Ultrasound diagnostic method for thymic ectopia

Abstract

FIELD: ultrasound diagnostics.SUBSTANCE: used for ultrasound diagnostics of ectopia of the thymus. A convolutional neural network (CNN) trained on reference ultrasound images of the orthotopic thymus is used. Ultrasound examinations of the neck, thyroid gland, and mediastinum are performed, and automated comparison of scanning parameters is performed in real time using a computer program that contains an image processing module that implements sequential data filtering using a Gabor filter followed by a trained CNN. The scanning parameters used are tissue isoechogenicity, clarity, evenness of contours, ovoid shape, heterogeneous structure of reduced echogenicity with fine-point hyperechoic inclusions, and the absence of pronounced central vascularization. When the similarity coefficient reaches 90% or more, a high probability of ectopia of the thymus is diagnosed.EFFECT: increasing the efficiency of diagnosing ectopically located thymus by automating the analysis of ultrasound images and objectifying diagnostic criteria.1 cl, 1 ex

Description

[0001] The invention relates to medicine (in particular, to immunology and pediatrics) and is a method for diagnosing the presence and location of an ectopically located organ (thymus and others) by comparing and subsequently recognizing (with an audible alert) the identity of the ultrasound image of an orthotopic, previously known organ or tissue of the patient, with that obtained during ultrasound scanning at the supposed location of the desired objects of study in the same patient.

[0002] A method for diagnosing ectopic pregnancy is known (Patent No. 2638290 C1 Russian Federation, IPC A61B 5 / 055. Method for diagnosing ectopic pregnancy: No. 2016128909: declared 14.07.2016: published 12.12.2017 / T. M. Ishutina, N. G. Pavlova, V. M.). The known method is based on the use of magnetic resonance imaging (MRI) with T2-weighted images (T2-WI) in axial and coronal projections with thin slices (1 mm). The method allows visualization of the fallopian tubes, determination of the presence of an ectopic ovum, the depth of chorionic villus invasion, the stage of the disease and its complications (for example, hematosalpinx), examining for the presence or absence of certain diagnostic patterns.

[0003] A drawback of the known method was the subjectivity of pattern interpretation. Diagnostic symptoms (e.g., "white button sign" or "cheesecake sign") require precise recognition of shape, contours, and signal intensity, which can be difficult due to anatomical variations or image blur. The lack of quantitative criteria for pattern assessment (e.g., precise values ​​of trophoblastic membrane thickness or hematoma density) reduces the objectivity of the diagnosis.

[0004] Also, the well-known method requires expensive equipment (MRI with a magnetic field strength of 1.5 T or higher), making it unavailable in some medical institutions, especially in regions with limited equipment. MRI is also a relatively time-consuming procedure, unlike ultrasound.

[0005] The technical result of the invention consists in increasing the efficiency of diagnosing foci of an ectopically located organ, with subsequent more effective provision of medical care and prevention.

[0006] A method for ultrasound diagnosis of the presence and location of an ectopic organ is proposed. This method involves the formation of a basic, reference profile of the orthotopic thymus with specified parameters of shape, size, echogenicity, and vascularity. This method differs in that ultrasound examinations of anatomical areas with a high probability of ectopia are performed and an automated comparison of the scanning parameters with the basic, reference profile is performed using a Gabor filter and CNN. For comparison, real-time characteristics such as tissue isoechoicity, clarity and smoothness of contours, ovoid shape, a heterogeneous structure of reduced echogenicity with fine-point hyperechoic inclusions, and the absence of pronounced central vascularity are used. A high probability of ectopia outside its typical location is assessed when a similarity coefficient of ≥90% is achieved.

[0007] The proposed method for ultrasound diagnosis of the presence and location of an ectopically located organ (thymus and others) in a patient. The method involves comparing the ultrasound characteristics of an orthotopic organ (previously known and recorded in the patient) with ultrasound images obtained during ultrasound scanning of anatomical areas with a high probability of ectopia. The method is based on the fact that the tissue of an ectopic organ retains morphological and visual characteristics identical to its orthotopic counterpart, allowing for the identification of areas outside the typical location.

[0008] The increased effectiveness of the proposed method is due to the reduced subjective influence in the diagnosis of thymic ectopia. In current practice, diagnosis is performed visually, making it dependent on an individual assessment of the location and structural features of the thymus by a specialist. Ectopic thymic tissue can be small and localized in anatomically difficult to access or atypical areas, increasing the likelihood of missing a pathological change during expert interpretation of the examination results.

[0009] To do this, an ultrasound scan (unlike its MRI counterpart) of the orthotopic thymus is first performed, recording its parameters—shape, size, echogenicity relative to surrounding tissue, and vascularity. This data is saved in the software as a reference profile. The doctor then scans the areas where ectopia is most likely: the cervical region, mediastinum, and thyroid tissue. Image comparison occurs in real time using a machine learning algorithm that analyzes key criteria—tissue isoechoicity, clear, smooth contours, ovoid shape, heterogeneous structure with fine hyperechoic inclusions, and the absence of pronounced central vascularity. A combination of a Gabor filter and a convolutional neural network (CNN) is used for automated analysis of ultrasound images.The computer program used contains an image processing module that implements sequential data filtering using a Gabor filter to highlight tissue texture features, followed by a convolutional neural network (CNN) trained on reference ultrasound images to identify ectopic lesions. When a similarity coefficient of 90% or higher is reached, the system generates an audible signal, indicating a high probability of ectopia.

[0010] Thus, unlike the well-known prototype, which uses MRI, the proposed method is based on ultrasound diagnostics, which reduces the cost of the examination and shortens the diagnostic time. Furthermore, automated analysis using CNN eliminates the subjectivity of interpretation typical of visual analysis of MRI images.

[0011] The thymus is today considered a key central element of the immune system, regulating the development of T-lymphocytes, the formation of immune tolerance, and protection against infectious, oncological, and autoimmune diseases. Deviations in its structural and functional state are associated with the risk of immunodeficiency, immune dysregulation, organ transplant problems, and other pathologies. Thymus function depends on genetic factors, embryonic development, age-related involution, and potential damage throughout life. However, the medical community remains insufficiently aware of thymus-mediated diseases.

[0012] 1. Embryogenesis of the thymus and mechanisms of ectopia formation

[0013] Embryonic development of the thymus begins in the 6th week of intrauterine life from the third (and partially the fourth) branchial arches. Typically, the organ rudiment (or its embryonic cells) migrates from the cervical region to the anterior mediastinum (orthotopic position) through the thymopharyngeal duct. Sometimes, during the migration process, tissue fragments may remain (usually in the cervical region), which form ectopic foci of the thymus. By the 8th week of embryogenesis, the connection of the orthotopic (and in cases of ectopic) thymus with the branchial arches ceases and it is populated by lymphocytes from the bone marrow. After birth, the organ increases in volume, reaching its maximum during puberty [1].

[0014] 2. Clinical significance of thymic ectopia

[0015] Ectopia of the thymus gland (thymus) is a condition in which thymus tissue, in addition to the anterior mediastinum (orthotopic position), is localized outside the typical position. The incidence of this finding varies widely: from 5% to 50% in the population, and is reported in extremely rare population-based epidemiological studies worldwide. This is likely due to low motivation and the imperfections and complexity of previously used diagnostic methods, especially intravital ones. In pediatrics, detection of ectopia of the thymus is necessary not only as a safeguard against the development of intrathymic syndrome after thymectomy of the orthotopic organ during open heart surgery, but also in the event of critical organ involution. The latter occurs quite frequently in children with congenital heart defects, and other surgical approaches are often unavailable.

[0016] The relevance of the problem is not only due to what is presented in the previous paragraph, but is also due to the fact that today there are no sufficiently clear scientific works on the functional and morphological assessment of the ectopic thymus (and other organs and systems), which can most directly (or indirectly) affect the quality and duration of life.

[0017] In the rare studies available, ectopic foci are most often found in the cervical region in children (49.5% of those examined) and in the anterior mediastinum in adults (53.1%). They are less common in thyroid tissue (0.95%) [2]. These areas retain functional activity and may be able to compensate for the deficiency of the orthotopic thymus, especially after its removal (thymectomy). According to some authors, thyroid "nodules" detected by ultrasound examination are in most cases areas of ectopic thymus tissue [3]. Reactive enlargement of ectopic foci of the thymus, due to the action of mainly infectious stressors, discovered by chance, was often considered as a tumor formation and caused difficulties for diagnosticians, due to both the low awareness of the medical community about this phenomenon, and the difficulty of confirming the genesis of these formations as ectopic foci [4,5].In this regard, there was a need for histological confirmation, which is inevitably associated with invasive interventions.

[0018] Thus, thymic ectopia is an important yet underappreciated phenomenon in clinical practice. Its detection can improve the prognosis of patients, for example, after cardiac (and other) surgeries with combined forced thymectomy, and also aid in the rehabilitation of immunodysregulatory conditions associated with orthotopic thymus pathomorphisms. In Russia (as well as worldwide), the introduction of population-based epidemiological intravital ultrasound examinations (as the most accessible, safe, and sufficiently informative) of orthotopic and ectopic organs and systems (in particular, the thymus) and accompanying modern diagnostic methods is relevant to improving the quality of medical care. The use of a Gabor filter allows for the identification of tissue texture features that are difficult to assess visually (e.g., fine-point hyperechoic inclusions), while CNN provides an objective assessment, eliminating subjective physician error.This reduces the risk of missing ectopia in complex anatomical areas (for example, in thyroid tissue, where ectopia, according to research, occurs in 0.95% of cases).

[0019] 3. Clinical associations and research

[0020] Despite global data, an analysis of 112 autopsy reports of children in Kuzbass who died due to various causes (stressors) did not reveal a single described case of an ectopically located organ. Some children showed clear signs of accidental thymus involution associated with a critical decrease in its mass and volume, combined with clinical signs of immunodysregulatory conditions (sepsis, generalized infection). Other children showed an increase in the size of the orthotopic thymus gland, which was also associated with a violation of the functional activity of the thymus. Based on this, the question remains fundamentally important: can probable ectopic tissue maintain its structure and function, compensating for the lost activity of the orthotopic thymus, which has undergone the above-mentioned critical involutions under conditions of exposure to extreme stressors on the body? [6]

[0021] A study of children with sudden infant death syndrome (SIDS) revealed a contradictory picture of the thymus status: some patients had thymomegaly, while others had more pronounced involutional changes, correlating with a history of intrauterine infections [6]. These data suggest that thymus disorders may be a risk factor for fatal outcomes in SIDS. Pathological examinations of children in this group also did not reveal the described ectopic foci of thymic tissue, making conclusions about its distribution in the body and the morphological state of the thymus gland incomplete.

[0022] Ectopic foci capable of compensatory activity could modulate the immune response and influence prognosis.

[0023] This study confirms the lack of interest in Russian medical practice in identifying (including at autopsy) ectopic thymic tissue (or other organs). Internationally, this practice is also represented by very few studies, where targeted ultrasound examinations and autopsies have found a prevalence of ectopic thymus ranging from 5% to 50% in the population. These studies have not received due evaluation and subsequent more detailed study of the function of the ectopic organ, but the above results cannot be ignored from a scientific and practical perspective.

[0024] Congenital heart defect correction surgeries that involve complete removal of the thymus (thymectomy) are associated with an increased risk of developing combined immunodeficiency or immune dysregulation. Studies have shown that patients who have undergone thymectomy have an increased risk of developing immunodeficiency compared to those who have preserved the thymus [7]. This underscores the critical role of the organ in maintaining adaptive immunity in children. However, when ectopic thymic foci are present, they are likely to compensate for the function of the removed orthotopic organ. One study found that ectopic thymic tissue in the cervical region or mediastinum retains the ability to mature T-lymphocytes, which reduces the severity of postoperative immunodeficiencies (author ?).This suggests that for patients with congenital heart defects undergoing thymectomy, preoperative diagnosis of ectopia using ultrasound scanning will preserve immune potential by compensating for orthotopic thymus function. This will reduce the risk of immunodeficiency compared to the group without a diagnosis of ectopia[8].

[0025] The problem of thymic ectopia remains underestimated in clinical practice, despite its critical role in maintaining immune homeostasis and compensating for organ function after thymectomy. Integrating automated ultrasound into diagnostic standards will reduce the risk of immunodeficiency after surgery and provide a comprehensive picture of the immune system in children with risk factors for SIDS, as well as severe and long-term infectious diseases.

[0026] Reduce the frequency of invasive examinations by improving the accuracy of differential diagnosis.

[0027] These changes will require specialized software development and clinical trials, but will be an important step in closing the gap in domestic and international research on thymic ectopia.

[0028] The proposed device allows for the identification of tissue texture features (small hyperechoic spots, contours) that are difficult to assess visually. The built-in CNN, trained on reference ultrasound images, compares the scan parameters with those of an orthotopic thymus, eliminating subjective physician error. This improves the accuracy of ectopia diagnosis in complex anatomical areas (e.g., thyroid tissue).

[0029] 3. Modern diagnostic methods and difficulties in the Russian Federation

[0030] Diagnostics of ectopia include ultrasound, CT, MRI, and scintigraphy. However, the use of these methods is limited due to high cost and insufficient funding. Detecting ectopia requires highly skilled ultrasound technicians and is time-consuming, which reduces the availability of testing. In the Russian Federation, there are no studies on the prevalence of ectopia and its association with immune disorders. This is due to limited healthcare resources and insufficient awareness among physicians of the significance of this phenomenon.

[0031] It is important for practice to implement standardized imaging algorithms that will reduce the likelihood of diagnostic errors. To improve the accuracy and accessibility of thymic ectopic foci diagnosis, it is necessary to develop a standardized ultrasound algorithm based on comparative analysis. The proposed approach includes four key steps:

[0032] 1. Obtaining an ultrasound image of the orthotopic thymus and forming a reference profile with parameters of shape, size, echogenicity, and vascularity.

[0033] The doctor records the parameters of the orthotopic thymus (shape, size, echogenicity, vascularization) in the patient.

[0034] 2. Scanning of anatomical areas with a high probability of ectopia

[0035] The data obtained in the first stage are used as a reference for searching for potential ectopic foci in known atypical locations (cervical region, thyroid gland, mediastinum).

[0036] 3. Automated comparison of scanning parameters with a reference profile using a Gabor filter and CNN that highlight similar ultrasound features in real time:

[0037] • tissue isoechoicity,

[0038] • clear, even contours,

[0039] • ovoid shape,

[0040] • heterogeneous structure of reduced echogenicity with small-point hyperechoic inclusions,

[0041] • absence of pronounced central vascularization

[0042] 4. Automated recognition with sound alert. When a region identical to the orthotopic thymus based on key parameters is detected, the system generates a sound alert, informing the physician of the high probability of ectopia. The sound alert is generated when the similarity coefficient reaches ≥90%. This reduces the risk of missing ectopic foci due to visual fatigue and speeds up the diagnostic process.

[0043] The method can be widely implemented in practice, as there will be sufficient scientific motivation for comparative studies of the immune profile in individuals with only an orthotopic thymus and those with both orthotopic and ectopic localizations. In the latter case, a more promising positive prognosis cannot be ruled out, resulting in a later delay in the onset of age-related changes, cancer, infectious, systemic, and other diseases. Conversely, a negative prognosis cannot be ruled out. The method can be incorporated into standard examinations of patients with suspected immunodeficiency, immune dysregulation, recurrent infections, or before cardiac surgery with involuntary thymectomy.

[0044] Advantages of the approach:

[0045] - Increased accuracy. Automated analysis minimizes physician error, especially in complex anatomical cases.

[0046] - Time saving. Reducing the duration of the examination allows for an increase in the volume of diagnostic procedures without compromising quality.

[0047] - Training of specialists. The use of age-specific, practical morphometric (morphological) parameters of the thymus creates a unified methodological basis for training ultrasound physicians.

[0048] The proposed method is highly versatile and can be adapted for diagnosing ectopic organs whose tissues have distinct ultrasound characteristics, such as the thyroid gland (e.g., detection of the lingual lobe or follicular structures in unusual locations), the pancreas (detection of the islets of Langerhans outside the typical abdominal location), and the parathyroid glands. For organs with unclear or variable ultrasound features, additional studies are required. For this purpose, the machine learning algorithm can be trained on reference ultrasound parameters specific to each organ. For example, to diagnose thyroid ectopia, the CNN algorithm is trained on reference ultrasound parameters, including high nodule echogenicity, the presence of calcifications, and smooth contours. For the pancreas, the key criteria are hypoechogenicity relative to surrounding tissues and the linear structure of the islets of Langerhans.To assess functional activity, Doppler ultrasonography is used to analyze vascularization and elastography to assess tissue density. This adaptation will standardize the diagnosis of rare anomalies, such as thoracic ectopic pancreas or cervical thyroid remnants, reducing the time and cost of examinations. Furthermore, the method can be expanded to analyze the functional characteristics of organs, opening new horizons for personalized medicine.

[0049] In a context of limited healthcare resources, the implementation of this method will optimize ectopia diagnosis, reduce the costs of additional tests, and improve patient prognosis. Implementing this technology requires the development of specialized software compatible with existing ultrasound machines, as well as clinical trials to verify its effectiveness. This will be an important step in filling the gap in Russian research on thymic ectopia.

[0050] Clinical example:

[0051] Child D., 6, presented with complaints of a neck mass discovered by his mother accidentally during palpation during the height of an acute respiratory infection (acute nasopharyngitis and bronchitis). The medical history revealed that two days after the onset of the illness, the child developed a painless, rounded mass approximately 1 cm in diameter in the projection of the thyroid gland. During the pediatrician's examination, signs of an ongoing infectious and inflammatory process were noted (pharyngeal hyperemia, catarrhal nasal discharge, dry cough), but no significant intoxication was observed. Palpation of the mass was painless; the structure was firm, elastic, mobile, and had clear contours. The child was referred for a thyroid ultrasound at his place of residence. Based on the examination results, a consultation with a surgeon was recommended for a fine-needle biopsy of the mass to determine its origin.

[0052] However, before the invasive intervention, the child's mother sought consultation, based on the results of which it was decided to conduct a repeat ultrasound examination of the thyroid gland area and compare the ultrasound morphometric parameters of the formation with the ultrasound picture of the thymus.

[0053] During the initial ultrasound examination of the orthotopic thymus in the anterior mediastinum, its parameters were recorded: ovoid shape, isoechoicity relative to surrounding tissues, finely punctate hyperechoic inclusions, and lack of pronounced vascularization. An ultrasound examination of the neck in the projection of the thyroid gland revealed a mass with similar characteristics: isoechoicity, clear contours, a heterogeneous structure with finely punctate inclusions, and minimal vascularization.

[0054] Due to ultrasound data corresponding to cervical ectopia of the thymus, a decision was made to postpone invasive intervention and conduct observation until the symptoms of the infectious disease (ARI) are eliminated.

[0055] The child was observed for two weeks until full recovery. After the child's condition returned to normal, a repeat ultrasound of the thymus and thyroid gland was performed. This revealed a threefold reduction in the size of the cervical mass, consistent with reactive hyperplasia of the ectopic thymus in response to the infectious stressor.

[0056] Bibliography:

[0057] 1. Kacker A, April M, Markentel CB, Breuer F. Ectopic thymus presenting as a solid submandibular neck mass in an infant: case report and review of literature. Internat J of Pediat Otorhinolaryngol. 1999; 49(3): 241-245.

[0058] 2. Vedernikova A.V., Rovda Yu.I., Minyaylova N.N., Shmakova O.V., Khobotkova T.S., Chernykh N.S., Khalivopulo I.K., Shabaldin A.V., Sizova I.N., Yunkina Ya.V., Sukhareva O.S. ECTOPIA OF THE THYMUSCLE GLAND IN CHILDREN: PREVALENCE, DIAGNOSIS AND CLINICAL SIGNIFICANCE / / Mother and Child in Kuzbass. 2023. No. 2 (93). P. 58-65.

[0059] 3. Panferova TR, Nilulina AL, Serebryakova IN, Polyakov VG. The ultrasound diagnosis of ectopic thymus tissue in the thyroid gland in children. Onkopediatria. 2015; 2(2): 109-114. Russian (Panferova TR, Nikulina AL, Serebryakova IN, Polyakov VG. Ultrasound diagnostics of ectopic thymus tissue in the thyroid gland in children / / Onkopediatria. 2015. Vol. 2, No. 2. P. 109-114.) DOI: 10.15690 / onco.v2i2.1341.

[0060] 4. Abakir N, Eravcı FC, Emlik GD. Symptomatic solid ectopic cervical thymus in a 2-month-old infant: case report. Turk Arch Otorhinolaryngol. 2021; 59: 154-157. DOI: 10.4274 / tao.2021.2021-2-16.

[0061] 5. González AMH, Rivera DM, Peralta MP. Ectopic cervical thymus: a case report. Rev Colomb Radiol. 2018; 29(3): 4975-4978.

[0062] 6. Rovda Yu.I., Vedernikova A.V., Dadonov V.V., Badalyan A.F., Shevchuk D.Yu., Kuzmakova A.S., Sukhareva O.S., Shabaldin A.V., Shmakova O.V., Minyaylova N.N., Zinchuk S.F., Chernykh N.S. ASPECTS OF ACCIDENTAL INVOLUTION (AI) OF THE THYMUS IN CHILDREN WHO DIED FROM INFECTIOUS AND NON-INFECTIOUS CAUSES, AS WELL AS WITH SUDDEN INFANT DEATH SYNDROME (SIDS) / / Mother and Child in Kuzbass. 2025. No. 1 (100). P. 4-12.

[0063] 7. Ponseti JM, Gamez J, Vilallonga R, Ruiz C, Azem J, Lóópez-Cano M, Armengol M. Influence of ectopic thymic tissue on clinical outcome following extended thymectomy in generalized seropositive nonthymomatous myasthenia gravis. Eur J Cardiothorac Surg. 2008; 34(5): 1062-1067. DOI: 10.1016 / j.ejcts.2008.07.049.

[0064] 8. Zieliński M, Kuzdzał J, Szlubowski A, Soja J. Transcervical-subxiphoid-videothoracoscopic "maximal" thymectomy-operative technique and early results. Ann Thorac Surg. 2004; 78(2): 404-9; discussion 409-410. DOI: 10.1016 / j.athoracsur. 2004.02.021.

Claims

A method for ultrasound diagnostics of thymus ectopia, including conducting an ultrasound examination, characterized in that a convolutional neural network (CNN) trained on reference ultrasound images of the orthotopic thymus is used, ultrasound examinations of the neck, thyroid gland and mediastinum are performed and automated comparison of scanning parameters in real time using a computer program that contains an image processing module implementing sequential data filtering using a Gabor filter, followed by a trained CNN, the scanning parameters used are isoechoicity of tissue, clarity, evenness of contours, ovoid shape, heterogeneous structure of reduced echogenicity with fine-point hyperechoic inclusions, absence of pronounced central vascularization, upon reaching a similarity coefficient of 90% or more, a high probability of thymus ectopia is diagnosed.