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EP1071367A1 - Formation d'images multicoupe de flux sanguin cerebral par imagerie par resonance magnetique de marquage de spin arteriel en continu - Google Patents

Formation d'images multicoupe de flux sanguin cerebral par imagerie par resonance magnetique de marquage de spin arteriel en continu

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Publication number
EP1071367A1
EP1071367A1 EP99918519A EP99918519A EP1071367A1 EP 1071367 A1 EP1071367 A1 EP 1071367A1 EP 99918519 A EP99918519 A EP 99918519A EP 99918519 A EP99918519 A EP 99918519A EP 1071367 A1 EP1071367 A1 EP 1071367A1
Authority
EP
European Patent Office
Prior art keywords
image
labeling
slice
blood flow
irradiation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99918519A
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German (de)
English (en)
Other versions
EP1071367A4 (fr
Inventor
David C. Alsop
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Pennsylvania Penn
Original Assignee
University of Pennsylvania Penn
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Filing date
Publication date
Application filed by University of Pennsylvania Penn filed Critical University of Pennsylvania Penn
Publication of EP1071367A1 publication Critical patent/EP1071367A1/fr
Publication of EP1071367A4 publication Critical patent/EP1071367A4/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/026—Measuring blood flow

Definitions

  • the present invention relates to a technique for imaging regional cerebral blood flow (CBF) noninvasively using MRI with radio frequency arterial spin labeling and, more particularly, to a labeling technique which permits extension of this technique to a multi-slice examination.
  • CBF regional cerebral blood flow
  • CBF CBF imaging with Single Photon Computed Tomography - 2 -
  • PET Positron Emission Tomography
  • Xenon enhanced CT Xenon enhanced CT
  • PET imaging of CBF has also been an important tool for mapping task induced brain activity in normal and pathologic states .
  • Magnetic Resonance Imaging MRI provides the greatest sensitivity to structural abnormalities.
  • a robust MRI based method for clinical imaging of CBF would allow both an anatomical and a functional assessment within the same examination.
  • the higher spatial resolution of MRI as compared to nuclear medicine methods will lead to better image quality.
  • MRI of CBF can be performed either with intravascular contrast agents or by Arterial Spin Labeling (ASL) .
  • ASL Arterial Spin Labeling
  • ASL electromagnetically labels water proton spins in the feeding arteries before they flow into the tissue.
  • ASL is attractive since it can reduce the risk, complexity, and cost of a study. It is also more readily quantified and repeated than contrast agent methods.
  • ASL Arterial Spin Labeling
  • EPISTAR EPISTAR
  • FAIR FAIR
  • SCL continuous arterial spin labeling
  • CASL produces more than twice the signal of pulsed techniques.
  • multi-slice imaging is complicated by effects of the electromagnetic labeling on the image intensity, as well as the relatively long time required for blood to flow from the arteries into the thick slab of tissue to be imaged.
  • the present invention relates to a method for generating two sets of images which are identical except for the effects of blood flowing into the imaged slices. Subtraction of the two images can provide images of blood flowing in large vessels, sometimes referred to as angiograms, or perfusion, sometimes referred to as tissue specific blood flow, depending upon the timing of the imaging sequence.
  • the present invention relates to the use of amplitude modulated RF irradiation prior to the acquisition of one set of images, hereafter referred to as the control images, and the use of unmodulated RF irradiation prior to the acquisition of the second set of images, hereafter referred to as the labeled images .
  • the present invention employs the amplitude modulated RF irradiation prior to the control image acquisition to mimic all the blood flow unrelated effects of the constant RF irradiation while leaving the blood signal positive. While prior art techniques for the control image were only effective in a single thin slice at a particular - 4 - angular orientation or required a second RF coil, the amplitude modulated control approach of the invention is effective for any number, orientation, and thickness of slices.
  • the invention relates to a method for imaging blood flow into a sample such as a tissue sample or a large blood vessel.
  • a preferred embodiment of the inventive method comprises the steps of: perturbing arterial spins of blood flowing into the sample by applying a constant RF irradiation together with a magnetic field gradient; acquiring a first image of the sample; applying amplitude modulated RF irradiation with a magnetic field gradient which, together, mimic the effects of constant RF radiation unrelated to blood flow; acquiring a second image of the sample; and generating a difference signal based on the first image and the second image that represents a blood flow image of blood flowing into the sample .
  • the first image is acquired after a delay period by detecting a magnetic resonance signal reflected off of the sample.
  • the delay period is set either to allow the blood having the perturbed spins to flow into the tissue before the images are captured (i.e., to capture a perfusion image), or to ensure that the images are captured while the blood is still in the blood vessel (i.e., to capture a large vessel blood flow image) .
  • the second image is acquired in a similar fashion shortly after the amplitude modulated RF irradiation is applied.
  • the analog magnetic resonance signals are preferably digitized and processed to measure blood flow via known techniques .
  • Figure 1A illustrates a single slice experiment in which the control labeled images are acquired with labeling applied at an equal distance distal to the slice (solid line) to compensate for the spatially dependent off resonance effects.
  • Figure IB illustrates the amplitude modulated irradiation technique of the invention whereby two inversion planes are created close to the original labeling plane.
  • Figure 2 illustrates a pulse sequence timing diagram for the entire sequence used to amplitude modulate the RF pulse in accordance with the method of the invention.
  • Figure 3 illustrates the percent difference between labeling and control images in a phantom as a function of frequency.
  • Figure 4 illustrates coronal images acquired in a human study with the label and control respectively placed at the ponto-medullary junction and 2 cm above the brain as indicated on the sagittal Tl images on the left of the figure.
  • Figure 5 illustrates a plot of the residual subtraction errors caused by imperfect matching of off-resonance saturation.
  • Figure 6 illustrates the efficiency of spin labeling with amplitude modulated control as a function of modulation frequency relative to a single slice labeling.
  • Figure 7 illustrates echoplanar images from eight axial slices (top row) used to generate CBF sensitive images (second row) as well as acquired Tl maps (third row) used to generate quantitative images of CBF (bottom row) .
  • Figure 1 illustrates control methods for CASL imaging of CBF.
  • RF irradiation used to label inflowing blood as it crosses the labeling plane (dashed line) also causes direct effects on image intensity that vary with distance from the labeling plane.
  • the established method of controlling for off resonance saturation with a single RF coil was to apply an inversion distal to the slice during the control image, as illustrated in Figure 1A.
  • Figure 1A illustrates a single slice experiment in which the control labeled images are acquired with labeling applied at an equal distance distal to the slice
  • the performance of amplitude modulation of the RF irradiation as a control will depend on how perfectly the spins are doubly inverted, and on how well the off-resonance saturation of the labeling irradiation is matched. If the spins are partially labeled by the amplitude modulated control, then the difference between the labeled and control images will decrease. This can be thought of as a loss of efficiency for labeling of blood flow. If the control does not perfectly match the off-resonance saturation of the labeling, then a difference between the images will occur even in the absence of blood flow. This would represent a systematic error in the blood flow measurement . Both of these properties of the control were assessed experimentally as described below.
  • Spin labeling was performed for single slice CBF imaging except for the amplitude modulated control and the acquisition of more than one slice. Specifically, a TR of 4s, temporal interleaving of labeled and control images, and a post-labeling delay were employed.
  • the post-labeling delay reduced the sensitivity of the CBF image to the transit time from the labeling plane, attenuated the signal from intraluminal arterial spins, and decreased the off-resonance saturation of the image intensity by the labeling RF.
  • the post-labeling delay also allows time for all of the labeled - 9 - blood to enter the tissue before imaging so that saturation of labeled spins by the imaging excitation pulses need not be considered.
  • the duration of the labeling irradiation was determined by the post-labeling delay, the imaging time and TR. For a post-labeling delay of 1.2s, the irradiation was applied for 2.3s.
  • a pulse sequence timing diagram for the entire sequence is shown in Figure 2. In the timing diagram of Figure 2, labeling RF signals and gradients are applied during the labeling period. Rapid gradient echo echoplanar imaging was used to acquire images from the 8 slices.
  • Tl maps are necessary for quantification of the CBF images. Unlike in the single-slice implementation, it was necessary to leave the labeling gradient on during Tl mapping to accurately measure the Tl shortening effect of the off-resonance saturation. In all other ways the protocol was identical. The entire Tl mapping protocol required 3 minutes for all slices.
  • All raw echo amplitudes were saved and transferred to a workstation for reconstructing the images.
  • a correction for image distortion and alternate k-space line errors was performed on each image using data acquired during a phase encoded reference scan.
  • the correction for distortion involves the measurement of magnetic field nonuniformity throughout the image.
  • a side-effect of this correction is that image regions where insufficient MR signal is present to accurately measure the magnetic field are set to zero.
  • the magnitude images were then averaged and the CBF weighted images were calculated by subtraction of labeled images from the control images.
  • An algorithm to remove subtle motion artifacts from the images was performed on the individual images prior to averaging for more accurate evaluation of the performance of the control .
  • the phantom consisted of a cylindrical plastic container, 10 cm in diameter and 20 cm long, filled with the gelatinous mixture.
  • the phantom was placed in the standard head coil of the scanner with the axis parallel to the axis of the magnet.
  • Single-slice images employing the CBF labeling strategy were acquired in a plane perpendicular to the axis of the phantom.
  • a labeling RF irradiation of 35 mG and a labeling gradient of 0.25 G/cm applied along the frequency direction of the image were used. Images were acquired with amplitude modulation frequencies of 125, 250 and 500 Hz.
  • Off-resonance saturation was analyzed by averaging the images across the phase direction so that plots of off-resonance saturation as a function of frequency could be generated.
  • weak saturation of signal at the labeling plane occurred even when the RF amplitude was set to zero in software. This indicated that a small amount of RF was leaking past the modulator.
  • the saturation could be eliminated by setting the RF amplitude to a small negative value corresponding to 2% of the RF amplitude used for labeling.
  • a constant value of 2% of the signal amplitude was subtracted from the software values of all of the labeling related RF amplitudes to compensate for this carrier leakage. Failure to correct for this leakage would cause systematic error in the CBF measurement.
  • the leakage is a subject independent phenomenon, it can be calibrated with phantom measurements and need never be measured in subjects.
  • Human Studies Three different human studies were performed. In one study, the amplitude modulated control method was tested for systematic offset due to imperfect matching of the - 11 - off-resonance saturation for label and control. Two subjects were scanned with a control modulation frequency of 250 Hz, an RF irradiation amplitude of 35 mG, a post-labeling delay of 1.2 s, and a 0.25 G/cm labeling gradient.
  • Images from eight 8 mm thick slices were obtained from both subjects when the labeling was applied to the carotid and vertebral arteries at the ponto-medullary junction, to generate CBF images, and also when the labeling was applied distal to the imaging slice at the top of the brain, which should produce no flow-related signal in the absence of systematic error.
  • One of the subjects was scanned in the axial plane while the other was scanned in the coronal plane to emphasize the flexibility of slice geometry made possible by the amplitude modulated control technique of the invention.
  • CBF measurement was compared with the single slice method.
  • CBF images were acquired in a single axial slice through the basal ganglia and thalamus in nine subjects. Images were acquired with both the single slice method, where the control is labeling distal to the slice, and the multi-slice method. All subjects were studied with a 0.25 G/cm labeling gradient, an RF irradiation amplitude of 35mG, a control modulation frequency of 250 Hz, a post-labeling delay of 1.2 s, and a labeling plane offset of between 4 and 8 cm from the slice. Between 15 and 45 difference images were averaged for each subject.
  • the single slice and multi-slice methods were also compared at RF amplitudes of 30 and 20 mG.
  • the methods were also compared with modulation frequencies of 62.5 Hz, 100 Hz, 125Hz, 200 Hz and 500 Hz.
  • Figure 4 shows the coronal images acquired with label and control placed at the ponto-medullary junction and 2 cm above the brain as indicated on the sagittal Tl images on the left of the figure.
  • Multi-slice difference images acquired with the proximal labeling (top right) demonstrate signal from CBF. Images acquired with the distal labeling (bottom right) show no significant signal. In other words, while the scans with the ponto-medullary junction label show strong perfusion signal in all distal regions of the brain, those with the label above the brain show no significant signal.
  • the image intensity was averaged across the slice and phase directions, similar to the phantom analysis, and the results were plotted in Figure 5.
  • the average difference signal was obtained by averaging the images of Figure 3 across the anterior-posterior and right-left directions. Distance - 13 - from the labeling plane was converted into frequency offset for plotting. As shown, proximal labeling at the ponto-medullary junction produced a small but very significant change in the image intensity due to CBF, while distal labeling above the brain produced no significant signal change consistent with negligible off-resonance errors for offset frequencies above 2 kHz.
  • the mean efficiency ratio of the multi-slice and single slice methods was 61.6% ⁇ 6.7% across the nine subjects when a modulation frequency of 250 Hz was used. This efficiency was found to drop rapidly when the amplitude of the RF was lowered; the efficiency at 30 mG was 58% and at 20 mG it was only 35%. As shown in Figure 6, the efficiency of spin labeling with amplitude modulated control as a function of modulation frequency relative to a single slice labeling with 36 mG amplitude irradiation improved to 75% when the modulation frequency was lowered. This suggests that a modulation frequency of 62.5 Hz is more desirable than 250 Hz.
  • Quantification of the CBF images was next performed using prior art methods for single slice imaging.
  • the average of the labeled images was first subtracted from the average of the control images and then divided by the intensity of an image obtained in the absence of off resonance saturation. - 14 -
  • Quantitative CBF values were derived by segmenting the tissue into gray and white matter based on the Tl maps and using a partition coefficient of 0.98 for gray matter and 0.82 for white matter.
  • the measured CBF values are consistent with values for quantitative cerebral blood flow (ml 100 g- 1 min-i) obtained previously using single slice methods and with other measurements of CBF, as represented for four normal volunteers in Table 1.
  • the invention relates to a method for multi-slice CBF imaging using CASL with an amplitude modulated control .
  • This control strategy is both highly effective at controlling for off-resonance effects and efficient at doubly inverting inflowing spins, thus retaining the signal advantages of CASL versus pulsed ASL techniques .
  • the method is readily implemented using standard hardware, is effective in both gray and white matter, and allows flexible selection of the imaging and labeling planes. Because the control method is applied at the same location as the labeling and gives equal effect across a wide range of frequencies, there should be no errors associated with static magnetic field inhomogeneity or asymmetry in the off-resonance spectrum.
  • the labeling method is therefore highly desirable even for single-slice CBF imaging applications. This approach should also be applicable to blood flow measurements in organs other than the brain. Also, although the above studies were carried out in eight slices, the number of slices is limited only by the image acquisition time and Tl of blood and tissue.
  • CASL CBF imaging to a multi-slice modality in accordance with the techniques of the invention overcomes a major obstacle to clinical applications.
  • the techniques of the invention have already been successfully applied in patients with cerebrovascular disease. CBF measurements using this approach are also likely to provide a sensitive and quantitative measure of cerebrovascular reserve when carried out in conjunction with acetazolamide administration or C0 2 inhalation. Numerous other potential clinical applications can be envisioned, including the differential diagnosis of dementing disorders and cerebral neoplasms.
  • quantitative CBF measurements have applications to clinical and basic neuroscience, for imaging regional CBF changes during sensorimotor or cognitive tasks or following pharmacological challenges, and for population-based studies of changes in - 17 - regional CBF and metabolism.

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Abstract

La présente invention concerne un procédé de formation d'images multicoupe de flux sanguin cérébral par marquage de spin artériel en continu (CASL) avec une régulation modulée d'amplitude qui est à la fois très efficace pour la régulation d'effets de résonance extérieurs et également pour la double inversion de spins d'entrée, ce qui permet de maintenir les avantages de signaux de CASL par opposition aux techniques de marquage de spin artériel par pulsions.
EP99918519A 1998-04-13 1999-04-13 Formation d'images multicoupe de flux sanguin cerebral par imagerie par resonance magnetique de marquage de spin arteriel en continu Withdrawn EP1071367A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US8150698P 1998-04-13 1998-04-13
US81506P 1998-04-13
PCT/US1999/008087 WO1999052429A1 (fr) 1998-04-13 1999-04-13 Formation d'images multicoupe de flux sanguin cerebral par imagerie par resonance magnetique de marquage de spin arteriel en continu

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EP1071367A1 true EP1071367A1 (fr) 2001-01-31
EP1071367A4 EP1071367A4 (fr) 2002-08-07

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8320647B2 (en) 2007-11-20 2012-11-27 Olea Medical Method and system for processing multiple series of biological images obtained from a patient
US9911206B2 (en) * 2015-01-13 2018-03-06 Siemens Healthcare Gmbh Time efficient ASL imaging with segmented multiband acquisition

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10133278A1 (de) 2001-07-09 2003-01-23 Univ Eberhard Karls Verfahren und Vorrichtung zur Darstellung einer Fluidperfusion
US6717405B2 (en) 2002-04-12 2004-04-06 Beth Israel Deaconess Medical Center, Inc. Arterial spin labeling using time varying gradients
JP3920140B2 (ja) * 2002-05-13 2007-05-30 株式会社東芝 Ｍｒｉ装置及びフロー定量化装置
DE102004051763A1 (de) * 2004-10-23 2006-04-27 Universitätsklinikum Schleswig-Holstein Verfahren zur MRT-Darstellung eines Blutgefäßes und/oder des von dem Blutgefäß versorgten Territoriums

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5285158A (en) * 1992-08-06 1994-02-08 Wisconsin Alumni Research Foundation NMR angiography using fast pulse sequences with preparatory pulses
US5320099A (en) * 1992-08-07 1994-06-14 Trustees Of The University Of Penna. MR angiography using steady-state transport-induced adiabatic fast passage

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8320647B2 (en) 2007-11-20 2012-11-27 Olea Medical Method and system for processing multiple series of biological images obtained from a patient
US9123100B2 (en) 2007-11-20 2015-09-01 Olea Medical Method and system for processing multiple series of biological images obtained from a patient
US9911206B2 (en) * 2015-01-13 2018-03-06 Siemens Healthcare Gmbh Time efficient ASL imaging with segmented multiband acquisition

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Publication number Publication date
EP1071367A4 (fr) 2002-08-07
WO1999052429A1 (fr) 1999-10-21

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