WO2000022450A1

WO2000022450A1 - Measuring device, nuclear magnetic resonance tomograph, a measuring method, and an imaging method

Info

Publication number: WO2000022450A1
Application number: PCT/DE1999/003280
Authority: WO
Inventors: Stefan Posse
Original assignee: Forschungszentrum Jülich GmbH
Priority date: 1998-10-12
Filing date: 1999-10-12
Publication date: 2000-04-20
Also published as: JP2002527169A; DE19846869A1

Abstract

The invention relates to a measuring device which comprises at least one recording means for recording measurement signals, and a transformation means for transforming the measurement signals into digital measurement data. According to the invention, the measuring device is characterized in that the recording means and/or the transformation means are respectively designed such that they record measurement signals with a different resolution at different times and/or at different locations and/or they transform the measurement signals differently.

Description

description

Measuring device, nuclear magnetic resonance scanner, measuring method and

Imaging technique

The invention relates to a measuring device with at least one detection means for receiving measurement signals and with a transformer for transforming the measurement signals into digital measurement data.

The invention relates in particular to measuring devices with which an imaging method can be carried out. An imaging method is a method in which at least one image is generated from measurement signals. In the imaging method, raw data that is usually recorded is converted into desired image information by means of a suitable transformation, in particular a two-dimensional or three-dimensional Fourier transformation.

The invention further relates to a method in which

Measurement signals are recorded and transformed into digital measurement data and an imaging method. In particular, the invention relates to a nuclear magnetic resonance scanner.

Nuclear magnetic resonance (NMR) is used to obtain spectroscopic information about a substance. A combination of nuclear magnetic resonance spectroscopy with techniques of magnetic resonance imaging (MRI) technology gives a spatial picture of the chemical composition of the substance.

In medical research in particular there is a need to obtain information about brain activity or, in a broader sense, information about blood flow or To obtain deoxyhemoglobin concentration changes in human and titanium organs. The neuronal activation manifests itself in an increase in blood flow in activated brain areas, with a decrease in the blood deoxyhemoglobin concentration. Deoxyhemoglobin (DOH) is a .paramagnetic substance which reduces the magnetic field homogeneity and thus accelerates the T ₂ ^* signal relaxation.

The protons of the

Hydrogen in the water.

Localization of brain activity is made possible by using an examination with functional imaging methods that measure the change in NMR signal relaxation with a time delay (echo time). This is also known as susceptibility-sensitive measurement. The biological mechanism of action is known in the literature under the name BOLD-E ect (Blood Oxygen Level Dependent Effect) and leads to susceptibility-sensitive magnetic resonance measurements with a field strength of a static magnetic field of, for example, 1.5 Tesla up to approx. 10% image brightness modulations in activated brain regions. Instead of the mechanism of action detected with the endogenous contrast agent DOH, other mechanisms of action can also occur, which cause susceptibility changes by means of exogenous contrast agents.

Fast magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) make it possible to investigate the BOLD effect in vivo depending on brain activation states, see: S. Posse et. al .: Functional Magnetic Resonance Studies of Brain Activation; Seminars in Clinical Neuropsychiatry, Vol. 1, No 1, 1996; Pp. 76-88.

NMR imaging methods create layers or volumes selected, which provide a measurement signal under the appropriate irradiation of high-frequency pulses and the application of magnetic gradient fields, which is digitized and stored in a two- or three-dimensional field in the measuring computer.

The desired image information in pixels or voxels is obtained (reconstructed) from the raw data recorded by means of a two- or three-dimensional Fourier transformation. A reconstructed slice image consists of pixels (= picture element), a volume data set consists of voxels (= volume element). A pixel is a two-dimensional picture element, for example a square.

The image is composed of the pixels. A voxel is a three-dimensional volume element, for example a cuboid, which - due to measurement technology - has no sharp boundaries. The dimensions of a pixel are usually only on the order of 1, those of a voxel on the order of 1 nm ² . The geometries and dimensions can be variable.

By comparing the signal curve measured by means of functional imaging in each pixel with the temporal curve of a model function, a stimulus-specific neuronal activation can be detected and spatially localized. A stimulus can be, for example, a somatosensory, acoustic, visual or olfactory stimulus as well as a mental or motor stimulus

Task. The model function, or the model time series, describes the expected signal change in the magnetic resonance signal as a result of neuronal activation. These can be derived, for example, from the paradigm of the respective experiment using empirical rules. It is important to consider a time delay of the model function compared to the paradigm (sluggish reaction of blood flow to neuronal activation).

It is already known how brain activation can be represented by activation images that were obtained from nuclear spin-omorphic data. The activation images can even be calculated and displayed in real time, which means that a data record can be converted into an image before the next data record is measured. The time interval is typically 1 to 3 seconds.

The invention has for its object to design a generic measuring device so that it is suitable for detecting different measurement signals with the highest possible resolution.

According to the invention, this object is achieved in that the detection means and / or the transformation means is designed in such a way that it detects and / or transforms measurement signals with different resolutions at different times and / or at different locations.

A particularly effective selection of the measurement data can be achieved in that the measurement device is designed in such a way that it contains at least one control unit for controlling the detection means and / or the transmission means.

The control unit can be, for example, a computer or a component of a computer. The term _^ Computer "is in no way intended to be limiting. This may be be any suitable unit for performing calculations, for example a workstation, a personal computer, a microcomputer or a circuit suitable for performing calculations.

A particularly advantageous embodiment of the measuring device is characterized in that it has at least one memory unit, the memory unit containing information for the variable transformation of the measurement signals into the measurement data.

The term “storage unit” is meant in a general sense. The embodiment of the storage unit is irrelevant, since it is only necessary to store values or non-volatile memories are known.

The invention furthermore relates to carrying out a generic method in such a way that measurement signals with different resolutions are acquired and / or transformed differently at different times and / or at different locations.

It is particularly advantageous to carry out the method in such a way that the measurement signals are detected differently and / or transformed differently to an extent that corresponds to at least one model.

The model describes an actual course of the

Measuring signals or an expected course of the measuring signals or a combination of an expected course of the measuring signals and an actual course of the measuring signals. For example, it is a model function that assigns a measurement signal an extent in which it is in the Measurement data is transformed. However, a direct calculation of the extent is not necessary since it can also be approximated in a suitable way or replaced by a table corresponding to particularly advantageous values.

The model indicates, for example, the extent to which the measurement signals are stored and / or converted into the digital measurement data.

It is also expedient that the model determines the resolution with which the measurement signals are detected.

An advantageous embodiment of the method is characterized in that the model is determined before the measurement.

Another, likewise advantageous embodiment of the method according to the invention is characterized in that the model is changed during the measurement.

A further improvement in measuring sensitivity can be achieved by changing the model on the basis of a predetermined starting model.

This takes place, for example, in that the resolution with which signals are acquired and / or converted varies in time and / or location.

It is particularly advantageous to compress the measurement signals and / or the measurement data. The compression factor can vary over the measurement. Such a variation is particularly useful for series of measurements in which activations and rest periods alternate. A higher compression factor can be selected for the rest periods. Particularly useful areas of application of the invention are shown below. They relate in particular to a measuring device that is used in an imaging method.

With the aid of the measuring device, reconstructed slice images or volume data sets are determined from the measurement signals of at least one sample.

The imaging method is, for example, a spectroscopic imaging method, in particular nuclear magnetic resonance spectroscopy. However, the imaging method can also be used in other areas, for example for the graphic display of ultrasound examinations. Since such examinations are generally carried out in vivo, it is expedient that the imaging method is suitable for being carried out in the real measurement time, that is to say in real time.

In particular, a fast spectroscopic

Imaging method realized, the changes in the NMR signal relaxation determined.

The spectroscopic imaging method is preferably a spectroscopic echo pianar

Imaging method. Spatial coding takes place in the shortest possible period of time, which is repeated several times during a signal drop and is usually 10 to 100 ms. By repeating the echo planar coding several times during a signal drop wxro. a course of the signal drop is shown in the sequence of reconstructed individual images.

The number of images that are encoded during the signal drop depends on the relaxation time and the Coding time Δt for a single picture.

In order to detect changes in relaxation with the highest possible sensitivity, a criterion for an optimal choice of the measurement time window depending on the relaxation time constant, the coding time for a single image and the type of data post-processing was found.

The criterion consists in considering a difference signal between different relaxation states.

The difference signal has a maximum in time, which is close to the mean relaxation time for small relaxation changes.

Preferred evaluation methods, further advantages, special features and expedient further developments of the invention result from the following illustration of preferred exemplary embodiments of the invention on the basis of example calculations and drawings.

From the drawings shows:

1 shows an experimental difference signal of a functional relaxation time change in a selected picture element as a function of dε2 measuring time after signal excitation,

2 shows a relative, scaled increase in the contrast-to-noise ratio CNR _» compared to the contrast-to-noise ratio CNRi of an individual measurement for different evaluation methods as a function of the measurements, Fig. 3 in a first partial image A, a detection of

Brain activation in four steps using a conventional imaging method and in partial image _B a detection of brain activation using a method according to the invention,

The preferred embodiments of the invention provide in particular to detect a difference signal at different times. These points in time lie within a time interval _x .

In particular, it is a difference signal between a relaxation curve in an excited state and a relaxation curve in a ground state.

An example is a difference signal (vertical axis ⁾ between a functional relaxation time change ⁽ fMRI signal) in the human brain in a selected image element in the visual cortex during a visual one

Stimulation with an oscillating. Light as a function of the measuring time after signal excitation (horizontal axis ⁾ measured by means of fast spectroscopic imaging is shown in FIG.

This is a particularly simple case in which the difference signal is formed by a difference signal from a relaxation signal during activation and a relaxation signal during a rest state. However, the term “difference signal” is in no way limited to difference signals, but, like the term “difference function”, includes all cases in which differences between measurement curves are detected or evaluated. The measurement is initially carried out with a time interval between the measuring points of approximately 10 to 100, for example 18 milliseconds. The fMRI signals are determined by MRI examinations of the brains of test subjects. A light source, in particular a matrix of luminescent diodes (Light Emitting Diode LED), is positioned in the immediate vicinity of the test person's face and excited to signal flashes. The excitation frequency is preferably around 8 Hz. An action of the lightning signal via a signal synchronized with ^'a carrier signal of a scanner time interval of several seconds, for example 5 seconds, followed by an approximately equally long rest period followed. The scanner is a Vision I, 5 Tesla full-body scanner from Siemens Medical Systems, Erlangen, in standard equipment with a magnetic gradient of 25 mT / m. Such a scanner is able to switch gradients elder within approximately 150 μs.

The imaging method is preferably an echo planar imaging method, for example a conventional Ξcho planar method - EPI (Echo Planar Imaging).

This includes, for example, repeated use of two-dimensional echo planar image coding. Spatial coding takes place in the shortest possible time, which is repeated several times during a signal drop and is preferably 20 to 100 ms. The repetition of the echo planar coding several times during a signal drop shows a course of the signal drop in the sequence of reconstructed individual images. Such an equally advantageous implementation of the method according to the invention is preferably carried out using PEPSI (Proton-Echo-Planar-Spectroscopic-Imaging). In an expedient embodiment of the method, the resolution is adapted to the strength of the relaxation signals. If there are several similar signals whose difference signal is to be examined, it is even more advantageous to adapt the resolution to the difference function. The functional relationship between the resolution and the difference function is preferably chosen so that the value for the resolution is higher for a larger signal.

Assuming an exponential drop in the relaxation curves, the result shown in FIG. 1 results

Difference signal ΔS (t):

AS (t) = S ₀ (e- "^{τ> a)} - e-" ^m ) ^w

where T ₂ ^* (a) and T ^* (b) are relaxation time constants in an activated state (a) and in a basic state (Baseline State - b) and wherein S ₀ denotes an output signal entity.

Assuming a slight change in the relaxation time ΔT ₂ *, the signal difference ΔS (t) is:

(2)

where T ₂ * denotes the relaxation time in the basic state.

There is an essentially bell-shaped curve, the has a maximum at t = T ₂ ^* . In a preferred measurement field of about 1.5 Tesla ärke _t t assumes a typical value of about 70 ms.

The maximum is:

AT

10.37

T

(3)

A preferred embodiment of the invention provides that it is assumed that noise effects are a so-called white, thermal noise with an average close to zero and a standard deviation σ.

By means of suitable implementation forms of the evaluation method, an increased signal-to-noise ratio is achieved compared to a single point measurement. While in a single measurement the contrast-noise ratio (Contrast Noise Ratio CNR ^{) of} the formula

can correspond to those shown here

Implementation forms of the evaluation method an increased contrast-to-noise ratio can be achieved.

A first embodiment of a preferred evaluation method provides for summing the measured effect for N times and forming an average signal. The average signal gives a good measure of Ξ ₀ T _Z. Assuming constant measurement intervals Δt for each individual measured value recording and the same noise level in each

Point applies to the summed signal (t = i X Δt):

(5)

using the inequalities Δt << T ₂ (6) and N >> 1 (7).

A comparatively small change in T _z , as occurs, for example, in the case of blood oxidation (BOLD effect / Blood Oxygen Level Dependent effect), is expressed in the contrast C reproduced below:

_(B)

where x is defined as follows:

Λ Γ Λ + V -LΛt x ^≡ - -

(9)

The noise effects in the summed signal according to formula 8 have the standard deviation:

2Nσ (10) The contrast-to-noise ratio is as follows:

As can be seen, for example, from FIG. 2, the contrast-to-noise ratio has a maximum at x = 3.2. 2, the contrast-to-noise ratio CNR is a function of the length of the measurement time after signal excitation, the relaxation rate R2 = 1 / Υ∑ ^' and a coding time Δt for various

Data evaluation method: summation of the individual measurements (summation), exponentially weighted summation (exponentially weighted summation), optimally weighted summation (weighted summation, weighted filter) and for curve fitting (fitting).

A maximum Kon as-to-noise ratio can be achieved if the measurements are made up to the time

T _nas = NΔt = 3.2T ₂ ^' (12).

For an appropriately chosen N, the contrast-to-noise ratio is maximum and, according to the formula:

₍₁₃ >

maximum 0, 6.

To further increase the contrast-to-noise ratio it is expedient to carry out a weighted summation of the signal according to equation 14.

A weighting factor w (t _N ) according to formula 15 is preferably used in formula 14.

-Rl-t w (t _n ) = R2i _n 'en (15)

An expected relaxation rate in a sample to be examined is included in the weighting factor w (t _N ). This is preferably the average relaxation rate in the sample examined.

The following formula results for the contrast-to-noise ratio:

At _d ies _e r V _a rian _{te de} s evaluation method, the increase takes _d is _S i _g na _l - _R of C _h - _Ve r _h ä _lt ni _s s _s in the multi-point measurement a particular _t he _s as high as 1, 4 on . The measurement time is in turn preferably 3.2 T ₂ \ By such a weighted summation, it is possible, an even better _R e _s u _{LTAT f} or _{s a} r _a _Cont stverhältnis to achieve than with a conventional summation. Even in the simple case that within the jΞloc curve shown in FIG. 1 the resolution is higher by a factor of 2 than in other time ranges, the noise is reduced by a factor of l / v2.

Another variant of the evaluation method is that an adaptation procedure (fit method ^{) is carried out} by adapting the relaxation curve to exponentially falling curves.

Hereinafter, the _V orteilhaftigkeit the evaluation method according to the invention from a consideration of the theory of noise effects and on the basis of experiments shown.

The total signal S _r (t results as follows:

S _r (t _n ) = S _n e ^{K tn} + g _r {t _n ) + h _r {t _n )

\ J

_P7 _*

Here s _Q e ^{} 1} denotes the pure signal, g _t ι ^{t »} ; e ⁱ n white noise and h _(t influence of physiological interference of the test sample, wherein s ⁱ ch preferably are signals having a low frequency.

The index r case takes values from 1 to NR and means Anzai _i l of _W iederholungen the relaxation ^{measurements;} the index n takes values from 1 to N and counts the number of echo signals during a relaxation measurement.

In order to extract a change in relaxation as a function of brain activation from this measured signal, various approaches, explained using the following formulas, are possible: With a summation over the echo signals, ⁱ results

while the formula is based on a weighted summation

results, where applies

- R2 * tw (t _n \ = R2t _n 'e ^"( 20 ^).

Another _V is experienced a fit procedure, as is shown by the following formula:

? - =!.? ^" - 2 _r ) <= S (t _n ) ~ Sn € ^" ~ ^"n (21)

~ ^r { ^" Or ⁷ - ^r J 0

_{A s} in the general considerations may _Ü w assumed here it - _^ he is the _A _rs, πc-ß _ft ctcrr fiMti-.i * * -tβi is ^ the white noise is zero or close to zero. The contrast-to-noise ratio ₍ CNR) results from ΔS divided by the total noise. The difference value is then determined for at least two measurements.

According to another preferred embodiment of the invention For each individual echo signal, a correlation analysis is carried out over several relaxation measurements, which take place one after the other. The correlation analysis is carried out in a known manner, an implementation according to the article by Peter A. Vandettini et al. in: Magnetic

Resonance in Medecine, vol. 30, pp. 161-173, 1993, to which full reference is made, is particularly expedient.

The expected value for the correlation coefficient (c.c.) is

(σ.c.) = cc ₀ 1- (22), where

2AS ²

The correlation coefficient c.c. exhibits a standard deviation

on.

This is followed by a combination of the correlation coefficients, for example by averaging.

An experimental upper test of the evaluation method according to the invention was carried out using MRI examinations of the brains of test subjects. A light source, in particular a matrix of luminescent diodes (light emitting diode LED), was positioned in the immediate vicinity of the test subjects' faces and stimulated to signal flashes. The

Excitation frequency is 8 Hz. The signal flashes take effect over a time interval of several seconds, for example 5 seconds, synchronized with a carrier signal of a scanner, which is followed by an approximately equally long idle interval. The scanner is a Vision 1, 5 Tesla full-body scanner from Siemens Medical Systems, Erlangen, in standard equipment with a magnetic field gradient of 25 mT / m. Such a scanner is able to switch gradient fields within approximately 150 μs.

TURBO-PEPSI (Proton-Echo-Planar-Spectroscopic-Imaging) was used as the spectroscopic imaging method.

Data is adjusted according to the exponential function:

using a non-linear least-square fit.

Of voxels in which the signal intensity at the first echo is 10% of the maximum measured in the entire image

Signal amplitude exceeded and where the

Correlation coefficient between the measured data and the fitted data exceeded 0.95, were parametric

Images of T ₂ ^* , the output signal amplitude Ξ ₀ and of χ ^{2 are} formed. These parameters were set to 0 in the other voxels. With the use of these criteria, with the exception of the ventricles, excellent fit of the fitted data to the experimental results was achieved in all brain regions. In most voxels, the correlation coefficient exceeded 0.99.

Alternatively, the echoes of each relaxation measurement are averaged and subsequently both for the

10 parametric images as well as a correlation analysis for the averaged images.

The experiments showed extensive activation areas of the primary visual cortex (V _x ) as well as in adjacent regions 15 (V ₂ ) of the visual cortex.

The invention has a number of advantages. This includes optimizing the detection sensitivity for quantitative measurement of the relaxation time and the ₂₀ qualitative change in relaxation. This makes it possible, with the highest possible imaging Bandbre ⁱ te _(shortest time coding) has minimal spatial distortion to use, and by a measurement of an optimum number of codes to signal excitation e ⁱ ne

? c to achieve maximum sensitivity.

The evaluation method can be used in real-time measurements to enable relaxation changes to be analyzed in vivo. One according to the invention is expediently

-? n measuring device designed so that it carries out the evaluation process.

The imaging methods according to the invention are particularly versatile. It has been found useful to have a ₃₅ summation or, more advantageously, a weighted one Use summation, which can be done at a higher speed and without loss of sensitivity compared to curve fitting. A summation or a weighted summation has the advantage that it represents a particularly robust evaluation method.

In addition, with the aid of the invention it is possible to achieve an optimal adjustment of the measuring sensitivity at all measuring field strengths, in particular at measuring field strengths from 0.1 Tesla to 15 Tesla, for example by selecting the number of echo signals as a function of the intrinsic relaxation time, the number N is preferably selected according to formula 12.

All subjects showed strong activation in the primary visual cortex (V _x ) and in neighboring areas. The observed changes in the functional signal measured with TTJRBO-PEPSI ranged from 3 to 20% depending on the echo time, the location and the respective test subject. The excitation has a maximum near TE = T ₂ ^* . When comparing ΞPI and TURBO-PEPSI images with TE = 72.5 ms, very similar activation images were determined.

When using a correlation limit of 0.4, it was also possible to detect smaller signal changes with echo times of, for example, 12.5 ms to 228 ms. Averaging the correlation images reduces the intensity of noise effects compared to EPI. The spatial extent of the activation zone and the number of increased correlation coefficients in the visual cortex increase with the number of echoes added up. Experiments with a longer excitation time (7 to 12 seconds) show larger correlation coefficients than in measurements with shorter excitation times (e.g. 3 seconds ⁾ receive. It can be seen that a particularly high gain in sensitivity can be achieved by summing the first, preferably the first 6 to 10, in particular the first 8 echo signals corresponding to the plateau of the CNR curve in FIG. 2.

The gain in sensitivity is particularly advantageous for short-time measurements, in particular real-time measurements, because a change in relaxation can be effectively determined even with a few measured values. In summary, it can be said that optimum sensitivity at any magnetic field strengths is achieved by multi-echo detection of the difference signal.

The examples shown explain the measuring device and the imaging method using NMR measurements on the human brain. Of course, both the measuring device and the evaluation method can be used to examine other samples of living or non-living material.

Claims

claims

1. Measuring device with at least one detection means for recording measurement signals, with a

Transformation means for transforming the measurement signals to digital measurement data, dadurchge ^¬ indicates that the detection means and / or the transformation means is designed so that it is detected at different times and / or on verschxedenen locations measuring signals having a different resolution and / or transformed different.

2. Measuring device according to claim 1, d a d u r c h g e k e n n z e i c h n e t that it contains at least one control unit for controlling the detection means and / or the transformation means.

3. Measuring _V orrichtung according to any one of claims 1 or 2, dadurchgekennzeich - net that it comprises at least a memory unit, wherein the storage unit contains information about the variable transformation of the measurement signals in the measurement data.

4. Nuclear magnetic resonance scanner, so that it contains at least one measuring device according to one of claims 1 to 3.

Measuring method in which measuring signals are recorded and transformed into digital measuring data, characterized in that measuring signals are recorded with different resolutions at different times and / or at different locations are and / or transformed differently.

6. The method according to claim 5, that the measurement signals are detected differently and / or transformed differently to an extent that corresponds to at least one model.

7. The method of claim 6, d a d u r c h g e k e n n z e i c h n e t that the model is determined before the measurement.

8. The method according to any one of claims 5 or 6, d a d u r c h g e k e n n z e i c h - n e t that the model is changed during the measurement.

9. The method of claim 8, d a d u r c h g e k e n n z e i c h n e t that the model is changed starting from a predetermined start model.

10. The method according to any one of claims 5 to 9, so that the compression of the measurement signals and / or the measurement data takes place.

11. The method according to claim 10, d a d c h g e k e n e i c n e t that the compression of the measurement signals and / or the measurement data for signals measured at different times and / or at different locations varies.

12. Imaging method in which at least one image is generated from measurement signals, thereby indicates that the method is carried out according to one of claims 5 to 11.