This document pertains generally to magnetic resonance spectroscopy, and more particularly, but not by way of limitation, to contrast from rotating frame relaxation by adiabatic pulses.
Relaxation is a measure of the differences in the way that a molecule, such as water for example, relaxes following excitation. The relaxation rate constants of the spins located in different environments are different. A magnetic resonance image can be generated that is sensitive to the density of the water but in different tissues, the water concentration (or the density) changes little.
Relaxation provides a measure as to the environment in which the water molecule is located. For example, a water molecule excited by a radio frequency (RF) pulse gives energy off to the environment by interacting with other magnetic dipoles.
Among other factors, the rate constant depends on interaction between nearby molecules in the environment.
Longitudinal relaxation is characterized by time constant T1, e.g. time constant at which a disturbed magnetic vector returns to alignment with a static magnetic field.
Transverse relaxation, or spin-spin relaxation, is characterized by a time constant T2 at which the magnetization vector dephase in the plane perpendicular to the static magnetic field. The plane perpendicular to the static magnetic field is called the transverse plane.
Current methods for assessing relaxation and generating contrast in the rotating frame are inadequate.
In the drawings, which are not necessarily drawn to scale, like numerals describe substantially similar components throughout the several views. Like numerals having different letter suffixes represent different instances of substantially similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.
The following detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention may be practiced. These embodiments, which are also referred to herein as “examples,” are described in enough detail to enable those skilled in the art to practice the invention. The embodiments may be combined, other embodiments may be utilized, or structural, logical and electrical changes may be made without departing from the scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined by the appended claims and their equivalents.
In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one. In this document, the term “or” is used to refer to a nonexclusive or, unless otherwise indicated. Furthermore, all publications, patents, and patent documents referred to in this document are incorporated by reference herein in their entirety, as though individually incorporated by reference. In the event of inconsistent usages between this document and those documents so incorporated by reference, the usage in the incorporated reference(s) should be considered supplementary to that of this document; for irreconcilable inconsistencies, the usage in this document controls.
Transverse relaxation in the rotating frame (T2ρ) is believed to be the dominant relaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echo pulse sequence when no delays are used between pulses in the CP train. The exchange-induced and dipolar interaction contributions (T2ρ,ex and T2ρ,dd) depend on the modulation functions of the adiabatic pulses used. Adiabatic pulses having different modulation functions can be used to generate T2ρ contrast in images. In one example, images of the human occipital lobe are generated at magnetic field of 4T. T2ρ time constants can be measured using an adiabatic CP pulse sequence followed by an imaging readout. In one example, adiabatic full passage pulses of the hyperbolic secant HSn (n=1 or 4) family having significantly different amplitude modulation and frequency modulation functions were used with no time delays between pulses. A dynamic averaging (DA) mechanism (e.g. chemical exchange and diffusion in the locally different magnetic susceptibilities) provides a partial explanation to describe differences in brain tissue water proton T2ρ time constants. Measurements of the apparent relaxation time constants (T2†) of brain tissue water as a function of the time between centers of pulses (τcp) at 4T and 7T permits separation of the DA contribution from that of dipolar relaxation. In various examples, a method is presented for assessing T2ρ relaxation influenced by DA in tissue, and also means to generate T2ρ contrast in MRI.
Chemical exchange (CE) between spins located at different magnetic sites with different chemical shifts or diffusion of spins through magnetic field inhomogeneities contribute to transverse relaxation in vivo. Collectively, these relaxation processes are referred to here as dynamic averaging (DA). Dephasing due to molecular diffusion in microscopic susceptibility gradients or CE occurs for example around paramagnetic proteins, organelles, and capillaries. The apparent transverse relaxation time constant (T2†) decrease due to DA can be used for in vivo quantification of brain iron because of its relevance to several neurodegenerative disorders including Parkinson's and Alzheimer's disease as well as for understanding the mechanisms of blood oxygenation level dependent (BOLD) contrast. The model of T2† decrease due to DA describes transverse relaxation induced by paramagnetic complexes and also relaxation in blood.
Proton relaxation studies are motivated by the importance of relaxation-based contrast in clinical applications of MR imaging and spectroscopy. An exemplary contrast method is based on the fully adiabatic Carr-Purcell (CP) technique. The dependence of the T2† values of human brain tissue water and cerebral metabolite N-acetylaspartate and total creatine proton signals on the temporal spacing (τcp) of pulses in the CP train at high magnetic fields (4T and 7T) may reflect DA. In one example, relaxation techniques were used to generate contrast for monitoring response to gene therapy in rat glioma and for investigating the acute cerebral ischaemia in rats.
Rotating frame transverse relaxation (time constant, T2ρ) dominates during adiabatic pulses used in a CP pulse sequence. A theory is presented for the two-site-exchange (2SX)-induced T2ρ contribution (T2ρ,ex) from a system of otherwise identical spins with a nonzero chemical shift difference (δω≠0) in the fast chemical exchange limit (FXL). T2ρ,ex and the T2ρ contribution from dipolar interactions (T2ρ,dd) with rotational correlation times τc>10−9s during adiabatic pulses depends on the frequency modulation and amplitude modulation functions used for the adiabatic pulses. T2ρ measurements using adiabatic full-passage (AFP) pulses, such as hyperbolic secant HSn (n=1 or 4) pulses provides a method for determining chemical exchange rate constants. The present adiabatic CP method generates tissue contrast originating in T2ρ mechanisms.
T2ρ contrast in human brain tissue 1H2O MRI is generated by using AFP HS1 and HS4 pulses. Theoretical formalisms for T2ρ,ex and T2ρ,dd can be used to quantify the observed contrast. In one example, T2† measurements of water in brain tissue are generated as a function of the temporal spacing, τcp, of HSn pulses in the CP pulse sequence at 4T and 7T field strengths.
Consider first the relaxations during the interpulse time intervals (τip) in an adiabatic CP pulse sequence and during the AFP pulses. First, relaxation during the adiabatic pulses is described.
During AFP pulses in a CP train, the transverse relaxation is dominated by T2ρ. Because the effective magnetic field, ωeff(t), is time dependent during the adiabatic rotation, T2ρ is also time dependent and thus is a function of the pulse modulation functions, ω1(t) and ωRF(t). Here, ω1(t) is the time-dependent RF amplitude and ωRF(t) is time-dependent frequency of the pulse in rad/s. The amplitude of HSn pulses are given by:
ω1(t)=ω1maxsech[β[2t/Tp−1]n], Eq. 1
where t∈[0, Tp], β is a truncation factor (sech(β)=0.01), ω1max is the maximum value of ω1(t) in rad/s, Tp is the pulse duration, and n=1 and 4 for HS1 and HS4 pulses, respectively. As n gets larger, the amplitude-modulation functions of the HSn pulses become flatter and time evolution of magnetization significantly changes with the change of n. With respect to the carrier frequency ωc (the center frequency in the bandwidth of interest), the frequency modulation for HS1 pulse is given by:
ωRF(t)−ωc=A tan h[β[2t/Tp−1]], Eq. 2
and for the HS4 pulse is given by:
where A is the amplitude of the frequency sweep in rad/s. During AFP pulses, ωeff(t) changes its orientation at the instantaneous angular velocity, dα(t)/dt, with:
where Δω(t)=(ω0−ωRF(t)) and ω0 is the Larmor frequency. The effective field during an adiabatic pulse is given by:
ωeff(t)=√{square root over (ω12(t)+Δω2(t))}{square root over (ω12(t)+Δω2(t))}. Eq. 5
For a system of two equivalent nuclei in a single site, the instantaneous rotating frame transverse relaxation rate constant due to dipolar interactions is given by:
where
Here r is the inter-nuclear distance and h is Planck's constant. Eq. 6 can be used to calculate R2ρ,dd during AFP pulses.
The rotating frame 2SX transverse relaxation for spin populations with δω≠0 (the anisochronous mechanism) can be derived. The instantaneous exchange-induced transverse relaxation rate constant in the FXL (τex−1>>δω) during the adiabatic pulses can be approximated as in Equation 7:
R2ρ,ex=PAPB(δω)2 cos2ατex, Eq. 7
where PA and PB are the fractional spin populations at sites A and B, and τex, is the correlation time for exchange (≡(τA−1+τB−1)−1). Note that R2ρ,ex is single-valued only in the FXL.
A possible mechanism of the relaxations in tissue is CE between spins with δω=0 (the isochronous case). This situation can be described for free precession. For the 2SX case (between site A and site B) in the slow and intermediate exchange regimes, the signal intensity (SI) decay is described by biexponentiality (e.g., the sum of two exponential functions: the coefficients are equal to the populations of sites A and B and the relaxation rate constants equal to (1/T2A+1/τA) and (1/T2B+1/τB), when T2A≠T2B, and when the system is in the slow-exchange-limit, SXL). Here T2A and T2B are the transverse relaxation rate constants of the sites A and B in the absence of chemical exchange. In this case, the FXL obtains only if the rate constant characterizing the exchange kinetics, τex−1, is also sufficiently greater than the transverse relaxographic shutter-speed, |R2A-R2B|, where R2A≡T2A−1 and R2B≡T2B−1. In the FXL, the relaxation is governed by the monoexponential decay function with the relaxation rate constant:
R2=R2APA+R2BPB Eq. 8
Transverse relaxation rate constants R2A,B denote relaxation other than CE such as dipolar interactions or cross-relaxations. Under RF irradiation, transverse relaxation due to cross-relaxations differs from the relaxation during free precession.
To calculate the average effective relaxation rate constant
Theory predicts both the R2ρ,ex and R2ρ,dd rate constants to be dependent on the choice of amplitude modulation and frequency modulation functions for the adiabatic pulses via their α- and ωeff dependencies.
Relaxation during the interpulse time interval τip is independent of the RF pulse parameters. The Luz-Meiboom CE theory, derived originally in the Redfield limit, that describes the T2† decrease during the CP pulse sequence caused by CE between spins with different chemical shifts δω, e.g., the anisochronous 2SX mechanism, was generalized to include a diffusion process. The transverse relaxation rate constant is given by:
Here τ=τex or τd, where τd is diffusion correlation time. When DA is not the only relaxation mechanism and additional relaxation pathways are operative, the relaxation rate constant is given by:
R2=R2,DA+R20 Eq. 11
Here, R20 describes the other relaxation mechanisms, such as dipolar interaction or cross-relaxation. This theory allows determination of the τ, PAPB(δω)2, and R2,DA values. Because R2ρ,dd is virtually independent of magnetic field strength between 4T and 7T and R2,DA is significantly magnetic field strength dependent, measurements of the transverse relaxation rate constants at different static magnetic field strengths allows separation of the R2,DA and R20 contributions to R2.
Signal intensity decay during the adiabatic CP pulse sequence can be described by the exponential decay functions during the pulses and during the interpulse time intervals with the rate constants R2ρ(t) and R2, respectively:
SI(n)=S0exp(−
where m is a number of pulses in the adiabatic CP train and τip=τcp−Tp. From Eq. 12 the general expression for the relaxation rate constant during the adiabatic CP pulse sequence can be derived and expressed as:
Eq. 13 predicts that with no time delays between adiabatic pulses (i.e., τcp=Tp) relaxation is governed by T2ρ relaxation.
In one example, MRI studies were performed on healthy volunteers using instruments having Varian Unity INOVA consoles (Varian Associates, CA, USA) interfaced to a 90 cm bore 4T magnet (OMT, Inc., Oxon, UK) and to a 90 cm bore 7T magnet (Magnex Scientific, UK). 1H quadrature surface coils consisting of two geometrically decoupled turns (each 7 cm in diameter) were used for the measurements. T2ρ and T2† images were measured with a segmented spiral readout, using (0.7 mm)2 in-plane resolution, FOV=(18 cm)2, 2562 matrix, 8 segments, acquisition time (AT)=35 ms, and thickness=3 mm. Shimming was performed with a fully adiabatic version of the fast automatic shimming technique by mapping along projections, FASTMAP. Before the excitation pulse in the sequences, the fat signal at 1.3 ppm was suppressed by variable-power RF pulses with optimized relaxation delays, VAPOR. Two dummy scans were used to achieve a steady state prior to data collection.
T2ρ measurements were performed using variable numbers of HS1 or HS4 pulses in the CP-train of the fully adiabatic pulse sequence, denoted CPHS1 and CPHS4, respectively (
Each AFP pulse had an adiabaticity factor R equal to 20 (≡ATp/π) with Tp set to 3 ms. The RF field amplitude ω1max/2π=2.5 kHz in all measurements. For the T2ρ measurements, five subjects were scanned with no delays between AFP pulses in the CP-train. In one example, T2ρ measurements, T2† were measured with a double spin echo (DSE) pulse sequence (
The τcp dependence of the T2† time constants at 4T (6 subjects) and 7T (5 subjects) was investigated using the CPHS1 pulse sequence. The length of the CP train was incremented keeping τcp constant throughout the sequence. Because TR of the pulse sequence was constant during the acquisition and TE was varied significantly when the measurements were performed with long τcp, the longitudinal relaxation process was also taken into account. Possible contamination by CSF can also influence the measurements of T2†. Thus, the estimations of T2† were performed using a bi-exponential decay function:
SI=A1exp(−TE/T2†)+A2exp(−TE/TL). Eq. 14
Here TL spans the values of the transverse relaxation time constants of CSF 1H2O and includes the longitudinal relaxation time constant T1, of the brain tissue 1H2O. To estimate the variations of the fast component of the bi-exponential decay (attributed to the T2† of brain tissue) with the change of the TL, the assumed relaxation time constant TL was varied in the range 0.5-2.5 s. Within the range of TL examined, the average change of the T2† of brain tissue was within ±3.3% and the estimation of the δω varied within 2%.
In particular,
When the interpulse time intervals are varied to achieve the different TEs with a constant number of AFP pulses, the T2ρ relaxation imposes a constant weighting on the T2† measurements. This is also the case with the DSE measurements. On the other hand, when T2†s are measured with the adiabatic CP pulse sequence having different τcp values and incrementing the number of pulses in the train, both relaxation pathways (e.g. T2ρ and relaxation during free precession) contribute to the measurements of T2†.
T2ρ and T2† maps from the same region of interest from single subject measurements are presented in
The averaged intersubject results (MEAN±SD) of the T2ρ measurements from brain tissue regions are summarized in Table 1. Inspection of this table reveals an increase in the T2ρ measured when HS4 versus HS1 pulses were used (p<0.03), with a ratio of T2ρ(CPHS4)/T2ρ(CPHS1)=1.18 (multisubject data, n=5, Table 1). For exchange-induced T2ρ,ex obtained from the anisochronous water/ethanol mixture with CPHS1 and CPHS4 pulse sequences, the ratio T2ρ,ex(CPHS4)/T2ρ,ex(CPHS1) was ˜1.5 when using the same RF amplitude (ω1max/2π=2.5 kHz). A value of T2ρ(CPHS4)/T2ρ(CPHS1)=1.18 measured here suggests that relaxation pathways other than the anisochronous DA must contribute to lH2O transverse relaxation in the brain.
aSignificant difference between CPHS1 and CPHS4 (p < 0.03, two-tailed).
bSignificant difference between CPHS1 and DSE (p < 0.01, two-tailed).
T2† measurements as a function of τcp in the CP pulse sequence was performed at 4T and 7T as illustrated in
In particular,
Fitting of the experimental data measured in human brain at 4T and 7T using Eqs. 10 and 13 yielded: δω(7T)/δω(4T)≈1.07. However, linear increase of δω with magnetic field strength (a factor of 1.75 here) is required by the anisochronous DA model (Eq. 10). Therefore, this result indicates that, in addition to anisochronous DA, other mechanisms contribute to transverse relaxation of brain 1H2O and these should be considered during the adiabatic CP pulse sequence. A likely possibility is the dipolar interaction mechanism. Thus, assume that R2,dd=R20. Fitting to the experimental data was obtained using R2ρ,dd=6.0±0.4 s−1, with Eqs. 10, 11, 13 and the ratio δω(7T)/δω(4T)=1.59±0.25 (
In one example, the same parameters obtained from the measurements of T2† dependence on τcp in the adiabatic CP pulse sequence at 4T and 7T were used for the simulation of the T2ρ measurements performed with CPHS1 versus CPHS4 pulse sequences. Taking into account contributions due to dipolar relaxations (Eq. 9), agreement was noted between theory and the T2ρ measurements with the CPHS1 and CPHS4 pulse sequences. A ratio of T2ρ(CPHS4)/T2ρ(CPHS1)≈1.18 was obtained.
The observed increase of the T2ρ(CPHS4) versus T2ρ(CPHS1) cannot be attributed to conventional magnetization transfer (MT), because MT generally causes a reduction in image SI in tissue, which is contrary to the changes noted. Although a small contribution from a positive Nuclear Overhauser Effect (NOE) associated with the fast motional regime can lead to an increase in the SI, it cannot be completely ruled out.
The isochoronous CE mechanism between spins at different sites A and B with δω=0 and T2A≠T2B can also lead to a change of the T2† time constants through changes in the apparent populations of the sites A and B and the time constants T2A and T2B (Eq. 8). The experimental results and theoretical analysis suggested that T2ρ contrast generated by HS1 and HS4 pulses is sensitive to the DA in the human brain.
Thus, it appears that adiabatic pulses with different modulation functions can be exploited to directly assess T2ρ relaxation and to generate tissue contrast in the human brain. Analysis of the T2† time constants measured using adiabatic CP pulse sequences can take into account both T2ρ relaxation during the adiabatic pulses and the relaxation due to the free precession during the interpulse time intervals. Modeling based on the anisochronous DA mechanism (in the FXL) alone leads to an impossible dependence of δω on magnetic field. One or more other relaxation channels must therefore contribute to transverse relaxation during an adiabatic CP pulse sequence. A probable contribution appears to be relaxation due to dipolar interactions. For dipolar relaxation between identical spins, the dependence of the T2ρ time constants on the modulation functions of the AFP pulses was found to be insignificant. Thus, DA is the major mechanism in the brain tissue contributing to the T2ρ dependence on the modulation functions of AFP pulses.
In addition to T2ρ relaxation, T1ρ contrast can also be generated by adiabatic HSn pulses in human brain at, for example, a field of 4T. In particular, the present subject matter considers dipolar cross-correlations mechanism in tissue.
For example, during a train of adiabatic full passage (AFP) pulses of the HSn family placed prior to the excitation by the adiabatic half passage (AHP) pulse, magnetization follows the time-dependent effective magnetic field ωeff(t) during the AFP pulses. When the time between pulses is zero (or approximately zero), magnetization decay during the pulse train is governed mainly by time-dependent longitudinal relaxation in the tilted double rotating frame, T1ρ. T1ρ relaxation is significantly dependent on the choice of adiabatic pulses with different modulation functions. Accordingly, the present subject matter allows for T1ρ relaxation contrast of 1H2O in the human brain and measurement of relaxation parameters of the dipolar relaxation pathways.
The transverse relaxation in the rotating frame (T2ρ) is the dominant relaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echo pulse sequence with no delays between refocusing pulses. Exchange-induced T2ρ(T2ρ,ex) and the T2ρ due to dipolar interactions (T2ρ,dd) was found to depend on the modulation functions of the adiabatic pulses used. This property of adiabatic pulses can be used to generate the T2ρ contrast in the human occipital lobe 1H2O at 4T magnetic field. It was shown that dynamic averaging (DA), e.g. chemical exchange and diffusion in the locally different magnetic susceptibilities, is the major mechanism contributing to the T2ρ dependence on the modulation functions of the adiabatic full passage (AFP) pulses of the HSn (n=1,4) family in brain tissue.
Consider next the adiabatic T1ρ contrast generated by an adiabatic train of HS1 and HS4 pulses placed prior to the excitation by the adiabatic half passage (AHP) pulse with no time intervals between pulses. Adiabatic T1ρ contrast originates from dipolar cross-correlations (e.g., interference between dipolar relaxation pathways), and the DA mechanism has just a minor contribution to the R1ρ relaxation rate constants in the human brain tissue. Adiabatic T1ρ contrast provides a possibility to directly assess dipolar type of interactions (i.e., cross-correlations) in living tissue. In general, adiabatic pulses exhibit B1 insensitivity.
NMR relaxation in tissue is subject to complex mechanisms including chemical exchange and magnetic interactions between different molecular constituents in several tissue compartments. A two-site model that represent extracellular (as well as interstitial) and intrasellular water reservoirs, respectively, was studied. These two reservoirs are coupled by the two-site exchange (2SX) mechanism that represents water diffusion through cell membranes.
In one example, three issues are considered: 1) orientational order of 1H dipolar interactions and its contribution to the relaxation dispersion; 2) the effect of cross-correlations between water protons and the macromolecules associated protons; 3) 2SX between two water reservoirs and CE between labile protons (associated with macromolecules) and water.
In
Adiabatic T1ρ contrast based on the difference in the modulation functions of the adiabatic pulses, was generated in the human brain. This relaxation contrast provide a direct assessment of the dipolar relaxations in tissue. Adiabatic T1ρ contrast may facilitate investigation, characterization and diagnosis of neurodegenerative disorders, cancer and stroke.
In one example, a method includes applying a pulse sequence (including an adiabatic pulse train and an excitation pulse) to a specimen, receiving a magnetic resonant image from the specimen and determining relaxation based on the signal. As noted elsewhere in this document, the order of the pulse train and the excitation pulse are tailored for a particular relaxation. A number of relaxation mechanisms can be studied with the present subject matter and one example includes selecting one or more mechanisms from a plurality of mechanisms and the sequence is tailored based on the selected mechanism. The sequence can be configured in terms of pulse order, modulation function, pulse duration and power level (amplitude). In one example, the adiabatic pulse train includes a plurality of adiabatic full passage pulses and the excitation pulse includes an adiabatic half passage pulse.
The term contrast denotes a difference. In the context of magnetic resonance spectroscopy, contrast refers to a perceivable difference in properties that makes a feature of an image distinguishable from other features, including, for example, a background. By way of example, in a stroke patient, contrast between carotid arteries and plaque allows detection, identification and determination of progression of disease formation.
In one example, relaxation is measured during an adiabatic pulse with time-dependent RF radiation. The RF radiation is modulated to generate different functions. Relaxation mechanism can be selectively assessed based on the design of the pulse sequence applied. For example, the pulse train can be followed by an excitation pulse for analysis of T1ρ and the order reversed for analysis of T2ρ relaxation. Furthermore, the RF radiation can be tailored, in terms of the amplitude and waveform (phase and frequency) to achieve different purposes. In particular, the different relaxation mechanisms can be discerned by suitable modulation and tailoring of the pulse sequence using adiabatic pulses as well as non-adiabatic pulses. In one example, relaxation is measured during an adiabatic full passage pulse train.
In one example, data regarding isochronous exchange, or dipole-dipole interaction, is generated based on T1ρ as function of time. In one example, data regarding anisochronous exchange is generated based on T2ρ as function of time. In one example, anisochronous exchange correlates to a difference in pH.
In one example, the sequence includes applying an adiabatic pulse at a radio frequency and aligned on an axis different than that of the static magnetic field. Magnetic resonance data corresponding to relaxation time is generated based on a signal received by a receiving coil. In one example, the relaxation time is viewed in frame of reference rotating in a plane lying substantially perpendicular to the first axis. Contrast can be generated based on difference data corresponding to a first and second pulse sequence. The pulse sequences can be modulated in amplitude and frequency. In one example, a delay period between adjacent pulses of the pulse sequence is configured to produce a desired result. Relaxation time can be determined in a rotating frame that is aligned transversely or longitudinally.
Other examples, in addition to those specifically described above, are also contemplated. For example, one or more radio frequency pulses of the pulse train can be modulated to yield a particular relaxation rate constant. For instance, the duration or amplitude of the waveform of individual pulses in the pulse train can be modulated to obtain a particular relaxation. By modulating the amplitude, frequency and phase of the pulse train, the observable relaxation rate in the rotating frame of reference can be modulated.
In one example, one or more pulses of the pulse train satisfy the adiabatic condition sometimes expressed as |ωeff(t)|>>|dα/dt|. In one example, one or more pulses of the pulse train are non-adiabatic pulses.
In one example, the train has no interpulse interval between adjacent pulses. In one example, a brief interpulse interval separates adjacent pulses of the pulse train.
In one example, multiple runs are executed for a particular specimen in a region of interest with each run including a particular pulse train and excitation pulse. The pulses of the different pulse trains can include frequency modulated, amplitude modulated or phase modulated pulses configured for a particular relaxation with each train having different modulation or each pulse within a train having different modulation.
One example of the present subject matter includes a method for generating a contrast for magnetic resonance spectroscopy (T2ρ and T1ρ) based on modulating a function that defines the shapes of the pulses in a pulse train. The shapes (trajectory) of the pulses are tailored or modulated to increase persistence of a received signal and to enhance sensitivity.
In one example, the pulse train includes adiabatic pulses or other pulses that sweep as a function of time. By modulating the pulse, the present subject matter allows modulating of the contribution arising from exchange and dipole-dipole interaction. The pulse can be modulated in terms of the amplitude of the radio frequency and the frequency (phase). In addition, a time delay or interval can be adjusted.
For example, in a sample of ethanol and water (an OH group), the chemical exchange is fast (the system is in the fast exchange regime) and a spectrum reveals a single resonance at the frequency of water. By changing the adiabatic pulse modulation the relaxation rate constant can be modulated. Relaxation rate constants measured at different pH levels were measured with the different pulses of the hyperbolic secant (HSn) family and described well by the theory that was derived.
The pulse sequence can be modulated by changing the number of pulses (increasing or decreasing), changing a delay time period (insert, remove or adjust a time period) and changing the pulse modulation function (amplitude, frequency or phase).
The underlying processes for T1 and T2 differ. One factor contributing to T1 is dipole-dipole interactions. The nucleus of a water molecule has a magnetic dipole which can convey energy to other molecules (each also having magnetic dipoles) that are tumbling at particular frequencies in the RF range. Dipole-dipole interactions are similar to transitions in energy levels. After exposing the sample to RF excitation, the magnetic dipoles of the particular water molecule and the neighboring dipoles tumble and release energy as they resume alignment with the magnetic field.
The T2 process occurs by dipole-dipole interactions and by other mechanisms, including dynamic averaging. Dynamic averaging includes chemical exchange and diffusion. Chemical exchange refers to the exchange of protons in a water molecule with protons in other nearby water molecules. For example, water molecule has hydrogen atoms that are chemically exchanging with other hydrogens, such as hydroxel groups on on DNA, macromolecules, enzymes, membranes, or other large molecules. Dynamic averaging leads to a dephasing. The magnetic susceptibility of a tumor, a blood vessel and brain tissue all give rise to different local magnetic field variations. The spins in the different tissue will precess at different frequencies based on the local field strength within the tissue. Thus, the magnetic resonance relaxation parameters will be different. Other lesser factors in addition to dynamic averaging, such as dipolar relaxation pathways, also contribute to T2 relaxation. The cross relaxations and the relaxations due to chemical shift anisotropy are believed to be less significant than the auto (self)-relaxations and the dynamic averaging.
In one example, a magnetic resonance image is generated by acquiring a signal following excitation. For example, an excitation pulse is applied and after some time delay (called the echo time or TE), the signal is acquired. In the case of a 180 degree excitation pulse, the acquired signal is referred to as a spin echo.
During the time delay, chemical exchange, diffusion and other process will have caused the signal to decay. If detected early, the signal will have a greater magnitude and after a delay, the signal intensity will be lower.
The amount of signal decay depends on the environment of the water molecule as well as the types of macro molecules or type of membranes. For example, in cancers, the process of signal decay is catalyzed by pH. Cancers have a relatively acidic extracellular pH.
Both relaxation times T1 and T2 are a function of the chemical exchange process. In addition, time T1 is also a function of dipole-dipole interaction.
In the present subject matter, the signal is received in conjunction with the application of a continuous series of excitation pulses. It is believed that continuous application of pulses can suppress certain contribution and thus, avoid decay of the signal.
To achieve this result, the excitation pulses are modulated in a particular manner. In one example, the frequency of the pulses are modulated and can be described as adiabatic full passage.
In one example, decay can be suppressed completely or suppressed to a selected degree based on the modulation of the excitation pulses. For instance, two images can be acquired using different pulse trains, with each train having different pulse shapes, frequency or modulation. A difference image based on the different pulse trains can reveal the contribution from, for example, chemical exchange only.
In one example, the present subject matter allows separation of the two contributions (chemical exchange and dipole-dipole interaction) in a T2 image.
In one example, the contrast can be made specific to a particular pH and thus allow imaging or spectroscopy of, for example, a tumor having an acidic extracellular pH.
The present subject matter reduces the masking effect of the chemical exchange process caused by dipole-dipole interaction, thus allowing an image based on different pH values. For example, a disease or condition that produces a change in the dipole-dipole interaction in one direction can be obscured by a chemical exchange in the opposite direction.
At high magnetic field strength, the magnetic resonance image is dominated by the exchange contribution. The difference in resonance frequency (when the hydrogen is in different positions) changes linearly with the magnetic field. With a larger chemical shift difference, the dephasing process occurs more rapidly, thus yielding a bigger difference in frequency. Chemical exchange is a more dominating effect as magnetic field strength rises. For example, at a magnetic field of 4T chemical exchange is dominant. As to dipole-dipole interaction, there is little dependence on magnetic field strength. At lower fields, the relative magnitude of dipole-dipole interaction is comparable to that of chemical exchange.
In addition to generating changes in the exchange contribution, selection of the pulse train shape can also generate changes in the dipole-dipole contribution.
The pulse train shape can be selected to modulate the contribution to relaxation arising from chemical exchange and to modulate the contribution to relaxation arising from dipole-dipole interaction.
In one example, the radio frequency excitation pulse can be selected to keep the chemical exchange process focused and thus prevent dephasing of the magnetization.
The term T2ρ corresponds to a radio frequency pulse applied in the rotating frame and at the same frequency as the spins precess. Magnetization dephases (phase coherence is lost) because of the exchange process, dipole-dipole interaction and B1 inhomogeneity. The inability to, for example, provide a perfectly homogenous RF field causes the rate at which the spins evolve to vary and since the effective B1 field is varying, then phase coherence will also vary.
The present subject matter includes a particular sort of pulse sequence to achieve T2ρ contrast. The shapes of the pulses are changed to modulate the contrast.
In one example, a continuous RF pulse train or sequence (with one pulse following another) and having a frequency dependence (including, for example, those having frequency swept pulses, or adiabatic full passage). In an adiabatic full passage pulse, the frequency of the RF sweeps from one side of resonance to the other side of resonance.
The present subject matter allows for extended excitation of the sample and thus permits gathering of more information (improved signal to noise ratio) and faster image generation. The time dependence of the effective field sweep determines the relaxation rate constants caused by the different relaxation mechanisms.
The rate constant for laboratory frame longitudinal relaxation (R1) is particularly sensitive to the molecular fluctuations of magnetic dipolar interactions, but only those at high frequencies near that (ω0) of the Larmor precession (i.e., in the MHz range). It is believed that dipolar fluctuations in tissue occur at lower frequencies (i.e., in the kHz range). The rotating frame longitudinal relaxation rate constant (R1ρ) is driven principally by dipolar fluctuations at frequencies near that (ωeff) of the effective Larmor precession in the simultaneous presence of the RF and laboratory magnetic fields. Since this can be “tuned” by adjustment of ω1, the (Rabi) frequency measure of the RF amplitude, it is believed that this can provide experimental access to the relevant lower frequencies by modulating the pulse train, the present subject matter allows selection of the molecular motions that contribute to relaxation. For example, the motions occurring between water and large molecules instead of water and intermediate size molecules can be isolated since larger molecules tumble more slowly. In other words, the dipole-dipole relaxation contribution for MR contrast can be modulated based on the pulse train modulation function selected.
In one example, a difference image is generated by subtracting images acquired by different modulation functions and normalizing.
For example, two images are acquired using adiabatic full passage pulse trains based on HS4 and HS1. The difference of these two images is then normalized by one of the images to generate a difference image which exhibits contrast. For instance, a bright region in the difference image corresponds to a larger difference which may indicate a more dynamic averaging and dark regions may indicate CSF which exhibits low levels of dynamic averaging and thus low sensitivity to the type of pulse applied in the pulse train.
The present subject matter provides a contrast for MR imaging and provides a method and system to increase the persistence of the signal as well as enhance sensitivity because the signal decays more slowly. Detection and identification of progression of diseases such as breast cancer, brain tumor and stroke detection and plaque formation are exemplary applications for the present subject matter.
In one example, both the B1 field and the radio frequency sweep is a function of time. By modulating the pulse, the contribution to relaxation can be modulated. For instance, pulse modulation allows modulation of the exchange and the dipole contributions. The pulses of the pulse train can be modulated in many ways including phase, frequency and amplitude.
For example, by changing the amplitude of the radio frequency pulse, the relaxation process reveals sensitivity to changes in pH level. Such a mechanism for contrast using MR imaging may be useful for detection of cancerous cells since cancer cells typically have a low extracellular pH and benign tumors don't have an acidic extracellular pH.
In one example, plaque can be distinguished from other tissue by configuring the pulse sequence in terms of pulse length, peak power, pulse modulation function and inter-pulse time interval. As another example, a particular body part or tissue can be examined by suitably configuring the pulse sequence. The relaxation is measured during the radio frequency adiabatic pulse wherein the pulse is modulated over time.
It is to be understood that the above description is intended to be illustrative, and not restrictive. For example, the above-described embodiments (and/or aspects thereof) may be used in combination with each other. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. In the appended claims, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.
The Abstract of the Disclosure is provided to comply with 37 C.F.R. §1.72(b), requiring an abstract that will allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, various features may be grouped together to streamline the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the claimed embodiments require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter may lie in less than all features of a single disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment.
This document claims the benefit of priority, under 35 U.S.C. § 119(e), to Shalom Michaeli et. al, U.S. Provisional Patent Application Ser. No. 60/616,257, entitled “TRANSVERSE AND LONGITUDINAL RELAXATION TIME CONTRAST IN THE ROTATING FRAME GENERATED BY ADIABATIC RF PULSES,” filed on Oct. 6, 2004, which is incorporated herein by reference.
This work was supported by NIH grants CA92004, RR08079, NS 40801, EB 00422, the Keck Foundation, the MIND Institute, the National Foundation for Functional Brain Imaging and the US Department of Energy. The United States government has certain rights in the technology disclosed herein.
Number | Name | Date | Kind |
---|---|---|---|
5256967 | Foo et al. | Oct 1993 | A |
5274331 | Macovski | Dec 1993 | A |
5404882 | Santyr | Apr 1995 | A |
6650116 | Garwood et al. | Nov 2003 | B2 |
6717405 | Alsop | Apr 2004 | B2 |
6958606 | Le Roux | Oct 2005 | B2 |
7053618 | Zhu | May 2006 | B2 |
20020153889 | Garwood et al. | Oct 2002 | A1 |
20030052677 | Pines et al. | Mar 2003 | A1 |
20030069464 | Muntermann | Apr 2003 | A1 |
20030193332 | Shah | Oct 2003 | A1 |
20030218459 | Reddy et al. | Nov 2003 | A1 |
20030234647 | Beaudoin et al. | Dec 2003 | A1 |
20040051527 | Mugler III, et al. | Mar 2004 | A1 |
20040056659 | Kupce | Mar 2004 | A1 |
20040091937 | Dalvit | May 2004 | A1 |
20040162483 | Kimura | Aug 2004 | A1 |
20040181146 | Yarnykh | Sep 2004 | A1 |
Number | Date | Country | |
---|---|---|---|
20060244447 A1 | Nov 2006 | US |
Number | Date | Country | |
---|---|---|---|
60616257 | Oct 2004 | US |