MRI IN GLAUCOMA (PART 2)

Diffusion-weighted imaging (DWI):

The DWI method is a non-invasive functional imaging analysis of the internal structure and tissue components of lesions at the molecular motion level by detecting the diffusion movement of water molecules in vivo.It can detect the cerebrospinal fluid flow in the subarachnoid space of the optic nerve in a non-invasive manner.

It has been found that the flow range ratio of NTG patients was significantly lower than that of healthy control participants. This finding suggests that impaired cerebrospinal fluid dynamics may play a role in the pathophysiology of NTG.

Cio et al. found that there were global differences in structural connectivity and local graph theoretical measures in glaucoma patients, and these changes far exceeded the main visual pathways. The results support the hypothesis that whole brain structural reorganization occurs in patients with glaucoma, which is specific to structural connections. 

This finding means that glaucoma can be categorized in the recently defined category of a brain disconnection syndrome.

The results provide indirect evidence that unknown factors may limit the reorganization of white matter after visual loss in glaucoma patients.

There are several limitations to DWI. First, DWI delineates that random Brownian motion of water in normal and pathological neural tissue environments changes. Reduced water diffusion has been shown to be sensitive to many diseases in the brain but is not specific to glaucoma. Therefore, the detection results of DWI may be affected by other factors and cannot be used as a biomarker of glaucoma neurodegeneration. Second, according to the partial volume effect and image slice direction, the diffusion limitation of the optic nerve may be ignored due to the small size of the optic nerve. Therefore, in the case of insufficient spatial sampling, the incidence of limited diffusion in the optic nerve may be underestimated. Thin slices (e.g., 3 mm) arranged parallel to the optic nerve should improve the sensitivity of optic nerve diffusion limitation. Third, although the sensitivity and accuracy of rs-EPI and rFOV-EPI are similar, their image quality in the orbital segment is significantly higher, and there are still artifacts in the optic canal segment and the intracranial segment.

Diffusion tensor imaging (DTI):

Based on conventional DWI, the new neuroimaging technology of DTI is an MRI method that goes by the assumption that water molecules diffuse with a Gaussian distribution to measure and obtain the anisotropy information of different tissues. 

The dislocation of water molecules in nerve fibers and axons can be detected by the diffusion of water molecules along axons without a gadolinium contrast agent. Doing so can reveal abnormalities of the white matter structure and brain connection. 

The DTI technology is the most commonly used method in MRI, and it can quantitatively measure the integrity of microstructure and tissue in vivo. It has been widely used to study the differences of white matter bundles in the visual pathway in glaucoma patients. Microstructural differences of white matter structures have been found in the optic nerve, optic tract, optic chiasm, optic radiation, and the occipital lobe of glaucoma patients. 

It is believed that DTI may reveal early axonal injury with more sensitivity than a conventional MRI can.

Some researchers argue that DTI can be used to distinguish different glaucoma subtypes. 

Compared to the established ophthalmic diagnostic methods, these new imaging techniques seems to enable earlier diagnosis of NTG.

Studies by Schreiber et al. further support the hypothesis that glaucoma can be considered a pan-neurodegenerative disease. The mechanism of brain injury outside the visual pathway in POAG patients is not the direct extension of visual pathway degeneration, but the primary neuropathological process of the transmission mechanism of neurodegenerative lesions. Giorgio et al. found that compared with the healthy control group, patients with NTG and POAG had significantly more gray matter atrophy in their visual system and non-visual brain areas, and significantly more changes in DTI-derived anatomical connections. 

The diffuse structural and functional abnormalities of the brain of a patient with glaucoma may, at least in part, be unrelated to the increase of IOP and subsequent retinal degeneration. 

Murai et al. have used DTI to report a significant correlation between optic radiation axon injury and decreased cerebral glucose metabolism in the striate cortex of POAG patients.

The DTI method has been widely used to evaluate microstructural abnormalities of white matter in the brain; however, it has some limitations. For example, due to the existence of organelles, cell membranes, and other barriers, water molecules often show non-Gaussian diffusion in biological tissues. Therefore, the practicability and sensitivity of the DTI model may not be completely optimal. In addition, DTI studies have shown damage to the integrity of the overall microstructure in the visual pathway of patients with glaucoma. 

The mechanism behind the difference of directional diffusion rate in glaucoma DTI research is not clear, and the pathophysiology of glaucoma may be more complex than the deterioration of the axon and myelin sheath.

MRI IN GLAUCOMA (PART 1)

 

Magnetic resonance imaging (MRI) is currently not a standard investigation in most glaucoma patients. However, a number of studies have shown striking central nervous system (CNS) changes in MRI studies in such patients.

The advanced MRI used in glaucoma brain detection mainly involves the following 7 types of methods: 

1. MRI quantitative morphometry; 

2. Blood oxygenation level dependent functional MRI (BOLD-fMRI); 

3. Diffusion-weighted imaging (DWI); 

4. Magnetic resonance spectroscopy (MRS); 

5. Diffusion tensor imaging (DTI); 

6. Diffusion kurtosis imaging (DKI); and 

7. Magnetization transfer imaging (MTI).

MRI quantitative morphometry:

It is now possible to image brain structure, volume, and microstructural damage.

The techniques for quantitative evaluation of brain morphology can be divided into 2 types: voxel-based morphometry (VBM), and surface-based morphometry (SBM).

The VBM technique uses a statistical method to allocate the probability that a voxel is occupied by gray matter, whereas SBM determines the vertices defining the interface surface of gray matter cerebrospinal fluid (CSF) and gray and white matter, and uses these vertices to estimate the thickness of the cerebral cortex with submillimeter accuracy.

Using MRI VBM, Hernowo et al. found that the volume of all structures of the visual pathway in glaucoma patients was significantly reduced, including the optic nerve, optic chiasm, optic tract, LGN, and optic radiation. The volumetric MRI techniques have observed a decrease in occipital surface area or visual cortex volume in both hemispheres of glaucoma patients.

In terms of the severity of glaucoma, Wang et al. used T1 weighted MRI images to conduct VBM and SBM analysis on the whole brain. They found that in patients with glaucoma, the left LGN volume was negatively correlated with the bilateral optic cup disk ratio, the right LGN volume was positively correlated with the average deviation of the right VF, and the right V1 cortical thickness was negatively correlated with the right optic cup disk ratio. In patients with primary open angle glaucoma (POAG), these changes in brain visual structure can reflect the clinical severity of glaucoma.

Blood oxygenation level-dependent functional MRI (BOLD-fMRI):

The BOLD effect is the most commonly used method to obtain information related to brain function. It is an indirect measurement of cortical activity. The BOLD-fMRI is a non-invasive imaging method that uses deoxyhemoglobin as the natural contrast agent in vivo to monitor blood oxygen levels of the brain in real-time.

Different Rs-fMRI studies of glaucoma have shown decreased connectivity in regions associated with vision. 

POAG results in decreased cortical activity in the visual cortex, including the central region. Primary angle closure glaucoma (PACG) showed decreased activity in the bilateral secondary visual cortex (BA18). 

Reduction of BOLD activity may also involve many areas of non-visual pathways.

PACG is mainly related to frontal lobe dysfunction. Chen et al. used the ReHo method and found that PACG was involved in abnormal spontaneous brain activities in multiple brain regions, such as the left fusiform gyrus, left anterior cerebellar lobe, right frontotemporal space and right insula, bilateral middle occipital gyrus, and the right paracentral lobule. 

Patients with PACG show abnormal spontaneous neural activity in the visual cortex, sensorimotor cortex, frontal lobe, frontal parietal lobe network, and the DMN. This indicates that the visual, cognitive, and emotional functions of individuals with PACG may be impaired.

Zhang et al. used Rs-fMRI to analyze the brains of patients with NVG and revealed dysfunction in the brain regions of the right romantic operculum, left antagonist cingulate and paracingulate gyri, left precuneus, and the right caudate. Peng et al. observed abnormal spontaneous activity in NVG patients in the right cuneus, right middle occipital gyrus, left cingulate gyrus, right precuneus, left medial frontal gyrus, right superior frontal gyrus, and left middle frontal gyrus. These abnormal changes in specific brain regions can be considered possible clinical indicators of NVG.

In terms of the severity of glaucoma, some researchers have observed that in mild and moderate cases of glaucoma, the primary visual cortex seems to be more affected than other advanced visual areas. For example, abnormal spontaneous neural activity in the left wedge, bilateral middle temporal gyrus, and the right prefrontal cortex have been shown to be associated with the severity of POAG.

At present, fMRI is a very interesting clinical research tool for understanding how glaucoma functionally affects the central nervous system; however, it still has some limitations. First, fMRI technology is based on the premise that neural networks are associated with anatomic known visual regions, but other neural network components which may be affected by glaucoma cannot be clearly defined. Second, fMRI signal has low-temporal resolution due to down-sampling and indirectly measures underlying neuronal activity.