Ultrasound has great possible to help in the differential diagnosing of malignant and benign thyroid lesions, but interpretive booby traps exist and the truth is still hapless. To get the better of these troubles, we developed and analyzed a scope of cognition representation techniques for qualifying the intra-nodular vascularisation of thyroid lesions. The analysis is based on informations obtained from 20 nodules ( 10 benign and ten malignant ) taken from 3D contrast-enhanced ultrasound images. Fine needle aspiration biopsy and histology confirmed malignance. Discrete Wavelet Transform ( DWT ) and texture algorithms are used to pull out relevant characteristics from the thyroid images. The resulting characteristic vectors are fed to three different classifiers: K-Nearest Neighbor ( K-NN ) , Probabilistic Neural Network ( PNN ) , and Decision Tree ( DeTr ) . The public presentation of these classifiers is compared utilizing Receiver Operating Characteristic ( ROC ) curves. Our consequences show that combination of DWT and texture characteristics coupled with K-NN presented good consequences with the country of under the ROC curve of 0.987, a categorization truth of 98.9 % , a sensitiveness of 99.8 % , and a specificity of 98.1 % . Finally, we have proposed a novel integrated index called Thyroid Malignancy Index ( TMI ) made up of DWT and texture characteristics, to name benign or malignant nodules utilizing merely one index. We hope that this TMI will assist clinicians in a more nonsubjective sensing of benign/malignant thyroid lesions.


The National Cancer Institute estimated the figure of new thyroid malignant neoplastic disease instances to be 44,670 and the predicted figure of deceases due to this malignant neoplastic disease to be 1,690 in 2010 ( 1 ) . Another database paperss a recent rise in the figure of instances of thyroid carcinoma, with an estimated addition of 3 % per twelvemonth in the incidence of thyroid malignant neoplastic disease ( 2, 3 ) . Although the incidence of thyroid malignant neoplastic disease appears to be increasing, the figure of patients evaluated with a thyroid nodule without carcinoma remains far greater. Thyroid nodules are really common and may happen in more than 50 % of big population with approximately 7 % of thyroid nodules being diagnosed as malignant ( 4 ) . In general, the incidence of thyroid nodules is on the rise due to the wider usage of cervix imagination ( 5 ) .

Such statistics indicate that there is an pressing demand for cost-efficient thyroid diagnosing support systems. Cost efficiency is of import because a big figure of trials must be performed in order to observe a comparatively little figure of malignant neoplastic disease instances. In footings of diagnosing technique, Fine Needle Aspiration Biopsy ( FNAB ) is considered to be the “ gilded criterion ” technique for the diagnosing of thyroid nodules ( 6 ) . However, FNAB is excessively labour intensive to be used for big scale showings and has many booby traps ( 7 ) . A more effectual sensing scheme is to analyse medical images, because in this instance the diagnosing procedure can be automated. Such systems are called as Computer Aided Diagnosis ( CAD ) systems. Use of thyroid images for the diagnosing is possible, because the image texture indicates the histopathologic constituents of the thyroid nodules. Now, holding established the possibility of utilizing thyroid images for malignant neoplastic disease sensing, we need to turn to the issue of cost efficiency. There is a broad scope of medical imaging modes available which could be used for thyroid nodule diagnosing. Ultrasound imagination is, by a big border, the most cost effectual of these modes. Bastin et Al. ( 8 ) have shown that ultrasound features of thyroid nodules can foretell the hazard of malignance ( solid nodule, hypoechogenicity, microcalcification, macrocalcification, unclear borders, intranodular vascularity, and taller-than-wide form ) . Unselected nodules without any leery ultrasound characteristics showed a lower hazard of malignance ( & lt ; 2 % ) , whereas malignance rates were much higher in nodules with at least two leery characteristics. Recent guidelines endorsed this attack of utilizing combinations of ultrasound characteristics to steer nodule choice for all right needle aspiration. Chen et Al. ( 9 ) have shown that among the legion textural characteristics used for the differential thyroid malignance diagnosing, the sum mean value reflected echogenicity and was able to distinguish between follicles andA fibrosisA baseA thyroid nodules.A FibrosisA showed lowest echogenicity and lowest difference amount mean value. Enlarged follicles showed highest echogenicity and the difference sum mean values.

There is a broad scope of different ultrasound imaging methods in being. One of them is frequence encoded Doppler Ultrasound ( DUS ) imaging which has been used for the designation of flow in thyroid tumours. However, the function of DUS in the rating of thyroid nodules for malignance has non yet been accurately studied ( 10 ) . Internal flow without or with minimum peripheral flow on DUS and Resistance Index ( RI ) a‰? 0.70 were used to separate between malignant and benign thyroid nodules faithfully. Nodules with prevalent peripheral vascularization and minimum or no internal vascularization, and RI below 0.70 were found to be likely benign. Doppler surveies need a quantitative rating of the internal nodule flow to avoid subjective readings and partial visions caused by the bidimensional nature of the traditional High Resolution Ultrasound ( HRUS ) . The sonographic characteristics like the size and echogenicity of the tumours, the presence of cystic countries or calcifications, and noticeable blood flow on colour Doppler imagination of Hurthle Cell Neoplasms ( HCNs ) of the thyroid were studied ( 11 ) . They concluded that the Hurthle cell neoplasms showed a spectrum of sonographic visual aspects from preponderantly hypoechoic to hyperechoic lesions and from peripheral blood flow with no internal flow to extensively vascularized lesions. They besides indicated that the distinguishing benign and malignant HCNs was hard utilizing ultrasound and FNA techniques, and hence, complete remotion of the lesion is the lone safe option. Contrast-Enhanced Ultrasound ( CEUS ) imagination was introduced to heighten the differential diagnosing of lone thyroid nodules. The feasibleness of CEUS imagination of the thyroid secretory organ and the potency of this method for qualifying lone thyroid nodules were studied ( 12 ) . They assessed the baseline echogenicity and the dynamic enhancement form of each nodule, in comparing with next thyroid parenchyma. Their consequences show that CEUS of thyroid secretory organ was a executable technique. However, overlapping findings seem to restrict the potency of this technique in the word picture of thyroid nodules. Recently, enhancement forms of thyroid nodules on gray-scale contrast-enhanced ultrasound were evaluated for the differential diagnosing ( 13 ) . Their consequences show that CEUS sweetening forms were different in benign and malignant lesions. Ringing sweetening was prognostic of benign lesions, whereas heterogenous sweetening was helpful for observing malignant lesions.

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The application of ultrasonographic contrast agents that lead to an betterment in the differential diagnosing of thyroid nodules was studied ( 14 ) . In the group of benign lesions, in the patients affected by nodular goitre, an intra-nodular perfusion as opposite to the healthy environing parenchyma was observed. Even though the ultrasound contrast agent technique has a limited invasivity and is more expensive than FNA, the preliminary information of this pilot survey suggested that this method may be utile to distinguish benign from malignant thyroid nodules.

In this survey, we used Discrete Wavelet Transform ( DWT ) and texture based characteristic extraction methods for the differential diagnosing of malignant and benign thyroid lesions. We used these characteristics from CEUS images because this imagination method is cost-efficient and more efficient in distinguishing benign from malignant lesions. The undermentioned subdivision presents the stuffs and methods used for characteristic extraction, categorization, and statistical analysis. In the subsequent consequences subdivision, both categorization consequences and associated statistical analysis are discussed. The literature presented in this debut subdivision forms the footing for a treatment. The treatment subdivision undertakings the proposed thyroid diagnosing technique into a wider position by comparing the consequences of the proposed system with antecedently published categorization consequences. In the decision subdivision of this paper, we highlight both the cost effectivity and the truth of the proposed method.

Materials and Methods

Figure 1 shows the block diagram of the proposed system. In general, computing machine aided diagnosing systems can be constructed with a characteristic extraction subsystem and a categorization subsystem. In this work, we used both DWT and texture based characteristics. The extracted characteristic vectors were fed to one of the three classifiers: K-Nearest Neighbor ( K-NN ) , Probabilistic Neural Network ( PNN ) , and Decision Tree ( DeTr ) . The function of each single constituent in the block diagram is described in this subdivision.

Insert Figure 1 here


Twenty patients with antecedently confirmed diagnosing of lone thyroid nodule were enrolled in this survey. Ten topics were male ( age: 53.5 A± 13.3 old ages ; scope: 22 – 71 old ages ) and ten were female ( age: 50.1 A± 10.8 old ages ; scope: 25 – 68 old ages ) . All the patients signed an informed consent prior to take parting in the experiment. The experimental protocol was approved by the ethical commission of the Endocrinology Section of the “ Umberto I ‘ ” Hospital of Torino ( Italy ) .

All topics underwent a clinical scrutiny, hormonal profile, and ultrasound ( B-Mode and Color Doppler ) scrutiny of the lesion. Then, 2.5 milliliter of ultrasound contrast agent ( Sonovue, Bracco, Italy ) was administered intravenously and a 3-D volume incorporating the lesion was acquired. Due to bulkiness and weight of external mechanical scanning systems and the variableness associated with the nodules dimension and its place, we preferred to execute a freehand scanning. A trained operator with more than 30 old ages of experience in cervix echography ( R.G. ) performed all the scans. The high frame rate of the device compared to the slow motion of the investigation ensured that there was no spread between next frames. The mean frame rate of the device during acquisition was 16 Hz.

Images were acquired by a MyLab70 ultrasound scanner ( Biosound-Esaote, Genova, Italy ) equipped by a LA-522 additive investigation working in the scope 4-10 MHz. All the images were acquired at 10 MHz. The volumes were transferred in DICOM format to an external workstation ( Apple PowerPc, double 2.5 GHz, 8 G RAM ) equipped with processing and Reconstruction package.

All the topics underwent ultrasound-guided FNAB of the thyroid lesion. Among the 20 nodules, ten were found to be malignant ( six papillary, one follicular and one Hurtle cells carcinoma ) , and 10s were benign ( struma nodules ) . We acquired 40 informations sets from each of the 10 patients diagnosed with malignant nodules. Similarly, we acquired 40 informations sets from each patient holding benign thyroid nodules. Overall, our survey contains 400 benign and 400 malignant informations sets. The 10 patients who were diagnosed with malignant nodules underwent thyroidectomy. The histo-pathological analysis confirmed the diagnosing of malignant carcinoma for all the 10 patients. The consequences of the FNAB were used as mention for the benign nodules: all were struma nodules. Figures 2 ( a ) and 2 ( B ) show the typical benign and malignant thyroid images.

Insert Figure 2 here

Feature extraction

Feature extraction is one of the most of import stairss in machine-controlled CAD systems, because this measure extracts relevant and representative characteristics from measurement informations such as images and signals. In this work, DWT and texture characteristics were extracted from CEUS images.

DWT characteristic extraction: DWT is a utile and efficient tool for many image processing applications. DWT uses filter Bankss which are composed from finite impulse response filters ( 15 ) . These filters are used for break uping signals into low and high base on balls constituents. The low base on balls constituents contain information ( in the signifier of coefficients ) about slow changing signal features, and the high base on balls constituents contain information about sudden alterations in the signal. When DWT is applied to images, there are four different filtrating possibilities:

Low base on balls filtering is performed on both rows and columns. The ensuing LL coefficients contain most of the image ‘s entire energy.

Low base on balls filtering is performed on the rows, and high base on balls filtrating on the columns. The ensuing HL coefficients contain the perpendicular inside informations of the image.

High base on balls filtering is applied to the rows, and low base on balls filtering to the columns. The ensuing LH coefficients contain the horizontal inside informations of the image.

High base on balls filtering is conducted on the rows and columns ( HH coefficients ) . The ensuing HH coefficients contain the diagonal inside informations of the image, and they are the finest-scale ripple coefficients.

Decomposition is farther performed on the LL sub-band to achieve the following coarser graduated table of ripple coefficients.

Insert Figure 3 here

In our work, the CEUS images were foremost converted to a grayscale representation and so DWT was applied. Figure 3 shows the complete passband construction for a 2D sub-band transform with three degrees. In this work, we have used Daubechies ( Db ) 8 as the female parent ripple.

The single sub-bands are represented as matrixes and these matrixes are combined to organize a characteristic. The method for uniting the matrix elements is the same for all sub-band characteristics. All the elements within the single rows of the matrix are added and the elements of the resulting vector are squared before adding to organize a scalar. Finally, this scalar is normalized by spliting it by the figure of rows and columns of the original matrix. A2, H2, H1, V2, V1, D2, D1 ( as shown Figure 3 ) indicate the A2, H2, H1, V2, V1, D2, D1 ( as shown in Figure 1 ) .

Texture characteristic extraction: Texture features step smoothness, saltiness, and regularity of pels which form an image. These steps describe a common relationship among strength values of neighbouring pels repeated over an country larger than the size of the relationship ( 16 ) . There are two common attacks to texture analysis: statistical analysis and structural analysis. In the statistical attack, scalar measurings of the textures are obtained. This attack characterizes textures as smooth, coarse, or farinaceous etc. These methods are based on both distributions and relationships between strength values of pels. Measures include information, contrast, and correlativity based on the grey degree accompaniment matrix. Structural texture analysis is more complex when compared to the statistical attack ( 17 ) . It presents elaborate symbolic descriptions of the image. Parameters that are extracted utilizing the statistical attack are more suited for image analysis than those obtained utilizing the structural method ( 18 ) . In this subdivision, the statistical parametric quantities extracted from the CEUS images are briefly described. The Grey Level Co-occurrence Matrix ( GLCM ) of an M A- N image I is defined ( 15 ) by

[ 1 ]

where, and denotes the cardinality of a set. The chance of a pel with a gray degree value i holding a pel with a grey degree value J at a distance off in an image is

[ 2 ]

Based on the above mentioned, we obtain the undermentioned characteristics:

, [ 3 ]

, and [ 4 ]

. [ 5 ]

The homogeneousness characteristic measures the similarity between two pels that are apart. Denseness and grade of upset in an image are measured by energy and information characteristics. In general, the information characteristic will hold a maximal value when all elements of the accompaniment matrix are the same. The symmetricalness projections indicate outstanding waies within the texture of CEUS images, and hence, symmetricalness is an of import discriminatory characteristic of these images.

Classifiers used

There are three classifiers used in this work, viz. K-Nearest Neighbor ( K-NN ) , Probabilistic Neural Network ( PNN ) , and Decision Tree ( DeTr ) . They are briefly described in this subdivision.

K-Nearest Neighbor ( K-NN ) : K-NN is based on the minimal distance from a question case to the preparation samples. The K-nearest neighbours are determined utilizing this method. After garnering these K-nearest neighbours, the bulk of them are used for the anticipation ( 19 ) .

Probabilistic Neural Network ( PNN ) : PNN is a specific type of two layer radial footing web which is frequently used for categorization. The first bed of nerve cells in a PNN has radial footing activation maps. This bed computes the distance vector by measuring the distances between the input and preparation vectors. The 2nd bed ( competitory bed ) sums the parts of each input categories and produces a vector of chances as the end product of the input categories. The so called compete transportation map, at the end product of the 2nd bed, selects the upper limit of these chances and assigns a 1 for the selected category and a 0 for all other categories ( 20 ) .

Decision Tree ( DeTr ) : DeTr classifier generates a tree and a set of regulations to stand for the theoretical account in order to place different categories from a given information. The regulations can be used to acknowledge the unknown informations ( 21 ) .

Statistical analysis

The pupil ‘s t- trial is a signifier of arrested development analysis used to measure whether the two groups have different agencies on some step. A If there is less than 5 % opportunity of acquiring the ascertained differences by opportunity, so a statistically important difference between the two groups is reported.A The lower ‘p ‘ values indicate that these groups are clinically important.

The Receiver Operating Characteristic ( ROC ) curve is a secret plan in a two dimensional infinite. The x-axis is `1 – specificity ‘ and the y-axis is `sensitivity ‘ . Sensitivity, besides known as true positive fraction, refers to the chance that a trial consequence is positive when a disease is present. The Area under the ROC curve ( AUC ) indicates the classifier public presentation across the full scope of cut-off points. Conventionally, the country under the ROC curve must fall in the scope between 0.5 and 1 ( 22 ) . An country closer to one indicates that the classifier has a better truth. The country under the ROC curve is a good index for the classifier public presentation ( 23 ) .

Thyroid Malignancy Index ( TMI )

In this work, we have used Entropy, Homogeneity and Symmetry texture features to develop an incorporate index TMI. It is hard to track how these three texture characteristics vary in a patient for doing an appropriate diagnosing. Hence, we have formulated an integrated index by uniting these characteristics in such a manner that the index is distinguishable for benign and malignant nodules. The TMI is defined as follows.

[ 6 ]

Such an incorporate index would assist in a faster and more nonsubjective sensing of benign and malignant thyroid nodules.


We have used 740 images for preparation and 80 images for proving. Ten-fold stratified transverse proof method was used to prove the classifiers. Using this technique, the whole dataset was split into 10 equal parts ( approximately ) . Nine parts of the informations ( developing set ) were used for classifier development and the built classifier was evaluated utilizing the staying one portion ( trial set ) ( i.e. 760 images were used for preparation and 40 images for proving each clip ) . This process was repeated 10 times utilizing a different portion as the trial set in each instance. Average of the truth, sensitiveness, specificity, positive prognostic truth, and AUC was calculated for all 10 creases to obtain the overall public presentation steps. The scope of characteristics, categorization consequences, and the scope of TMI are given in the undermentioned subdivisions.

Table I paperss the consequences of statistical analysis of the DWT and texture characteristics. The last column of this tabular array shows the p-value of the characteristics. The fact that all p-values are below 0.0001 indicates that all characteristics are clinically important. The homogeneousness, symmetricalness and all the DWT characteristics are higher for malignant nodules compared to benign because benign images ( Figure 2 ( a ) ) have more construction compared to malignant thyroid images ( Figure 2 ( B ) ) . The images with more construction, such as the benign thyroid images, have more fluctuations in the grayscale values compared to the malignant thyroid images, and hence have higher information values.

Insert Table I here

Table II presents the categorization consequences obtained by utilizing the extracted DWT and texture characteristics in the three classifiers. The first column indicates the classifier used. The following four columns present the mean figure of True Negatives ( TN ) , False Negatives ( FN ) , True Positives ( TP ) , and False Positives ( FP ) obtained over the 10 creases. The mean categorization truth is shown in column 6. Columns 7, 8, and 9 show the mean values of the sensitiveness, specificity, and AUC, severally. The categorization truth for all three tested classifiers is good above 96 % . It is besides apparent from the consequences that the K-NN classifier performs better than DeTr and PNN with a higher truth of 98.9 % . Figure 4 shows the ROC curves of the three classifiers. It can be clearly seen from the figure that, the K-NN performs better than the other two classifiers.

Insert Table II here

Insert Figure 4 here

Thyroid malignance index consequences

Table III shows the TMI values ( average criterion divergence ) for the two categories. It can be seen from the tabular array that they are clearly different from each other without any convergence. Figure 5 shows the box secret plan of the average value of TMI indices foregrounding the separation between the two categories clearly.

Insert Table III here

Insert Figure 5 here


The recent progresss in ultrasound techniques have paved the manner for many research workers to suggest new imaging algorithms to name the malignance in thyroid carcinoma. Ultrasound methods for thyroid malignant neoplastic disease diagnosing are cost-efficient, and these methods perform every bit good as other thyroid malignant neoplastic disease diagnosing methods. In this subdivision, we present the comparing of the consequences obtained utilizing our technique and other techniques in the literature which besides aim to name malignant thyroid nodules.

Finley et Al. ( 24 ) classified benign and malignant thyroid nodules utilizing molecular profiling. In their survey, they carried out bunch analysis utilizing 62 samples from two categories ( benign and malignant ) . The consequences of their survey show sensitiveness and specificity of 91.7 % and 96.2 % , severally. Cerutti et Al. ( 25 ) proposed a pre-operative diagnostic method to separate benign and malignant thyroid carcinoma based on cistron look. A entire thyroidectomy was the intervention of pick, and a negative consequence was confirmed on lasting pathology in 20 instances. The immunohistochemistry right classified 29 of 32 fine-needle aspirations ( 90.6 % ) and 23 of 27 follicular thyroid adenomas ( 85.2 % ) . The writers of this survey were non satisfied with both sensitiveness and specificity, and hence, they proposed further work to increase both steps.

Patton et Al. ( 26 ) differentiated between malignant and benign lone thyroid nodules by fluorescent scanning. They demonstrated a sensitiveness of 93.8 % in the designation of malignant neoplastic disease. However, the truth in the differentiation between benign and malignant tissues was merely 77.0 % . Regardless of the cost, the categorization truth was low for province of the art CAD systems. The B-mode sonographic images of inflamed and healthy tissues were differentiated automatically utilizing texture characteristics ( 27 ) . A categorization success rate of 100 % was achieved with every bit few as one optimum characteristic among the 129 texture features tested. The stableness of the consequences with regard to sonograph scene, A thyroid glandA cleavage and scanning way was tested.A In this work, writers have studied the normal and inflamed ultrasound images.

Therefore, based on the above facts, we felt the necessity for a better technique that can better the categorization efficiency and that is besides more economical. In our survey, we proposed a CAD system for the sensing of benign and malignant thyroid lesions from ultrasound images. Our proposed method is simple and does non affect intensive calculation. We have proposed a novel integrated index called Thyroid Malignancy Index ( TMI ) that can be used to place benign and malignant conditions with high truth. Furthermore, we used the extracted characteristics in classifiers and concluded that a combination of DWT and texture parametric quantities coupled with a simple K-NN classifier can be used for machine-controlled categorization. Our proposed system is able to place the unknown category with an truth, sensitiveness and specificity of more than 96 % . In add-on to this, the proposed TMI is distinguishable for each of the two categories, and hence, can assist in faster, easier, more cost-efficient, and more nonsubjective sensing of benign and malignant lesions.


There is a demand for the cost-effective biomedical diagnostic support systems. In this work, we have investigated the public presentation of the proposed CEUS based thyroid malignant neoplastic disease CAD system utilizing texture and DWT parametric quantities. The extracted DWT and texture characteristics were fed as input to the three different classifiers to compare their public presentations. Our consequences show that the combination of DWT and texture characteristics coupled with K-NN classifier presented a categorization truth of 98.9 % , sensitiveness of 99.8 % and 98.1 % specificity.

In order to do the distinction faster and more nonsubjective, we have gone one measure further and formulated a non-dimensional incorporate index ( given by Eqn. 6 ) that is composed of texture characteristics. Based on the information presented in Table III and Figure 5, it is apparent that this integrated TMI Index can be employed for the diagnosing of benign and malignant nodules efficaciously. The advantage of this Integrated Index is the fact that, in order to do a diagnosing, the doctor needs to merely look at the value of merely one incorporate index alternatively of look intoing the scope of each single characteristic. Hence, this TMI can be used as an accessory tool for the clinicians to traverse look into their diagnosing.


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