RU2815158C1 - Method for differential radiation diagnosis of adrenal tumors in children using multispiral computed tomography with intravenous contrast enhancement - Google Patents

Abstract

FIELD: medicine; oncology.

SUBSTANCE: invention relates to X-ray diagnostics, and can be used for differential diagnosis of adrenal tumors in children. Multispiral computed tomography with intravenous contrast enhancement is performed. Thereafter, a malignancy index (MI) is calculated. If MI is more than 0.5, malignant nature of formation is diagnosed.

EFFECT: method provides selecting the most effective approach to managing the patients by determining the nature of the neoplasm.

1 cl, 7 dwg, 3 tbl, 2 ex

Description

The invention relates to medicine, to oncology, namely to radiation diagnostics, multislice computed tomography (MSCT) with intravenous contrast, to methods for semi-automatic calculation of signal intensity in the structure of adrenal tumors for the purpose of differential diagnosis between different histological types of tumors, mainly between malignant ones.

Classification of adrenal tumors

Malignant tumors of the adrenal glands, according to various authors, account for 0.02-0.06% of all malignant tumors.

Adrenal formations can be post-traumatic hemorrhagic in nature, arise as a result of an infectious lesion, and cystic formations of a benign nature can occur. There is also a wide variety of primary adrenal tumors. Secondary neoplastic lesions of the adrenal glands are also not uncommon, for example, in lung cancer. Incidentally discovered formations of the adrenal glands are called incidentalomas, which are divided into hormonally active and hormonally inactive; in the future, it is necessary to classify the identified formation into a more specific category.

There are many different classifications of primary adrenal tumors. For the first time, D.A. tried to solve the problem of creating a clinical classification of adrenal cortex cancer by stages. Macfarlan et al. in 1958. They identified 4 stages based on the TNM classification. Later, the TNM classification was modified by M. Sullivan. Also one of the most convenient is the clinical and morphological classification proposed by Micali and co-authors in 1985. In 1963 O.V. Nikolaev proposed the division of all tumors of the adrenal cortex in accordance with the predominance of the secretion of certain hormones: adodosteromas, glucosteromas, corticoestromes, androsteromas and mixed tumors.

There is a known method for semi-quantitative assessment of changes, based on the processing of one section with the largest number of hypointense inclusions (Nicola Schieda, Abdulmohsen Alrashed, Trevor A Flood, et al. Comparison of Quantitative MRI and CT Washout Analysis for Differentiation of Adrenal Pheochromocytoma From Adrenal Adenoma AJR Am J Roentgenol . 2016 Jun; 206(6):1141-8. doi: 10.2214/AJR.15.15318. Epub 2016 Mar 24.)

Its disadvantage is that changes detected in one section are extrapolated to the entire tumor volume, which can lead to distortion of the real picture. The overwhelming majority of adrenal tumors on axial sections have an irregular shape.

Currently, there are no other methods for assessing and counting microhemorrhages and microvessels and the presence of inclusions in the structure of adrenal neoplasms in the domestic literature.

In foreign literature, there are similar methods for measuring tumors, but not in all of the proposed protocol and there are no proposals for the derived malignancy formula. (Nicola Schieda, Abdulmohsen Alrashed, Trevor A Flood, et al. Comparison of Quantitative MRI and CT Washout Analysis for Differentiation of Adrenal Pheochromocytoma From Adrenal Adenoma AJR Am J Roentgenol. 2016 Jun; 206(6):1141-8. doi: 10.2214 /AJR. 15.15318. Epub 2016 Mar 24; Rosalind Gerson, Wendy Tu, Jorge Abreu-Gomez, et al. Evaluation of the T2-weighted (T2W) adrenal MRI calculator to differentiate adrenal pheochromocytoma from lipid-poor adrenal adenoma Eur Radiol. 2022 Dec; 32(12):8247-8255. doi: 10.1007/s00330-022-08867-4. Epub 2022 Jun 9.)

The objective of the invention is to create a more effective method for determining the histological identity of an adrenal tumor using MSCT with intravenous contrast in the mode of images weighted by magnetic susceptibility for the purpose of differential diagnosis of tumors.

The technical result of the claimed method is to develop an objective method for assessing the internal structure of adrenal tumors and to improve the differential diagnostic capabilities of multi-slice computed tomography between adrenal tumors of different histological origins.

The inventive method is carried out as follows:

Computed tomography was performed on a SIEMENS “SOMATOM Emotion” and Phillips “Brilliants” X-ray computed tomograph.

MSCT includes two stages: at the first stage, the abdominal cavity and retroperitoneal space are examined using standard methods; The examination is performed with the patient lying on his back with his arms extended above his head (to prevent possible artifacts from the bones of the upper extremities). The point of intersection of the midsagittal line of the body with a horizontal line drawn through the xiphoid process of the sternum is selected as the center of the area under study. To obtain a targeting image (topogram), the “Abdomen” mode was used, while the abdominal cavity was visualized in the coronal scanning plane. The topogram is used to plan the axial sections necessary to complete the first stage of the study. The position of the sections is programmed so that the scanning area includes the space from the diaphragmatic surface of the liver to the bifurcation of the aorta and the inferior vena cava. The thickness of the slice is 6 mm, the size of the field of view is 25-30 cm. The first stage of the study allows you to assess the condition of all organs of the abdominal cavity and retroperitoneal space, determine the localization of the adrenal glands, and identify pathological formations in one or both glands.

Obtaining thin sections and reducing the scanning field allows you to study in detail the structure and contours of the adrenal glands, measure the size of all parts of the gland (body, lateral and medial legs). If a pathological formation is detected, its structure is studied in detail, the densitometric characteristics of different parts of the tumor are assessed, and the relationship of the pathological formation with adjacent parenchymal organs and large vessels is determined. For more accurate spatial orientation at the location of the tumor, images in the coronal and sagittal scanning planes are reconstructed from a series of axial sections.

In order to clarify the nature of the identified changes, a contrast agent was administered. The contrast agents used were: “Ultravist-240” from SCHERING; "Omnipak-240" from NYCOMED IMAGING at the rate of 0.5-1 ml/kg body weight. The study under contrast enhancement conditions is carried out using axial sections obtained at the second stage immediately after injection.

Native phase with chest capture.

The arterial phase is 1 sec, the first post-contrast image is obtained after 20 sec, then at 4 minutes of the study.

Venous phase 20 sec

Excretory phase 240 sec

Signal normalization was not performed for data analysis.

Signal intensity - how bright or dark the structure appears against the background of surrounding tissue or, in quantitative analysis, the average signal intensity (SI) in the area of interest.

Signal heterogeneity - the presence and severity of uneven distribution of the structure signal against the background of surrounding tissues or during quantitative analysis, the spread of signal intensity values within the studied area, which can be assessed as the absolute value of the standard deviation of signal intensity (SD SI) or the ratio of SI SI to the value itself IP in the area of interest.

These characteristics are available for simple visual analysis, but they can also be assessed quantitatively using a standard workstation interface, which allows you to set specific quantitative reference values for these indicators.

The IP in the proposed method was also assessed by its absolute value.

In the 64-bit Radiant viewer program, a zone of interest is selected in the axial plane, including point (microhemorrhages, calcification) and linear (microvessels, fibrosis) structures.

Then, using manual segmentation, intratumoral structures are identified on each section using a cursor in the form of a solid circle, after which the program automatically summarizes all sections with selected areas of interest, calculates the total volume of microhemorrhages and constructs a three-dimensional object. Next, the software automatically calculates the volume, shows the maximum and minimum density values and the standard deviation of the heterogeneity.

The method is illustrated in figures 1-7.

Figure 1. A CT slice is shown in transverse projection in the native phase.

Using the Radiant viewer 64 bit program, when measuring with an ellipse, the maximum, average and minimum value of the density of the formation (tumor) of the adrenal gland is determined.

Using ROC curves (Figure 2), the point of separation of CT indicators into malignant and non-malignant formations is identified. The following indicators were statistically significant:

CT density pre-arterial phase (native)

Using the ROC curve (Area under the curve was 0.817 (95% CI 0.727-0.906, p = 0.001), the Youden critical point is determined - the density value of 31 HU (Hounsfield), the sensitivity of which was 95.0% with a specificity of 60.0 %. At a density less than this value, the probability of a malignant formation is low (6/27 = 22.2%), and higher - high (95/109 = 87.2%, p = 0.0001). On the graph, you can select another critical the point where the specificity is higher - 33.5..., the sensitivity in which was 79.2% with a specificity of 71.4%. At a density <33.5... the probability of a malignant formation is low (21/47 = 44.7%), and >33.5 - high (80/89=89.9%, p=0.0001).

SD CT native phase

Using the ROC curve (Figure 4), the area under the curve was 0.639 (95% CI 0.536-0.741), p = 0.015, the Youden critical point is determined - the SD value is 10.0, the sensitivity of which is 82.9% with a specificity of 45 ,4%. When the index is less than this value, the probability of a malignant nature of the formation is high (44/51=86.3%"), and above it is low (57/85=67.1%, p=0.015).

Figure 3. A CT slice is shown in the transverse projection in the arterial phase. Using the Radiant viewer 64-bit program, when measuring with an ellipse, the maximum, average and minimum value of the density of the formation (tumor) of the adrenal gland is determined.

Figure 5. A CT slice is shown in the transverse projection in the venous phase. Using the Radiant viewer 64 bit program, when measuring with an ellipse, the maximum, average and minimum value of the density of the formation (tumor) of the adrenal gland is determined.

Figure 6. A CT slice is shown in transverse projection during the excretory phase. Using the Radiant viewer 64 bit program, when measuring with an ellipse, the maximum, average and minimum value of the density of the formation (tumor) of the adrenal gland is determined.

CT density post-venous phase (CT post)

Using the ROC curve (Figure 7), the area under the curve was 0.692 (95% CI 0.589-0.794, p = 0.001), the Youden critical point was determined - the density value was 67.4 HU, the sensitivity of which was 70.3% at specificity 65.7%. At a density less than this value, the probability of a malignant formation is low (30/53 = 56.6%), and higher - high (71/83 = 85.5%, p = 0.0002).

Thus, the following indicators were statistically significant:

To identify prognostic factors among the indicators for which threshold values were found, a univariate regression analysis was performed.

As can be seen from the table, all indicators are statistically significant. At the second stage, multivariate regression analysis is carried out. The regression model, built by the stepwise elimination method, had a coefficient of determination of 0.81 at p = 0.0001, which allows it to be used in practice. Coefficients for calculating the malignancy index were obtained.

To make an individual prognosis for the presence of a malignant formation, the malignancy index is calculated using the formula:

IZ=0.014* CT native - 0.030* SD CT native + 0.007* CT post,

where: IZ is the malignancy index, standard calculated coefficients for CT modes in the native phase (0.014), for the SD standard deviation indicator in the native phase (0.030), for the CT indicator in the post-venous phase (0.007) and the density value itself in the corresponding phases of the study.

If the resulting amount is more than 0.5, the malignant nature of the formation is predicted. If the amount is less than 0.5, the presence of malignant growth is unlikely.

The sensitivity of this model was 90.1%, specificity - 57.1%, accuracy - 81.6%. the predictive value of a positive result is 85.8%, the predictive value of a negative result is 66.7%.

Thus, the claimed method increases the diagnostic capabilities of multislice computed tomography with contrast for adrenal tumors, which facilitates the selection of optimal management tactics for patients with adrenal tumors.

Clinical example No. 1.

A 2.4-year-old girl (I/B 11/1201) diagnosed according to histological examination with stage 1 ganglioneuroma of the left adrenal gland. Both studies were completed.

FROM (CT) = 0.014 * 23.68 - 0.030 * 10.19 + 0.007 * 48.42 = 0.365

According to CT data, the Malignancy Index was 0.365, i.e. Based on the examination data, a conclusion can be made about the non-malignant nature of the formation.

Clinical example No. 2.

A 2.5-year-old girl (I/B 15/2354) diagnosed according to histological examination with stage 1 neuroblastoma of the right adrenal gland. Both studies were completed.

FROM (CT)=0.014*31.51 - 0.030*5.2+0.007*68.73=0.766

According to CT data, the Malignancy Index was 0.766, i.e. Based on the examination data, a conclusion can be made about the malignancy of the formation.

Claims (5)

A method of radiological differential diagnosis of adrenal tumors in children, which consists in performing multislice computed tomography with intravenous contrast, after which the malignancy index (MI) is calculated using the formula: MI = 0.014* CT native - 0.030* SD CT native + 0.007* CT post , Where CT native – average signal intensity of the adrenal gland in the native phase; SD CT native - the absolute value of the standard deviation of the signal intensity of the adrenal gland in the native phase; CT post - average signal intensity of the adrenal gland in the post-venous phase, and, if the IZ is more than 0.5, then the malignant nature of the formation is diagnosed.