DE10318429B4 - Method for determining functional parameters of the lung - Google Patents

Abstract

Method for determining functional parameters of the lung, wherein images of the lungs are created at different phase points of respiration, wherein the change in tissue density is determined by sectional comparison of the image recordings, wherein by means of an imaging system, in particular an MR device, in the frame Proton density is determined as a measure of the tissue density, wherein the two-dimensional or three-dimensional image recordings are segmented into macroscopic areas, for each area an alveolar signal value is determined as the sum of the alveoli and the surrounding tissue derived signals over the area, from which by comparing the alveolar signals of the same At various phases of respiration, the alveolar ventilation as a measure of tissue density is determined using the formula V = (S1-S2) / (S1-SR), where S1 and S2 are the alveolar signals and SR is the background noise signal.

Description

For the diagnosis and treatment of lung diseases, it is necessary to measure the functional parameters of the lungs by location and time. In healthy people, the lung is almost homogeneous, that is macroscopically, the lung is inhaled evenly filled with fresh air and emptied evenly when exhaling. The very thin lung tissue is traversed by a few large and many small blood vessels and bronchi. In a number of different lung diseases, certain areas do not participate in the exchange with fresh air. Such areas may, for example, be filled with mucus, for example pneumonia = pneumonia. Such areas can already be partially recognized with today's X-ray and MR methods.

In certain diseases, however, parts of the lung are filled with air, without any exchange with the fresh air or replacement is at least hindered. In asthma, a narrowing of the airways leads to an at least delayed, but usually insufficient, expiration of the air. This not only leads to a correspondingly reduced performance of the lung, but over a longer period of time to permanent damage to the lung tissue (emphysema). The most common cause of this, especially in young patients, are asthmatic diseases or allergies and metabolic diseases (cystic fibrosis and others), which lead to a local constriction or even collapse of the airways and in the longer term to a destruction of the lungs.

In order to be able to recognize such functional lung diseases, so-called hyperpolarized gases have hitherto been introduced as contrast agents in the lung, among other things. These gases with a nuclear spin are polarized under laser bombardment in a static magnetic field and administered to the patient for inhalation. The concentration of hyperpolarized atoms can then be recorded in the MR scanner. Unfortunately, the corresponding isotopes are extremely rare, or extremely difficult to provide (for example, He _{3 forms} only 0.01% of the naturally occurring helium and, due to the low density after release in the atmosphere, leaves the earth forever) or deliver because of the low Resonance frequency and the poor degree of hyperpolarization only a comparatively low contrast. This is for example the case for Xe ₁₂₉ with a frequency of approximately ¼ of the proton frequency and a degree of hyperpolarization of only a maximum of 10%, while at He _{3 it} would be approximately 60%. In addition, the apparatus-related expense of the MR scanner when using hyperpolarized gases is not to be underestimated. Because of the lower resonant frequency with respect to protons, a correspondingly dedicated RF system is required, which entails additional costs. In addition, HPG MR measurement is limited in its repeatability, as these gases do not contribute to oxygen saturation and therefore are considered critical in patients with impaired lung function. Alternatively, a study with radioactive gases (lung scintigraphy) is possible.

From the US 2003/0055331 A1 For example, a method for endobronchial diagnosis through the use of imaging is known. Furthermore DE 100 55 564 A1 and the US Pat. No. 6,338,836 B1 pointed.

The invention has for its object to provide a method which allows a fast, cheap, radiation-free and better spatially resolved detection of functional defects of the lungs, as well as an accurate detection of the action of therapies.

This object is achieved by a method according to claim 1.

While exhaling an increase in tissue density occurs in normal-functioning lung tissue, this is not the case for areas where there is no exchange with the fresh breath and which consequently do not change their volume during inhalation and exhalation.

In asthmatic or otherwise diseased lung tissue, the density decreases only delayed and / or to a lesser extent during exhalation.

According to the present invention, the tissue density change is determined by determining the proton density as a measure of the tissue density by means of an imaging system, for example a spiral CT device, but in particular by means of an MR device.

ist, wobei S_ni das Messsignal ist, das von einer der n₁ Alveolen und dem sie umgebenden Gewebe erzeugt wird, so ändert sich beim Einatmen dieses Signal dadurch, dass das gleiche betrachtete Messvolumen nunmehr von n₂ Alveolen ausgefüllt wird, wobei n₂ kleiner ist als n₁. Das Signal einer einzelnen Alveole bleibt wie gesagt aufgrund des unveränderten Gewebeanteils gleich, sodass das gesamte MR-Signal S₂ nunmehr ist

The determination of the alveolar ventilation by the determination of the proton density is based on the fact that the measurement signal emanates almost exclusively from the walls of the alveoli and the remaining lung tissue, while the air contained in them makes almost no contribution to the measurement signal. Assuming that the entire MR signal

where S _{ni is} the measurement signal from one of the n ₁ alveoli and the surrounding tissue is generated when inhaled, this signal changes in that the same measurement volume under consideration is now filled by n ₂ alveoli, where n _{2 is} smaller than n ₁ . As already stated, the signal of a single alveol remains the same due to the unchanged tissue component, so that the entire MR signal S _{2 is} now

Since S _{ni is} constant, S ₂ deviates from S ₁ and allows the calculation of alveolar ventilation.

The alveolar ventilation (V) is given by: V = (S ₁ -S ₂ ) / (S _{1 -SR} ).

Here, S _{R is} the signal of background noise (the inhaled air).

From the temporal change of the ventilation further functional data such as the ventilation speed, the tidal volume, the residual volume or the reserve capacity can be calculated, which can then also be graphically represented in a corresponding manner.

Furthermore, 2D images or 3D images of the lungs are segmented into macroscopic areas, wherein for each area the difference to the air is determined as a measurement signal and compared with the measurement signal of the same area to another phase point of the respiration.

In order to compare in each case the same areas with each other, which can indeed move considerably when breathing in and out, can be provided according to a further feature of the present invention that anatomical features such. As the blood vessels, the diaphragm or the bronchi, segmented in the lungs and the areas are associated to the features and that for locating the mutually comparable measuring volumes, the shifts of the areas is determined by the displacement of the anatomical features. This recognition of the respective same area on the basis of the position between certain blood vessels can also be exploited in such a way that the stretching or compression is calculated from the displacement of the areas between the images recorded at different phase points of the respiration.

Finally, it is also within the scope of the invention that a color-coded map of the areas is superimposed on the anatomical image of the thorax, wherein each area is colored according to the change in the proton density and / or the speed of the change.

In addition, the present invention also enables an improved quantitative assessment of the efficacy of asthma therapy using lung functional magnetic resonance (fMRL). Asthma therapies are very expensive and associated with high case numbers.

A quantitative assessment of the effectiveness of an asthma therapy is, for example, in US 6,338,836 B1 described in which the asthma patients hyperpolarized gases and asthma provokants are administered with and without therapeutic agents and the generated MR images are compared with each other. However, this known evaluation method is subject to the restriction that it can be used only a few times, since a hyperpolarized gas contributes to oxygen saturation and therefore should be viewed critically from the outset in patients with impaired lung function, especially asthma patients.

It is conceivable that the assay for evaluating the efficacy of aromatherapeutics is carried out by means of the functional magnetic resonance examination of the lung according to the invention, wherein after an fMRL without additions to the respiratory gas the patient is administered an inhalation substance which contains an asthma agent and / or a therapeutic agent, preferably using a dose whose effect is not measurable integrally across the lungs with a pulmonary function test site, because the change is below the biological fluctuation range.

Thereafter, a measurement is again performed without administration of additional inhalants to detect changes from the first step, for example, across the entire lung. Advantageously, a new map of the lung is shown, which shows where deviations have occurred.

Finally, it is then decided in a fourth step whether the second step is repeated with an increased dose or whether the examination can be ended. Accordingly, if necessary, further steps of an investigation with regard to the dose increased inhalants and subsequent control measurements can be connected.

Further advantages, features and details of the invention will become apparent from the following Description of an embodiment and with reference to the figures. Showing:

1 a schematic representation of a lung in the exhaled and

2 a schematic representation of a lung in the inhaled state,

3 a representation of a cubic measurement volume in the exhaled state, which is filled by n ₁ alveoli,

4 a schematic representation of the same cubic measurement volume in the inhaled state, in which this measurement volume is filled by n ₂ alveoli,

5 an MR image of a lung, with different regions 1, 2 and 3 marked in a lung to be viewed separately,

6 the proton density over two respiratory cycles in areas 1, 2 and 3 of 5 .

7 the calculated results of regional ventilation determined in the measurements in ml / cm ³ , and

8th a flow chart for an evaluation of an asthma therapy using the method according to the invention of a functional magnetic resonance of the lung (fMRL).

In 1 is the lungs at maximum expiration and in 2 shown at maximum inspiration. To prepare these images, the patient is positioned in an MR scanner so that the lung is in the FOV. From various phases of the breathing, in the illustrated embodiment with maximum inspiration and maximum expiration, an MR image is produced in each case. The change in the proton density as a function of the phase point of the respiration (or time) gives a measure of the homogeneity and thus also of any functional lung diseases.

For this purpose, the 2D image of the lung can be divided into macroscopic areas, for example 100 squares, by means of a computer. The computer then determines the signal difference for each square in comparison to the air for inspiration and expiration. The computer also segments the blood vessels of the lungs and associates the segments with these vessels.

In each case to compare the same lung area in the inhaled and exhaled state, so for example, despite the shift in inhalation, the measuring volume M1 in 1 also applicable with the same measuring volume M1 in 2 to compare, in which the schematically drawn blood vessels 1 and 2 as well as the remaining tissue have changed their distance significantly (b> a), the above-mentioned segmentation is made to the vessels or other features, such as the bronchi or the diaphragm. The computer then determines the displacement of each segment between inhalation and expiration and the density change.

The 3 and 4 each show a measuring volume M1, for example, the measuring volume M1 in the 1 and 2 in the inhaled and exhaled state. This cubic measurement volume M1 is determined by n ₁ alveoli in the exhaled state according to 1 filled. The entire MR signal S ₁ is

Based on the fact that it is healthy lung tissue, the cubic measurement volume in the inhaled state is filled by fewer, namely n ₂ , alveoli. The signal of a single alveol remains the same, as there is an unchanged tissue portion. The entire MR signal is

It is important that S _ni = constant.

The alveolar ventilation (V) is given by: V = (S ₁ -S ₂ ) / (S _{1 -SR} )

Here, S _{R is} the signal of background noise (the inhaled air).

The 5 shows an MR image, wherein in the right-hand drawn lung three measuring ranges M1, M2 and M3 are marked, in which different lung functions are present.

The 6 shows the proton density over two respiratory cycles respectively in the area of the areas M1, M2 and M3, whereby in addition also the noise signal is drawn in, which is practically negligible.

The 7 shows the regional ventilation in ml / cm ³ , which can be calculated from the measured data, which shows considerable differences for the three lung areas represented by the measurement volumes M1, M2 and M3.

The data obtained may be displayed by the computer superimposing on the anatomical image of the thorax a color-coded map of the segments, each color segment being colored according to the change in proton density and / or the rate of change.

Instead of determining the proton density change and thus also the tissue density change using the method described above, the computer can also directly determine the elongation of the lung segments from the displacement of the blood vessels and then combine these measurements with the previously indicated measurement. If one assumes that emphysema is present at a certain point, this means that the two adjacent blood vessels do not change their distance in contrast to an approach in the rest of the lung. This allows a determination of the elongation of the corresponding lung segments.

The computer takes into account not only the maximum inspiration and expiration, but also advantageously phase points in between. From this, the local inspiratory and expiratory velocity can be determined and, alternatively or additionally, for example, color-coded, displayed.

The presented invention represents a completely new paradigm of the diagnosis of functional lung diseases. Because of the short measuring time and the lack of radiation exposure for the patient, it is cheap and can also be used in the context of screenings. In the long term, youthful ventilation defects lead to emphysema, that is, a rapid reduction in lung vitality. These patients then need an overnight oxygen supply at the age of 50 or 60 and have only a very short life expectancy due to their high susceptibility to, for example, pneumonia (pneumonia).

The 8th shows a flowchart of a method for the quantitative assessment of the effectiveness of an asthma therapy.

First, the patient is registered and positioned in the MR scanner. This is followed by a functional MR measurement of the lung (fMRL) to determine the starting position. The patient is then administered a substance for inhalation containing an asthma agent, preferably in a dose whose effect is not measurable integrally across the lung with a pulmonary function test, because the change is below the biological variation range. This is followed by another fRML measurement. If there is no response from the asthma provoker, the provocative administration step is repeated at a higher dose and the above measurement cycle is performed. If a response to the asthma provocative occurs, a bronchodilator / asthma therapy is administered and then measured to determine if the asthma therapy has responded. If the dose is insufficient or the agent is ineffective, re-administration of the asthma medicinal product may be re-administered at a higher dose or with an altered active substance. If the dose was sufficient for a satisfactory improvement to occur, the evaluation procedure is terminated.

Claims (6)

Method for determining functional parameters of the lung, wherein images of the lungs are created at different phase points of respiration, wherein the change in tissue density is determined by sectionally comparing the image recordings, wherein by means of an imaging system, in particular an MR device, in the frame Proton density is determined as a measure of tissue density, wherein the two-dimensional or three-dimensional image recordings are segmented into macroscopic areas, for each area an alveolar signal value is determined as the sum of the alveoli and the surrounding tissue derived signals over the area, from which by comparing the alveolar signals of the same areas at different phase points of the respiration alveolar ventilation as a measure of the fabric density according to the formula V = (S ₁ - S ₂₎ / (S ₁ - S _R) is determined, where S ₁ and S _2, the Alveolensignale and S _R, the signal of the background noise are. A method according to claim 1, characterized in that the image recordings are created at maximum inspiration and expiration. A method according to claim 1 or 2, characterized in that anatomical features are segmented in the lung and the location of the areas are determined to the features and that the localization of the areas to be compared with the displacement of the areas is determined by the displacement of the anatomical features. A method according to claim 3, characterized in that an elongation or compression of the areas from the displacement of adjacent anatomical features are determined. Method according to one of claims 2 to 4, characterized in that an anatomical image of the thorax is a color-coded map of the areas is superimposed, each area is colored according to the change in the density of protons and / or the speed of change. Method according to one of the preceding claims, characterized in that further local or global functional parameters of the lung, in particular the ventilation, the tidal volume, the residual volume or the reserve capacity, are calculated from the change in tissue density.

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