These perfusion-imaging methods allow the estimation of several important hemodynamic parameters, which include blood flow, blood volume, and the mean transit time MTT. So far, the major applications have been in the assessment and management of patients with acute stroke and tumors.
Changes in hemodynamic parameters can precede abnormalities on conventional MRI, and knowledge of whether a lesion is associated with increased or decreased blood flow or blood volume can frequently help narrow the differential diagnosis and aid patient management. Additionally, measurement of contrast agent permeability, such as a transport constant related to the permeability-surface area K trans and the fractional volume of the extravascular extracellular space EES, v e , may be useful to evaluate diverse diseases.
Given their relationship with the underlying biology, they have been proposed as sensitive biomarkers to assess medical or surgical therapies. The objective of this review is to describe the basic physical principles behind these techniques.
The review discusses the following sections: 1 perfusion MRI methods and sources of perfusion signals, 2 physical principles of perfusion MRI, 3 perfusion MRI protocols, 4 perfusion MRI parameters, 5 perfusion signal dynamics, 6 quantifications of perfusion MRI signals, 7 sources of error, 8 current development issues, 9 outlines of clinical applications, and 10 summary of perfusion MRI.
This review summarizes comprehensive updated knowledge of the physical principles and techniques of perfusion MRI. Dynamic susceptibility contrast-MRI is one of the exogenous contrast-based methods, and relies on the intravenous injection of a paramagnetic contrast agent, such as those involving gadolinium Gd chelates, to generate a well-defined bolus. Most of the Gd chelates, e. This technique utilizes very rapid imaging to capture the first pass of the contrast agent, and it is therefore also known as bolus tracking MRI.
Dynamic contrast-enhanced-MRI is the other exogenous contrast-based method. After the bolus of the contrast agent is injected, hemodynamic signals of DCE-MRI depend on the T 1 relaxation time, and increase because of the T 1 shortening effect associated with the paramagnetic contrast agent 2. DCE-MRI uses rapid and repeated T1-weighted images to measure the signal changes induced by the paramagnetic tracer in the tissue as a function of time. In this method, the contrast agent is also intravenously injected to generate bolus.
T1-weighting is not affected by extravasation. Extracellular contrast media diffuse from the blood into the EES of tissue at a rate determined by tissue perfusion and permeability of the capillaries and their surface area.
Shortening of the T 1 relaxation rate caused by the contrast medium is the mechanism of tissue enhancement so-called T 1 or relaxivity-based methods. Arterial spin labeling gives absolute values of perfusion of tissue by blood.
This technique utilizes arterial water as an endogenous diffusible tracer, which is usually achieved by magnetically labeling the incoming blood 3. Therefore, ASL is completely noninvasive, using no injected contrast agent or ionizing radiation and is repeatable for studying normal or abnormal physiology and its variation with time. ASL requires the subtraction of two images, one in which the incoming blood has been labeled and the other in which no labeling has occurred. The ASL difference signal depends on the blood T 1 relaxation time and the labeling decays after a long delay time.
Table 2 lists sources of signals of the three types of perfusion MRI techniques. The T 1 and T 2 relaxation rates i. This increase results from the interaction of the water protons with the unpaired electrons of the paramagnetic ion or chelate and is proportional to the concentration of the contrast agent.
This technique is based on the susceptibility changes after injecting the contrast agent. The contrast agent is a paramagnetic material, which distorts the magnetic field, and reduces T 2 around the vessel because of an increased susceptibility effect. The contrast agent increases the R 2 relaxation rate in a tissue by the relationship of 4 :.
Two compartments must be considered: the intravascular and extravascular compartments. When the tracer remains intravascular, the compartmentalization of the contrast agent creates strong, microscopic susceptibility gradients, which extend beyond the vessel size.
The contrast agent increases the R 1 relaxation rate in a tissue by the relationship of. The relaxivity is dependent upon the field strength, the chemical nature of the contrast agent and the tissue 6. The contrast concentration in tissue can be calculated if the values of r 1 , T 10 , and T 1 for the tissue are known.
However, if assuming the relaxivity is independent of the tissue type 7 , the outcome of the kinetic analysis of DCE-MRI data is independent of the value chosen for r 1. Recent evidence suggests that with appropriate sequence optimization, the effect of water exchange in DCE-MRI is negligible 8.
Contrast agents that are rapidly extracted into the tissue are mainly monitored by T1-weighted imaging, as the resulting change is a positive increase in signal intensity, which can be clearly visualized. This technique is based on the subtraction of an image obtained with magnetic blood labeling known as the 'label' image from an image obtained without labeling known as the 'control or reference' image.
Typically, for one image the water protons in the blood are tagged, such as by inverting their magnetization at the level of the large feeding arteries.
Tagged blood flows into the imaging slab, following a transit delay to allow these tagged spins to enter the imaging plane and exchange with tissue. Thus, tagged blood flows into capillary sites with T 1 of blood T 1b and exchanges into tissues from capillary vessel of T 1 of tissue T 1t. Some of the tagged blood can also flow out through the venous system. The resulting 'label' image reflects how, after a delay, these protons reach the capillaries in the slice of interest and diffuse in the tissue water space.
The second image the 'control' image is obtained without labeling the incoming blood. In ideal conditions, the difference signal is proportional to the amount of blood delivered to the slice during the delay period, and therefore should reflect perfusion, since all other static effects should cancel out.
In the blood vessel, the T 1 relaxation time of blood decays with the T 1 of blood after tagging. In the tissue, the T 1 of blood is exchanged almost freely and is mixed with the T 1 of tissue water. The mixed T 1 relaxation produces the apparent R 1 relaxation rate of the following equation,.
In CASL, the magnetization of the arterial blood flowing through a major artery is continuously labeled usually by inversion using radiofrequency pulses; it is based on a steady state approach 3 , One of the CASL labeling methods is double adiabatic inversion 11 for multi-slice acquisition.
A continuous radiofrequency field is applied for a few seconds along with a field gradient. In contrast, PASL involves a relatively short radiofrequency pulse, which results in the labeling usually inversion of the blood in a large region adjacent to the imaging volume. PASL labeling methods include: signal targeting with alternating radio frequency 12 , flow alternating inversion recovery 13 , 14 , proximal inversion with control for off-resonance effects 15 , transfer insensitive labeling technique 16 , double inversion with proximal labeling of both tagged and control images 17 , and in-plane slice-selective double inversion for both the control and the labeling scans This labeling is not spatially selective, avoiding transit time problems, and can be made sensitive to different blood velocities.
Table 3 lists imaging sequences for the three types of perfusion MRI techniques. When a gradient-echo GE acquisition is used, static field inhomogeneities are experienced in large vessels, resulting in signal losses, due to the presence of microscopic field perturbation in the vessels.
In addition, dephasing in small vessels causes signal losses due to diffusion. An advantage of GE acquisitions is their increased contrast-to-noise ratio CNR ; however, a major disadvantage is their large vessel contamination. When spin-echo SE acquisition is used, the signal loss is greatly reduced because the dephasing is partially refocused. As with GE acquisitions, dephasing in small vessels causes signal losses due to diffusion.
Therefore, SE measurements are mainly sensitive to vessel sizes comparable to the water diffusion length during the time of echo, which corresponds to capillary size vessels; whereas GE measurements are equally sensitive to all vessel sizes 4.
Therefore, the SE signal theoretically yields preferential sensitivity in detecting changes in small vessels: SE-based perfusion-weighted imaging PWI shows a reduced appearance of large vessels and may therefore be more representative of capillary perfusion, while GE-based techniques exhibit higher CNR Typically, a double dose of standard Gd chelate 0.
This acquisition requires rapid imaging sequences, such as Cartesian or spiral EPI. This is usually scanned with a T1-weighted imaging sequence with 2D or 3D dynamic acquisition. GE measurements are sensitive to all vessel sizes, but SE measurements are more sensitive to small vessels. Commonly, 3D GE acquisition methods, such as fast spoiled gradient echo, fast low angle shot FLASH , or T1-weighted high resolution isotropic volume examination, are used to obtain volume.
Values of baseline T 1 for each voxel are used to calculate the post-injection T 1. In the clinical application, a constant baseline T 1 value is often used rather than mapping it because of scan time limitation. Inflow effects in the larger vessels should be minimized if arterial input function AIF needs to be measured. This can be done with a non-selective inversion- or saturation prepulse in a 2D acquisition.
Since the contrast for this technique is related to the preparation module i. It is usually scanned with a sequence with short echo time TE to maximize SNR and with long repetition time TR to allow the labeled blood to reach an imaging plane. A single time-point or dynamic acquisition using the Look-Locker method is used with 2D or 3D excitation 23 , 24 , Furthermore, 3D-based imaging acquisition is being developed to improve the SNR 26 , 27 , Macrovascular signal contributions are usually dependent on two factors: a crusher gradient and a post-delay time.
With a short post-delay time, the labeled blood still remains in large vessels at the time of imaging. Bipolar gradients with a very small b-value have been used to crash signals from the large vessels.
Therefore, ASL signals are contributed by large vessels if crusher gradients are not used or if a short post-delay time is used after labeling; this applies for both GE and SE sequences. In contrast, this contribution can be minimized by using the crusher gradient and the long post-delay time.
In this case, ASL signals are mainly contributed by small vessels. Recent developments in ASL pulse sequences were reviewed in detail in reference Table 4 lists common imaging parameters for the three types of perfusion MRI techniques.
In DSC-MRI, a bolus of a Gd-based contrast agent administered as a short venous injection of a few seconds duration will have a width of approximately seconds by the time it reaches the brain, creating a signal dip of about ten to twenty seconds or longer.
To faithfully record the tracer concentration during this passage, images must be acquired at a rate much faster than the time it takes the bolus to pass through the tissue i. TE is chosen long enough to produce sufficient CNR due to susceptibility effects, but not long enough to diphase all signals during the maximum contrast agent concentration.
A relatively large flip angle is used, although not long enough to introduce unwanted T 1 contamination The volume scan time is depended on TR. The scan duration is relatively short. The flip angle is also small due to short TR. The optimal setup depends to some extent on the tissue under investigation, and the clinical constraints in terms of coverage and spatial resolution, but also on the objective of the measurement.
The temporal resolution of the imaging sequence is dictated by the chosen analysis technique. Thus mapping kinetic parameters from DCE-MRI traditionally requires compromise in terms of spatial resolution, temporal resolution, and volume coverage. With current MRI technique, the volume scan time is usually between 5 and 10 seconds. For the breast or other large field-of-view areas, this time is increased up to 20 seconds.
The volume scan time must be as short as possible to track the contrast agent. In order to provide adequate data for pharmacokinetic analysis data, collection will typically continue for in excess of 5 minutes. The length of the total acquisition time is particularly important for accurate measurement of the fractional volume of EES, v e. Recently, a new dual temporal resolution-based, high spatial resolution, pharmacokinetic parametric mapping method has been described In the protocol, a high temporal resolution pre-bolus is followed by a high spatial resolution main bolus to allow high spatial resolution parametric mapping for tumors.
The measured plasma concentration curves from the dual-bolus data were used to reconstruct the high temporal resolution AIF necessary for accurate kinetic analysis. Arterial spin labeling is scanned with a relatively long TR to allow for the labeled blood to travel and exchange with the tissue and short TE to maximize SNR.
Because of the long TR, a large flip angle is also used. The ASL volume scan time is dependent on 2 x TR because two images the label and control images must be acquired for each volume.
The scan duration is also relatively long because of the need for multiple repeated scans to increase SNR. It is not uncommon to acquire at least 40 averages to improve SNR.
A group consensus recommendation for a protocol for clinical applications was recently published in reference The model used for perfusion quantification is based on the physical principles of tracer kinetics for non-diffusable tracers 33 and relies on the assumption that the contrast material remains intravascular in the presence of an intact brain-blood barrier BBB.
Series images are acquired before, during, and after injecting the contrast agent. While passing through the microvasculature, a bolus of the contrast agent produces decreases in the MR signal intensity. The time course images can be divided into three stages: the baseline, the first passage of the bolus, and the recirculation period During the baseline period, images are acquired before the arrival of the bolus, and the time course signals are therefore usually constant.
During the first passage of the contrast agent, the contrast agent arrives at the voxel and the DSC-MRI signal quickly decreases until the peak signal change corresponding to the time of maximum contrast agent concentration. After the minimum signal is reached, the signal intensity partially returns to baseline values. Finally, during the recirculation period which often partially overlaps with the first passage , the DSC-MRI signal decreases again although to a smaller degree and a slower rate , due to re-entering the contrast agent.
After this period, signals theoretically recover up to the baseline. The signal intensity-versus-time curves are converted into concentration-versus-time curves, assuming a linear relationship between the change in relaxation rate, and the concentration. A gamma-variate function 35 is then sometimes fitted to the resulting concentration time course, to eliminate the contribution of tracer recirculation. Hemodynamics of contrast agent obtained with dynamic susceptibility contrast MRI signal intensity time course in arbitrary units , for voxel.
Series images are acquired before, during, and after injecting contrast agent. While passing through microvasculature, bolus of contrast agent produces decreases in magnetic resonance signal intensity. The time course of enhancement is related to the changes, which depend on the physiological parameters of the microvasculature in the lesion and on the volume fractions of the various tissue compartments. Three major factors determine the behavior of low-molecular-weight contrast medium in tissues during the first few minutes after injection: blood perfusion, transport of contrast agent across vessel walls, and diffusion of contrast medium in the interstitial space.
Overall, for a bolus injection of the contrast agent into the blood circulation, there is always an initial increase in its concentration in the plasma and possibly some leakage into the interstitium for the duration of the injection Fig. Afterwards, the plasma concentration continuously decreases because of diffusion into the body and clearance through the kidneys to the urine; whereas the tissue concentration can increase for a while and then decrease, depending on various physiological variables.
The dynamic acquisition pattern is similar to that of DSC-MRI: images are acquired before, during, and after injecting the contrast agent. Most benign and malignant lesions show signal enhancement in the first few minutes after bolus administration of a Gd-based contrast agent.
The normal tissue may also show enhancement. Hemodynamics of contrast agent obtained with dynamic contrast-enhanced MRI signal intensity time course in arbitrary units , for voxel. Time course of enhancement is depended on physiological parameters of microvasculature in lesion, and on volume fractions of various tissue compartments. For bolus injection of contrast agent into blood circulation, there is always initial increase in its concentration in plasma.
To minimize the definition error of the bolus width of labeled blood in a single-time point experiment on PASL, two labeling times were introduced in a sequence known as quantitative imaging of perfusion using a single subtraction QUIPSS II In this sequence, the first labeling time TI1 was defined by the interval between the labeling pulse and a saturation pulse, which effectively defined the labeled bolus width.
The second labeling time TI2 was defined by the interval between the labeling pulse and the excitation pulse of image acquisitions. This method can be used with any labeling techniques and is involved by the saturation of the inverted region a short time after inversion.
This saturation acts to chop off the tail of the bolus, reducing the arrival time sensitivity. This method can be used to minimize quantification errors of blood flow with a long TI2 labeling time for PASL during data acquisition 36 , A similar strategy was also proposed for CASL to minimize the arterial transit time error in the single measurement, which is based on a long post-labeling delay PLD time of typically 0.
For the single-time point ASL, a single compartment model is used for flow quantification with the concept of free diffusible water and, despite their simplifying assumptions, they are recommended for most clinical studies Alternatively, ASL signals can be acquired with increasing labeling times or delay times.
Figure 3 shows the subtracted hemodynamic signal between control and labeled images on an ASL experiment. The curve shows three phases. The first phase is the baseline period. By kinetic analysis of these data, one may compute cerebral blood flow and volume, as well as mean transit time. These measures can capture the degree of tumor angiogenesis, an important biologic marker of tumor grade, histology, and prognosis, particularly in gliomas.
Perfusion imaging is based on rapid imaging echo planar imaging of the first pass of the contrast agent and can be performed by using either a gradient-echo or a spin-echo pulse sequence. In DSC imaging, the intensity decreases in areas of greater contrast concentration due to changes in local susceptibility.
This differs from dynamic contrast-enhanced DCE MRI, in which a T1-weighted sequence detects an increase in intensity proportional to contrast concentration. Calculating imaging biomarkers from perfusion signal time curves involves several steps; Figure 1 depicts the most commonly used steps. MRI perfusion imaging is capable of estimating the volume of blood that passes through the capillary bed per unit of time.
The quantification can be performed in a relative or absolute manner. Although absolute quantification is preferable, it is much more challenging to perform in clinical practice due to many potential imaging and data processing artifacts. Thus, DSC typically produces images that are visually reviewed, and any measurements are expressed as a ratio to normal-appearing white matter. Relative cerebral blood volume rCBV measurements have been shown to correlate with tumor grade and histologic findings of increased tumor vascularity.
After the data are acquired, the baseline is defined; this often includes removal of the first 3 time points due to saturation effects. The start and end points of the bolus are calculated. Subsequently, the baseline signal intensity is calculated and the signal-time curves are converted to concentration-time curves. This is done for each voxel in the imaging volume. The rCBV image is the most important of the perfusion images for analyzing brain tumors and is computed by integrating the area under the time-concentration curve.
The latter two measures are frequently used in stroke imaging, but are of limited value in tumors. For routine clinical practice, visually inspecting the color maps can help to detect normal versus abnormal regions Figure 2.
This kind of assessment can be very useful in the clinical setting, but it depends on the windowing technique parameters used to present the data.
Figure 3 demonstrates the effect of this phenomenon on time-intensity curves. Instead of returning to baseline, the signal returns to a point higher than the initial baseline due to T1 effects, resulting in underestimation of the integration area.
The sequence type and parameters can affect how the concentration-time curves are distorted. Therefore, the CBV would be overestimated. When T1 effects dominated eg, when high flip angle and short repetition time were used , the measured transverse relaxation-rate-time course underestimated the true transverse relaxation-rate-time course; thus, the CBV would be underestimated.
However, animal studies suggest preloading is not very effective. K2 refers to the leakage rate detected during DSC tumor imaging. GE-DSC sequences tend to be more sensitive to larger vessels, such as veins, while SE-DSC techniques tend to show greater sensitivity to smaller vessels capillaries that should be more specific for tumor vessels.
However, imaging patients with GE sequences can be challenging after surgery because hemorrhage or metallic foreign bodies can produce signal loss and artifact. Recently, a combination of the two techniques has been emerging, since it can provide simultaneous perfusion and permeability measurements. Transitioning DSC perfusion imaging from 1. Practically, this means a higher signal-to-noise ratio SNR for a given dose of contrast 20 or that less contrast can be used in patients with limited renal function.
The correlate is that increased field strength leads to greater enhancement of T2 effect compared to 1. Because of the increased T1 effects at higher field, leakage is underestimated.
Due to their thermal energy, water molecules in tissue undergo a continuous random motion referred to as Brownian motion. While diffusion technically refers to the movement or transport of some substance without bulk motion within a medium like water, it also refers to the motion of water that occurs without bulk motion. Because water spins will run into constituents of cells, and because those cellular components have different concentrations in different parts, they will spread at different rates and not behave in the same way when moving in different directions.
Signal intensity is represented by the following equation:. In this equation, ADC is the apparent diffusion coefficient and b is the gradient factor commonly referred to as the b-factor. Sensitivity to diffusion-based contrast is controlled primarily by the b value.
The apparent diffusion coefficient is an average of the diffusion process occurring in the tissues. Qualitatively, Eq. As the diffusing spins move inside the field, they are affected differently by the field; thus, their alignment with each other is destroyed.
Drink plenty of water in the hours and day after the test. This will help flush out the remaining radioactive tracer in your body. A radiologist will read and interpret your exam and will send these results to your healthcare provider. Ask your healthcare provider about when you can expect to learn the outcome of your scan. You and your healthcare provider can use the results to help formulate your treatment plan. Health Home Treatments, Tests and Therapies.
Why might I need a brain perfusion scan? For example, your healthcare provider may recommend a brain perfusion scan if you have one of the following conditions: Epilepsy Dementia Stroke or transient ischemic attack Subarachnoid hemorrhage Carotid stenosis Cerebral vasculitis Brain tumor Recent head injury You also might need a brain perfusion scan if you need an operation on one of the vessels in your brain or neck and your healthcare provider wants to examine the flow of blood through your brain.
What are the risks of a brain perfusion scan? How do I get ready for a brain perfusion scan? What happens during a brain perfusion scan? The following is an overview of what you might expect: You will lie down on the exam table. In some cases, a technician or nurse will insert an IV into a vein in your hand or arm, which might be slightly painful. A healthcare professional will give you the tracer, either by IV, by mouth, or by inhalation.
It may take an hour or so for the tracer to travel through your body. You may need to drink a contrast material for certain kinds of studies.
Once you are comfortable and positioned, the radiographer will return to the control console, leaving you in the MRI machine. From here, the radiographer will control the scanner to instruct the machine which part of the body to examine, and which views will best investigate your particular condition. You will be able to communicate with the radiographer at all times. If at any time you feel anxious or uncomfortable about being in the tunnel claustrophobia , you can talk to the radiographer who might decide to take you out of the scanner.
You will be aware of humming and knocking noises going on around you, which indicates that the scanner is running. It is normal to feel a little warm during the scan. You will be asked to hold your breath for short periods from time to time during the scan, so that you remain still to help produce the best images possible. The MRI machine can be noisy, so you will be provided with headphones, and you can listen to music you are welcome to bring your own CD and speak with the radiographer.
You will also be given a squeeze ball to hold in your hand during the scan. Squeezing the ball will make the radiographer aware that you wish to speak. A microphone is located within the MRI machine. A radiologist specialist doctor , who will supervise the procedure, might require injection of contrast medium gadolinium during the scan.
The contrast medium can assist in identifying abnormalities within the heart muscle, and to highlight the blood vessels. If contrast medium is to be used, the injection is given while you are inside the scanner, using the small needle that may have been placed in your arm at the beginning of the study. The injection is given through an extension tube connected to the needle. The hospital radiology department or radiology practice where you are having the scan is equipped to deal with this on the rare occasions that it arises.
If you are having a cardiac stress perfusion MRI , injection of both contrast and adenosine will be given during the scan. Many people experience flushing of the face during the adenosine injection, whereas others might feel a discomfort around the jaw and tightness in the chest. These effects are short-lived and usually end soon after the injection is given. Usually there are no after effects.
You will be free to continue the day you have planned once the scan is complete. The examination uses very different technology to a normal X-ray, and does take more time to carry out. Depending on the problem being investigated, the scan time can vary from 20 to 45 minutes. Particularly complex heart conditions can require up to an hour of scanning. Once you have completed the pre-scan questionnaire and have been assessed as safe to enter the MRI machine, there are no significant risks from the MRI machine itself.
Most people are suited to this examination, although there are some restrictions due to the strength of the magnet and its possible effects on devices or implants, such as pacemakers. Occasionally, scanning cannot be carried out if you are upset by the enclosed space of the magnet claustrophobia. An alternative test might then be recommended by your doctor.
For children where structural assessment of the heart is required, a general anaesthetic might be required to ensure the child keeps very still, so that accurate images can be obtained. This will have to be done in a hospital. If a contrast medium gadolinium injection is required for the scan, there is a very small risk of an allergic reaction. Recently, a condition called nephrogenic systemic fibrosis NSF has been identified as a rare but significant side effect of contrast injection.
This complication is more likely to occur in those people with very poor kidney function, including people who are already on dialysis a process that filters the blood of patients whose kidneys are not functioning properly using a kidney machine.
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