Patent Application
20240389856
The present specification is directed to perfusion magnetic resonance imaging (MRI), and specifically dynamic susceptibility contrast MRI with deoxyhemoglobin as the contrast agent.
The present specification is directed to Deoxyhemoglobin, an endogenous substance, is a paramagnetic agent capable of disturbing the magnetic field in and around the blood vessels. Through tightly modulating the oxygenation of blood and preserving isocapnic conditions, using the RespirAct™ RA-MR (Thornhill Medical™, Toronto, Canada), the contrast of deoxyhemoglobin can be modulated in the form of a bolus, which behaves similarly to intravenously injected gadolinium. Thus, deoxyhemoglobin has the potential to be used in perfusion magnetic resonance imaging (MRI) as dynamic susceptibility contrast (DSC).
Deoxyhemoglobin contrast has been used to locate arteries based on the earlier blood oxygen level dependent (BOLD) signal arrival time, higher BOLD signal strength, and shorter mean transit time. However, additional strategies of identifying arteries with oxygen modulation are required to improve the sensitivity and specificity of results.
An aspect of the specification provides a method of identifying the vascularity of cerebral tissue in a subject using deoxyhemoglobin as a contrast agent. A sequential gas delivery device is used to implement two hypoxic boluses. Each hypoxic bolus can be described as a drop in the partial pressure of oxygen in arterial blood (ΔPaO2) in the subject. The first bolus has a higher baseline than the second bolus, but the Δ PaO2 in the first and second boluses can be approximately the same.
While inducing the hypoxic boluses, a magnetic resonance imaging system is used to measure the magnetic signal and determine the change in magnetic signal (ΔSI) that results from each the first and second hypoxic boluses. The first and second changes in magnetic signal are compared, and based on the comparison, the voxel is characterized as either A predominantly extravascular voxel or a predominantly intravascular voxel. The voxel may be further characterized as predominantly arterial, predominantly venous or predominantly extravascular tissue.
An aspect of the specification provides a method of identifying the vascularity of cerebral tissue in a subject. A sequential gas delivery (SGD) device is used to implement repeated hypoxic boluses from at least 2 different baseline PaO2.
First, the SGD device induces a first change in partial pressure of oxygen in arterial blood (ΔPaO2) in the subject by targeting a first baseline PaO2 in the subject and subsequently targeting a first signal PaO2 in the subject. The first signal PaO2 is lower than the first baseline PaO2. While inducing the first change in PaO2, a magnetic resonance imaging (MRI) device determines a first change in magnetic signal (ΔSI) in a voxel of the subject's brain.
Next, the SGD device induces a second ΔPaO2 in the subject using the sequential gas delivery device by targeting a second baseline PaO2 in the subject and subsequently targeting a second signal PaO2 in the subject. The second signal PaO2 is lower than the second baseline PaO2 and the second baseline PaO2 is lower than the first baseline PaO2. While inducing the second ΔPaO2, the MRI device determines a second ΔSI in a voxel of the subject's brain.
Next, the MRI device compares the first and second ΔSI and, based on the comparison, outputs a signal at a user interface connected to the MRI device, the signal indicating whether the voxel is extravascular or intravascular. In specific examples, the signal indicates whether the voxel is predominantly arterial, predominantly venous or predominantly extravascular tissue.
In some examples, the first ΔPaO2 is approximately equal to the second ΔPaO2.
In further examples, comparing the first ΔSI and second ΔSI comprises calculating a difference between the first ΔSI and second ΔSI. The method includes the additional steps of outputting a signal at the user interface indicating that the voxel is extravascular if the first ΔSI is approximately equal to the second change in magnetic signal ΔSI, and outputting a signal at the user interface indicating that the voxel is intravascular if the second ΔSI is higher than the first ΔSI.
In yet further examples, comparing the first ΔSI and second ΔSI comprises dividing the second ΔSI by the first ΔSI to obtain a dividend. The method includes the additional steps of outputting a signal at the user interface indicating that the voxel is extravascular if the dividend is approximately 1, and outputting a signal at the user interface indicating that the voxel is intravascular if the dividend is greater than approximately 1.
In some examples, the method includes the additional step of comparing the dividend to a pre-determined threshold. If the dividend is less than or equal to the pre-determined threshold, the user interface outputs a signal indicating that the voxel contains a vein. If the dividend is greater than the pre-determined threshold, the user interface outputs a signal indicating that the voxel contains an artery.
In further examples, the method includes the additional step of maintaining normocapnia while inducing the first and second ΔPaO2.
In yet further examples, the first baseline PaO2 is between 85 and 100 mmHg.
In some examples, the second baseline PaO2 is between 75 and 85 mmHg.
Another aspect of the specification provides a non-transitory machine-readable medium comprising instructions that, when executed by a processor, cause the processor to perform the above-described method.
A further aspect of the specification provides an apparatus for identifying the vascularity of cerebral tissue in a subject. The apparatus includes a sequential gas delivery (SGD) device for controlling the partial pressure of oxygen in arterial blood in the subject. The SGD device may further control the partial pressure of arterial carbon dioxide in the subject.
Connected to the sequential gas delivery device is a processor which is configured to control the SGD device to induce a first and second change in partial pressure of oxygen in arterial blood (ΔPaO2) in the subject. To induce the first ΔPaO2, the processor controls the SGD device to target a first baseline partial pressure of oxygen in arterial blood (PaO2) in the subject and subsequently target a first signal partial pressure of oxygen in arterial blood (PaO2) in the subject. The first signal PaO2 is lower than the first baseline PaO2. To induce the second ΔPaO2, the processor controls the SGD device to target a second baseline partial pressure of oxygen in arterial blood (PaO2) in the subject and subsequently target a second signal partial pressure of oxygen in arterial blood (PaO2) in the subject. The second signal PaO2 is lower than the second baseline PaO2. The second baseline PaO2 is lower than the first baseline PaO2.
Connected to the processor is a sensor. The sensor is configured to determine a first change in magnetic signal (ΔSI) in a voxel of the subject's brain while the sequential gas delivery device induces the first Δ PaO2 and determine a second change in magnetic signal (ΔSI) in the voxel of the subject's brain while the sequential gas delivery device induces the second Δ PaO2.
The processor is further configured to receive the first and second ΔSI from the sensor and compare the two values. A user interface connected to the processor is configured to output a signal indicating whether the voxel is extravascular or intravascular based on the comparison.
In some examples, the user interface may be configured to output a signal whether the voxel is predominantly venous or arterial based on the comparison.
In some examples, the first Δ PaO2 is approximately equal to the second Δ PaO2.
These together with other aspects and advantages which will be subsequently apparent, reside in the details of construction and operation as more fully hereinafter described and claimed, reference being had to the accompanying drawings forming a part hereof, wherein like numerals refer to like parts throughout.
Embodiments are described with reference to the following figures.
Table 1 provides the definitions of abbreviations used herein.
“Vessel” or “blood vessel” herein refers to a vein, artery, or capillary.
“Extravascular” herein refers to components or events occurring outside the vascular system.
“Intravascular” herein refers to components or event occurring within the vascular system.
“Normocapnia” herein refers to a state of normal arterial carbon dioxide pressure in a subject, usually about 40 mmHg.
“Normoxia” herein refers to a state of normal oxygen pressure in a subject, usually about 80 to 100 mmHg.
“Hypoxia” herein refers to a state of depressed oxygen pressure in a subject's vascular system, usually below 80 mmHg.
“Hyperoxia” herein refers to a state of elevated oxygen pressure in a subject's vascular system, usually above 100 mmHg.
The present disclosure provides a system and method for identifying the vascularity of cerebral tissue using deoxyhemoglobin as a contrast agent. By inducing a deoxyhemoglobin bolus and measuring the resulting BOLD signal in a voxel, large blood vessels can be identified. A deoxyhemoglobin bolus produces a stronger BOLD signal in a vein or artery when the baseline PaO2 is lower, even if the change in [dOHb] is the same. This is because the oxyhemoglobin dissociation curve is steeper when the PO2 is lower. In contrast, voxels that contain mostly extravascular tissues will not be influenced by the baseline PO2 due to the lower blood volume (CBV).
The gas supplies 103 may provide carbon dioxide, oxygen, nitrogen, and air, for example, at controllable rates, as defined by the processor 110. A non-limiting example of the gas mixtures provided in the gas supplies 103 is:
The gas blender 104 is connected to the gas supplies 103, receives gases from the gas supplies 103, and blends received gases as controlled by the processor 110 to obtain a gas mixture, such as a first gas (G1) and a second gas (G2) for sequential gas delivery.
The second gas (G2) is a neutral gas in the sense that it has about the same PCO2 as the gas exhaled by the subject 130, which includes about 4% to 5% carbon dioxide. In some examples, the second gas (G2) may include gas actually exhaled by the subject 130. The first gas (G1) has a composition of oxygen that is equal to the target PETO2 and preferably no significant amount of carbon dioxide. For example, the first gas (G1) may be air (which typically has about 0.04% carbon dioxide), may consist of 21% oxygen and 79% nitrogen, or may be a gas of similar composition, preferably without any appreciable CO2.
The processor 110 may control the gas blender 104, such as by electronic valves, to deliver the gas mixture in a controlled manner.
The mask 108 is connected to the gas blender 104 and delivers gas to the subject 130. The mask 108 may be sealed to the subject's face to ensure that the subject only inhales gas provided by the gas blender 104 to the mask 108. In some examples, the mask is sealed to the subject's face with skin tape such as Tegaderm™ (3M™: Saint Paul, Minnesota). A valve arrangement 106 may be provided to the SGD device 101 to limit the subject's inhalation to gas provided by the gas blender 104 and limit exhalation to the room. In the example shown, the valve arrangement 106 includes an inspiratory one-way valve from the gas blender 104 to the mask 108, a branch between the inspiratory one-way valve and the mask 108, and an expiratory one-way valve at the branch. Hence, the subject 130 inhales gas from the gas blender 104 and exhales gas to the room.
The subject 130 may breathe spontaneously or be mechanically ventilated.
The gas supplies 103, gas blender 104, and mask 108 may be physically connectable by a conduit 109, such as tubing, to convey gas. Any suitable number of sensors 132 may be positioned at the gas blender 104, mask 108, and/or conduits 109 to sense gas flow rate, pressure, temperature, and/or similar properties and provide this information to the processor 110. Gas properties may be sensed at any suitable location, so as to measure the properties of gas inhaled and/or exhaled by the subject 130.
The processor 110 may include a central processing unit (CPU), a microcontroller, a microprocessor, a processing core, a field-programmable gate array (FPGA), an application-specific integrated circuit (ΔSIC), or a similar device capable of executing instructions. The processor 110 may be connected to and cooperate with the memory 112 that stores instructions and data.
The memory 112 includes a non-transitory machine-readable medium, such as an electronic, magnetic, optical, or other physical storage device that encodes the instructions. The medium may include, for example, random access memory (RAM), read-only memory (ROM), electrically erasable programmable read-only memory (EEPROM), flash memory, a storage drive, an optical device, or similar.
The user interface 114 may include a display device, touchscreen, keyboard, speaker, microphone, indicator, buttons, the like, or a combination thereof to allow for operator input and/or output.
Instructions 120 may be provided to carry out the functionality and methods described herein. The instructions 120 may be directly executed, such as a binary file, and/or may include interpretable code, bytecode, source code, or similar instructions that may undergo additional processing to be executed. The instructions 120 may be stored in the memory 112.
System 100 further includes an MRI device 102 for conducting magnetic resonance imaging on the subject 130. A suitable MRI system may include a sensor 118 such as a 3T MRI system. A suitable example of a 3T MRI system is the Signa HDxt 3.0T™, provided by GE Healthcare (Milwaukee, USA). In addition to the sensor 118, the MRI device 102 may further include a processor 126, a memory 128, and a user interface 124. Any description of the processor 126 may apply to the processor 110 and vice versa. Likewise, any description of memory 128 may apply to memory 112 and vice versa. Similarly, any description of instructions 122 may apply to instructions 120 and vice versa. Also, any description of user interface 124 may apply to user interface 114, and vice versa. In some implementations, the MRI device 102 and the SGD device 101 share one or more of a memory, processer, user interface, and instructions, however, in the present disclosure, the MRI device 102 and the SGD device 101 will be described as having respective processors, user interfaces, memories, and instructions. The processor 110 of the SGD device 101 may transmit data and instructions to the processor 126 of the MRI device 102. The processor 126 of the MRI device 102 may transmit data and instructions to the processor 110 of the SGD device 101. The system 100 may be configured to synchronize MRI imaging obtained by the MRI device 102 with measurements obtained by the SGD device 101.
The processor 126 may retrieve operating instructions 122 from the memory 128 or from the user interface 124. The operating instructions 122 may include image acquisition parameters. The parameters may include an interleaved echo-planar acquisition consisting of a number of contiguous slices, a defined isotropic resolution, a diameter for the field of view, a repetition time (TR), and an echo time. In one implementation, the number of contiguous slices is 27, the isotropic resolution is 3 mm, the field of view is 19.6 cm, the echo time is 30 ms, and the TR is 2000 ms, however a range of values will be apparent to a person of ordinary skill in the art. The operating instructions 122 may also include parameters for a high-resolution T1-weighted SPGR (Spoiled Gradient Recalled) sequence for co-registering the BOLD images and localizing the arterial and venous components. The SPGR parameters may include a number of slices, a dimension for the partitions, an in-plane voxel size, a diameter for the field of view, an echo time, and a repetition time. In one implementation, the number of slices is 176 m, the partitions are 1 mm thick, the in-plane voxel size is 0.85 by 0.85 mm, the field of view is 22 cm, the echo time is 3.06 ms, and the TR is 7.88 ms.
The processor 126 may be configured to analyze the images using image analysis software such as Matlab 2015a and AFNI (Analysis of Functional Neuroimages: US National Institutes of Health) or other processes generally known in the art. As part of the analysis, the processor 126 may be configured to perform slice time correction for alignment to the same temporal origin and volume spatial re-registration to correct for head motion during acquisition. The processor 126 may be further configured to perform standard polynomial detrending. In one implementation, the processor 126 is configured to detrend using AFNI software 3dDeconvolve to obtain detrended data.
The user interface 124 may include a display device, touchscreen, keyboard, speaker, indicator, microphone, buttons, the like, or a combination thereof to allow for operator input and/or output. Data generated and images acquired by the processor 126 may be displayed at the user interface 124.
At block 204, the SGD device 101 induces a first change in partial pressure of oxygen in arterial blood (ΔPaO2) in the subject 130. Block 204 may be performed in response to instructions 120 executed at the processor 110. As part of block 204, the SGD device 101 establishes a first baseline PaO2 in the subject 130 and subsequently targets a first signal PaO2 in the subject 130. The SGD device 101 may target the PaO2 value long enough for the sensor 118 to obtain a stable measurement. The length of time may depend on the signal-to-noise ratio (SNR), and the duration may be reduced if the SNR can be reduced. In some examples, 15 seconds is adequate. In further examples, 30 seconds is adequate. In other examples, the SGD device 101 may target the PO2 for at least five TR once the targeted PaO2 value is reached.
The first baseline PaO2 may be at or near normoxia. In particular examples, the first baseline PaO2 is approximately 85 to 100 mmHg. The first signal PaO2 is lower than the first baseline and may be selected to induce hypoxia in the subject 130. In particular examples, the first signal PaO2 is approximately 40 mmHg below the first baseline PaO2. In further examples, the first signal PaO2 is approximately 30 mmHg below the first baseline PaO2. In yet further examples, the first signal PaO2 and the first baseline PaO2 are selected such that the [dOHb] at the first signal PaO2 is 25% lower than the [dOHb] at the first baseline PaO2. The first baseline and first signal PaO2 are selected to induce a measurable [dOHb] signal in the subject 130. By targeting the baseline PaO2 followed by the signal PaO2, a hypoxic bolus is generated in the subject's pulmonary arteries which passes into the subject's brain. After targeting the first signal PaO2, the SGD device 101 may again target the first baseline PaO2 or return to normoxia, such that the bolus is transient. Targeting the signal PaO2 for brief amounts of time and returning to baseline or normoxia PaO2 may produce adequate signals while reducing subject discomfort associated with hypoxia.
While the SGD device 101 is performing block 204, the MRI device 102 determines the resulting change to a magnetic signal in the voxel. The MRI device 102 may perform this step in response to instructions 122 executed at processor 126 and received from the memory 128. The processor 126 may control the sensor 118 to measure a magnetic signal continuously or at discrete intervals while the SGD device 101 is inducing the first ΔPaO2. Because oxyhemoglobin is diamagnetic while deoxyhemoglobin is paramagnetic, the hypoxic bolus distorts the magnetic field of the MRI device 102. In one example, the sensor 118 measures a T2* dependent signal, also called the Blood Oxygen-Level Dependent (BOLD) signal. To determine the change in magnetic signal, the sensor 118 measures a first magnetic signal in the voxel while the SGD device 101 is targeting the first baseline PaO2 and subsequently the sensor 118 measures a second magnetic signal in the voxel while the SGD device 101 is targeting the first signal PaO2. To ensure that the measurements correspond with the targeted PaO2, the sensor 118 may measure the magnetic signal only after the processor 110 determines that the respective targeted PaO2 has been reached. In some examples, the sensor 118 measures the minimum signal detected when targeting the baseline PaO2 and then measures the maximum magnetic signal detected when targeting the signal PaO2. The measured magnetic signals may be stored in the memory 128.
At block 208, the MRI device 102 determines a first change in the magnetic signal (ΔSI). Block 208 is performed by the processor 126 in response to instructions 122 received from the memory 128. The processor 126 may compute the first ΔSI based on a comparison between the first and second magnetic signals measured at block 204. In some examples, the first ΔSI is calculated by subtracting the magnetic signal measured at the first baseline PaO2 from the magnetic signal measured at the first signal PaO2. In some examples, the first ΔSI is calculated according to Equation 1, where Slbaseline represents the magnetic signal measured at the first baseline PaO2 and Slpeak represents the magnetic signal measured at the first signal PaO2. The first ΔBOLD may be stored in the memory 128.
At block 212, the SGD device 101 induces a second change in partial pressure of oxygen in arterial blood (ΔPaO2) in the subject 130. Block 212 may be performed in response to instructions 120 executed at the processor 110. As part of block 212, the SGD device 101 establishes a second baseline PaO2 in the subject 130 and subsequently targets a second signal PaO2 in the subject 130. The SGD device 101 may target the PaO2 value long enough for the sensor 118 to obtain a stable measurement. The length of time may depend on the signal-to-noise ratio (SNR), and the duration may be reduced if the SNR can be reduced. In some examples, 15 seconds is adequate. In further examples, 30 seconds is adequate. In other examples, the SGD device 101 may target the PO2 for at least five TR once the targeted PaO2 value is reached.
The second baseline PaO2 may be at or near normoxia, but the second baseline PaO2 is lower than the first baseline PaO2. In particular examples, the second baseline PaO2 is approximately 75 to 85 mmHg. The second signal PaO2 is lower than the second baseline PaO2 and may be selected to induce hypoxia in the subject 130.
As part of blocks 204 and 212, the processor 126 may select the first and second baseline PaO2 based on the oxygen-hemoglobin dissociation curve. An example of an oxygen-hemoglobin dissociation curve 304 is shown in
In particular examples, the second signal PaO2 is approximately 40 mmHg below the second baseline PaO2. In further examples, the second signal PaO2 is approximately 30 mmHg below the second baseline PaO2. In yet further examples, the second signal PaO2 and the second baseline PaO2 are selected such that the [dOHb] at the second signal PaO2 is 25% lower than the [dOHb] at the second baseline PaO2. The second baseline and second signal PaO2 are selected to induce a measurable [dOHb] signal in the subject 130. By targeting the baseline PaO2 followed by the signal PaO2, a hypoxic bolus is generated in the subject's pulmonary arteries which passes into the subject's brain. After targeting the second signal PaO2, the SGD device 101 may again target the second baseline PaO2 or return to normoxia, such that the bolus is transient. Targeting the signal PaO2 for brief amounts of time and returning to baseline or normoxia PaO2 may produce adequate signals while reducing subject discomfort associated with hypoxia.
While the SGD device 101 is performing block 212, the MRI device 102 determines the resulting change to a magnetic signal in the voxel. The MRI device 102 may perform this step in response to instructions 122 executed at processor 126 and received from the memory 128. The processor 126 may control the sensor 118 to measure a magnetic signal continuously or at discrete intervals while the SGD device 101 is inducing the first ΔPaO2. Because oxyhemoglobin is diamagnetic while deoxyhemoglobin is paramagnetic, the hypoxic bolus distorted the magnetic field of the sensor 118. In one example, the sensor 118 measures a T2* dependent signal, also called the Blood Oxygen-Level Dependent (BOLD) signal. To determine the change in magnetic signal, the sensor 118 measures a third magnetic signal in the voxel while the SGD device 101 is targeting the second baseline PaO2 and subsequently the sensor 118 measures a fourth magnetic signal in the voxel while the SGD device 101 is targeting the second signal PaO2. To ensure that the measurements correspond with the targeted PaO2, the sensor 118 may measure the magnetic signal only after the processor 10 determines that the respective targeted PaO2 has been reached. In some examples, the sensor 118 measures the minimum signal detected when targeting the baseline PaO2 and then measures the maximum magnetic signal detected when targeting the signal PaO2. The measured magnetic signals may be stored in the memory 128.
At block 216, the MRI device 102 determines a second change in the magnetic signal (ΔSI). Block 208 is performed by the processor 126 in response to instructions 122 received from the memory 128. The processor 126 may compute the second ΔSI based on a comparison between the third and fourth magnetic signals measured at block 212. In some examples, the second ΔSI is calculated by subtracting the magnetic signal measured at the second baseline PaO2 from the magnetic signal measured at the second signal PaO2. In some examples, the first ΔSI is calculated according to Equation 1, where Slbaseline represents the magnetic signal measured at the second baseline PaO2 and Slpeak represents the magnetic signal measured at the second signal PaO2. The second ΔSI may be stored in the memory 128.
In
In
At block 220, the processor 126 compares the first ΔSI to the second ΔSI. In some examples, the comparison at block 220 comprises subtracting the first ΔSI from the second ΔSI to obtain a difference. In other examples, the comparison at block 220 comprises dividing the first ΔSI by the second ΔSI to obtain a dividend. The remaining steps in method 200 will be described with reference to examples where the first ΔSI is subtracted from the second ΔSI to obtain a difference.
To ensure that the first and second ΔSI are comparable, the difference between the first baseline PaO2 and the first signal PaO2 is approximately the same as the difference between the second baseline PaO2 and the second signal PaO2. In a non-limiting example, the first baseline PaO2 is 90 mmHg, the first signal PaO2 is 60 mmHg, the second baseline PaO2 is 80 mmHg, and the second signal PaO2 is 50 mmHg. In this example, both the first and second hypoxic boluses implement a drop of 30 mmHg. Because the BOLD signal is subject to considerable noise and drift, the difference between the baseline and signal PaO2 should be selected to provide a clear signal. In some examples, a 25% change in [dOHb] is sufficient to provide a clear signal, however smaller changes in [dOHb] may be effective if the signal-to-noise ratio (SNR) can be improved.
At block 224, the processor 126 determines whether or not the difference between the first ΔSI and the second ΔSI is significant. As part of block 224, the processor 126 may compare the difference to a pre-determined threshold. If the second ΔSI is significantly larger than the first ΔSI, the processor 126 characterizes the voxel as intravascular. The characterization indicates that the voxel predominantly contains intravascular components such as blood, or that the voxel contains a large blood vessel. If the second ΔSI is close to or approximately the same as the first ΔSI, the processor 126 characterizes the voxel as extravascular. The characterization indicates that the voxel predominantly contains extravascular components such as cerebral tissues, or that the voxel does not contain any large blood vessels.
In some examples, block 220 further includes determining whether the first ΔSI is greater than the second ΔSI. Regardless of the difference calculated at block 224, if the first ΔSI is greater than the second ΔSI, the processor 126 may nonetheless characterize the voxel as extravascular. In some examples, if the processor 126 determines that the first ΔSI is greater than the second ΔSI, the processor 126 may skip block 224 and proceed directly to block 232.
The reasoning behind this determination can be best understood with reference to the oxygen-hemoglobin dissociation curve, an example of which is shown in
The sensitivity of a voxel to the baseline PaO2 during implementation of method 200 will depend on the cerebral blood volume of said voxel. A voxel containing a large vessel will be sensitive to a shift in the baseline PaO2 and therefore the second ΔSI will be significantly greater than the first ΔSI. In contrast, a voxel containing only small vessels will be less sensitive to a shift in the baseline PaO2 and therefore the second ΔSI will be close to or approximately the same as the first ΔSI.
At block 228, the user interface 124 outputs a signal indicating that the voxel is intravascular. Block 228 is performed by the user interface 124 in response to a determination at block 224 that the second ΔSI is significantly larger than the first ΔSI, As part of block 228, the processor 126 controls the user interface 124 to output a signal indicating that the voxel is predominantly intravascular.
At block 232, the user interface 124 outputs a signal indicating that the voxel is extravascular. Block 232 is performed by the user interface 124 in response to a determination at block 224 that the second ΔSI is close to or approximately the same as the first ΔSI. As part of block 232, the processor 126 controls the user interface 124 to output a signal indicating that the voxel is predominantly extravascular.
The signals generated at blocks 228 and 232 may comprise a light, sound, colour, vibration, chart, image, alert, notification, alarm, verbal message, or the like. The signal at block 228 may be selected to contrast the signal output at block 232. In some implementations, the processor 126 generates an image of the subject's brain, or a portion of the subject's brain which is displayed by the user interface at block 228 or 232. The image includes a region corresponding to voxels which are coloured to indicate whether the voxel is predominantly intravascular artery or intravascular vein, or extravascular. In further examples, the method 200 is performed for a plurality of voxels and the processor 126 generates an image indicating whether each of the plurality of voxels is predominantly intravascular artery or vein, or extravascular.
In examples where the comparison at block 220 comprises dividing the second ΔSI by the first ΔSI to obtain a dividend, the processor 126 compares the dividend to a first pre-determined threshold. If the dividend is less than or equal to the first threshold, the processor 126 characterizes the voxel as extravascular and proceeds to block 232. If the dividend is greater than the first threshold, the processor 126 characterizes the voxel as intravascular and proceeds to block 228. In specific examples, the first threshold is 1 or approximately 1. If the dividend is 1 or close to 1, the second ΔSI is approximately the same as the first ΔSI, indicating that the voxel is predominantly extravascular, for reasons explained above with respect to
If the processor determines that the voxel is predominantly intravascular, the processor 126 may further compare the dividend to a second pre-determined threshold. If the dividend is less than or equal to the second threshold, the processor 126 determines that the voxel contains a vein. As part of block 232, the processor 126 controls the user interface 124 to output a signal indicating that the voxel contains a vein. If the dividend is greater than the second threshold, the processor 126 determines that the voxel contains an artery. In particular examples, the second threshold is approximately 2. As part of block 232, the processor 126 controls the user interface 124 to output a signal indicating that the voxel contains an artery.
The reasoning behind this determination is that the extraction fraction of the arterial blood is reduced during hypoxia. Therefore, the changes to [dOHb] in the veins is less than the changes to [dOHb] in the arteries. In voxels containing large arteries, the second ΔSI (generated from a low baseline) may be at least 200% larger than the first ΔSI.
It is noted that these relationships do not apply to voxels containing lower blood volumes, as is the case in tissue parenchyma. An arterial or venous voxel afflicted by tissue parenchyma may contain only 20% blood volume as compared to a healthy voxel.
Another way to distinguish voxels containing arteries is by comparing the magnetic signals measured by the sensor 118 while targeting the first and second baseline PaO2. The magnetic signal measured at baseline will be higher in arteries than in veins or extravascular tissue. In voxels that contain predominantly extravascular tissue, the magnetic signal at both the first and second baseline PaO2 will be relatively low. Similarly, in voxels that are predominantly venous, the magnetic signal at both the first and second baseline PaO2 will both be relatively low. In voxels that are predominantly arterial, the magnetic signal at both the first and second baseline PaO2 will be relatively high. In some examples, the processor 126 will determine the vascularity of the voxel based on both the magnetic signal at baseline and a comparison between the first and second ΔSI.
The method will now be described by way of example. In the following examples, a high baseline PaO2 corresponds to SaO2=98%, a low baseline PaO2 corresponds to SaO2=88%, and a medium baseline PaO2 corresponds to SaO2=93%. A small ΔPaO2 corresponds to a baseline SaO2 of 98% and a signal of 90% or a baseline SaO2 of 88% and a signal of 80%. A medium ΔPaO2 corresponds to a baseline of 98% and a signal of 84%. A high ΔPaO2 corresponds to a baseline SaO2 of 98% and a signal SaO2 of 75%.
Exemplary performance of method 200 is shown in
In some embodiments, instead of calculating ΔSI and basing the determination on a comparison between the first and second ΔSI, the processor 126 calculates the maximum relaxation rate and bases the determination on a comparison between the first and second maximum relaxation rates. The maximum relaxation rate for a voxel may be calculated according to Equation 2, where TE represents echo time and ΔR*2,max represents maximum relaxation time.
Echo time (TE) is the response time between the stimulus and the measure of the signal decay. TE may be calculated by the processor 126. Relaxation time represents the rate of signal decay or loss of synchronization from the radio wave frequency (RF) stimulus, which provides a measure of the dissipation of signal strength.
An example implementation of the method is shown in
The processor 126 may be further configured to repeat method 200 for a plurality of voxels. In some examples, the processor 126 may generate a brain map of the subject's brain or a portion of the subject's brain, the brain map indicating the location of arteries, veins, and cerebral tissue, based on the determinations made in method 200.
In the examples described above, the processor 126 classifies a voxel as vein, artery, or tissue, however the method 200 is not particularly limited. In other examples, the processor 126 assigns each voxel a score indicating the likelihood that it contains a vein, an artery, or tissue. In other examples, the processor 126 assigns each voxel a score indicating the relative blood volume in said voxel. The score is based on the dividend or difference calculated at block 220. The processor 126 may control the user interface 124 to display the score for one or a plurality of voxels. In further examples, the score may correspond to colour gradient and the processor 126 may generate a brain map displaying the scores for a plurality of voxels as colours. The brain map may be displayed at the user interface 124.
In the first row 1104, brain maps show the ΔR*2,max calculated by the processor 126 when the SGD device 101 implemented a hypoxic bolus from a high baseline PaO2. In row 1108, brain maps show the ΔR2,max calculated by the processor 126 when the SGD device 101 implemented a hypoxic bolus from a low baseline PaO2. In row 1112, brain maps show the dividend calculated by dividing the ΔR*2,max obtained from a low baseline PaO2 by the ΔR*2,max obtained from a high baseline PaO2. In row 1116, brain maps show the difference calculated by subtracting the R*2,max obtained from a low baseline PaO2 and the ΔR*2,max obtained from a high baseline PaO2.
Comparing row 1104 to row 1108 shows that higher ΔR*2max values are obtained from a lower baseline PaO2, but it is not clear where the vessels are located. Comparing row 1112 to row 1108 reveals the location of arteries. Areas that are brighter in row 1112 than in row 1108 indicate the presence of arteries. When comparing row 1016 to row 1112, it can be seen that extravascular voxels are dark in row 1112 and the only light areas indicate major arteries. In particular, the middle cerebral artery is prominent when comparing the axial slice in row 1116 to the axial slice in row 1112.
The present disclosure provides a new method for differentially highlighting the properties of venous and arterial voxels. By generating two deoxyhemoglobin boluses with the same hypoxic drop but distinct baseline oxygenations, arteries and veins can be distinguished. The bolus with the lower baseline oxygenation increases the signal of arterial and venous voxels while keeping tissue signal relatively unchanged. The signal changes for both venous and arterial voxels increase with a drop in baseline oxygenation, however the arterial signal change is much larger. Thus, the subtraction method allows high blood volume vasculature to be highlighted while the division method allows veins to be differentiated from arteries.
A further benefit of the disclosed method is that it is non-invasive and causes few adverse reactions. Because deoxyhemoglobin is an endogenous molecule that does not accumulate or recirculate, it is safe and possible to administer multiple boluses of the contrast agent. Repeated changes in [dOHb] are well-tolerated by individuals and therefore individuals and populations can be studied over time.
The many features and advantages of the invention are apparent from the detailed specification and, thus, it is intended by the appended claims to cover all such features and advantages of the invention that fall within the true spirit and scope of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation illustrated and described, and accordingly all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.
This application claims the benefit of U.S. provisional application entitled “Using Oxygen Modulation in Deoxyhemoglobin Contrast to Highlight Cerebral Arterial and/or Venous Regions” having Ser. No. 63/249,779, filed Sep. 29, 2021 and incorporated by reference herein.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2022/059311 | 9/29/2022 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63249779 | Sep 2021 | US |
