FMRI IMAGING

Abstract

The invention provides a method for performing a magnetic resonance measurement of an element in a target region, wherein the element has a magnetic resonance excitation spectrum peak with a linewidth L.sub.R, wherein the method comprises a measurement cycle (100) comprising: a magnetization transfer stage (110) comprising providing a plurality of pulses (115) of first radiation to the target region, wherein the plurality of pulses (115) are selected to provide a net pulse having a net pulse angle α.sub.N≤1°, and wherein the first radiation comprises a first frequency spectrum peak having a first linewidth L.sub.F, wherein the first frequency spectrum peak at least partially overlaps with the magnetic resonance excitation spectrum peak, and wherein L.sub.F>5*L.sub.R; an excitation stage (130) comprising providing a radio frequency pulse to the target region, wherein the radio frequency pulse excites the element resulting in a transverse magnetization of the element; and a measurement stage (140) comprising detecting a signal from the element, wherein the measurement stage (140) is temporally arranged at an echo time TE after the radio frequency pulse, wherein the echo time TE is smaller than a transverse relaxation time of the element in the target region.

Claims

1. A method for performing a magnetic resonance measurement of an element in a target region, wherein the element has a magnetic resonance excitation spectrum peak with a linewidth L.sub.R, wherein the method comprises a measurement cycle (100) comprising: a magnetization transfer stage (110) comprising providing a plurality of pulses (115) of first radiation to the target region, wherein the plurality of pulses (115) are selected to provide a net pulse having a net pulse angle α.sub.N≤1°, and wherein the first radiation comprises a first frequency spectrum peak having a first linewidth L.sub.F, wherein the first frequency spectrum peak at least partially overlaps with the magnetic resonance excitation spectrum peak, and wherein L.sub.F≥5*L.sub.R, wherein a total pulse power that is provided in the magnetization transfer stage is selected from the range of 2 W/kg-20 W/kg; an excitation stage (130) comprising providing a radio frequency pulse to the target region, wherein the radio frequency pulse excites the element resulting in a transverse magnetization of the element; and a measurement stage (140) comprising detecting a signal from the element, wherein the measurement stage (140) is temporally arranged at an echo time TE after the radio frequency pulse, wherein the echo time TE is smaller than a transverse relaxation time of the element in the target region.

2. The method according to claim 1, wherein the net pulse angle α.sub.N≤0.1°.

3. The method according to any one of the preceding claims, wherein L.sub.F≥10*L.sub.R.

4. The method according to any one of the preceding claims, wherein the transverse relaxation time is an observed transverse relaxation time T2*, and wherein the echo time TE≤0.9*T2*.

5. The method according to any one of the preceding claims, wherein the method comprises a plurality of measurement cycles (100), and wherein the magnetization transfer stage comprises suppressing magnetization of the element in a first compartment (10) to increase contrast between the first compartment (10) and a second compartment (20).

6. The method according to any one of the preceding claims, wherein the method comprises imposing a main magnetic field onto the target region, wherein the main magnetic field has a magnetic flux density of at least 1 T and of at most 5 T, and wherein the method comprises superimposing magnetic field gradients onto the main magnetic field.

7. The method according to any one of the preceding claims, wherein the element comprises hydrogen, and wherein the target region comprises a brain of an animal, wherein the method is for localizing a blood volume change in the target region,.

8. The method according to claim 7, wherein the method comprises subjecting the animal to a stimulus, wherein the stimulus is selected from the group comprising food, a drug, an image, a task, and a tactile stimulus.

9. The method according to any one of the preceding claims 7-8, wherein the method further comprises an analysis stage, wherein the analysis stage comprises localizing neuronal activity in the brain based on the signal.

10. The method according to claim 9, wherein the analysis stage comprises subjecting the animal to a follow-up action based on the localized neuronal activity, wherein the follow-up action is selected from the group comprising following a diet, a drug regime, an exercise regime and a medical treatment.

11. A system (200) for performing a magnetic resonance measurement of an element in a target region of a measurement subject, the system comprising a pulse generator (210), a control system (300), a sensor (220), and a measurement site (250) configured for hosting the measurement subject, wherein the element has a magnetic resonance excitation spectrum peak linewidth wherein in an operational mode the system (200) is configured to execute a measurement cycle (100) comprising: a magnetization transfer stage (110), wherein the pulse generator (210) provides a plurality of pulses of first radiation to the target region, wherein the plurality of pulses are selected to provide a net pulse having a net pulse angle α.sub.N≤1°, and wherein the first radiation comprises a first frequency spectrum peak having a first width L.sub.F, wherein the first frequency spectrum peak at least partially overlaps with a magnetic resonance excitation spectrum peak of the element, and wherein L.sub.F≥5*L.sub.R, wherein a total pulse power that is provided in the magnetization transfer stage is selected from the range of 2 W/kg-20 W/kg; an excitation stage (130), wherein the pulse generator (210) provides a radio frequency pulse to the target region, wherein the radio frequency pulse is selected to excite the element resulting in a transverse magnetization of the element; and a measurement stage (140), wherein the sensor (220) detects a signal from the element at an echo time TE after the radio frequency pulse, wherein the echo time TE is smaller than a transverse relaxation time of the element in the target region.

12. The system (200) according to preceding claim 11, wherein the net pulse angle α.sub.N≤0.1°, L.sub.F≥10*L.sub.R, wherein the transverse relaxation time is an observed transverse relaxation time T2*, and wherein the echo time TE≤0.9*T2*.

13. The system (200) according to any one of the preceding claims 11-12, wherein the operational mode comprises executing a plurality of measurement cycles.

14. The system (200) according to any one of the preceding claims 11-13, wherein the system (200) further comprises a magnetic field generator (260), wherein the magnetic field generator (260) is configured to impose in the operational mode a main magnetic field onto the target region, wherein the main magnetic field has a magnetic flux density of at least 0.2 T and of at most 5 T, and wherein in the operational mode the magnetic field generator (260) superimposes magnetic field gradients onto the main magnetic field, wherein the magnetic field gradients have independently selected magnetic flux densities of at most 300 mT/m.

15. The system (200) according to any one of preceding claims 11-14, wherein the system (200) comprises an MM system, wherein the measurement site (250) is configured for hosting at least part of a human body.

16. The system (200) according to claim 15, wherein the system (200) comprises a functional magnetic resonance imaging (fMRI) system.

17. A computer program product comprising program instructions for execution on a control system (300) functionally coupled to a nuclear magnetic resonance system, wherein the instructions, when executed by the control system (300), cause the nuclear magnetic resonance system to carry out the method according to any one of the preceding claims 1-8.

18. A computer program product comprising program instructions for execution on a control system (300), wherein the instructions, when executed by the control system (300), cause the control system (300) to analyze a signal obtainable with the method according to any one of the preceding claims 1-8.

2. The method according to claim 1, wherein the net pulse angle α.sub.N≤0.1°.

3. The method according to claim 1, wherein L.sub.F≥10*L.sub.R.

4. The method according to claim 1, wherein the transverse relaxation time is an observed transverse relaxation time T2*, and wherein the echo time TE≤0.9*T2*.

5. The method according to claim 1, wherein the method comprises a plurality of measurement cycles (100), and wherein the magnetization transfer stage comprises suppressing magnetization of the element in a first compartment (10) to increase contrast between the first compartment (10) and a second compartment (20).

6. The method according to claim 1, wherein the method comprises imposing a main magnetic field onto the target region, wherein the main magnetic field has a magnetic flux density of at least 1 T and of at most 5 T, and wherein the method comprises superimposing magnetic field gradients onto the main magnetic field.

7. The method according to claim 1, wherein the element comprises hydrogen, and wherein the target region comprises a brain of an animal, wherein the method is for localizing a blood volume change in the target region.

9. The method according to claim 7, wherein the method further comprises an analysis stage, wherein the analysis stage comprises localizing neuronal activity in the brain based on the signal.

11. A system (200) for performing a magnetic resonance measurement of an element in a target region of a measurement subject, the system comprising a pulse generator (210), a control system (300), a sensor (220), and a measurement site (250) configured for hosting the measurement subject, wherein the element has a magnetic resonance excitation spectrum peak linewidth wherein in an operational mode the system (200) is configured to execute a measurement cycle (100) comprising: a magnetization transfer stage (110), wherein the pulse generator (210) provides a plurality of pulses of first radiation to the target region, wherein the plurality of pulses are selected to provide a net pulse having a net pulse angle α.sub.N≤1°, and wherein the first radiation comprises a first frequency spectrum peak having a first width L.sub.F, wherein the first frequency spectrum peak at least partially overlaps with a magnetic resonance excitation spectrum peak of the element, and wherein L.sub.F≥5* L.sub.R, wherein a total pulse power that is provided in the magnetization transfer stage is selected from the range of 2 W/kg-20 W/kg; an excitation stage (130), wherein the pulse generator (210) provides a radio frequency pulse to the target region, wherein the radio frequency pulse is selected to excite the element resulting in a transverse magnetization of the element; and a measurement stage (140), wherein the sensor (220) detects a signal from the element at an echo time TE after the radio frequency pulse, wherein the echo time TE is smaller than a transverse relaxation time of the element in the target region.

13. The system (200) according to claim 11, wherein the operational mode comprises executing a plurality of measurement cycles.

14. The system (200) according to claim 11, wherein the system (200) further comprises a magnetic field generator (260), wherein the magnetic field generator (260) is configured to impose in the operational mode a main magnetic field onto the target region, wherein the main magnetic field has a magnetic flux density of at least 0.2 T and of at most 5 T, and wherein in the operational mode the magnetic field generator (260) superimposes magnetic field gradients onto the main magnetic field, wherein the magnetic field gradients have independently selected magnetic flux densities of at most 300 mT/m.

15. The system (200) according to claim 11, wherein the system (200) comprises an MRI system, wherein the measurement site (250) is configured for hosting at least part of a human body.

16. The system (200) according to claim 15, wherein the system (200) comprises a functional magnetic resonance imaging (fMRI) system.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0100] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying schematic drawings in which corresponding reference symbols indicate corresponding parts, and in which: FIGS. 1A-D schematically depict an embodiment of the method of the invention; FIG. 2 schematically depicts an embodiment of the system of the invention; FIGS. 3A-C schematically depict experimental results obtained with the method of the invention and a comparative example; and FIGS. 4A-B schematically depict further experimental results obtained with the method of the invention. FIGS. 5A-B schematically depict further experimental results obtained with the method of the invention. The schematic drawings are not necessarily to scale.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0101] FIGS. 1A-B schematically depict embodiments of the method of the invention. for performing a magnetic resonance measurement of an element in a target region, wherein the element has a magnetic resonance excitation spectrum peak with a linewidth L.sub.R.

[0102] FIG. 1A schematically depicts a measurement cycle 100 comprising a magnetization transfer stage 110, an excitation stage 130 and a measurement stage 140.

[0103] The magnetization transfer stage 110 may comprise providing a plurality of pulses 115 of first radiation to the target region. In the depicted embodiment, the plurality of pulses 115 are selected to provide a net pulse having a net pulse angle α.sub.N<1°, especially wherein α.sub.N=0. In particular, in the depicted embodiment the magnetization transfer stage 110 comprises providing two non-selective binomial pulses, with sub-pulses 116, of opposite phases and magnitudes in the proportions ±1/+2/±1. In embodiments, the first radiation may comprise a first frequency spectrum peak having a first linewidth L.sub.F, wherein the first frequency spectrum peak at least partially overlaps with the magnetic resonance excitation spectrum peak, and wherein L.sub.F≥5*L.sub.R.

[0104] The excitation stage 130 may comprise providing a radio frequency pulse to the target region, wherein the radio frequency pulse excites the element resulting in a transverse magnetization of the element.

[0105] The measurement stage 140 may comprise detecting a signal from the element. The measurement stage 140 may be temporally arranged at an echo time TE after the radio frequency pulse, especially wherein the echo time TE is smaller than a transverse relaxation time, especially a transverse relaxation time T2, or especially an observed transverse relaxation time T2*, of the element in the target region.

[0106] In specific embodiments, the excitation stage 130 and the measurement stage 140 may, together, comprise a multi-echo gradient-echo echo-planar imaging pulse sequence.

[0107] In the depicted embodiment, the method further comprises a (pseudo-random) gradient spoiler stage 120. The gradient spoiler stage 120 may especially be temporally arranged between the magnetization transfer stage 110 and the excitation stage 130. The gradient spoiler stage 120 may comprise imposing a (pseudo-random) gradient spoiler scheme (in three directions) onto the target region. The term “pseudo-random” may herein refer to the gradient spoiler schemes of successive gradient spoiler stages (in successive measurement cycles) being selected to avoid systematic effects. For example, if successive gradient spoiler schemes are identical, they may allow some coherence signal pathways to refocus and produce an unwanted signal, in the simplest instance a spin-echo.

[0108] FIG. 1A schematically depicts a single measurement cycle 100. In general, in embodiments, the method comprises a plurality of (successive) measurement cycles 100.

[0109] FIG. 1B schematically depicts an embodiment of the magnetization transfer stage 110. In particular, the effect of a binomial pulses with angles −α, 2α, −α is shown. The binomial pulse is selected to excite an element in a first pool, especially a free pool, which may undergo magnetization transfer with a (same) element in a second pool, especially a bound pool. Thereby, the binomial pulse may particularly affect the magnetization in the bound pool, which may be rapidly exchanging with the free pool. At the start of the magnetization transfer stage 110 (left side), the magnetization M.sub.1 in a first compartment 10 is essentially identical to the magnetization M.sub.2 in a second compartment 20. However, the magnetization transfer stage differentially affects the elements in the first compartment 10 and the second compartment 20, especially due to the second compartment comprising a higher proportion of elements in the second pool. In particular, in the first compartment 10, there is little magnetization transfer, and the binomial pulse therefore results in a net pulse of 0° for essentially all excited elements, resulting in M.sub.1 after the magnetization transfer stage 110 being essentially the same as M.sub.1 prior to the magnetization transfer stage 110. In the second compartment 20 there is, however, a substantial amount of magnetization transfer, resulting in a part of the elements receiving a net pulse angle substantially above 0, resulting in M.sub.2 substantially reducing as a result of the magnetization transfer stage 110.

[0110] Hence, the plurality of pulses may be selected to provide a net pulse having a net pulse angle α.sub.N<1° (for the free pool).

[0111] In exemplary embodiments, the first compartment 10 may be a blood tissue, and the second compartment 20 may be parenchyma. Hence, with the method of the invention, the magnetization of blood may be (essentially) unaffected and is returned to the longitudinal axis with the same value (M.sub.1). In the parenchyma there is (substantial) magnetization transfer with the bound pool and the magnetization (M.sub.2) is reduced at the end of the binomial pulse with respect to the magnetization (M.sub.2) before the binomial pulse.

[0112] In embodiments, the plurality of pulses 115 may especially have a pulse duration of at least 0.5 ms, such as at least 0.75 ms, especially at least 1 ms, such as at least 1.5 ms. In further embodiments, the plurality of pulses 115 may especially have a pulse duration of at least 3 ms, such as at least 5 ms, especially at least 6 ms, such as at least 7 ms. In further embodiments, the plurality of pulses 115 may especially have a pulse duration of at most 3 ms, such as at most 2 ms, especially at most 1.5 ms, such as at most 1 ms. In further embodiments, the plurality of pulses 115 may especially have a pulse duration of at most 15 ms, such as at most 12 ms, especially at most 10 ms, such as at most 7 ms. Hence, the sub-pulses 116 of the plurality of pulses 115 may, in embodiments, together have a pulse duration selected from the range of 0.5-15 ms.

[0113] FIGS. 1C-D schematically depict an embodiment of the method, wherein FIG. 1D is a zoomed in version of FIG. 1C. FIGS. 1C-D depict three spectra of intensity I (in a.u.) versus frequency G (in Hz), each normalized to an integral of 1. In particular, line L.sub.1 indicates the magnetic resonance excitation spectrum peak of the element in water, especially in blood and tissue; line L.sub.2 indicates the first frequency spectrum peak, and line L.sub.3 indicates the magnetic resonance excitation spectrum peak of the element in macromolecules of the tissue, such as protein chains. For visualization purposes, L.sub.3 is represented as a horizontal line to illustrate its broad linewidth; it will, however, be clear to the person skilled in the art that the linewidth is finite, and that the spectrum will have some structure. In the depicted embodiment, the first frequency spectrum peak at least partially overlaps with the magnetic resonance excitation spectrum peak. In particular, in the depicted embodiment. the first frequency spectrum peak is centered at the same frequency as the magnetic resonance excitation spectrum peak, i.e., centered at the Larmor frequency ω.sub.L of the element.

[0114] FIG. 1D schematically depicts that the element has a magnetic resonance excitation spectrum peak with a linewidth L.sub.R, especially at full width half maximum (FWHM). Similarly, the first frequency spectrum peak has a linewidth L.sub.F, especially at FWHM, wherein L.sub.F≥5*L.sub.R.

[0115] FIG. 2 schematically depicts an embodiment of the system 200 for performing a magnetic resonance measurement of an element in a target region of a measurement subject. The system 200 comprises a pulse generator 210, a control system 300, a sensor 220, and a measurement site 250 configured for hosting the measurement subject.

[0116] In embodiments, the pulse generator 210 may comprise or be functionally coupled to an RF coil 240. Hence, in embodiments, the system may comprise an RF coil 240.

[0117] In an operational mode the system 200 is configured to execute a measurement cycle 100. The measurement cycle 100 may comprise a magnetization transfer stage 110, an excitation stage 130, and a measurement stage 140. In embodiments, the operational mode may comprise executing a plurality of measurement cycles 100.

[0118] In the magnetization transfer stage 110, the pulse generator 210 may provide a plurality of pulses 115 of first radiation to the target region, wherein the plurality of pulses 115 are selected to provide a net pulse having a net pulse angle α.sub.N≤1°. In embodiments, the first radiation comprises a first frequency spectrum peak having a first width L.sub.F, wherein the first frequency spectrum peak at least partially overlaps with the magnetic resonance excitation spectrum peak, and wherein L.sub.F≥5*L.sub.R.

[0119] In the excitation stage 130, the pulse generator 210 may provide a radio frequency pulse to the target region, wherein the radio frequency pulse is selected to excite the element resulting in a transverse magnetization of the element.

[0120] In the measurement stage 140, the sensor 220 may detect a signal from the element at an echo time TE after the radio frequency pulse, wherein the echo time TE is smaller than a transverse relaxation time of the element in the target region.

[0121] In embodiments, the system 200 may further comprise a magnetic field generator 260. In the operational mode the magnetic field generator 260 may (be configured to) impose a main magnetic field onto the target region, especially via a main magnet 230. Hence, the system 200 may comprise a main magnet 230 functionally coupled with the magnetic field generator 260. In embodiments, the main magnetic field may have a magnetic flux density of at least 0.2 T.

[0122] In embodiments, the system 200 may comprise an X-gradient amplifier 261 functionally coupled to the magnetic field generator 260. In further embodiments, the system 200 may comprise a Y-gradient amplifier 262 functionally coupled to the magnetic field generator 260. In further embodiments, the system 200 may comprise a Z-gradient amplifier 263 functionally coupled to the magnetic field generator 260. In further embodiments, the system 200 may comprise a gradient coil 235 functionally coupled to one or more of the magnetic field generator 260, the X-gradient amplifier 261, the Y-gradient amplifier 262, and the Z-gradient amplifier 263, especially to the magnetic field generator 260, or especially to the X-gradient amplifier 261, the Y-gradient amplifier 262, and the Z-gradient amplifier 263.

[0123] In further embodiments, in the operational mode the magnetic field generator 260 may superimpose magnetic field gradients onto the main magnetic field. The magnetic field gradients may have independently selected magnetic flux densities of at most 300 mT/m.

[0124] In embodiments, the measurement cycle 100 may further comprise a gradient spoiler stage 120. In the gradient spoiler stage 120, the magnetic field generator may impose a (pseudo-random) gradient spoiler scheme (in three directions) onto the target region.

[0125] In embodiments, the system 200 may comprise an MRI system, especially wherein the measurement site 250 is configured for hosting at least part of a human body. In further embodiments, The system 200 may comprise a functional magnetic resonance imaging fMRI system.

Experiments

[0126] A set of experiments were performed using a multi-echo gradient-echo echo-planar imaging (EPI) pulse sequence with and without a magnetization transfer stage (MT). The two experiments are referred to as MT-on and MT-off. All other parameters were kept constant between the sets of experiments.

[0127] The experiments were performed with 16 human subjects using a simple visual stimulus paradigm as described in the Methods below.

Methods

[0128] To compare the multi-echo gradient-echo (ME-GE) EPI experiments with and without MT in terms of sensitivity, a typical EPI pulse sequence was modified.

Magnetization Transfer Stage

[0129] To suppress the tissue signal, a net 0° on-resonance MT preparation block was implemented into the multi-echo EPI. The MT preparation block consisted of two non-selective binomial RF pulses of opposite phases and magnitudes in the proportions ±1/+2/±1 (6 ms) and was followed by a pseudo-random gradient spoiler scheme (3 ms) in all three directions. To achieve a constant steady state of continuous tissue suppression, the MT-block was played out before each excitation.

Scanning Protocols

[0130] The MT-pulse angle was adjusted empirically to maximally attenuate grey matter signal while restricting attenuation of cerebrospinal fluid (as a proxy for a blood signal) to less than 10%.

[0131] Data were acquired on a Siemens MAGNETOM Prisma (3T) MRI scanner with a 32-channel head coil. The acquisition was based on a multi-echo gradient-echo EPI with MT-on and MT-off (also “BOLD”) conditions. In the MT-on condition, the MT-block was implemented as explained above whereas, in the MT-off condition, the RF-pulse of the MT-block was turned off while the timing conditions remained the same. The MT flip angle for the MT-on acquisition was ±77°/+154°/±77°. For both conditions, we acquired multi-echo data at echo times TE=6.9/18/28 ms. The first echo time was chosen to be as short as possible with the measurement setup. The upper limit was chosen to ensure that a strong standard BOLD signal would be recorded.

[0132] The acquisition protocol for the ME GE-EPI had the following parameters: in-plane resolution 3 mm isotropic and 38 slices without a gap for a coverage of 12 cm, FOV 80×80, and fat saturation performed before each RF excitation. The flip angle for RF excitation was based on the Ernst angle of grey-matter. Additional parameters are reported in the table below, wherein iPAT: In-plane Parallel Imaging acceleration factor, TR: repetition time, TE: echo times, rBW: readout bandwidth, FA: flip angle, and PF: partial fourier factor:

TABLE-US-00001 iPAT TR(ms) TE(ms) rBW (Hz/px) FA PF ME 3 2000 6.9/18/28 2718 50° 6/8

[0133] Anatomical scans were acquired for image registration using a sagittal 1 mm isotropic MP-RAGE with: TR of 2300 ms, TI of 900 ms, TE of 3 ms, FA 9°, turbo factor 16 and an in-plane acceleration factor of 2. The total acquisition time was 5:20 min. All imaging sequences were automatically aligned using an auto-align localizer sequence.

Data Acquisition

[0134] ME-GE EPI data were acquired from 16 subjects (10 M/6 F 26±6 years). The subjects were shown a hemifield (R/L) checkerboard flickering at 4 Hz randomly distributed across trials with a block design of [10 s on, 26-32 off ISI]. During the entire task, the subjects were asked to focus on the grey fixation cross in the middle of the screen and press the button box with the R/L index finger whenever the fixation cross changed color using the previous hemifield as a reference for R or L. The total duration of the task was 10 minutes. Stimuli were presented and button presses were recorded. Before performing the task in the scanner, subjects were instructed on a desktop computer located next to the scanning console to guarantee that the procedure was understood. Each subject performed two runs of ten minutes during a session with one MT-on and the other MT-off. The order in which MT-on/off was applied was counterbalanced across subjects.

Functional Processing

[0135] Before data preprocessing, DICOMs were converted to NIfTI's using dcm2niix, as described in Li et al. 2016, which is hereby herein incorporated by reference. For each MT-off run, the following preprocessing was performed using the FSL software library. First, head-motion parameters were estimated using a reference volume for BOLD data (transformation matrices, and six corresponding rotation and translation parameters) using MCFLIRT (FSL 5.0.11) as described in Jenkinson et al. 2002, which is hereby herein incorporated by reference. The BOLD data were then co-registered to the T1w reference using FLIRT (FSL 5.0.1), as described in Jenkinson and Smith 2001, which is hereby herein incorporated by reference, with the boundary-based registration cost-function as described in Greve and Fischl, 2009, which is hereby herein incorporated by reference. Co-registration was configured with nine degrees of freedom to account for distortions remaining in the BOLD reference. The BOLD data were resampled to generate preprocessed BOLD data in standard space, as described in Fonov et al. 2011, which is hereby herein incorporated by reference. These were smoothed with a 6 mm kernel and high pass filtered with a cut-off frequency of 1/100 s. The three echoes in MT-on and MT-off conditions were also averaged.

Data Analysis

[0136] MT-on and MT-off images were analyzed using FSL 6.0.1 to find the activation in: (1) right visual cortex for left hemifield, (2) left visual cortex for right hemifield and (3) their combination for both hemifields. The datasets were analyzed using FSL FEAT, as described in Woolrich et al. 2001, to estimate the activation during the checkerboard task for all subjects and for both conditions. The design matrix for the single-subject FEAT analysis modelled three explanatory variables (EV): (1) right hemifield trials vs. baseline, (2) left hemifield vs. baseline and finally (3) overlapping effects from right and left hemifield (R+L); each was convolved with a hemodynamic response and constant term. Additionally, three contrasts were set up, one contrast e.g., [1 0 0] ] for each EV.

[0137] A second-level analysis was then carried out, with FEAT, using mixed and fixed-effects. In the fixed-effect analysis, whole-brain data from multiple subjects can be statistically analyzed simply by concatenating time courses. In the mixed-effects analysis, a design matrix is created that allows explicit modeling of both within- and between-subject variance components, as described in Beckmann et al., 2003, which is hereby herein incorporated by reference.

[0138] To make inferences at the group level, a one-sample t-test was performed with fixed and mixed effects to access the difference in z-scores. The z-score maps were thresholded at z>2.3 at (p<0.05, Family wise error (FWE) corrected). The one-sample t-test was conducted by concatenating parameter estimates from each contrast at the single-subject.

[0139] Paired t-tests with fixed and mixed effect were performed at the significance of (p<005) to detect statistically significant differences between MT-on and MT-off (at same and different TE).

[0140] FIGS. 3A-C schematically depict fixed effect results.

[0141] Specifically, FIG. 3A schematically depicts the fixed effect results for MT-on (left side) and MT-off (right side) for different TE, specifically at TEs: T_1=6.9 ms, T_2=18 ms, and T_3=28 ms. As can be seen, there is an increase in activation with echo time for both MT-on and MT-off as increasing echo time makes the BOLD-effect more prominent. However, at T_1 MT-on provides statistically significant differences with respect to MT-off.

[0142] FIGS. 3B-C schematically depict fixed effect group-level visual activation z-score maps shown for (R+L) obtained from the paired t-test at (p<0.05). The results were masked with BOLD contrast at MT-off at T_3 to exclude irrelevant areas.

[0143] FIG. 3B schematically depicts the statistically significant differences between MT-on and MT-off at T_1, indicating there are clusters of activation visible specifically with the method of the invention.

[0144] FIG. 3C schematically depicts the statistically significant differences between MT-on and MT-off when both are averaged over T_1, T_2 and T_3, indicating that the method of the invention shows a statistically significant cluster of activation within the visual cortex.

[0145] FIGS. 4A-B schematically depict mixed effect results.

[0146] Specifically, FIG. 4A schematically depicts the mixed effect results for MT-on (left side) and MT-off (right side) for different TE, specifically at TEs: T_1=6.9 ms, T_2=18 ms, and T_3=28 ms. At all echo times activation is detected with MT-on, whereas there is no statistically relevant activation for MT-off except at T_3, which is indicative of BOLD contrast. Hence, the method of the invention may show brain activation at a shorter TE than BOLD.

[0147] FIG. 4B schematically depicts the statistically significant differences between MT-on and MT-off at T_1, indicating that the method of the invention detects statistically significant voxel activation in the virtual cortex at short TE.

[0148] The experiments describe above exemplify an additional underlying contrast mechanism that differs from BOLD. This is primarily based on the way in which the statistical maps vary as a function of TE: for standard BOLD the z-scores increase with TE as expected, with the maximum recorded at TE=28 ms, whereas with MT-on a distinctly different pattern is observed (also see FIG. 5B), especially at low TE.

[0149] FIG. 5A schematically depicts the effect of the method of the invention. In particular, it depicts the first compartment 10 and the second compartment 20 in four scenarios, wherein the first compartment 10 either changes in size (right) or not (left), for example, in the context of fMRI, due to local brain activation, and wherein the first compartment 10 and the second compartment are exposed to MT-ON conditions, indicated by reference number 50, or exposed to MT-OFF conditions, indicated by reference number 60. As depicted, when exposed to MT-ON conditions, the signal of the second compartment 20, for example the parenchyma, is repressed, which enables identification of the size change of the first compartment, such as an increase in blood (vessel) volume in the context of fMRI.

[0150] FIG. 5B schematically depicts further experimental results obtained with the method of the invention. In particular, FIG. 5 depicts the mean z-scores (left) and the number N of activated voxels (right) for above-described experiments for MT-on (top three rows) and MT-off (bottom three rows) at T_1, T_2, and T_3. In particular, the FIG. 5 depicts that the method of the invention facilitates the measuring of brain activity at T_1 and T_2, while at least maintaining the performance at T_3 as provided by MT-off.

[0151] Hence, the method of the invention enables measuring brain activation with high sensitivity at lower TE than conventional methods.

[0152] The term “plurality” refers to two or more. Furthermore, the terms “a plurality of” and “a number of” may be used interchangeably.

[0153] The terms “substantially” or “essentially” herein, and similar terms, will be understood by the person skilled in the art. The terms “substantially” or “essentially” may also include embodiments with “entirely”, “completely”, “all”, etc. Hence, in embodiments the adjective substantially or essentially may also be removed. Where applicable, the term “substantially” or the term “essentially” may also relate to 90% or higher, such as 95% or higher, especially 99% or higher, even more especially 99.5% or higher, including 100%. Moreover, the terms “about” and “approximately” may also relate to 90% or higher, such as 95% or higher, especially 99% or higher, even more especially 99.5% or higher, including 100%. For numerical values it is to be understood that the terms “substantially”, “essentially”, “about”, and “approximately” may also relate to the range of 90%-110%, such as 95%-105%, especially 99%-101% of the values(s) it refers to.

[0154] The term “comprise” includes also embodiments wherein the term “comprises” means “consists of”.

[0155] The term “and/or” especially relates to one or more of the items mentioned before and after “and/or”. For instance, a phrase “item 1 and/or item 2” and similar phrases may relate to one or more of item 1 and item 2. The term “comprising” may in an embodiment refer to “consisting of” but may in another embodiment also refer to “containing at least the defined species and optionally one or more other species”.

[0156] Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.

[0157] The devices, apparatus, or systems may herein amongst others be described during operation. As will be clear to the person skilled in the art, the invention is not limited to methods of operation, or devices, apparatus, or systems in operation.

[0158] The term “further embodiment” and similar terms may refer to an embodiment comprising the features of the previously discussed embodiment, but may also refer to an alternative embodiment.

[0159] It should be noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be able to design many alternative embodiments without departing from the scope of the appended claims.

[0160] In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim.

[0161] Use of the verb “to comprise” and its conjugations does not exclude the presence of elements or steps other than those stated in a claim. Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, “include”, “including”, “contain”, “containing” and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

[0162] The article “a” or “an” preceding an element does not exclude the presence of a plurality of such elements.

[0163] The invention may be implemented by means of hardware comprising several distinct elements, and by means of a suitably programmed computer. In a device claim, or an apparatus claim, or a system claim, enumerating several means, several of these means may be embodied by one and the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.

[0164] The invention also provides a control system that may control the device, apparatus, or system, or that may execute the herein described method or process. Yet further, the invention also provides a computer program product, when running on a computer which is functionally coupled to or comprised by the device, apparatus, or system, controls one or more controllable elements of such device, apparatus, or system.

[0165] The term “controlling” and similar terms herein especially refer at least to determining the behavior or supervising the running of an element. Hence, herein “controlling” and similar terms may e.g. refer to imposing behavior to the element (determining the behavior or supervising the running of an element), etc., such as e.g. measuring, displaying, actuating, opening, shifting, changing temperature, etc. Beyond that, the term “controlling” and similar terms may additionally include monitoring. Hence, the term “controlling” and similar terms may include imposing behavior on an element and also imposing behavior on an element and monitoring the element. The controlling of the element can be done with a control system. The control system and the element may thus at least temporarily, or permanently, functionally be coupled. The element may comprise the control system. In embodiments, the control system and the element may not be physically coupled. Control can be done via wired and/or wireless control. The term “control system” may also refer to a plurality of different control systems, which especially are functionally coupled, and of which e.g. one control system may be a control system and one or more others may be slave control systems.

[0166] The invention further applies to a device, apparatus, or system comprising one or more of the characterizing features described in the description and/or shown in the attached drawings. The invention further pertains to a method or process comprising one or more of the characterizing features described in the description and/or shown in the attached drawings. Moreover, if a method or an embodiment of the method is described being executed in a device, apparatus, or system, it will be understood that the device, apparatus, or system is suitable for or configured for (executing) the method or the embodiment of the method respectively.

[0167] The various aspects discussed in this patent can be combined in order to provide additional advantages. Further, the person skilled in the art will understand that embodiments can be combined, and that also more than two embodiments can be combined. Furthermore, some of the features can form the basis for one or more divisional applications.

CITED LITERATURE

[0168] Beckmann et al., “General multilevel linear modeling for group analysis in FMRI”, Neurolmage 20 (2003) 1052-1063.

[0169] Fonov et al., “Unbiased average age-appropriate atlases for pediatric studies”, Neurolmage 54 (2011) 313-327.

[0170] Greve and Fischl, “Accurate and robust brain image alignment using boundary-based registration”, Neurolmage 48 (2009) 63-72.

[0171] Jenkinson and Smith, “A global optimisation method for robust affine registration of brain images”, Medical Image Analysis 5 (2001) 143-156.

[0172] Jenkinson et al., “Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images”, Neurolmage 17,825-841 (2002). Li et al., “The first step for neuroimaging data analysis: DICOM to NIfTI conversion”, Journal of Neuroscience Methods 264 (2016) 47-56.

[0173] Woolrich et al., “Temporal Autocorrelation in Univariate Linear Modeling of FMRI Data”, Neurolmage 14,1370-1386 (2001).

FMRI IMAGING

Assignee

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Cpc classification

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G01R33/4806

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G01R33/4616

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G01R33/5615

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G01R33/4828

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International classification

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G01R33/46

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G01R33/48

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G01R33/561

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Abstract

Claims

Description