eksperimenti na živalih v sklopu predkliničnih študij. V teh študijah so eksperimenti izvedeni za namene odkrivanja in preskušanja novih terapevtskih metod za zdravljenje človeških bolezni. Rak jajčnikov je eden izmed glavnih vzrokov smrti kot posledica rakavih obolenj. Potreben je razvoj novih, učinkovitejših metod, da bi lahko uspešneje kljubovali tej bolezni. Časovno okno aplikacije novih terapevtikov je ključni dejavnik uspeha raziskovane terapije. Tumorska fiziologija se namreč razvija med napredovanjem bolezni. Eden izmed ciljev predkliničnih študij je spremljanje razvoja tumorskega mikro-okolja in tako določiti optimalno časovno okno za apliciranje razvitega terapevtika z namenom doseganja maksimalne učinkovitosti. Slikovne modalitete so kot raziskovalno orodje postale izjemno popularne v biomedicinskih in farmakoloških raziskavah zaradi svoje neinvazivne narave. Predklinične slikovne modalitete imajo nemalo prednosti pred tradicionalnim pristopom. Skladno z raziskovalno regulativo, tako za spremljanje razvoja tumorja skozi daljši čas ni potrebno žrtvovati živali v vmesnih časovnih točkah. Sočasno lahko namreč s svojim nedestruktivnim in neinvazivnim pristopom poleg anatomskih informacij podajo tudi molekularni in funkcionalni opis preučevanega subjekta. Za dosego slednjega so običajno uporabljene različne slikovne modalitete. Pogosto se uporablja kombinacija več slikovnih modalitet, saj so medsebojno komplementarne v podajanju željenih informacij. V sklopu te naloge je predstavljeno ogrodje za procesiranje različnih modalitet magnetno resonančnih predkliničnih modelov z namenom karakterizacije tumorskega tkiva. Metodologija V študiji Belderbos, Govaerts, Croitor Sava in sod. [1] so z uporabo magnetne resonance preučevali določitev optimalnega časovnega okna za uspešno aplikacijo novo razvitega terapevtika. Poleg konvencionalnih magnetno resonančnih slikovnih metod (T1 in T2 uteženo slikanje) sta bili uporabljeni tudi perfuzijsko in difuzijsko uteženi tehniki. Zajem slik je potekal tedensko v obdobju šest tednov. Podatkovni seti, uporabljeni v predstavljenem delu, so bili pridobljeni v sklopu omenjene raziskave. Ogrodje za procesiranje je narejeno v okolju Matlab (MathWorks, verzija R2019b) in omogoča tako samodejno kot ročno procesiranje slikovnih podatkov. V prvem koraku je pred generiranjem parametričnih map uporabljenih modalitet, potrebno izluščiti parametre uporabljenih protokolov iz priloženih tekstovnih datotek in zajete slike pravilno razvrstiti glede na podano anatomijo. Na tem mestu so slike tudi filtrirane in maskirane. Filtriranje je koristno za izboljšanje razmerja med koristnim signalom (slikanim živalskim modelom) in ozadjem, saj je skener za zajem slik navadno podvržen različnim izvorom slikovnega šuma. Uporabljen je bil filter ne-lokalnih povprečij Matlab knjižnice za procesiranje slik. Prednost maskiranja se potrdi v naslednjem koraku pri generiranju parametričnih map, saj se ob primerno maskiranem subjektu postopek bistveno pospeši z mapiranjem le na želenem področju. Za izdelavo parametričnih map je uporabljena metoda nelinearnih najmanjših kvadratov. Z modeliranjem fizikalnih pojavov uporabljenih modalitet tako predstavimo preiskovan živalski model z biološkimi parametri. Le-ti se komplementarno dopolnjujejo v opisu fizioloških lastnosti preučevanega modela na ravni posameznih slikovnih elementov. Ključen gradnik v uspešnem dopolnjevanju informacij posameznih modalitet je ustrezna poravnava parametričnih map. Posamezne modalitete so zajete zaporedno, ob različnih časih. Skeniranje vseh modalitet posamezne živali skupno traja več kot eno uro. Med zajemom slik tako navkljub uporabi anestetikov prihaja do majhnih premikov živali. V kolikor ti premiki niso pravilno upoštevani, prihaja do napačnih interpretacij skupnih informacij večih modalitet. Premiki živali znotraj modalitet so bili modelirani kot toge, med različnimi modalitetami pa kot afine preslikave. Poravnava slik je izvedena z lastnimi Matlab funkcijami ali z uporabo funkcij iz odprtokodnega ogrodja za procesiranje slik Elastix. Z namenom karakterizacije tumorskega tkiva so bile uporabljene metode nenadzorovanega razčlenjevanja. Bistvo razčlenjevanja je v združevanju posameznih slikovnih elementov v segmente. Elementi si morajo biti po izbranem kriteriju dovolj medsebojno podobni in se hkrati razlikovati od elementov drugih segmentov. Za razgradnjo so bile izbrane tri metode: metoda K-tih povprečij, kot ena izmed enostavnejšihmetoda mehkih C-tih povprečij, s prednostjo mehke razčlenitvein kot zadnja, nenegativna matrična faktorizacija. Slednja ponuja pogled na razčlenitev tkiva kot produkt tipičnih več-modalnih značilk in njihove obilice za vsak posamezni slikovni element. Za potrditev izvedenega razčlenjevanja z omenjenimi metodami je bila izvedena vizualna primerjava z rezultati histopatološke analize. Rezultati Na ustvarjene parametrične mape je imela poravnava slik znotraj posameznih modalitet velik vpliv. Zaradi dolgotrajnega zajema T1 uteženih slik nemalokrat prihaja do premikov živali, kar brez pravilne poravnave slik negativno vpliva na mapiranje modalitet in kasnejšo segmentacijo slik. Generirane mape imajo majhno odstopanje od tistih, narejenih s standardno uporabljenimi odprtokodnimi programi. Klastri pridobljeni z metodama K-tih in mehkih C-tih povprečij dobro sovpadajo z razčlenbami glede na njihovo inteziteto pri T2 in ADC mapah. Najobetavnejše rezultate po primerjavi s histološkimi izsledki podajata metoda mehkih C-povprečij in nenegativna matrična faktorizacija. Njuni segmentaciji se dopolnjujeta v razlagi tumorskega mikro-okolja. Zaključek Z izgradnjo ogrodja za procesiranje slik magnetne resonance in segmentacijo tumorskega tkiva je bil cilj magistrske naloge dosežen. Zasnova ogrodja omogoča poljubno dodajanje drugih modalitet in uporabo drugih živalskih modelov. Rezultati razčlenitve tumorskega tkiva so obetavni, vendar je potrebna nadaljna primerjava z rezultati histopatološke analize. Možna nadgradnja je izboljšanje robustnosti poravnave slik z uporabo modela netoge (elastične) preslikave. Prav tako je smiselno preizkusiti dodatne metode nenadzorovane segmentacije in dobljene rezultate primerjati s tukaj predstavljenimi

Computational methods to predict and enhance decision-making with biomedical data.

The proposed research applies machine learning techniques to healthcare applications. The core ideas were using intelligent techniques to find automatic methods to analyze healthcare applications. Different classification and feature extraction techniques on various clinical datasets are applied. The datasets include: brain MR images, breathing curves from vessels around tumor cells during in time, breathing curves extracted from patients with successful or rejected lung transplants, and lung cancer patients diagnosed in US from in 2004-2009 extracted from SEER database. The novel idea on brain MR images segmentation is to develop a multi-scale technique to segment blood vessel tissues from similar tissues in the brain. By analyzing the vascularization of the cancer tissue during time and the behavior of vessels (arteries and veins provided in time), a new feature extraction technique developed and classification techniques was used to rank the vascularization of each tumor type. Lung transplantation is a critical surgery for which predicting the acceptance or rejection of the transplant would be very important. A review of classification techniques on the SEER database was developed to analyze the survival rates of lung cancer patients, and the best feature vector that can be used to predict the most similar patients are analyzed

Efficient framework for brain tumor detection using different deep learning techniques

The brain tumor is an urgent malignancy caused by unregulated cell division. Tumors are classified using a biopsy, which is normally performed after the final brain surgery. Deep learning technology advancements have assisted the health professionals in medical imaging for the medical diagnosis of several symptoms. In this paper, transfer-learning-based models in addition to a Convolutional Neural Network (CNN) called BRAIN-TUMOR-net trained from scratch are introduced to classify brain magnetic resonance images into tumor or normal cases. A comparison between the pre-trained InceptionResNetv2, Inceptionv3, and ResNet50 models and the proposed BRAIN-TUMOR-net is introduced. The performance of the proposed model is tested on three publicly available Magnetic Resonance Imaging (MRI) datasets. The simulation results show that the BRAIN-TUMOR-net achieves the highest accuracy compared to other models. It achieves 100%, 97%, and 84.78% accuracy levels for three different MRI datasets. In addition, the k-fold cross-validation technique is used to allow robust classification. Moreover, three different unsupervised clustering techniques are utilized for segmentation

Convex non-negative matrix factorization for brain tumor delimitation from MRSI data

Background: Pattern Recognition techniques can provide invaluable insights in the field of neuro-oncology. This is because the clinical analysis of brain tumors requires the use of non-invasive methods that generate complex data in electronic format. Magnetic Resonance (MR), in the modalities of spectroscopy (MRS) and spectroscopic imaging (MRSI), has been widely applied to this purpose. The heterogeneity of the tissue in the brain volumes analyzed by MR remains a challenge in terms of pathological area delimitation. Methodology/Principal Findings: A pre-clinical study was carried out using seven brain tumor-bearing mice. Imaging and spectroscopy information was acquired from the brain tissue. A methodology is proposed to extract tissue type-specific sources from these signals by applying Convex Non-negative Matrix Factorization (Convex-NMF). Its suitability for the delimitation of pathological brain area from MRSI is experimentally confirmed by comparing the images obtained with its application to selected target regions, and to the gold standard of registered histopathology data. The former showed good accuracy for the solid tumor region (proliferation index (PI)>30%). The latter yielded (i) high sensitivity and specificity in most cases, (ii) acquisition conditions for safe thresholds in tumor and non-tumor regions (PI>30% for solid tumoral region; ≤5% for non-tumor), and (iii) fairly good results when borderline pixels were considered. Conclusions/Significance: The unsupervised nature of Convex-NMF, which does not use prior information regarding the tumor area for its delimitation, places this approach one step ahead of classical label-requiring supervised methods for discrimination between tissue types, minimizing the negative effect of using mislabeled voxels. Convex-NMF also relaxes the non-negativity constraints on the observed data, which allows for a natural representation of the MRSI signal. This should help radiologists to accurately tackle one of the main sources of uncertainty in the clinical management of brain tumors, which is the difficulty of appropriately delimiting the pathological area

Multiple Statistical Analysis Techniques Corroborate Intratumor Heterogeneity in Imaging Mass Spectrometry Datasets of Myxofibrosarcoma

MALDI mass spectrometry can generate profiles that contain hundreds of biomolecular ions directly from tissue. Spatially-correlated analysis, MALDI imaging MS, can simultaneously reveal how each of these biomolecular ions varies in clinical tissue samples. The use of statistical data analysis tools to identify regions containing correlated mass spectrometry profiles is referred to as imaging MS-based molecular histology because of its ability to annotate tissues solely on the basis of the imaging MS data. Several reports have indicated that imaging MS-based molecular histology may be able to complement established histological and histochemical techniques by distinguishing between pathologies with overlapping/identical morphologies and revealing biomolecular intratumor heterogeneity. A data analysis pipeline that identifies regions of imaging MS datasets with correlated mass spectrometry profiles could lead to the development of novel methods for improved diagnosis (differentiating subgroups within distinct histological groups) and annotating the spatio-chemical makeup of tumors. Here it is demonstrated that highlighting the regions within imaging MS datasets whose mass spectrometry profiles were found to be correlated by five independent multivariate methods provides a consistently accurate summary of the spatio-chemical heterogeneity. The corroboration provided by using multiple multivariate methods, efficiently applied in an automated routine, provides assurance that the identified regions are indeed characterized by distinct mass spectrometry profiles, a crucial requirement for its development as a complementary histological tool. When simultaneously applied to imaging MS datasets from multiple patient samples of intermediate-grade myxofibrosarcoma, a heterogeneous soft tissue sarcoma, nodules with mass spectrometry profiles found to be distinct by five different multivariate methods were detected within morphologically identical regions of all patient tissue samples. To aid the further development of imaging MS based molecular histology as a complementary histological tool the Matlab code of the agreement analysis, instructions and a reduced dataset are included as supporting information