RU2571708C1 - Diagnostic technique for prostate cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: technique involves prostate tomography followed by intravenous administration of a water-soluble contrast agent, which is presented by 50 ml of an iodine-containing non-ionic substance at a rate of administration of 5-7 ml/s. The tomography is performed in the dynamic mode by multispiral X-ray computed tomography in the three-dimensional mode 15, 18, 21, 24, 27, 30, 40, 45, 60, 70, 80 seconds from the moment of the administration of the contrast agent, at a slice thickness of 0.5mm. The formed images are analysed by constructing time variation curves of densitometric density of each volume picture element of the prostate and external iliac artery (EIA). A maximum average densitometric density of the EIA is calculated. Further, by each curve for each moment of time, a difference of the densitometric density of the volume picture element at this and following moment of time is determined by each curve; a segment with the maximum difference of the densitometric density is detected, and its maximum difference is related to the length of this segment. The derived value is further related to the maximum average density of the EIA. The calculated values reflex a specific volumetric blood flow in the volume picture element. The volumetric blood flow values for all the volume picture elements are used to plot a prostate perfusion chart, wherein the segments of the high volumetric blood flow corresponds to the tumour.

EFFECT: accurate localisation of prostate cancer, including the patients who are unable to be examined by magnetic resonant tomography.

2 dwg, 1 ex

Description

The invention relates to medicine, more specifically to urology, and may find application in the treatment of prostate cancer.

Prostate cancer (PCa) is an urgent public health problem. In terms of mortality among men, the disease is in second place. In Russia, in 2000, 37,442 patients with prostate cancer were registered with oncologists in Russia, in 2010 - 107,942 patients, an increase over the past 10 years was 155%. In 2012, about 25,000 new cases of prostate cancer were detected in our country.

Depending on the stage of the process, treatment of prostate cancer may be different (surgical or radiation therapy). In connection with the above, timely verification of the diagnosis is very important. The main methods for diagnosing prostate cancer are determining the level of prostatic specific antigen (PSA) in the blood serum, digital rectal examination and transrectal ultrasound examination (TRUS). According to the recommendations of the European Association of Urology, a multifocal prostate biopsy under ultrasound control is used for morphological verification of the diagnosis [Guidelines on Prostate Cancer. In: EAU Guidelines, edition presented at the 25th EAU Annual Congress, Barcelona 2010. ISBN 978-90-79754-70-0]. Biopsy schemes are most commonly used, which include taking 10-12 biopsy samples from standard points under ultrasound guidance. Widespread diagnostic methods such as TRUS, computed tomography (CT) with intravenous contrast and routine magnetic resonance imaging (MRI) with T-1 and T-2-weighted images play a minor role in identifying the exact location of malignant tumors during their growth within the prostate gland (pancreas) and in the selection of specific areas from which biopsy specimens should be taken. For more than 20 years, discussions have been ongoing about the feasibility of using MRI methods in pre-treatment staging of prostate cancer using dynamic MRI with contrast enhancement, which is considered especially reliable in the diagnosis of prostate cancer with spread beyond the capsule of the pancreas when there is no doubt about the presence of cancer. At the same time, there is no consensus in the literature on the diagnostic value of dynamic pancreatic MRI. Diagnosing prostate cancer without spreading beyond the pancreas is especially difficult. In the early stages of pancreatic cancer, computed tomography (CT) and positron emission tomography (PET) imaging also do not have clinical significance [JBR-BTR. 2010 Mar-Apr; 93 (2): 62-70].

As a prototype, we took the method of radiation diagnosis of prostate cancer through dynamic MRI of the prostate (RV) with intravenous contrast, described in [Oncourology 2013; 4: 25-36], which scans in T2-VI mode based on the Turbo Spin Echo (T2-VI TSE) pulse sequence without suppressing the adipose tissue signal and suppressing it in 3 projections (sagittal, coronary and oblique axial perpendicular to the vertical pancreas axis): field of view 250 mm, matrix 256 × 512, section thickness 3.0 mm, TR / TE = 5300-6800 ms / 117-118 ms; followed by analysis of the curves of the signal intensity over time and the calculation of the intensity at the point of "inflection" of the curve, the maximum value of the curve, the slope of the curve after the inflection point. Plots of tumor tissue have a high signal intensity at the “bend” of the curve with its subsequent decrease. However, the determination of the intensity at the point of “inflection” of the curve is variable and poorly reproducible due to the ambiguity of determining the moment of “inflection”, since the authors do not note which point of the “inflection” they use for analysis. In the graphs given by them, there are many such points. This does not follow from the examples of the method given by the authors, the results of which make a conclusion either about the relapse of the process, or about the suspicion of tumor localization, which indicates insufficient accuracy in determining the localization and prevalence of the process. The work, as they note, is of a research nature and so far has no practical significance.

Thus, the disadvantage of the prototype is the lack of accuracy in determining the location of prostate cancer. In addition, such a study cannot be performed in patients with artificial pacemakers, with intracranial ferromagnetic hemostatic clips, with insulin pumps, with neurostimulators, with various implanted metal structures during traumatological operations.

The technical result of the present invention is to increase the accuracy of diagnosis of prostate cancer by accurately determining the location of prostate cancer, as well as expanding the possibility of its use in medical practice.

This result is achieved by the fact that in the known method for diagnosing prostate cancer, including tomographic examination of the prostate after intravenous administration of a water-soluble contrast medium, according to the invention, 50 ml of iodine-containing non-ionic substance with a rate of administration of 5-7 ml / s are used as a contrast, tomographic study perform in dynamic mode by means of multispiral X-ray computed tomography in volume mode for 15, 18, 21, 24, 27, 30, 40, 45, 40, 60, 70, 80 s m The time of introduction of a contrast medium with a section thickness of 0.5 mm, an analysis of the obtained images is carried out by constructing curves of densitometric density over time for each voxel of the prostate gland and the external iliac artery; density of the external iliac artery, which is a perfusion map of the prostate gland, according to which t about the localization and prevalence of prostate cancer.

Having been involved in the treatment of prostate cancer for many years, including its initial stages, when the diagnosis of the tumor process is especially difficult, we have repeatedly faced the need to confirm the diagnosis by biopsy of the pancreas, a rather traumatic procedure, sometimes giving false negative results.

This prompted us to perform dynamic multispiral computed tomography (MSCT) of the pancreas in order to determine the localization and prevalence of the tumor. The choice of the method was primarily determined by the possibility of using it in all patients, including patients with artificial pacemakers, intracranial ferromagnetic hemostatic clips, insulin pumps, neurostimulators, and various implanted metal structures during traumatological operations. It turned out that the dynamic MSCT method allowed us to accurately diagnose the localization of the tumor in cases where other methods did not allow this. Having a specified location, we were able to reduce the invasiveness of the biopsy. Empirically, we determined the study modes that allowed us to identify not only the location of the tumor, but also the prevalence of the tumor process, which was of no small importance for the implementation of surgical intervention as the most effective treatment method.

The essence of the method is as follows.

Patients with a PSA level of 4 to 15 ng / ml, in whom a digital examination of the prostate and ultrasound can not obtain reliable information about the presence of a tumor, performs dynamic X-ray computed tomography.

A 50 ml non-ionic iodine-containing water-soluble radiopaque substance is intravenously administered to the patient using an automatic injector. The introduction is carried out with the following settings: injection rate - 7 ml / s, threshold pressure - 325 PSI. If a threshold pressure is reached during administration, the administration rate is automatically reduced to 5-6 ml / s.

Next, the patient undergoes dynamic MSCT, performing it in volume mode for 15, 18, 21, 24, 27, 30, 40, 45, 40, 60, 70, 80 s from the moment of administration of the contrast medium.

12 volumetric images are obtained in which each voxel reflects a change in densitometric density, which is due to the presence of a contrast agent in it.

Select a rounded site related to the external iliac artery. In the selected area, the average densitometric density at each time point is calculated.

In each voxel of the obtained images, densitometric density is measured (measurements are made in Hounsfield units). For each point in time, the difference between the densitometric density of the voxel at this point in time and in the subsequent one is calculated. Divides the time elapsed between two points. From the obtained values, the maximum is selected and divided by the maximum value of the average densitometric density of the “external iliac artery”. The obtained value reflects the specific volumetric blood flow velocity in the voxel.

Based on the values of the volume velocity obtained for all voxels, perfusion maps are constructed on which high volume velocity regions correspond to the tumor.

The essence of the method is illustrated by example.

Example 1

Patient R., 60 years old, was in the urology department of the Russian Science Center, Russian Chemistry and Chemistry, from 11/19/14 to 12/16/14.

From the anamnesis it is known that on 06/18/13, during the examination, he revealed an increase in PSA level to 5.97 ng / ml.

It is also known that in April 2013 the patient was operated on for a fracture of the bones of the right forearm - metal structures were implanted.

When performing transrectal ultrasound of the prostate, no pathological changes were detected.

Performing MRI of the pelvis was not possible due to the presence of metal structures.

It was decided to perform dynamic MSCT for the patient.

09/25/13 in the RSC RCHT performed dynamic MSCT of the pelvic organs. During the study, 50 ml of non-ionic iodine-containing radiopaque substance Omnipack® was administered intravenously to the patient at a rate of 7 ml / s. When conducting the study of the proposed method on the perfusion map, it is seen that at the base of the right lobe of the prostate gland there is a zone of increased blood flow - indicated by an arrow (Fig. 2), while this area is not visualized on a CT scan (Fig. 1).

09/26/13. According to the results of transrectal biopsy of the pancreas under ultrasound control from 5 sighting points of the site with increased blood flow, revealed as a result of dynamic MSCT, in 4 out of 5 micropreparations studied (histological study No. 3207/2013) - prostate adenocarcinoma. Gleason sum 6 (3 + 3). The results of a histological examination indicate an early tumor process.

When performing osteoscintigraphy, chest x-ray, data for a common process were not obtained. Radical surgical treatment was recommended for the patient.

Diagnosis before surgery: Prostate cancer cT2aN0M0.

Operation

11/26/13. Radical posterior prostatectomy.

The histological conclusion of the surgical material: Prostate adenocarcinoma: Gleason sum 6 (3 + 3); monofocal type of growth, the tumor node is located mainly at the base of the right lobe of the prostate gland.

Diagnosis after surgery: Prostate cancer pT2aN0M0.

There are no discrepancies between preoperative and postoperative diagnoses.

The PSA level in June 2014 was 0.0 ng / ml.

Thus, with the help of the proposed methodology, it was possible to visualize and adequately assess the prevalence of a prostate tumor and conduct radical surgical treatment.

To date, since 2012, the proposed method has been diagnosed in 35 patients. In all of them, a biopsy was performed taking into account the results of dynamic MSCT. In 20 of them, the PSA level was 4–9.9 ng / ml, and in 15 10–15 ng / ml. In 34 patients, the diagnosis was confirmed by biopsy. Only one patient with an initial PSA of 4 ng / ml had a negative result.

The proposed method in comparison with the known has several advantages:

1. Increase the accuracy of the study.

2. The ability to examine patients for whom MRI is not possible.

The method was developed in the computed tomography and operative urology departments of the Federal State Budget Scientific Center of the Russian Science Center for Chemotherapy and passed clinical testing in 35 patients with a positive result.

Claims (1)

A method for diagnosing prostate cancer, including a tomographic study of the prostate after intravenous administration of a water-soluble contrast agent, characterized in that 50 ml of iodine-containing nonionic substance is used as a water-soluble contrast agent at a rate of administration of 5-7 ml / s, the tomographic study is performed in a dynamic mode by means of multispiral X-ray computed tomography in volume mode for 15, 18, 21, 24, 27, 30, 40, 45, 60, 70, 80 s from the moment of introduction of cont substance, with a thickness of 0.5 mm sections, analyze the obtained images by plotting the curves of densitometric density over time for each voxel of the prostate gland and the external iliac artery, calculate the maximum average densitometric density of the external iliac artery, then for each curve for each point in time determine the difference between the densitometric density of the voxel at this point in time and later, identify the plot of the maximum difference densitometrically density and calculate its ratio to the duration of this section, then determine the ratio of the found value to the value of the maximum average density of the external iliac artery, the obtained values reflect the specific volumetric blood flow velocity in the voxel, based on the values of the volumetric velocity obtained for all voxels, make up a perfusion map of the prostate gland, where areas of increased volumetric blood flow velocity correspond to the tumor.

Images