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Ultrasound technology for accurate screening of “nodules” in the smallest detail

If you could “run” 1,590 meters per second, it would take only 26 seconds to run from Marathon Beach into the plaza in Athens. This is the speed of ultrasound propagation in the soft tissues of the human body, which is also the cornerstone of ultrasound for human disease diagnosis.

Ultrasound technology is essentially in the “shouting” and “listening” to achieve the internal structure of the object to explore. Ultrasound detector probe is a high-frequency sound waves issued by the mouth, but also a pair of sensitive ears, it first to the thyroid gland “shout” out of high-frequency, inaudible ultrasound, and then the reflected ultrasound back to receive. The ultrasonic waves that go back and forth through the thyroid gland and part of the reflection back, encounter different densities of tissue, 1 590 m / s speed changes, the reflected back to the ultrasonic waves also changed, the probe “hear” the ultrasound and then by the machine to translate the signal into images, but also into that dark room seems to be full of noise images. This is how thyroid ultrasound technology “hears” the subtle changes in the thyroid gland, and it is this ingenious method that has brought the diagnosis and treatment of thyroid disease to a new level.

Ultrasound technology, “listening” to nodules in the smallest detail
The thyroid gland is a very special organ. This butterfly-shaped organ is only about 5 cm x 2 cm in size, but it is the largest endocrine gland in the body and is very powerful. Like other organs and tissues in the human body, the thyroid gland is “equal” to cancer, but the size and characteristics of the thyroid gland make the diagnosis of thyroid cancer not an easy task.

For a long time, the screening method for thyroid nodules was somewhat tedious and primitive – palpation. Because the thyroid gland is superficial enough to move up and down with swallowing, a skilled surgeon can easily locate the thyroid gland and then carefully feel it to the touch to determine if it is smooth, mobile, etc.

The surgeon’s touch of the lump is only the first step; it is more important to determine the nature of the lump. For most lumps, if palpation reveals a smooth surface, good mobility and a soft texture, it can be considered to be benign; if the surface is irregular, rough, hard and poorly mobile, the lump is more likely to be malignant and has more distinctive features. But for the thyroid gland, the familiar criteria seem to be “out of order” all of a sudden. “There are many types of thyroid nodules, including substantial, cystic and cystic, and there is a lot of overlap between benign and malignant nodules, which is difficult to distinguish by clinical palpation alone.” Director Wu said. Parenchymal nodules are usually harder, cystic solid the next hardest, and cystic the softest, but both malignant and benign nodules may be present in these cases. And even the hardest textured thyroid nodules (which are usually considered to have a high probability of malignancy) have several benign conditions present. “Even an ultrasonographer, who identifies them by the two-dimensional image of the ultrasound, can sometimes misjudge them, let alone rely on hand palpation.”

In the past decade or so, as ultrasound technology continues to mature and develop, ultrasound is not only widely used in the examination of thyroid disease, but is also the cornerstone of clinical diagnosis of thyroid disease and assessment of benign and malignant nodules, which is the main reason for the rapid growth in the incidence of thyroid nodules today, and the level of diagnosis and treatment of thyroid disease has undergone a “sea change”, which has given countless patients with thyroid disease the opportunity for early intervention, timely and reasonable treatment.

Combined use of four ultrasound technologies for graded assessment with low omission
Currently, ultrasound is used for thyroid examination, namely two-dimensional ultrasound, color Doppler, elastic ultrasound, and ultrasonography, the first three of which are tissue imaging and the latter functional imaging. Due to the different nature of thyroid nodules, some characteristic structural and blood supply changes are produced, while the different evaluation indicators point to different nodule types. The ultrasound presentation of thyroid nodules is complex, varied and bizarre, and often results in different images of the same disease and different diseases, and physicians are often misled by them. The combined application of multiple ultrasound techniques can help us to get out of the dilemma, gradually exclude suspicious problems and improve the accuracy of ultrasound assessment of thyroid nodules.

Ultrasound (considered as the first eye of the ultrasonographer)

Ultrasound is a two-dimensional, black-and-white imaging technique that shows the structure and echogenicity of the thyroid gland at different depths and in different sections, observes the size and shape of the thyroid gland and the uniformity of the internal echogenicity distribution, shows the size, shape, margins, internal structure, echogenicity, aspect ratio, calcification, etc. of various nodules, and thus provides a comprehensive assessment of the nodules. It shows the size, morphology, margins, internal structure, echogenicity, aspect ratio, and type of calcification, etc., to evaluate the nodule classification and the nature of the nodule.

Doppler ultrasound (considered as the second eye of the sonographer)

Based on two-dimensional images, the Doppler ultrasound effect is applied to display and observe changes in the morphology of the distribution of blood vessels in the thyroid gland or nodule and to detect hemodynamic parameters, which adds to the qualitative assessment of thyroid nodules.

Flexible ultrasound (considered as the third eye of the sonographer)

To more accurately determine the texture of nodules, elastic ultrasound is an excellent option. This is a very clever method in which the sonographer applies slight pressure to the probe during the examination and the thyroid gland, along with the nodule, is squeezed, resulting in different degrees of strain on the “hard nodule” and the “soft nodule. The difference in strain rates between normal and abnormal tissue is picked up and color coded and displayed in red, green and blue (soft, medium and hard) to help us determine the hardness of the gland and whether the nodule is a hard or soft nodule, and thus further assess the nature of the nodule.

Director Wu has called these benign nodules that are hard and look like malignant nodules (after mechanization of bleeding benign nodules or ablation of benign nodules) as “zombie nodules”, and with ultrasonography, these “zombie nodules” are nowhere to be seen.

Ultrasonography (considered as the fourth eye of ultrasonographer)

Ultrasonography is an injection of an acoustic Novel microbubble contrast agent into a vein at the elbow of the body. The microbubble of the contrast agent dynamically displays the microvascular perfusion of the thyroid gland and nodules through the blood to observe and analyze the nodule vascular initiation, distribution of blood flow, perfusion and fading characteristics of blood flow. In general, most benign and malignant nodules have certain patterns and characteristics, but benign “zombie nodules” do not have enhanced perfusion, so a clear judgment can be made; similarly, the “white knight” of Hashimoto hyperplasia and focal Hashimoto nodules, ultrasound In addition, papillary carcinoma with an intact envelope is often misdiagnosed as a benign nodule by two-dimensional ultrasound, but ultrasonography has characteristic changes, i.e., radiolucent hyperperfusion in the center of the nodule, which is a unique manifestation of any kind of benign or malignant nodule. These are some of the advantages that make ultrasonography the fourth eye of the sonographer, and they are well deserved.

Accurate diagnosis of thyroid nodules
Modern medicine has gradually entered the era of precision medicine. Director Wu told us that accurate diagnosis of thyroid nodules is the basis of accurate treatment. To achieve accurate diagnosis of thyroid nodules, that is, to achieve the ultrasonography + cytology + genetics system.

Thyroid ultrasound risk stratification system (TI-RADS) is the first line of defense for thyroid cancer screening. ti-RADS assessment is divided into categories 1 to 5. Generally speaking, categories 2 and 3 indicate benign nodules, while category 4 nodules require caution. Category 4 is further divided into 4a, 4b and 4c, with 4a having a malignant risk of less than 10%, 4b less than 50%, 4c less than 90% and category 5 having a malignant risk greater than 90%. Director Wu said, “Ultrasound determines the grading, and if the nodules are greater than 0.5 cm in grade 4 or higher, fine needle aspiration cytology should be routinely recommended; fine needle aspiration is recommended for nodules greater than 2.5 cm in category 3. Standardized and accurate assessment of thyroid nodule classification and recommendation of valuable thyroid nodules for fine needle aspiration cytology is the first line of defense in thyroid cancer screening. Despite the excellent and convenient ultrasound technology, at least at this stage, the final verdict for nodules can only be given by “pathological diagnosis”. For this reason, the current “Guidelines for the diagnosis and treatment of thyroid diseases in China” only use the probability of benign and malignant as the basis for grading, and the final “gold standard” for diagnosis is still pathology.

The pathological diagnosis of thyroid fine needle aspiration cytology is the only gold standard for preoperative diagnosis, which is undoubtedly the second line of defense for clinical thyroid cancer screening. Of course, grading is not the only criterion for recommending puncture. In clinical work, Director Wu would recommend routine characterization by puncture for patients with benign thyroid nodules larger than 2.5 cm. If the nodule is in a high-risk location, such as under the envelope, in the dorsal segment, near the trachea or blood vessels, which may have more serious consequences if it is malignant, fine needle aspiration cytology will be recommended even if it is less than 5 mm. Director Wu reminds that the thyroid is unique in that even if the size of a cancerous nodule is very small, it does not equate to early stage cancer and carries a certain risk of metastasis. “We need to judge according to the situation and the site of cancerous nodules. If the site is special and high-risk, puncture is recommended even if the nodules are small. It is not uncommon for tiny nodules to break through the envelope and even invade the recurrent laryngeal nerve during surgery, and the consequences are serious.” The positive rate of thyroid fine needle aspiration cytology is not high due to a variety of factors, such as the accuracy of the puncture, the quality of the specimen and the pass rate. Also, there are some uncertainties in the cytologic pathology diagnosis, and even when classified as grade 3, 4 or 5 by fine needle aspiration cytology of the thyroid (TBSRTC), 10% to 30% are still diagnosed as malignant by the final histopathology.

Genetic testing, i.e. thyroid cancer tumor molecular marker testing, is a crucial diagnostic basis in the preoperative risk stratification assessment of thyroid cancer. The Guangdong Expert Consensus on Genetic Testing and Clinical Application of Thyroid Cancer (2020 Edition) states that: single gene refers to BRAF V600E testing, and multiple genes include RAS (NRAS, KRAS, HRAS), TERT, PIK3CA, etc. BRAF V600E gene is the most common mutation site in thyroid cancer, with a mutation rate of up to 80% in papillary carcinoma, and in benign The risk of malignancy of thyroid nodules with BRAF gene mutation reaches 99.8%, which can significantly improve the diagnosis rate of clinical papillary thyroid cancer and obviously make up for the lack of cytological pathological false negatives, so it is clinically regarded as the third line of defense for thyroid cancer screening.

The multi-gene test also increases the single gene detection rate of thyroid cancer by 10%-15%, and makes the assessment of malignant risk of thyroid nodules more than 90% accurate, which not only reduces the underdiagnosis rate of BRAF-negative papillary thyroid cancer, but also perfects the subtyping of thyroid cancer, and screens special types of thyroid cancer (follicular carcinoma, medullary carcinoma, hypofractionated carcinoma, undifferentiated carcinoma, metastatic carcinoma). This is the case. Therefore, thyroid fine needle aspiration multigene test is regarded as the last line of defense for preoperative diagnosis of thyroid cancer in clinical practice.

The human factor is the most important factor for the accuracy of thyroid
No matter clinicians or patients, the requirement for imaging examination is often the word “accurate”. And the accuracy of thyroid ultrasound mainly lies in two aspects-mechanics and people. Equipment factors can not be bypassed, the machine resolution, sensitivity will greatly affect the doctor’s recognition of the image analysis, “encounter poor resolution of the equipment, as if there is no presbyopia people with presbyopic glasses in looking at things, for the image of the subtle structure is very difficult to see, analysis. But the problem of equipment is not difficult to solve, the real role of the decision is still the level of the doctor.” Even though big data and artificial intelligence have been widely used in the field of imaging, the dynamic image determination of ultrasound cannot exist without the visual analysis of doctors. “A kind of two-dimensional image formed by the translation of mechanical waves presented on the screen of our instrument, the recognition and understanding of the image will test the level of the doctor.” This actually requires a test of the ultrasonographer’s overall ability.

A good ultrasonographer who can see in the smallest detail can not just stare at the images on the machine. “And ultrasound medicine is not a discipline that just reads images.” Director Wu lamented. A good sonographer must look beyond the screen and recognize that the patient being examined is a person walking on a timeline. “Ultrasound is a transient, dynamic examination, and the physician can only see the patient in the moment, but that is not enough to define the disease.”

Taking a detailed history can provide much of the basis for a differential diagnosis. “For example, in patients with cystic nodule hemorrhage mechanization, without further ultrasonography and fine needle aspiration, the ultrasound image and elastic grade would likely be evaluated as a category 4c or even a category 5 result.” This result can be highly significant for the clinician and also highly likely to send the patient into anxiety and stress. But if the patient ends up having the thyroid removed as a result, this leaves the patient with a needless loss. “In this case, if the patient is questioned and reports from several months ago are identified for comparison, the clues can often be found. Other patients may have undergone thyroid medication injections, ablation treatments, etc., which can also result in serious misjudgments and consequences based solely on the picture of the moment.”

From the patient’s perspective, even if the ultrasonographer does not ask, a recent or previous report of the same area can be provided to the physician to ask for an opinion, so that the accuracy of the diagnosis can be better improved.

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