Magnetic resonance imaging (MRI) is a highly precise diagnostic tool that produces detailed images of the brain and arteries. MRI can be used to detect early signs of cerebral ischemia and intracranial hemorrhage, and can determine which areas of the brain are irreversibly damaged by stroke. MRI plays an essential role for the study of the pathophysiology of stroke, the diagnosis and management of ischemic subjects, and for the development of alternative therapeutic approaches.

At Ace Therapeutics, we offer MRI services tailored to animal models of stroke for non-invasive and longitudinal monitoring of key events in the ischemic cascade, from the hyperacute to the chronic phase. We offer different MRI methods to study the onset, evolution, and consequences of stroke. We use specific imaging modalities at different stages of disease progression to ensure reliable data.

Related Services

• Magnetic Resonance Imaging (MRI) Service in Animal Models of Stroke

What Is MRI?

MRI is a non-invasive medical scan, which involves high magnetic fields and radio waves that take images of almost every internal part of the body: the brain, bones, muscles and blood vessels. MRI has also become a standard procedure in most preclinical centres now that we have high-resolution scans of small animals.

MRI in Animal Models of Stroke

MRI enables the study of stroke across various perspectives, from subcellular processes to systems biology. MRI has become one of the most powerful tools for scientists to study the onset, progression, and consequences of stroke, as well as to monitor the success of existing treatments or develop new therapeutic strategies.

T2-weighted Imaging

Cytotoxic edema and glutamate buildup during a stroke break the blood-brain barrier (BBB), leak into the extracellular space, and produce vasogenic edema. Such an excess of extracellular fluid can be seen on T2- or T2*-weighted MRI scans. In the chronic phase of the disease, the majority of imaging procedures consist of only T2- or T2*-weighted imaging, for lesion volumes.

• T2-weighted images can be obtained using conventional multi-slice multi-echo (MSME) or Fast Spin Echo (FSE)/Rapid Acquisition with Relaxation Enhancement (RARE) sequences. T2-weighted spin echo sequences are typically used to image ischemic lesions from 4 to 6 hours after stroke onset, extending into days or months.
• T2*-weighted images, typically acquired using gradient recalled echo (GRE) or Fast Low Angle Shot (FLASH) sequences, are also suitable for delineating ischemic lesions.
• Fluid attenuated inversion recovery (FLAIR) sequences have exceptionally long echo times (TE) and repetition times (TR), but are otherwise similar to T2 images. As a result, the abnormality will continue to glow, while the CSF will usually darken. Because FLAIR is extremely sensitive to disease, it is easier to distinguish between abnormalities and CSF.

Fig. 1 Multi-parameters of MRI to estimate ischemia-reperfusion injury after stroke in hyperglycemic rats. (Huang, et al., 2019)

Diffusion-weighted Imaging (DWI)

When blood flow drops below a certain threshold during a stroke, energy-dependent pumps fail, leading to cytotoxic edema, which alters water diffusion in brain tissue. Diffusion-weighted imaging (DWI) is highly sensitive to these early changes (4-6 h), detecting tissue damage minutes after stroke onset. DWI shows hyper-intense signals in areas of cytotoxic edema (ischemic core), where water diffusion is restricted. By applying different diffusion gradients, the apparent diffusion coefficient (ADC) can be quantified, with lower ADC values in regions of increased cytotoxic edema.

Fig. 2 DWI and ADC at the same planes and acquisition times of the rat brain. (Ramos-Cabrer, et al., 2018)

Perfusion-weighted Imaging (PWI)

A severe reduction in blood flow causes irreversible brain damage in the infarct core, detectable by DWI-MRI. PWI, however, identifies both the infarct core and areas with less severe perfusion reduction, where tissue damage may be reversible. In the early hours after stroke, a mismatch exists between PWI and DWI, which gradually reduces as the infarct core expands.

Diffusion Tensor Imaging (DTI)

DTI is valuable for studying white matter diseases and evaluating therapeutic responses. However, due to the small size and low quantity of white matter bundles in the rodent brain, DTI is not commonly used in routine preclinical stroke research with rodents. It is primarily applied in studies focused on functional recovery and brain plasticity after stroke. Original DTI approaches have evolved into a series of advanced white matter imaging techniques, including Diffusion Kurtosis Imaging (DKI), Diffusion Spectrum Imaging (DSI), Q-ball imaging, and persistent angular structure imaging (PAS-MRI).

Magnetic Resonance Spectroscopy (MRS)

Brain metabolism can be noninvasively monitored using voxel-based MRS or chemical shift imaging (CSI), focusing on specific metabolites like glutamate or analyzing multiple metabolites. In particular, chemical exchange saturation transfer (gluCEST) techniques enable the determination of glutamate levels through magnetization.

Dynamic Susceptibility Contrast (DSC)

Gadolinium-based contrast agents, commonly used in MRI, are paramagnetic substances that reduce T1 and T2 relaxation times, with a significant effect on T2* relaxation time. These are agents – normally packed by organic complexes to modulate their body-wide behavior and half-life – that are deployed in DSC brain perfusion scans. DSC records the temporary decrease in signal strength as the gadolinium bolus crosses the blood vessels and can be used to calculate cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) through kinetic modeling.

Magnetic Resonance Angiography (MRA)

MRA is crucial for imaging ischemic attacks, as it detects blood vessel obstructions. MRA can be contrast-enhanced angiography (CE-MRA) with an exogenous contrast agent to create T1-weighted images or arterial spin labeling (ASL) with an endogenous contrast of RF-labelled blood protons.

Arterial Spin Labeling (ASL)

ASL is a non-invasive MRI method for quantitatively measuring cerebral perfusion by using magnetically labeled blood as an endogenous tracer, eliminating the need for exogenous contrast agents or ionizing radiation. ASL provides absolute perfusion values by labeling incoming blood, typically through water protons, and requires subtracting two images: one with labeled blood and one without. ASL is useful for dynamic studies and functional MRI (fMRI), with strategies to improve background suppression and image readout.

Fig. 3 ASL CBF image, DSC CBF image, and ASL: DSC ratio maps from one animal of each of the three experimental groups. (Shen, et al., 2016)

1. Huang, W. Y., et al. (2019). Multi-parameters of magnetic resonance imaging to estimate ischemia-reperfusion injury after stroke in hyperglycemic rats. Scientific Reports, 9(1), 2852.
2. Ramos-Cabrer, P., & Padro, D. (2018). MRI in the study of animal models of stroke. Preclinical MRI: Methods and Protocols, 377-392.
3. Shen, Q., & Duong, T. Q. (2016). Magnetic resonance imaging of cerebral blood flow in animal stroke models. Brain circulation, 2(1), 20-27.