DE10260372B4 - Magnetic resonance imaging apparatus and method for spatially resolved imaging - Google Patents

Abstract

wobei
M₀ das Gradientenmoment nullter Ordnung,
y das gyromagnetische Verhältnis der Kernspins,
G(t') die zeitabhängige Gradientenfeldstärke des...A nuclear spin tomography apparatus for spatially resolved imaging the density distribution of nuclear spins in a selected viewing area in a MR contrast agent containing body, comprising:
- a static magnet,
Gradient devices for generating gradient pulses in three mutually orthogonal spatial directions,
A transmitting device for generating high-frequency signals,
A receiving device for high-frequency signals,
A device for controlling the gradient devices and the transmitting device,
- An evaluation device and
A display device,
wherein the device for controlling the gradient devices and the transmitting device is designed and programmed such that the body can be exposed to high-frequency and magnetic field gradient echo pulse sequences and to attenuate the magnetization of a medium flowing in at least one spatial direction in the body, image gradient of the gradient echo pulse sequences in at least one of the spatial directions in which the medium flows, subject to the condition:

in which
M _{0 is} the zero-order gradient moment,
y the gyromagnetic ratio of the nuclear spins,
G (t ') is the time-dependent gradient field strength of the ...

Description

The The invention relates to a magnetic resonance imaging apparatus and a method to the spatially resolved Image representation, in particular of human or animal bodies. The The device and the method are in particular for magnetic resonance (MR) tomography on the human and animal body suitable.

Lymphatic vessels in mammalian and human body have been under direct use of X-ray in the past Puncture of the lymphatic vessels and lymph nodes with simultaneous administration of X-ray contrast media shown (direct lymphography). These interventions are for the patient very painful and lead often too side effects.

to Presentation of lymphatic tissue may be used instead of X-ray also magnetic resonance imaging can be used. This technique is basically as well as the x-ray technique for visualization of the lymphatic vessels and lymph nodes due to a multiplanar layer guide and high soft tissue contrast well suited. In "Interstitial MR Lymphography with a Conventional Extracellular Gadolinium-based Agent: Assessment in Rabbits "; S.G.Ruehm, C.Corot, J.F.Debatin; Radiology; 2001; 218: 664-669, is the subcutaneous administration of gadoterate meglumine in rabbits described to represent the lymphatic system.

In experimental studies could with novel contrast agents one good differentiation of metastases in the lymphatic system and healthy Lymphoid tissue can be detected.

• (a) Wird das Kontrastmittel interstitiell gegeben, so gelingt nur eine Darstellung eines Teils des Lymphsystems.
• (b) Experimentelle (nicht zugelassene), eisenhaltige Kontrastmittel zeigen eine sehr langsame Aufnahme in die Lymphknoten. Dadurch ist es erforderlich, den zu untersuchenden Patienten zweimal einzubestellen, nämlich einmal um das Kontrastmittel zu verabreichen und einmal um die Untersuchung durchzuführen. Das zweimalige Einbestellen des Patienten ist im klinischen Alltag jedoch oft nicht praktikabel. Außerdem ergeben sich mit diesen Kontrastmitteln ungünstige Kontrasteigenschaften, nämlich einen negativen Kontrast (Signalabfall im Zielorgan) und Suszeptibilitätsartefakte. Beispielsweise können sehr kleine superparamagnetische Eisenoxidpartikel (USPIO), die mit Dextran überzogen sind, eingesetzt werden. Die Partikel werden in Phagozyten in funktionelles Lymphknotengewebe eingelagert, nicht jedoch in metastatisches Gewebe, in dem Phagozytose nicht stattfindet. Ein Maximum der Anreicherung dieses Kontrastmittels innerhalb der Lymphknoten ist erst etwa 24–48 h nach der Verabreichung erreicht. Die Zielstrukturen sind dunkel, da diese Stoffe als negative Kontrastmittel die Spin-Spin-Relaxationszeit T₂ und insbesondere T₂* durch ihren Suszeptibilitätseffekt deutlich vermindern.
• (c) Bei systemischer Gabe von lymphotropen Kontrastmitteln führt die sich dort einstellende lange Verweilzeit im Blut (intravasale Kontrastmittel) zu einer schweren Abgrenzbarkeit der üblicherweise unmittelbar neben den Blutgefäßen lokalisierten Lymphknoten. Beispiele für diese Kontrastmittel sind in: „Magnetic Resonance in Medicine"; P.A.Rinck; 4. Auflage; Blackwell Wissenschafts-Verlag, Berlin, 2001, angegeben. Auch die Darstellung arteriosklerotischer Ablagerungen in der Gefäßwand, so genannter Plaques, ist von besonderem Interesse. Da die meist intravasalen Kontrastmittel einen Signalanstieg im Inneren der Blutgefäße bewirken, ist es direkt nach der Verabreichung der Kontrastmittel nahezu unmöglich, einen Plaque in der Gefäßwand abzugrenzen. Die arteriosklerotischen Ablagerungen sind von den Blutgefäßen unmittelbar nach der Verabreichung in das Blutsystem nur sehr schwer unterscheidbar. Daher ist es wie zur Darstellung von Lymphknoten erforderlich, zwischen Gabe des Kontrastmittels und Darstellung mit einer Bildgebungstechnik eine lange Wartezeit verstreichen zu lassen. Zur Darstellung der Plaques können spezielle Kontrastmittel eingesetzt werden. Um die Plaques vom Inneren des Blutgefäßes zu differenzieren, kann ausgenutzt werden, dass das Kontrastmittel in den Plaques länger verbleibt als im Blutstrom, so dass die Plaques nach einer Wartezeit von etwa 12–48 h noch signalverstärkt, das Blut jedoch wieder signalärmer dargestellt werden. Wie für die Lymphographie ist es für die Darstellung der Plaques im klinischen Alltag aber oft nicht vertretbar, eine derart lange Wartezeit zwischen Verabreichung und Aufnahme einzuhalten, da ein Patient dann zweimal zur Untersuchung einbestellt werden müsste.

Depending on the contrast media used, the following disadvantages are found:

• (a) If the contrast agent is given interstitially, then only a representation of a part of the lymphatic system succeeds.
• (b) Experimental (unapproved), iron-containing contrast agents show a very slow uptake into the lymph nodes. This makes it necessary to insert the patient to be examined twice, once to administer the contrast agent and once to perform the examination. However, it is often impractical to order the patient twice in clinical practice. In addition, these contrast agents result in unfavorable contrast properties, namely a negative contrast (signal drop in the target organ) and susceptibility artifacts. For example, very small superparamagnetic iron oxide particles (USPIO) coated with dextran can be used. The particles are stored in phagocytes in functional lymph node tissue, but not in metastatic tissue in which phagocytosis does not take place. A maximum of accumulation of this contrast agent within the lymph nodes is reached only about 24-48 h after administration. The target structures are dark, since these substances as negative contrast agents significantly reduce the spin-spin relaxation time T ₂ and in particular T ₂ * by their susceptibility effect.
• (c) With systemic administration of lymphotropic contrast agents, the long dwell time in the blood (intravascular contrast agent) that occurs there leads to a severe delimitation of the lymph nodes, which are usually located directly next to the blood vessels. Examples of these contrast agents are given in: "Magnetic Resonance in Medicine", PARinck, 4th Edition, Blackwell Scientific Publishing, Berlin, 2001. Also, the presentation of arteriosclerotic deposits in the vessel wall, so-called plaques, is of particular interest Since most of the intravascular contrast agents cause a signal increase inside the blood vessels, it is almost impossible to delineate a plaque in the vessel wall immediately after the administration of the contrast media.The arteriosclerotic deposits are very difficult to differentiate from the blood vessels immediately after administration into the blood system For instance, as with the presentation of lymph nodes, it may be necessary to wait a long time between administering the contrast agent and imaging with an imaging technique, special contrast agents may be used to visualize the plaques, to differentiate the plaques from the inside of the blood vessel t that the contrast medium remains in the plaques longer than in the bloodstream, so that the plaques signal amplified after a waiting period of about 12-48 h, however, the blood are again signal reduced. However, as in the case of lymphography, it is often unreasonable for the presentation of plaques in clinical practice to keep such a long waiting time between administration and admission, since a patient would then have to be summoned twice for examination.

When examining a body, in particular a human or animal body, with a nuclear resonance experiment, either a so-called spin-echo sequence with 90 ° -180 ° excitation or instead of this excitation or in addition to this a measurable signal sequence with a gradient pulse sequence ( Gradient echo method). After the 90 ° radio-frequency pulse, in this case, first a gradient pulse is switched, for example in the x-direction. Thereafter, a gradient pulse in -x-Rich tion, ie applied with inverted gradient sign. As a result, the initially dephased spins refocus into a measurable signal that can be represented as a sum vector in a coordinate system rotating with ω ₀ .

For the spatially resolved representation of nuclear spins in a field of view (FOV: field-of-view) in a body, the nuclear spins must be able to be assigned to individual spatial elements. For this purpose, the effect is exploited that the Larmor frequency ω (x, t) is dependent on the magnetic field strength B (x, t). At a layer scan only a thin layer ( "slice") is upon application of a magnetic field gradient in the form of a gradient pulse during the 90 ° pulse in the z direction stimulated in which the magnetic field strength B ₀ just ω the Larmor frequency corresponding to _{the 0th} This ensures that only the cores For example, in the z-direction an easy assignment of nuclei in the x-direction and y-direction is achieved, after the application of the 90 ° -pulse further gradient pulses are propagated In the y-direction, a gradient circuit is inserted after the 90 ° pulse ("phase"). The location information in the y-direction is contained in the phase shift of the precessing nuclear spins caused by this temporarily switched gradient (phase encoding). The location information is made accessible from the response signal by Fourier transform (FT) analysis. In order to achieve different phase shifts in the y-direction and thus obtain a clear location information of the nuclear spins in this spatial direction, gradient circuits are inserted in successive pulse sequences which are incremented or decremented successively in increments, the phase gradients with gradient slopes between two maximum values + G and G are varied. In the same way, a first gradient circuit ("read") which contains the required information about the spatial resolution of the nuclear spins in the x-direction is also inserted in the x-direction To generate an echo signal, a second read gradient circuit with different polarity then becomes the first which, after a dephasing of the spins in the xy plane due to the first read gradient circuit, leads to a refocusing of the nuclear spins due to the switching of the second pulse, so that a response signal is produced If different magnetic fields in the range B ₀ ± ΔB are present during the refocussing, the signals originating from different locations can be separated on the basis of the different frequencies in the range ω ₀ ± Δω (frequency coding).

A Acceleration of the measurement can be achieved by the Nuclear spins are excited with an RF pulse leading to a tilt the net magnetization is less than 90 ° (flip angle α <90 °).

While the single layers in the body to be examined in the previously described 2D-FT can be examined one after the other, can also be a three-dimensional Representation of a body to be examined in a single pulse sequence be generated without stratification (3D-FT): For this purpose, the aforementioned Pulse trains for the phase and the readout gradient pulse applied. On the slice gradient pulse while the RF pulse follows in addition a downstream slice gradient pulse of inverted polarity, wherein the second slice gradient pulse in successive pulse sequences in increments between two maximum values + G and -G increased or is lowered.

to Representation of blood vessels (angiography) Various techniques have been used in some cases consist of the signal from the blood vessels in a recording sequence to suppress and in another with flow compensation, i. without dephasing the moved nuclear spins (signal carrier) to record. For the differentiation of the vessels from surrounding dormant tissue then becomes a difference between both images formed a good contrast between the vessels and created the surrounding tissue, the blood vessels bright being represented. A juxtaposition the procedure is in "Black Blood Angiography; W. Lin, M. Haacke, R. R. Eldman; in: "Magnetic Angiography, Concepts and Applications "(Ed .: E.J.Potchen, E.M.Haacke, J.E.Siebert, A. Gottschalk), Mosby, St. Louis (1993).

• a) Schon in der klassischen MR-Messsequenz, der Spin-Echo-Sequenz, werden bewegte Spins intrinsisch unterdrückt, da diejenigen Spins, die zwischen dem 90°-Anregungspuls und dem 180°-Refokussierungspuls die Messschicht verlassen, nicht zum MR-Signal beitragen. Dieser Laufzeiteffekt wird mit zunehmender Echozeit TE, die bei einer klassischen Spin-Echo-Sequenz mit 90°- und 180°-Puls doppelt so lang ist wie die Zeitspanne zwischen 90°-Puls und 180°-Puls, oder verringerter Schichtdicke stärker. Diese Technik ist jedoch für Gradientenechosequenzen ohne 180°-Pulse nicht geeignet. Daher kann dieser Effekt für eine schnelle Aufnahmezeit nicht genutzt werden: Es ist technisch allerdings fast unmöglich, in praktikablen Messzeiten dreidimensionale Volumina mit Spin-Echo-Sequenzen darzustellen, während dies mit schnellen Gradientenechoverfahren, speziell mit der mittels Kontrastmitteln verstärkten Magnetresonanz-Angiographie, in wenigen Sekunden gelingt.
• b) In konventionellen Magnetresonanz-Verfahren zur Unterdrückung von Blutgefäßsignalen wird das Signal der Blutgefäße außerhalb der Bildgebungsschicht gesättigt, indem beispielsweise parallel zur Messschicht sogenannte Saturationsschichten positioniert werden. Da hier keine 180°-Pulse bei der Signalauslese eingesetzt werden, kann dieses Sättigungsverfahren mit nahezu jeder beliebigen Bildgebungstechnik in der Magnetresonanztechnik kombiniert werden. Grundsätzlich wird mit diesem Verfahren der Vorteil ausgenutzt, dass Blut gegenüber anderen Geweben eine sehr lange T₁-Relaxationszeit hat und in der direkt auf die Sättigung folgenden Signalauslese in der Messschicht nur gesättigtes Blut vorhanden ist, das nahezu kein Signal liefert. In einer Variante dieses Verfahrens wird die Magnetisierung nur außerhalb der Messschicht invertiert. Danach wird solange gewartet, bis die Längsmagnetisierung der Signalträger im Blut (entlang der z-Achse) aufgrund der T₁-Relaxation einen Nulldurchgang aufweist. Die in die Messschicht eingeflossenen Signalträger im Blut tragen dann nicht zum MR-Signal bei.
• c) In Gradientenechobildern wurde schon relativ früh beobachtet, dass schnell aus einer Gefäßverengung strömendes Blut in einer bestimmten Verwirbelungszone (Jet) eine artifizielle Signalreduktion hervorruft. Dieser Effekt beruht darauf, dass bewegte Spins unter Einwirkung von Gradienten, die zur Ortskodierung in der MR-Bildgebung benötigt werden, eine zusätzliche Phase akkumulieren, die von der Bewegungsgeschwindigkeit der Spins abhängig ist. Im Jet treten innerhalb eines Bildelements (Pixel) viele verschiedene Phasen auf, so dass die phasenkohärente Addition der MR-Signale zu einer Reduktion des Summensignals im MR-Bild führt. Dieses Phänomen wird als intravoxel incoherent motion bezeichnet und ist auch aus der diffusionsgewichteten MR-Bildgebung bekannt. Dieser Effekt kann noch dadurch verstärkt werden, dass Gradienten so zur Bildgebung hinzugefügt werden, dass die Ortskodierung unbeeinflusst bleibt, während die geschwindigkeitsabhängige Phase maximiert wird. Diese Technik wird Black Blood Angiography genannt. Sie wird in Verbindung mit Spin-Echo-Sequenzen implementiert, um deren zusätzliche Signalunterdrückung auszunutzen. Umgekehrt kann dieser Effekt auch zur Darstellung von Blutgefäßen verwendet werden, indem zwei Datensätze ohne und mit zusätzlicher Gradientenschaltung voneinander subtrahiert werden (Rephase/Dephase Imaging).

Since the beginning of clinical MR imaging, methods have been used to suppress MR signals from moving signal carriers. In the following, the essential methods for the suppression of moving MR signal carriers will be discussed:

• a) Even in the classical MR measurement sequence, the spin-echo sequence, moving spins are intrinsically suppressed since those spins that leave the measurement layer between the 90 ° excitation pulse and the 180 ° refocusing pulse do not contribute to the MR signal , This transit time effect increases with increasing echo time TE, which is twice as long as the time interval between 90 ° pulse and 180 ° pulse, or reduced layer thickness in the case of a classical spin echo sequence with 90 ° and 180 ° pulses. However, this technique is not suitable for gradient echo sequences without 180 ° pulses. Therefore, this effect for a However, it is technically almost impossible to display three-dimensional volumes with spin-echo sequences in practicable measuring times, while this can be done in just a few seconds with fast gradient echo methods, especially with contrast-enhanced magnetic resonance angiography.
• b) In conventional magnetic resonance methods for the suppression of blood vessel signals, the signal of the blood vessels outside the imaging layer is saturated, for example by positioning so-called saturation layers parallel to the measurement layer. Since no 180 ° pulses are used in signal selection, this saturation method can be combined with virtually any imaging technique in magnetic resonance technology. Basically, this method exploits the advantage that blood has a very long T ₁ relaxation time compared to other tissues and in the signal read-out following the saturation directly in the measurement layer only saturated blood is present which provides almost no signal. In a variant of this method, the magnetization is inverted only outside the measuring layer. Thereafter, it is waited until the longitudinal magnetization of the signal carriers in the blood (along the z-axis) has a zero crossing due to the T ₁ relaxation. The signal carriers in the blood that have flowed into the measuring layer then do not contribute to the MR signal.
• c) In gradient echo images, it was observed relatively early that blood flowing rapidly from a vasoconstriction causes artificial signal reduction in a specific turbulence zone (jet). This effect is due to the fact that moving spins, accumulated by the gradients required for spatial encoding in MR imaging, accumulate an additional phase that depends on the speed of movement of the spins. In the jet, many different phases occur within a picture element (pixel), so that the phase-coherent addition of the MR signals leads to a reduction of the sum signal in the MR image. This phenomenon is called intravoxel incoherent motion and is also known from diffusion-weighted MR imaging. This effect can be further enhanced by adding gradients to the imaging so that the spatial encoding remains unaffected while maximizing the rate-dependent phase. This technique is called Black Blood Angiography. It is implemented in conjunction with spin-echo sequences to take advantage of their additional signal rejection. Conversely, this effect can also be used to visualize blood vessels by subtracting two sets of data without and with additional gradient switching (Rephase / Dephase Imaging).

to Appearance of blood vessels used in clinical practice either the spin-echo method, made even more efficient by built-in dephasing gradients (Black Blood Angiography), or the Rephase / Dephase method, the main ones used for the positive representation of the peripheral arteries. Both techniques are not yet in combination with contrast agents been used. Rather, this affects the intrinsic contrast of the moving blood to the blood vessel presentation out. In the Rephase / Dephase method, this means that in the Subtraction of the two datasets Only then bright, if enough fresh blood flows into the measuring layer.

Indeed are also known by means of Black Blood Angiography, for example, for the presentation of arteriosclerotic deposits used in blood vessels have been. So is in "Extracranial Carotid Arteries: Evaluation with "Black Blood MR Angiography"; R. R. Eldelman, H. P. Mattle, B.Wallner, R.Bajakian, J.Kleefield, B.Kent, J.J. Skillman, J.B.Mendel, D.J.Atkinson; Radiology; 1990; 177: 45-50, a juxtaposition the Bright Blood Angiography to the Black Blood Angiography to the representation of pathological changes of the carotid artery. Black Blood Angiography is said to be opposite Bright Blood Angiography offer the benefit of functional disorders very much can be shown exactly. For the representation of lesions in black blood angiography a 2D spin-echo method was used since gradient echo sequences were not suitable, the moving nuclear spins to suppress, although the studied layers were saturated. To a suppression too would have achieved the echo time TE extended Need to become. This would have however, to a reduction of the resolution of the structures to the Blood vessels and led to a reduced contrast between blood vessel and muscle tissue.

With the hitherto known method for the suppression of blood vessels succeeds it basically, to avoid their appearance if no contrast agent in the bloodstream is available. However, it will shorten the relaxation times Given contrast agents, it is in the layers shown in a human or animal body almost impossible, pathological Structures in the lymphatics and of arteriosclerotic deposits in the blood vessels without recognize further, especially if they are relatively small.

However, in DE 101 27 930 A1 describe a method of effective stenosis identification in a peripheral arterial vessel structure using an MR image in which a passage of a contrast agent bolus is followed by a patient. High frequency and gradient echo pulse sequences with flux-sensitive gradients are generated.

Of the present invention has for its object to find means with which in particular small pathological structures easily can be recognized and displayed. Above all, a high-contrast, overlay-free and unique Representation of adjacent blood vessels in human or animal body lying, non-moving structures with an extremely fast Image capture possible be. In particular, metastases in lymphoid tissue and in plaques be easily and quickly recognizable and presentable.

The Problem is solved by the magnetic resonance imaging apparatus specified in claim 1 and the method specified in claim 4. Advantageous embodiments The invention are specified in the subclaims.

Provided hereinafter and in the claims indicated that magnetic field gradient echo pulse sequences in a to be switched in certain spatial direction, this is to be understood as meaning that the sequences in one or any two or all three Room directions can be switched. In the same way by stating that the magnetization of flowing medium be weakened in one spatial direction can, understand that the magnetization in one or two arbitrary Spaces or in all three directions can be weakened.

A magnetic resonance (MR) contrast agent is used to visualize pathological structures with microscopic dimensions in some cases in the lymphatic system and in the blood vessels by means of magnetic resonance tomography, which is recorded by the body to be examined. For image display, an MRI apparatus is used for obtaining data for a spatially resolved image representation of the magnetic resonance behavior of the atomic nuclei in a selected viewing area in a body. The device is designed and programmed for this purpose such that the device exposes the body to radio frequency and magnetic field gradient echo pulse sequences which generate magnetization in the body. The magnetization of signal carriers (spins of atomic nuclei, in particular ¹ H-nuclei), which are in at least one spatial direction flowing medium, in particular blood, are attenuated by dephasing the spins of the atomic nuclei in this flowing medium, so that a representation of itself in the immediate vicinity of the fluid medium structures is greatly simplified, even if they are microscopic, since blood is thereby shown dark. Only by administering an MR contrast agent is it possible to find the sought-after fine structures in a targeted manner and to recognize them with certainty.

By Realization of the invention can For example, lymph nodes of a particular region in the human or animal body or the entire body with high spatial resolution be represented because on the one hand, the moving signal carrier the blood vessels are suppressed and the target structures on the other hand reinforced by contrast agents so that they stand out very well. The blood vessels signal intensity becomes selective according to the invention suppressed so that, for example, the lymph nodes are shown in close proximity to large blood vessels and demarcated against the vessel can be. The same applies to arteriosclerotic deposits, so-called plaques, in the blood vessel walls.

By contrast, conventional saturation techniques developed to suppress moving signal carriers can not be used to delineate the lymph nodes and plaques in combination with contrast agents since the saturated magnetization in the presence of the contrast agents recovers within a few milliseconds and is available in the subsequent signal read-out. This effect is caused by the massive T ₁ reduction dependent on the contrast agent concentration. In contrast, the dephasing of the nuclear spins according to the invention by the use of gradient pulse sequences in the presence of contrast agents is easily achievable and therefore superior. Compared to the Rephase / Dephase imaging method, the inventive method is faster by about a factor of 2, since it can be dispensed with the Rephase part of the method.

• a) Sie sollen mit der gewählten Sequenz zu einer Signalverstärkung im MR-Bild führen.
• b) Sie sollen sich in der Zielstruktur anreichern, d.h. im lymphatischen Gewebe bzw. in arteriosklerotischen Ablagerungen. Hierzu ist es selbstverständlich erforderlich, dass die Kontrastmittel zur Darstellung von Lymphknoten lymph-gängig und zur Darstellung von Plaques plaque-gängig sind.
• c) Sie sollten sich auch im Blutgefäßsystem anreichern.

For the representation in particular of lymphatic tissue and arteriosclerotic deposits in Blood vessels are used MR contrast agents, which may be advantageous tailored to the particular application. The contrast agents should preferably fulfill the following conditions:

• a) They should lead to a signal amplification in the MR image with the selected sequence.
• b) They should accumulate in the target structure, ie in the lymphatic tissue or in arteriosclerotic deposits. For this purpose, it is of course necessary that the contrast media for the display of lymph nodes are common and plaque-plaque common.
• c) They should also accumulate in the blood vessel system.

to Detection of metastases of the lymphatic system are, for example, the previously mentioned coated iron oxide particles in the form of USPIO suitable. Indeed need Coated iron oxide particles for a longer time for enrichment in the lymph nodes. Furthermore these contrast agents are not due to the negative contrast Representation of the lymphatic vessels suitable.

Particularly advantageous are, inter alia, gadolinium-containing compounds. For lymphography are polymeric compounds, such as those of L.Harika, R.Weissleder, K.Poss, C. Zimmer, MIPapisov, TJBrady in: "MR Lymphography with a Lymphotropic T ₁ -Type MR Contrast Agent: Gd-DTPA-PGM";MRM;1995; 33: 88-92 and by G. Staatz, CC Nolte-Ernsting, A. Bucker et al., In: "Interstitial T ₁ Heavy-Dedicated MR Lymphography with Use of the Dendritic Contrast Agent Gadomer-17 in pigs"; Rofo. Fortschr. Geb. Röntgenstr. New picture. traversing .; 2001; 173: 1131-1136, as well as lipophilic compounds which form aggregates or micelles, such as those of B. Mißelwitz, J. Platzek, B. Radchel, JJ Oelleringer, HJ Weinmann in: "Gadofluorine 8: Initial Experience with a New Contrast Medium for Interstitial MR Lymphography ';Magma;1999; 8: 190-195 and by G. Staatz, CC Nolte-Ernsting, GB Adam et al. in: "Interstitial T ₁ -Weighted MR Lymphography: Lipophilic Perfluorinated gadolinium chelate in Pigs", Radiology, 2001; 220: 129-134 described compounds, can be used.

Especially suitable compounds are already within a very short time Enriched in lymphatic tissue after administration. These are preferably polar radicals, for example Sugar residues, as well as fluorinated side chains gadolinium complexes, which aggregates into micelles of 4-6 nm in size are. Such compounds are described, for example, in WO 02/14309 A1 described. With these contrast agents, the MR examination after administration already within a few minutes to carried out to an hour become. Also for the presentation of arteriosclerotic deposits (plaques) can These special gadolinium compounds are used.

Furthermore, it is also possible to use compounds of other paramagnetic metal ions, for example compounds of Mn (II), Dy (III) and Fe (III). Gd (III), Mn (II) and Fe (III) compounds act as positive contrast agents as these agents reduce the longitudinal relaxation time T ₁ so that those parts in an MR image into which the contrast agent has been incorporated , are lightened. On the other hand, Dy (III) compounds as well as iron oxide particles act as negative contrast agents, because they decrease T ₂ and in particular T ₂ * by their susceptibility effect, so that the parts in an MR image into which these contrast agents have been taken become darker appear. In this respect, the latter compounds are not as well suited as Mn (II) and Fe (III) compounds.

Instead of the abovementioned contrast agents, it is also possible to use other types of contrast agent, for example nitrogen oxides, which, like the metal ions mentioned, are paramagnetic. Furthermore, gas-filled microbubbles are proposed, which may be filled, for example, with nitrogen or perfluoropropane. Such systems are exemplary in US 6,315,981 A described.

Furthermore, instead of paramagnetic or superparamagnetic substances, diamagnetic compounds which do not contain ¹ H but also other signal carriers, for example fluorohydrocarbon compounds, can be used as contrast agents. In this case, instead of ¹ H-MR tomography, a ¹⁹ F MR tomography is carried out, since the ¹⁹ F nucleus also has a nuclear spin of ½, the gyromagnetic ratio for ¹⁹ F being markedly different from that for ¹ H, so that these atomic nuclei form an image contrast in the MR image. These should be those compounds that are included in the target structures. If these compounds have a long residence time in the blood, the target structures can be selectively visualized with the present invention without the blood vessels preventing recognition of these structures.

The MR contrast agent may be the human or animal body in particular intravenous be administered. However, the contrast agent can in principle also intraarterial, percutaneously, in particular subcutaneously, moreover orally, intraperitoneal, intramuscular or be given in another way.

In order to attenuate the magnetic resonance signals of spins in flowing medium, use is made according to the invention of the effect that the spins dephase the atomic nuclei contained in the examination region in the body to be examined during the movement, while this does not apply to non-moving spins. This can be achieved by suitable switching of the magnetic field gradient pulses. In order to determine the conditions under which the signals are attenuated, the following equation is used for the phase of the respective nuclear spins, which is location and time dependent and which is a function of the location x within a gradient field, the time-dependent gradient field strength G (t ') and of the time t 'after an excitation of the atomic nuclei with a radio-frequency pulse is:

The Constant y is the gyromagnetic ratio and is for the in Magnetic resonance imaging mainly used protons in practical units 2π · 42,577 MHz / T.

If the excited atomic nuclei now move while a gradient is switched on, with a component of motion parallel to the spatial direction of the gradient, then the location x at which the atomic nuclei are located at time t 'will also be time-dependent. Therefore, equation [1] can be reworded as follows:

Hence, by developing into a Taylor series and neglecting higher terms, the following relationship results:

x ₀ is the origin of the atomic nucleus when moving during a gradient pulse sequence, and v ₀ is the constant velocity of the flowing medium. As an abbreviation for the time integrals multiplied by y, M ₀ and M _{1 are} introduced, giving the following relationship: φ (t) = x 0 · M 0 + v 0 · M 1 , [2a]

M ₀ is known as the zero-order gradient moment and M ₁ is the first-order gradient moment. Time-dependent gradient moments of the i-th order M _i (t), which have already been neglected in equation [2a], are defined as follows:

Gradient circuits in which M ₀ (zero-order gradient moment) is zero are required for generating echo signals generated by gradient circuits, since the nuclear spins rephase only under this condition. Conventional gradient circuits in which M ₁ (first-order gradient moment) is zero are said to be flux-compensated because here nuclear spins moving at a constant velocity in a flowing medium do not experience additional dephasing caused by the motion, so they interfere with imaging appear bright. From the definition of the gradient moments M _{i it} follows that with short times only the low moments contribute to the signal phase, while higher moments scale with t ⁱ and thus remain small.

maximiert wird, wobei

y

das gyromagnetische Verhältnis der Atomkerne,

G(t')

eine zeitabhängige Gradientenfeldstärke in dieser Raumrichtung und

t

die fest vorgegebene, seit dem Einstrahlen eines Hochfrequenzpulses zur Anregung der Atomkerne verstrichene Zeitspanne

sind.From the above, it follows that M ₁ must be as large as possible to suppress the signals of moving nuclear spins, since the dephasing in this case is particularly large. This means that the magnetic resonance signals of the medium flowing in the at least one spatial direction in the body can be attenuated by means of flow depperature gradient pulses by virtue of a first-order gradient moment M ₁ (t) in this spatial direction according to the following relationship:

is maximized, where

y

the gyromagnetic ratio of atomic nuclei,

G (t ')

a time-dependent gradient field strength in this spatial direction and

t

the fixed predetermined, since the irradiation of a high-frequency pulse to excite the atomic nuclei elapsed time

are.

By consideration of gradient moments higher Order according to equation [3] with i> 1 can a dephasing of even such flowing media can be achieved not only have a constant speed, but while the gradient circuits are also accelerated or decelerated.

In a preferred embodiment of the invention, the magnetization of the medium flowing in the at least one spatial direction in the body is attenuated by dephasing the spins by having gradient moments of the i-th order M _i (t), in particular first-order gradient moments M ₁ (t), be maximized in this spatial direction.

v_max

eine maximale Geschwindigkeit des fließenden Mediums in dem zu untersuchenden Körper ist, bis zu der eine Dephasierung nicht effektiv erreicht wird.

If, for example, atomic nuclei within a _{pixel are} at the same rate within a velocity interval from 0 to v _max and the associated nuclear spins are imaged with the same signal intensity, then the sum signal of these nuclear spins disappears if and only if the phase caused by M ₁ is exactly 2π (ie 360 °), so that the following relationship applies: 2π = v Max · M 1 [4] in which

v _max

is a maximum velocity of the flowing medium in the body to be examined, to which dephasing is not effectively achieved.

Even for speeds greater than v _max , the sum signal remains very small, so that v _max can be interpreted as a limit speed below which signal suppression in the flowing medium does not function effectively. This means that the signal of moving nuclear spins is then retained and not suppressed when these nuclear spins move at a speed that is less than v _max . Therefore, the knowledge of the typical speeds in blood vessels to be examined is of interest in order to be able to use the invention effectively. Since blood moves only very slowly in venous structures, these structures are generally well recognizable, since the nuclear spins contained therein are not dephased and thus suppressed. However, this is not detrimental to the visualization of lymphoid tissue and plaques since they are more likely to be adjacent to the arteries. If also venous flow is to be suppressed, then stronger and / or longer gradient circuits must be used.

In general, a given gradient circuit will have a non-zero first-order gradient moment M ₁ such that the gradient circuit is not flux-compensated. Such gradient circuits are usually used for receiving non-moving signal carriers. However, to suppress slow flow, gradient moments are required that are not achieved by typical imaging gradients.

Thereby that special gradient circuits are used, which contribute to Can cause flow dephasing, in an embodiment of the invention conventional imaging 2D or 3D gradient echo pulse sequences, in particular flow compensated gradient echo pulse sequences, the flow dephasing gradient pulses are inserted.

If the gradients in an existing gradient echo pulse sequence used for imaging, for example in a flow-compensated gradient echo pulse sequence, are to be modified in such a way that a large first-order gradient moment M ₁ arises, then the already existing image range addition, a new sequence, the flow-dephasing gradient pulse sequence, which satisfies the condition according to equation [4] and thus leads to a maximization of M ₁ , is added. This condition is necessary so that the spatial coding of the magnetic resonance signals remains unaffected, so that the following relationship is fulfilled:

This condition is clearly interpretable by the fact that + M ₀ then just represents the area under a gradient-time curve. An easy way to accomplish this relationship is to use bipolar gradient pulses, ie, two gradients of different polarity, the respective strength and length of which may be different, but in particular the pulses may be equally strong and long.

For example can the nuclear spins in a spatial direction by switching a gradient pulse with the time integral A to be dephased by a certain amount. By later Switching a second gradient pulse with the time integral -A in the same Spatial direction, non-moving signal carriers are completely rephased again, not moving signal carriers.

As an alternative to the variant in which the flow-dephasing gradient pulses are added to a flow-compensated gradient echo pulse sequence, in another embodiment of the invention a non-flux-compensated gradient echo pulse sequence can also be assumed. After adding the further pulse sequence, however, the above conditions must be fulfilled, according to which M ₀ = 0 (equation [5]) and M ₁ according to equation [4] is maximized.

When using contrast agents to better represent microscopic structures in lymph nodes or arteriosclerotic deposits, the selected pulse times for the gradient moments must be very small, since the relaxation times are very short because of the use of contrast agents. However, when using very short gradient pulses, a correspondingly high gradient field strength is to be switched in the short period of time that is available. In the implementation of motion-sensitive gradient pulses, therefore, the following technical boundary conditions must continue to be observed: For the generation of gradient pulses gradient systems are used, which consist of current-carrying coils. These coils are driven by a current amplifier. These amplifiers can only provide finite power, so the amount of gradient field strength is limited in practice. For example, gradient field strength in clinical magnetic resonance imaging is currently limited to 30-40 mT / m: | G (t) | ≤ G Max [6a]

This Value may be higher in the future.

In addition, since the coil turns of the gradient system are an inductance, Lenz's rule requires a minimum amount of time to switch to a maximum gradient field strength. Of course, as well as the maximum gradient field strength, this minimal time span depends on the respective technical possibilities, so that a reduction in the time required depends on technical progress. The rise time is usually given in the form of a slew rate s _max :

G_bipolar:

die maximale Gradientenfeldstärke,

t_ramp:

die Anstiegs-/Abfallzeit beim Einschalten/Ausschalten des Gradientenfeldes,

t_plateau:

die Zeitspanne, während der G_bipolar erreicht ist, und

t_sep:

die Zeitspanne zwischen zwei Gradientenpulsen

sind. Zur näheren Erläuterung dieser Parameter wird auf 1 verwiesen.For example, the aforementioned conditions according to equations [6a] and [6b] can be realized simply by using a long-pulse flow deputter gradient pulse sequence. For example, the gradient moment of the first order M _{1 can be given} for a bipolar gradient pulse by M 1 (t; G bipolar , t ramp , t plateau , t sep ) = γ · G bipolar · (T ramp + t plateau ) * (2t ramp + t plateau + t sep ) [7] in which

G _bipolar:

the maximum gradient field strength,

t _ramp :

the rise / fall time when switching on / off the gradient field,

t _plateau :

the period of time during which G reaches _bipolar , and

t _sep :

the time span between two gradient pulses

are. For a more detailed explanation of these parameters is on 1 directed.

For contrast agent-assisted investigations according to the invention, the gradient pulses for flow dephasing are to be kept as short as possible. In particular, the gradient pulses additionally used for the flow depuration should be as short as possible, since a shortening of the longitudinal relaxation time T ₁ caused by the contrast agent is inevitably accompanied by a shortening of the transverse relaxation time T ₂ . If long gradient pulses were switched under these conditions, the echo times TE for the signal read-out would be extended so that, as a consequence, an accelerated T ₂ decay would result in a strong signal loss for both moving and stationary signal carriers.

In a preferred embodiment In accordance with the invention, the gradient pulse sequence comprises flow dephasing gradient pulses in the three (in the Cartesian coordinate system orthogonal to each other standing) spatial directions. The gradient echo pulse sequences in the respective spatial directions are there by inserting the Flow Degradation Gradient Pulses in Imaging Gradient Echopulse Sequences educated.

Of course you can too Flow dephasing gradient pulses in only one or only two spatial directions be incorporated into imaging gradient echo sequences. This may be advantageous, for example, when flowing medium should not be attenuated in the spatial directions in which the Flußdephasiergradientenpulse not inserted become. In particular, it may be of interest to suppress the aorta by: Flußdephasiergradientenpulse be switched in the z direction.

The gradient echo pulse sequences can be chosen in any desired way, provided that only M ₀ = 0 and M _{1 are} as far as possible maximal, since the exact shape of these gradient pulses is irrelevant to the realization of the present invention. However, the time required to insert the additional flow dephasing gradient pulses should be short in order to minimize the echo times of the sequence. This is necessary because the signals of all contrast enhancement structures in a body have a shortened T ₂ decay, which would lead to massive signal loss at long echo times.

• 1. In einer ersten nicht erfindungsgemäßen Implementierung werden bipolare Gradientenpulse in Frequenz- und Phasenkodierrichtung vor der Signalauslese und in Schichtselektionsrichtung nach der Hochfrequenzanregung zwischen die eigentlichen Bildgebungsgradienten zusätzlich eingefügt (siehe hierzu auch 2a und 2b). Die Parameter G_bipolar, t_ramp und t_sep können beispielsweise fest vorgegeben werden, so dass sich für eine minimale Plateauzeit t_plateau = 0 ms ein maximaler Wert für v_max ergibt. Um auch größere Gradientenmomente erster Ordnung M₁ (und damit kleinere v_max) realisieren zu können, kann die Gradientenechopulssequenz beispielsweise so programmiert werden, dass mit zunehmender Echozeit TE > TE_min symmetrisch Plateauzeiten t_plateau gemäß
  
  eingefügt werden. Damit können das Gradientenmoment erster Ordnung M₁ gemäß Gleichung [7] und die Geschwindigkeit v_max, oberhalb der eine massive Unterdrückung der Signale zu erwarten ist, indirekt über die Echozeit TE gemäß Gleichung [4] eingestellt werden.
• 2. In der erfindungsgemäßen Implementierung werden die gesamten Bildgebungsgradienten einer vorgegebenen Pulssequenz, die zwischen Hochfrequenzanregung und Signalauslese verwendet werden, so neu berechnet, dass die zusätzlichen Gradientenbeiträge zur Maximierung des Gradientenmoments erster Ordnung M₁ ein über eine Grenzgeschwindigkeit v_max vorgegebenes Gradientenmoment erster Ordnung M₁ realisieren und gleichzeitig das Gradientenmoment nullter Ordnung M₀ des ursprünglichen Gradientenzuges nicht verändern (siehe hierzu 2c). Hierbei ist es häufig erforderlich, die Echozeit TE des Gradientenzuges zu verlängern. Die mit dieser Implementation realisierten Echozüge sind immer kürzer als die unter 1. beschriebenen Züge, da hier Bildgebungs- und Flussdephasiergradientenpulse gleichzeitig und nicht nacheinander ausgespielt werden. Das bei vorgegebenen Randbedingungen gemäß den Gleichungen [6a] und [6b] kürzeste Gradiententiming wird in einem solchen Ansatz durch numerische Optimierung gefunden.

In principle, the invention can be implemented in two embodiments. For this purpose, two different variants of the flow dephasing are used. Both variants have in common that a gradient echo pulse sequence is switched that fulfills the conditions that M ₀ = 0 (equation [5]) and M ₁ according to equation [4] is maximized. In addition, the constraints formulated in Equations [6a] and [6b] are to be observed:

• 1. In a first implementation not according to the invention, bipolar gradient pulses are additionally inserted in the frequency and phase coding direction before the signal readout and in the slice selection direction after the high frequency excitation between the actual imaging gradients (see also FIG 2a and 2 B ). For example, the parameters G _bipolar , t _ramp and t _sep can be fixed, so that a maximum value for v _max results for a minimum plateau time t _plateau = 0 ms. In order to be able to realize even larger first-order gradient moments M ₁ (and thus smaller v _max ), the gradient echo pulse sequence can be programmed, for example, so that with increasing echo time TE> TE _min symmetrical plateau times t _plateau according to _FIG
  
  be inserted. Thus, the first order gradient moment M ₁ according to equation [7] and the speed v _max , above which a massive suppression of the signals is to be expected, can be set indirectly via the echo time TE according to equation [4].
• 2. In the inventive implementation, the entire imaging gradients of a predetermined pulse sequence to be used between RF excitation and signal readout are recalculated so that the additional Gradientenbeiträge to maximize the first order M ₁ Gradientenmoments a above a threshold speed v _max predetermined gradient moment of the first order M ₁ realize and at the same time do not change the zero-order gradient moment M _{0 of} the original gradient curve (see 2c ). In this case it is often necessary to extend the echo time TE of the gradient. The echo trains implemented with this implementation are always shorter than the trains described under 1., since here imaging and Flußdephasiergradientenpulse simultaneously and not be played one after the other. The shortest gradient timing given given boundary conditions according to Equations [6a] and [6b] is found in such an approach by numerical optimization.

Basically, the difference between the two methods is greatest at high limit velocities v _max of nuclear spins which can be dephased with relatively short and weak gradient pulses, while the flow-dither gradient pulse sequences provide the significant contribution to gradient timing compared to the low gradient image gradient echo pulse sequences , so that the echo times differ only slightly.

Consequently stand basically two methods of suppression of signals in moving media by dephasing nuclear spins to disposal, in which the gradient echo pulse sequences to be used are flow-phasing gradient pulse sequences in at least one spatial direction, wherein the gradient echo pulse sequences in the respective spatial direction by insertion of respective Flußdephasiergradientenpulse formed in imaging gradient echo sequences or according to the invention according to the above boundary conditions are calculated. By the inserted or newly calculated sequences are dephased nuclear spins that are move in the spatial directions in which the flow dephasing gradient pulses are effective.

Basically the reading of data for imaging are made arbitrarily. An advantageous pulse sequence is the so-called FLASH sequence (Fast Low Angle Shot), in which an excitation pulse with a flip angle α <90 °, for example 25 °, irradiated and gradient pulses are used for refocusing. additional Gradients are used for imaging and flow dephasing. The to Data acquisition time required is reduced when the excitation pulse irradiated with a flip angle α <90 ° becomes.

to Acceleration of the recording are basically also multipulse sequences can be used, for example, EPI (echo planar imaging). In these Sequences are irradiated only one excitation pulse and successively a variety of gradient pulses for spatially resolved imaging switched so that refocusing signals with each readout gradient pulse to be obtained. Because with can in a gradient echo pulse sequence, for example, data for a series or an entire matrix in k-space (obtained data before the Conversion into the location-coded image data by Fourier transformation) be recorded. EPI is advantageous from the standpoint that the data is scanned quickly. However, there is in this case, the disadvantage that when taking pictures of many body regions, especially in the abdominal area, artifacts show the modifications, For example, segmented EPI, make necessary.

In a main variant of the present invention, the data is recorded point by point with separate gradient echo pulse sequences such that a new excitation pulse is radiated for each point. Although this procedure is somewhat more time-consuming than the methods in which multipulse sequences are used. However, the method is much more robust than a method with multipulse sequences. EPI also has the disadvantage that image blurs and signal losses occur at the relatively long echo times when using contrast agents that accelerate T ₂ * decay.

In an alternative procedure according to the invention, it is also possible to use an imaging sequence in which first a transverse magnetization is generated by initially orienting the spins aligned in the z direction at least partially by irradiating a 90 ° pulse or a pulse with a flip angle α <90 ° folded into the xy plane, then the spins are dephased with a suitable moving dephasing gradient gradient pulse for which M ₀ = 0, and the spins are finally flipped back to the z direction by a second 90 ° pulse. The magnetization thus stored in the z-direction is thereby impressed as an additional contrast, the dephasing, so that it can be read with any imaging sequence. However, this embodiment has the disadvantage over the FLASH sequence that the rapid T ₁ relaxation caused by the contrast agents again levels the contrast impressed in the z direction.

Farther it is also conceivable that in addition a 180 ° pulse is irradiated for refocusing. Very disadvantageous about this The procedure is, however, that the data acquisition a clear longer Takes more time than just switching a readout gradient for refocusing. In addition, will This also radiates much more energy into the body to be examined. this leads to to a disadvantageous load on the examination object.

To further speed up the recording technique, the data acquisition can also be reduced by not having the maximum data in a data to be subjected to Fourier transformation matrix is recorded in k-space. For example, in one embodiment, only one half of the data set may be taken and the other half filled with zeros. In another embodiment, only 80% of the lines are recorded in k-space. The remaining part is again filled with zeros. In all such cases, a limited resolution of the image is accepted. However, this is in many cases sufficient for clinical diagnosis, at least for a first orienting examination.

• – einen statischen Magnet, insbesondere einen supraleitenden Elektromagnet,
• – Gradientenvorrichtungen zur Erzeugung von Gradientenpulsen in drei orthogonal aufeinander stehenden Raumrichtungen, diese Vorrichtungen werden von stromdurchflossenen Spulen gebildet,
• – eine Sendevorrichtung zur Erzeugung von Hochfrequenzsignalen, es handelt sich hierbei insbesondere um eine RF-Sendespule,
• – eine Empfangsvorrichtung für Hochfrequenzsignale, es handelt sich hierbei vorzugsweise um eine RF-Empfangsspule,
• – eine Vorrichtung zur Ansteuerung der Gradientenvorrichtungen und der Sendevorrichtung, es handelt sich hierbei um Verstärker, sowie um programmierbare Vorrichtungen, mit denen die Gradientenpulssequenzen generiert werden können, ferner handelt es sich hierbei auch um programmierbare Vorrichtungen, mit denen die Sende- und Empfangsspulen angesteuert werden können,
• – eine Auswertevorrichtung und
• – eine Anzeigevorrichtung.

The device according to the invention has the following essential features:

• A static magnet, in particular a superconducting electromagnet,
• Gradient devices for generating gradient pulses in three mutually orthogonal spatial directions, these devices are formed by current-carrying coils,
• A transmitting device for generating high-frequency signals, in particular an RF transmitting coil,
• A reception device for high-frequency signals, this preferably being an RF reception coil,
• - A device for controlling the gradient devices and the transmitting device, these are amplifiers, as well as programmable devices with which the gradient pulse sequences can be generated, and this is also about programmable devices with which the transmitting and receiving coils are controlled can,
• - An evaluation device and
• A display device.

The Transmitting device and the receiving device can in a preferred embodiment of Invention be realized by a common device. In This case is additional a switch provided to drive these devices serves and switches between the transmission mode and the reception mode.

to closer explanation The following figures are used in the invention, in the context of the individual examples to be discribed. They show in detail:

1 : a schematic representation of a gradient echo pulse sequence;

2a : a schematic representation of a flux-compensated gradient echo pulse sequence for recording two-dimensional MR data without special gradient circuits for suppressing moving MR signal carriers;

2 B a schematic representation of a gradient echo pulse sequence for recording two-dimensional MR data in a first embodiment of the invention with inserted Flußdephasiergradientenpulsen (marked dark);

2c a schematic representation of a gradient echo pulse sequence for recording two-dimensional MR data in a second embodiment of the invention with newly calculated Flußdephasiergradientenpulsen, which are used simultaneously for imaging and suppression of moving MR signal carrier;

3 : Frames captured with a 3D gradient echo pulse sequence with flow dephasing in a spatial direction from a Copenhagen rat after administration of a lymph-directed MR contrast agent;

4 : Comparing single images taken with a 3D gradient echo pulse sequence from a Copenhagen rat, with and without flow dephasing gradient circuits in all three spatial directions;

5 : High-resolution gradient echo MR images of a Watanabe rabbit 12 h after administration of a plaque-common MR contrast agent without and with signal suppression of moving signal carriers in all three spatial directions;

6 : High-resolution gradient echo MR images as in 5 , 28 h after administration of the plaque-common MR contrast agent.

In 1 First, a schematic representation of a gradient echo _{pulse sequence} for illustrating the parameters G _bipolar , t _ramp , t _plateau and t _sep in a plot of G (t) (gradient field strength) over time t is shown. The meaning of the individual parameters is explained in more detail above.

In 2 gradient echo pulse sequences are reproduced for image presentation.

In 2a First, a sequence is shown that has no Flußdephasiergradientenpulse for dephasing moving nuclear spins, but a sequence with flow compensation, ie, a sequence in which M ₀ and M _{1 are} each zero. The illustration shows the gradient circuits in the three spatial directions over time.

In the upper display ("G _slice "), the gradient pulse sequence for the _{slice selection} in the z-direction is shown, and an excitation RF pulse is irradiated during the first gradient pulse.This slice gradient pulse selects a particular slice, because only there is the slice gradient pulse selected The subsequent pulses in the z-direction with inverse or the same polarity are used to refocus the defocusing caused by the first pulse and to set the condition that both M ₀ and M _{1 become} zero.

Pulses for phase coding of the nuclear spins are shown schematically in the lower representation ("G _phase "): With each repetition of the pulse sequence shown, the magnitude and polarity of this phase gradient pulse is changed incrementally between two extreme values -G _phase and + G _phase .

The readout gradient pulses are reproduced in the middle representation ("G _read ") The pulse sequence, as in the case of the slice gradient pulses, is calculated in such a way that the conditions of M ₀ = 0 and M ₁ = 0 are satisfied In the last pulse, the signal of the nuclear spins in the xy plane is formed by refocusing, which is recorded.

In 2 B is a schematic representation of the gradient echo pulse sequence for recording two-dimensional MR data reproduced in a non-inventive embodiment. This sequence contains on the one hand the sequence 2a which does not have any flow-dephasing gradient pulse sequences but only flow-compensated imaging gradient pulse sequences. In addition, dark labeled gradient circuits are shown, which have additionally been inserted into the imaging sequences and which are used for dephasing the nuclear spins in moving media without affecting the imaging gradient echo pulse sequences. In this case, the first-order gradient moments M _{1 have been} inserted in all spatial directions (slice, phase and readout) so that suppression of the signals of nuclear spins that move in any spatial direction during the measurement takes place.

In 2c is a schematic representation of the gradient echo pulse sequences for recording two-dimensional MR data reproduced in an embodiment of the invention. In these sequences are originally in 2a Imaging gradient echo pulse sequences shown no longer separately recognizable. These gradient echo pulse sequences have been created by recalculation taking into account flow depperature gradient pulse sequences.

The Examples described below were on clinical MR scanners implemented.

Example 1:

In a first variant not according to the invention, inserted bipolar gradient echo pulse sequences were used on a 1.5 Tesla whole body tomograph (Magnetom Vision, Siemens, Erlangen), which has a maximum gradient field strength G _max = 25 mT / m and a maximum rate of rise s _max = 42 T / ( m · s).

When The starting sequence was a 3D FLASH sequence whose parameters for the Optimized imaging of small animals (high spatial resolution) was.

To demonstrate the effectiveness of suppression of the signal from blood vessels, a Copenhagen rat with stimulated lymph nodes was given a contrast agent in an animal study. The contrast agent was chosen so that it remained in the blood stream for a long time and there massively shortened the relaxation times T ₁ and T ₂ . It was a gadolinium complex with a fluorinated side chain that followed the chemical name has: [10- {(RS) -1 - [({[(5S) -6- {4 - [(heptadecafluorooctyl) sulfonyl] piperazin-1-yl} -5 - {[(alpha-D-) mannopyranos-1-O-yl) oxy] acetylamino} -6-oxohexan-1-yl] carbamoyl} methyl) -carbamoyl-kappa O] ethyl} -1,4,7,10-tetraazacyclododecane-1,4,7- triacetato (3 -) - kappa N1, kappa N4, kappa N7, kappa N10, kappa O1, kappa O4, kappa O7] -gadolinium. 50 μmol Gd / kg body weight was injected iv.

In a first experiment, selective bipolar flow dephasing gradient pulse sequences were first inserted in a spatial direction. The pictures are in 3 recognizable:
The conditions for the recording were as follows: echo time TE = 14.0 ms, size of the field of view FOV = 60 × 120 mm ² ; Layer thickness SL = 0.32 mm; Matrix: 104x256; BW = 150 Hz / pixel; flip angle α = 15 °; Recording time TA = 3 min 42 s.

In the upper shot in 3 the inguinal lymph nodes of the rat are clearly visible through a strong enhancement of the contrast medium (arrows). It can be seen that blood vessels that run in the direction of the inserted gradient pulses are displayed with little signal. Since the contrast agent used was taken up by the lymphatic system, in which the speed of movement of the signal carriers is very low compared to the bloodstream, a signal-rich representation of the lymph nodes was achieved.

In the lower picture in 3 It can also be seen that the aorta (open arrows), which runs in the readout direction, shows no signal because of the suppression in the readout direction. In contrast, the normal renal vein (closed arrow) was not suppressed because a corresponding flow dephasing gradient pulse sequence was not switched in this direction. However, the signal from the renal vein could have been significantly reduced if suitable flow-dephasing gradient pulse sequences had been additionally switched in this direction. However, this would require relatively large first-order gradient moments M ₁ , since the speed of the signal carriers in the veins would be relatively low, so that it would have been necessary to reduce v _max .

In 4 For example, images taken with a 3D gradient echo pulse sequence, without and with flow-phasing gradient circuits, are shown in comparison to each other, again recorded on a Copenhagen rat. In this case, bipolar gradient pulses were inserted in all three spatial directions. The corresponding shots are on the right side of 4 to see. On the left side, images obtained without insertion of flow-dephasing gradient circuits are shown.

In this experiment, the motion sensitivity v _{max was changed} in the range from 2.56 cm / s to 36.5 cm / s by varying the echo time TE from TE _min = 9.4 ms to 18 ms. The other parameters were: G _bipolar = 20 mT / m; t _ramp = 0.6 ms; t _plateau = ½ (TE - TE _min ) = 0 to 8.6 ms; t _sep = 3.7 ms; TR = 19.1 ms to 25.5 ms; Size of the field of view FOV = 40 × 80 mm ² ; Layer thickness SL = 0.5 mm; Matrix: 128x256; BW = 150 Hz / pixel; flip angle α = 25 °; Recording time TA = 2 min 29 s.

The Pulse sequence was implemented so that with increasing echo time TE (from top to bottom in the recording sequence) ever smaller speeds sufficient to suppress the signal of moving spins.

As prolonged echo time TE also causes a reduction of the MR signal a reinforced T ₂ decay, the experiment was carried out to flow dephasing in all echo times without the usual gradient.

The figure shows a comparison of the two image series, which shows how the MR signal in the aorta was increasingly suppressed with decreasing v _max , so that the iliac lymph nodes lying next to the aorta were always better distinguishable from the aorta. A clear delimitation against the aorta succeeded only below 10 cm / s.

Example 2:

A second variant was implemented on a 1.5 Tesla whole body tomograph (Magnetom Symphony, Siemens, Erlangen) with a maximum gradient field strength G _max = 30 mT / m and a maximum slew rate s _max = 120 T / (m · s).

In an animal experiment, a Watanabe rabbit was given the aforementioned intravascular gadolinium contrast agent [10 - {(RS) -1 - [({[(5S) -6- {4 - [(heptadecafluorooctyl) sulfonyl] piperazin-1-yl} - 5 - {[(alpha-D-mannopyranos-1-O-yl) oxy] -acetylamino} -6-oxo-hexane-1-yl] carbamoyl} methyl) carbamoyl-kappa O] ethyl} -1,4,7,10-tetraazacyclododecane-1,4,7-triacetato (3 -) - kappa N1, kappa N4, kappa N7, kappa N10, kappa O1, kappa O4, kappa O7] -gadolinium injected in an amount of 0.1 mmol / kg body weight iv, which accumulates in plaques. At a given speed sensitivity of v _max = 10 cm / s echo times between 8.0 ms and 9.5 ms were realized depending on the spatial resolution. Image data were taken with and without flow dephasing in all three spatial directions after a long time after administration.

In 5 the image data obtained after 12 h after the administration and in 6 the image data acquired after 28 h after administration of the contrast agent.

Even after 28 h, the contrast signal in the blood vessels was still so strong that it was only in the flow-dephased image data that plaques could be clearly identified:
In the 5 Recordings taken were taken under the following conditions: TR = 16 ms; TE = 9.4 ms; FOV = 135 x 180 mm ² ; SL = 2 mm; Matrix: 307 × 512; BW = 245 Hz / pixel; α = 30 °; TA = 2 min 37 s.

In this figure are high-resolution Gradient echo MR images without (left images) or with (right Recordings) signal suppression moving signal carrier shown. While with flow dephasing the inside of the blood vessels (arrows) dark against the bright, contrast-enhancing plaque deposited it was not in the picture without flow dephasing possible, Identify plaques.

For inclusion in 6 the following parameters were used: TR = 14 ms; TE = 8.5 ms; FOV = 200 × 200; SL = 2 mm; Matrix: 205 × 256; BW = 245 Hz / pixel; α = 30 °; TA = 1 min 32 s.

In this figure, images of the rabbit are shown 28 hours after the administration of the plaque-gadolinium complex complex, the left image without and the right signal-suppressed with signal suppression in all three spatial directions (v _max = 10 cm / s) were obtained. As in 5 Only in the flowdephasierten measurement plaques (arrows) could be separated from the blood vessels.

Claims (6)

Magnetic resonance tomography apparatus for spatially resolved imaging of the density distribution of nuclear spins in a selected viewing area in a body containing an MR contrast agent, comprising: a static magnet, gradient devices for generating gradient pulses in three mutually orthogonal spatial directions, a transmitting device for generating high-frequency signals, a receiving device for high-frequency signals, a device for controlling the gradient devices and the transmitting device, an evaluation device, and a display device, wherein the device for controlling the gradient devices and the transmitting device is designed and programmed such that the body can be exposed to radio frequency and magnetic field gradient echo pulse sequences, and in order to attenuate the magnetization of a medium flowing in at least one spatial direction in the body, image gradients of the Gr Adientenechopulssequenzen in at least one of the spatial directions in which the medium flows, in compliance with the condition:

where M _{0 is} the zero-order gradient moment, y is the gyromagnetic ratio of the nuclear spins, G (t ') is the time-dependent gradient field strength of the gradient pulse, t' is the time, and t is the fixed time elapsed since the application of a radio-frequency pulse to excite the nuclear spins calculated that the respective first-order magnetic moment M _{1 of} these gradient echo pulse sequences:

where M _{1 is} the first order gradient moment and y, G (t '), t' and t have the aforementioned meanings, is maximized with respect to the maximum adjustable gradient field strength and maximum achievable slew rate of the gradient echo pulse sequences. Magnetic resonance tomography apparatus according to claim 1, characterized in that M ₁ satisfies the following relationship: M 1 (t; G bipolar , t ramp , t plateau , t sep ) = γ · G bipolar · (T ramp + t plateau ) * (2t ramp + t plateau + t sep ) where G _{bipolar is} the maximum gradient field strength, t _{ramp is} the rise / fall time when the gradient field is turned on / off, t _{plateau is} the time span during which G is _bipolar , and t _{sep is} the time interval between two gradient pulses. Magnetic resonance tomography apparatus according to one of the preceding Claims, characterized in that the MR contrast agent is lymph and / or plaque common. A method for spatially resolved imaging of the density distribution of nuclear spins in a selected viewing area in a body wherein MR contrast agent is applied to the body and where image data is acquired from the viewing area by a magnetic resonance imaging apparatus by exposing the body to radio frequency and magnetic field gradient echo pulse sequences; in that the magnetization of medium flowing in at least one spatial direction in the body is attenuated by virtue of the fact that imaging gradients of the gradient echo pulse sequences in at least one of the spatial directions in which the medium flows satisfy the condition:

where M _{0 is} the zero-order gradient moment, y is the gyromagnetic ratio of the nuclear spins, G (t ') is the time-dependent gradient field strength of the gradient pulse, t' is the time, and t is the fixed time elapsed since the application of a radio-frequency pulse to excite the nuclear spins calculated that the respective first-order magnetic moment M _{1 of} these gradient echo pulse sequences:

where M _{1 is} the first order gradient moment and y, G (t '), t' and t have the aforementioned meanings, is maximized with respect to the maximum adjustable gradient field strength and maximum achievable slew rate of the gradient echo pulse sequences. Method according to Claim 4, characterized in that M ₁ satisfies the following relationship: M 1 (t; G bipolar , t ramp , t plateau , t sep ) = γ · G bipolar · (T ramp + t plateau ) * (2t ramp + t plateau + t sep ) where G _{bipolar is} the maximum gradient field strength, t _{ramp is} the rise / fall time when the gradient field is turned on / off, t _{plateau is} the time span during which G is _bipolar , and t _{sep is} the time interval between two gradient pulses. Method according to one of claims 4 or 5, characterized in that the MR contrast agent is lymph and / or plaque-common.