Patent Publication Number: US-6662037-B2

Title: Method and apparatus to improve myocardial infarction detection with blood pool signal suppression

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuing application and claims priority of U.S. Ser. No. 09/681,081 filed Dec. 29, 2000 now U.S. Pat. No. 6,526,307. 
    
    
     BACKGROUND OF INVENTION 
     The present invention relates generally magnetic resonance imaging (MRI), and more particularly, to a method and apparatus, including a new pulse sequence, to achieve greater sensitivity in detecting infarcted myocardial tissue. 
     MRI utilizes radio frequency pulses and magnetic field gradients applied to a subject in a strong magnetic field to produce viewable images. When a substance containing nuclei with net nuclear magnetic moment, such as the protons in human tissue, is subjected to a uniform magnetic field (polarizing field B 0 ), the individual magnetic moments of the spins in the tissue attempt to align with this polarizing field (assumed to be in the z-direction), but precess about the direction of this magnetic field at a characteristic frequency known as the Larmor frequency. If the substance, or tissue, is subjected to a time-varying magnetic field (excitation field B 1 ) applied at a frequency equal to the Larmor frequency, the net aligned moment, or “longitudinal magnetization”, M Z , may be nutated, or “tipped”, into the x-y plane to produce a net transverse magnetic moment M t . A signal is emitted by the excited spins after the excitation signal B 1  is terminated (as the excited spins decays to the ground state) and this signal may be received and processed to form an image. 
     When utilizing these signals to produce images, magnetic field gradients (G x G y  and G z ) are employed. Typically, the region to be imaged is scanned by a sequence of measurement cycles in which these gradients vary according to the particular localization method being used. The resulting MR signals are digitized and processed to reconstruct the image using one of many well-known reconstruction techniques. 
     Myocardial infarction is a type of cardiac syndrome in which oxygen is deprived from a portion of the heart. The size of the myocardial infarct has been demonstrated to have a strong correlation with patient outcome/recovery. Myocardial perfusion imaging is a technique in which regions of abnormal or impaired blood flow to the heart are detected by tracking the passage of a tracer or contrast agent through myocardial tissue. Regions of impaired blood flow or poor perfusion would not exhibit the presence of the contrast material or tracer whereas in tissues with normal perfusion, the presence of the contrast material or tracer would be indicated. 
     The imaging of tissue (blood) perfusion is closely related to the imaging of blood flow in vascular structures, such as in MR angiography (MRA). As with MRA, MR perfusion imaging is performed by injecting a volume a contrast agent, such as gadolinium chelate, into the blood stream, conventionally via an intravenous injection. The volume or mass of contrast agent administered is typically referred to as a bolus as it is delivered in a tight volume at a relatively high volume delivery rate (usually 1-5 ml/sec). Differing agents can either decrease the T 1  of blood to enhance the detected MR signal, or decrease the T 2  of blood to attenuate the detected MR signal. As the bolus passes through the body, the enhanced or attenuated signal increases or decreases the signal intensity observed in perfused tissue, but not in the non-perfused tissue. The degree of signal change in the observed tissue as compared with baseline images acquired prior to the arrival of the contrast material can be used to determine the degree of tissue perfusion. Since perfusion measurements are based on the change in tissue signal intensity between the baseline and during the first pass passage of the contrast material, it is important that the MR signal strength be made insensitive to variations from other factors unrelated to the primary mechanism for signal intensity changes due to perfusion. One such variable is the magnitude of the longitudinal magnetization M z , which is tipped into the transverse plane by the RF excitation pulse in the MR pulse sequence. After each excitation, the longitudinal magnetization is reduced and recovers magnitude at a rate determined by the T 1  constant of the particular spins being imaged. If another pulse sequence is played out before the longitudinal magnetization has fully recovered, the magnitude of the acquired MR signal will be less than the signal produced by a pulse sequence which is delayed long enough to allow full recovery of the longitudinal magnetization. Moreover, if the delay time varies as a result of variations in the patient&#39;s cardiac heart rate, the amount of longitudinal magnetization available will vary between heartbeat to heartbeat. This will cause fluctuations or variations in the signal intensity in the myocardial tissue independent of perfusion. It is known that the use of a saturation RF pulse with a flip angle of 90° will set the longitudinal magnetization to zero. Thus by waiting a pre-determined and fixed time after the saturation RF pulse before imaging, the re-growth the longitudinal magnetization is dependent on the tissue spin-lattice relaxation time, T 1 . Since the contrast agent effects T 1 , the use of a saturation RF pulse will yield a signal intensity that is dependent on the concentration of the contrast material present in a region of myocardial tissue and not variations in the patient&#39;s heart rate. The same technique is also applicable to T 2  or T 2   *  shortening agents. 
     Typically, perfusion imaging is a technique used to rapidly acquire images during the first pass of the contrast agent/bolus through the blood stream by using carefully optimized pulse sequence parameters. The goal of myocardial perfusion imaging is to detect and characterize any abnormal distribution of myocardial blood flow. Perfusion deficits are indicative of areas of compromised blood flow. These perfusion deficits may be transient, whereby the region of myocardial tissue is still viable and continues to receive some supply of blood, or acute where the blood flow to that region has been compromised sufficiently to render cellular damage to the myocardial tissue (i.e., myocardial infarction). Non-viable infarcted tissue undergoes cellular changes that damage the ability of the myocardial tissue or muscle to contract. Hence, regions of myocardial infarction are often characterized by having abnormal cardiac wall motion at rest. Under certain conditions where the tissue is still viable, with increased blood flow to that region, the myocardial tissue begins normal contractile motion. This type of characteristic is attributed to stunned or hibernating myocardium where the tissue is still viable but severely under perfused. 
     The area of cellular damage or myocardial infarction is often assessed to better determine the course of patient management. In some cases, in the periphery of the infarcted tissue, some recovery of function may be possible. However, in regions where the damage leads to micro-vascular obstruction, no recovery is possible. The use of imaging of myocardial infarcted regions allows the assessment of the extent of the cardiac injury and permits the monitoring of the patient&#39;s response to a specific treatment regimen. 
     In order to assess for the presence of myocardial infarction, an inversion recovery pulse sequence is routinely employed to suppress normal myocardial tissue subsequent to the administration of the contrast bolus, which is typically between 0.1 and 0.2 mmol/kg of gadolinium contrast material. In this application, the bolus has the effect of shortening the T 1  time of the blood. 
     During the first pass of the contrast material, under resting conditions, the infarcted region may be identified by regions of abnormal perfusion. That is to say, the infarcted zones, having very low blood perfusion would be hypo-intense relative to normal, healthy myocardium. With recirculation of the contrast material, transport of the contrast material to the site of the myocardial infarct is by the limited blood flow to the affected region or by diffusion into the extra-cellular space. Consequently, the uptake of contrast material by infarcted tissue occurs at a much slower rate than normal, healthy myocardial tissue. As the uptake of the contrast material is slow, so is the wash-out of the contrast material from the infarcted zones. This yields a phenomena whereby the infarcted region is hypo-intense during the first pass of the contrast material, reaches iso-intensity at some point in time, and at a much later or delayed time following the initial administration of contrast material, is hyper-intense relative to the normal, healthy myocardium. 
     Since gadolinium contrast material will concentrate in infarcted tissue, an inversion recovery magnetization preparation pulse sequence is designed with an inversion time, TI, to suppress signal from normal, healthy myocardial tissue to yield regions with high signal intensity in the infarcted zones. However, as the concentration of contrast material in the blood is still relatively high, but less than that in infarcted tissue, the ventricular blood pool will still exhibit high signal intensity relative to the infarcted tissue such that delineation of the myocardial boundaries with the ventricular blood pool cavity is difficult. That is, an MR image of blood acquired using a fast gradient echo pulse sequence, or similar technique, will display blood with a high signal intensity with respect to adjacent stationary tissue of the vessel structure. However, it is important in the diagnosing of the extent of myocardial infarction to be able to discriminate between the margins of the infarcted tissue, especially sub-endocardially, and the ventricular blood cavity. 
     It would therefore be desirable to have a method and apparatus that is capable of myocardial infarction detection with suppression of blood pool signal, in order for the myocardial borders to be accurately defined against a low signal intensity background of normal myocardial tissue or blood in the left ventricle. 
     BRIEF DESCRIPTION OF INVENTION 
     The present invention relates to a technique for acquiring MR images to detect infarcted myocardial tissue that solves the aforementioned problems. 
     The invention includes the use of a blood suppression pulse used in conjunction with an inversion recovery pulse in a gated, segmented k-space gradient echo acquisition to improve the delineation of infarcted myocardium from the ventricular blood pool. The technique uses a notched inversion RF pulse with a stop-band positioned over the imaged slice. In this manner, the contrast in the imaged slice is unaffected by the blood suppression pulse. The inversion time is chosen such that blood inverted in the pass-band of the notched RF pulse, will be at or close to the null point at the time of the gradient echo read-out segment. It is expected that the concentration of the contrast material in the infarcted zones is higher than in the normal, healthy myocardium about 5-15 minutes after the administration of the contrast material. Since the concentration of the contrast material in blood is higher than that of the normal, healthy myocardium, signal intensity of the ventricular blood is higher than that of the normal myocardium. The relative concentration of the contrast material between the infarcted tissue and blood is not well defined as it is affected by several physiological factors. It is safe to assume that the concentration of contrast agent in the ventricular blood is at least as high as that in the infarcted tissue, leading to both tissues having similar T 1  relaxation times and similar signal intensities. 
     It is thus desirable to employ a technique that suppresses signal from the ventricular blood and not from the infarcted region. A conventional slice-selective inversion pulse would null signal from both blood and the infarcted tissue. A solution to this problem requires a new approach for blood suppression while leaving the signal from the infarcted zone relatively unaffected. 
     The notched inversion pulse inverts the spins of blood outside of the imaged slice while not affecting the spins in the imaged slice. At some time after the applied notched inversion pulse, selected for the time needed to null signal from contrast-enhanced blood, blood from within the imaged slice would be replaced by spins from outside of the slice, thereby achieving blood suppression without affecting the signal from the infarcted zones. 
     In accordance with one aspect of the invention, a method of acquiring MR images with blood pool suppression includes applying a pulse sequence that includes a notched inversion pulse. The notched inversion pulse is designed to suppress blood pool about the region-of-interest. 
     In accordance with another aspect of the invention, an MR pulse sequence is disclosed a notched inversion RF pulse. The notched inversion RF pulse is transmitted after a primary slice-selection inversion RF pulse and has a stop-band coincident with that of the primary slice-selective inversion RF pulse. 
     In accordance with yet another aspect of the invention, a computer system is disclosed for use with an MRI apparatus having a computer programmed transmit a notched inversion RF pulse with an inversion time selected to invert regions outside a desired imaging slice such that signals from blood flowing into the desired imaging slice are suppressed. 
    
    
     Various other features, objects and advantages of the present invention will be made apparent from the following detailed description and the drawings. 
     BRIEF DESCRIPTION OF DRAWINGS 
     The drawings illustrate one preferred embodiment presently contemplated for carrying out the invention. In the drawings: 
     FIG. 1 is a schematic block diagram of an NMR imaging system for use with the present invention. 
     FIG. 2 is a pulse sequence diagram illustrating relative temporal positions of various RF pulses with respect to an R—R interval in accordance with the present invention. 
     FIG. 3 is a diagram illustrating relative spatial and frequency extents and positions of the RF pulses shown in FIG.  2 . 
    
    
     DETAILED DESCRIPTION 
     Referring to FIG. 1, the major components of a preferred MRI system  10  incorporating the present invention are shown. The operation of the system is controlled from an operator console  12  which includes a keyboard or other input device  13 , a control panel  14 , and a display  16 . The console  12  communicates through a link  18  with a separate computer system  20  that enables an operator to control the production and display of images on the screen  16 . The computer system  20  includes a number of modules which communicate with each other through a backplane  20   a . These include an image processor module  22 , a CPU module  24  and a memory module  26 , known in the art as a frame buffer for storing image data arrays. The computer system  20  is linked to a disk storage  28  and a tape drive  30  for storage of image data and programs, and it communicates with a separate system control  32  through a high speed serial link  34 . The input device  13  can include a mouse, joystick, keyboard, track ball, touch screen, light wand, voice control, or similar device, and may be used for interactive geometry prescription. 
     The system control  32  includes a set of modules connected together by a backplane  32   a . These include a CPU module  36  and a pulse generator module  38  which connects to the operator console  12  through a serial link  40 . It is through link  40  that the system control  32  receives commands from the operator which indicate the scan sequence that is to be performed. The pulse generator module  38  operates the system components to carry out the desired scan sequence and produces data which indicates the timing, strength and shape of the RF pulses produced, and the timing and length of the data acquisition window. The pulse generator module  38  connects to a set of gradient amplifiers  42 , to indicate the timing and shape of the gradient pulses that are produced during the scan. The pulse generator module  38  also receives patient data from a physiological acquisition controller  44  that receives signals from a number of different sensors connected to the patient, such as ECG signals from electrodes attached to the patient. And finally, the pulse generator module  38  connects to a scan room interface circuit  46  which receives signals from various sensors associated with the condition of the patient and the magnet system. It is also through the scan room interface circuit  46  that a patient positioning system  48  receives commands to move the patient to the desired position for the scan. 
     The gradient waveforms produced by the pulse generator module  38  are applied to the gradient amplifier system  42  having G x , G y , and G z  amplifiers. Each gradient amplifier excites a corresponding physical gradient coil in an assembly generally designated  50  to produce the magnetic field gradients used for spatially encoding acquired signals. The gradient coil assembly  50  forms part of a magnet assembly  52  which includes a polarizing magnet  54  and a whole-body RF coil  56 . A transceiver module  58  in the system control  32  produces pulses which are amplified by an RF amplifier  60  and coupled to the RF coil  56  by a transmit/receive switch  62 . The resulting signals emitted by the excited nuclei in the patient may be sensed by the same RF coil  56  and coupled through the transmit/receive switch  62  to a preamplifier  64 . The amplified MR signals are demodulated, filtered, and digitized in the receiver section of the transceiver  58 . The transmit/receive switch  62  is controlled. by a signal from the pulse generator module  38  to electrically connect the RF amplifier  60  to the coil  56  during the transmit mode and to connect the preamplifier  64  during the receive mode. The transmit/receive switch  62  also enables a separate RF coil (for example, a surface coil) to be used in either the transmit or receive mode. 
     The MR signals picked up by the RF coil  56  are digitized by the transceiver module  58  and transferred to a memory module  66  in the system control  32 . When a scan is completed, an array of raw k-space data has been acquired in the memory module  66 . As will be described in more detail below, this raw k-space data is rearranged into separate k-space data arrays for each image to be reconstructed, and each of these is input to an array processor  68  which operates to Fourier transform the data into an array of image data. This image data is conveyed through the serial link  34  to the computer system  20  where it is stored in the disk memory  28 . In response to commands received from the operator console  12 , this image data may be archived on the tape drive  30 , or it may be further processed by the image processor  22  and conveyed to the operator console  12  and presented on the display  16 . 
     The present invention includes a method and system suitable for use with the above-referenced NMR system, or any similar or equivalent system for obtaining MR images. 
     Referring to FIG. 2, the radio-frequency (rf) section of a pulse sequence  100  is shown illustrating the relative temporal positions of various RF pulses and with respect to an R—R interval of an ECG cycle  102 . The first RF pulse played out is a slice-selective inversion pulse  104  having an inversion time TI as measured from the peak of the slice-selective inversion pulse  104  to a peak of a first excitation RF pulse  106  for image acquisition  108 . The slice-selective inversion pulse  104  is designed with a section thickness of between 1.0 and 3 times the section thickness of an imaged slice, as will be described with reference to FIG.  3 . The slice-selective inversion pulse is preferably played out with an inversion time of approximately 100-450 msec, in one embodiment. This inversion time is selected to null signal from normal myocardium and is varied depending on the concentration of the contrast material used (which impacts the residual concentration of the contrast material in normal, healthy myocardium), and the delay time from the initial contrast material administration. 
     After the slice-selective inversion pulse  104  is transmitted, a notched RF inversion pulse  110  is transmitted to invert the longitudinal magnetization from blood outside of the imaged slice-of-interest. Preferably, the notched RF inversion pulse, also referred to as a blood suppression pulse, has an inversion time TI BSP  of approximately 120-150 msec. (in one embodiment). In this manner, the longitudinal magnetization of blood outside of the imaged slice-of-interest recovers from an inverted state through zero or null. It is anticipated that the blood flow during this TI BSP  time is sufficient that the blood outside of the imaged slice-of-interest will flow into the region when the image slice is acquired so that the longitudinal magnetization of the blood is close to its null point. This expanded region substantially reduces the signal from blood within the image slice. 
     As previously alluded to, the pulse sequence  100  also includes at least one, but preferably a number of excitation RF pulses  112  to acquire data  108 . The acquisition of data takes place, preferably, in the mid-diastole region. It is also preferable to acquire the data during a single breath-hold by the patient. The excitation RF pulses  112  of the pulse sequence  100  are of a known segmented k-space gradient echo imaging technique. Although the aforementioned technique is described with reference to a two-dimensional acquisition strategy, it is also applicable for a three-dimensional image acquisition sequence with segmented acquisition across multiple cardiac cycles. 
     Referring now to FIG. 3, the relative spatial positions and section thickness of the primary slice-selective inversion pulse  104 , the notched blood suppression pulse  110 , and the imaged slice  106  are shown. Initially, it is noted that the width  114  of the pass-band  116  of the slice-selective inversion RF pulse  104  is selected to accommodate cardiac and respiratory motion of the imaged slice during the inversion time TI. This pass-band  116  is therefore selected approximately 13 or more times that of the imaged section thickness  118 . The notched RF suppression pulse  110  has a stop-band  120  that is coincident with that of the pass-band  116  of the primary slice-selective inversion RF pulse  104 . The width  122  of the stop-band  120  of the notched RF pulse  110  is sized about the same as that of the pass-band  116  of the slice-selective inversion pulse  104 . The pass-bands  124  of the notched RF pulse  110  are sized large enough to invert regions outside the imaged slice  106  to include blood that may flow into the region-of-interest of the imaged slice during data acquisition. Because the inversion time for blood suppression is less than that used for normal myocardial tissue suppression, the inversion time of the blood suppression pulse  110  is less than the inversion time for the slice-selective inversion RF pulse  104 . The inversion time of the blood suppression pulse  110  must also take into account the time after the initial contrast material is administered and the amount of the dose administered. It is also noted that the notched RF blood suppression pulse  110  has a 180° flip angle, in one embodiment but can have a flip angle from 90° to 180°. 
     The application of the notched RF pulse  110  for blood suppression does not affect the primary slice-selective inversion pulse  104  for normal myocardial tissue suppression. Therefore, the equations used to determine the necessary inversion times for both contrast-enhanced blood and normal myocardium are uncoupled and independent. The equations necessary to achieve nulling of normal, healthy myocardium are well known and are given by: 
     
       
           M   Z ( t )= M   Z,EQ  cos α exp (− t/T   1 )+ M   o (1 exp (− t/T   1 )) (Eqn. 1) 
       
     
     where M Z (t) is the longitudinal magnetization at the of image acquisition, M Z,EQ  is the equilibrium longitudinal magnetization after image acquisition and just prior to application of the inversion recovery rf pulse, α is the inversion recovery rf pulse flip angle, M o  is the thermal equilibrium longitudinal magnetization, T 1  is the spin-lattice relaxation time, and t is the time after the inversion pulse. Note that Eqn. (1) is general and applicable to both myocardial suppression and blood suppression:as the technique previously described allows for the uncoupling of the myocardial and blood suppression equations. 
     The present invention has been shown to be an effective blood suppression technique to detect the presence of infarcted myocardial tissue. Without a blood suppression RF pulse, there is difficulty in distinguishing between enhanced infarcted myocardial tissue and the ventricular blood cavity. With this blood suppression technique, the endo-cardial boundaries of the infarcted tissue can be clearly delineated, thereby allowing better appreciation of the extent of myocardial infarction. 
     Accordingly, the invention includes a method of MR imaging with blood pool suppression that includes administering a contrast agent into the blood stream of a patient, and then applying a pulse sequence having a slice-selective inversion RF pulse and a notched inversion RF pulse. With a contrast bolus of gadolinium contrast material, and a dosage of between 0.1-0.2 mmol/kg, it is preferable to wait 5-15 minutes after the administration of the contrast material for normal myocardium suppression. The slice-selective RF pulse is designed to suppress myocardial tissue, and is followed by the notched inversion RF pulse that is designed to suppress blood pool. The suppression of blood pool signal is preferably done in a region larger than that where data is acquired so that when acquiring MR data, the blood that has flowed into the region is nulled. An MR image can then be reconstructed from the acquired MR data to assess a presence of myocardial infarction. This technique not only increases the sensitivity to detect infarcted myocardial tissue, but also allows much better discrimination between the endo-cardial boundaries of the infarcted tissue and the ventricular cavity. 
     The invention also includes a computer programmed to control an MRI system, such as that disclosed with reference to FIG. 1, and also programmed to apply a pulse sequence such as that disclosed with reference to FIGS. 2 and 3. That is, the computer is programmed to transmit a slice-selection inversion pulse to suppress signals from normal myocardial tissue, and then transmit a notched inversion RF pulse with an inversion time selected to invert regions inside and outside of a desired imaging slice such that signals from blood flowing into the desired imaging slice are also suppressed. The computer is also programmed to transmit excitation RF pulses, and then cause the acquisition of data from the desired imaging slice wherein the data has signal suppression from both normal myocardial tissue and blood. Note that to reduce the inversion delay times (TI and TI BSP ), partial inversion rf pulses with flip angles from 90° to 180° may be used without loss of effect. 
     Experimental data using the present technique provided results with marked improvement over images without blood suppression. Two sets of images were acquired of the same subject approximately 4 minutes apart. The first set of images had no blood suppression, while the second set employed the blood suppression technique of the present invention. The resulting images show a significant reduction in blood signal and the endo-cardial boundaries of the infarcted tissue that can be clearly differentiated in the blood suppressed images, whereas the images acquired without blood pool suppression do not clearly show the boundaries nor the infarcted areas nearly as well. The acquisition parameters were: 32 cm FOV, 9 mm section thickness, 256 by 192 matrix, 2 NEX, TR/TE/flip=6.6/1.7/20, TI=200 msec, TI BSP =150 msec. 
     The present invention has been described in terms of the preferred embodiment, and it is recognized that equivalents, alternatives, and modifications, aside from those expressly stated, are possible and within the scope of the appending claims.