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• Parkinson′s Disease - Direct Visualization of the Substantia Nigra and Surroundings with 7.0T Brain Imaging

Parkinson's disease (PD) is a representative neurodegenerative disorder that is caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Therefore, the SN is a region, which has been the focus for an accurate diagnosis of PD. Some believed that iron is deposited in the SN and, therefore, T2*, or susceptibility effect would appear. Increasing the static field to 7.0T could provide a further increase of the SNR and contrast, thus enabling us to obtain high contrast images. Indeed, for the first time at 7.0T we have observed the clear and unambiguous boundaries and surroundings of the SN as shown in the images above (Fig. 1). All of the images were acquired using a 2D T2* weighted gradient echo sequence.
Encouraged with these ultra fine high resolution images, we have performed an experiment which consists of both a control group and a Parkinson's group. The control group consisted of 8 subjects aged 40–65 years old, and the PD group included 5 early patients (Hoehn and Yahr Stage 1) aged 45–65 years old and 5 advanced patients (Hoehn and Yahr Stage 3) aged 54–65 years.
In the normal control group (Fig. 2 (a), Control), the boundaries between the SN and CP appear smooth, and show a clean “ARC” shape stretching from posterior to anterior (yellow line), notably ventrally. This clean and smooth arc between the SN and CP (crus cerebri) towards the lateral and anterior aspects is totally lost in PD as shown in Fig. 2 (b). These deformed arc shape boundaries (both Fig. 2 (b) and (c)) are the hallmarks of PD patients. The reason for the deformed appearance is believed to be due to the loss of DA neurons in the SN (both SNc and SNr), which alters the boundaries between the CP and SN and in turn, leads to the degradation of the cortical fibers.

Fig. 2. Typical selected axial view images of normal control and PD patients obtained from 7.0T T2* weighted imaging. Note the boundaries between the SN and CP, which show the difference between normal and PD patients.

In addition, phase contrast image processing work is also under study, and some preliminary results are shown in Fig. 3 for the above three cases.

Fig. 3. Phase images of a normal control and a PD patient obtained from 7.0T T2* weighted imaging.

• Direct Targeting in Deep Brain Stimulation (DBS)

Fig. 4. The subthalamic nucleus (STN) and substantia nigra (SN) areas are shown, which are the two most important areas in Parkinson's disease. However, the STN and SN are not visible in conventional MRI and usually require additional information, such as cadaver images as shown in (A). Conventional low field images appear poor as shown in (B). In (C), a 7.0T image is shown and the STN and SN are clearly visible, suggesting its potential use in DBS. Legends: STN, Subthalamic Nucleus; SN, Substantia Nigra; GPi, internal Globus Pallidus; GPe, external Globus Pallidus; Pu, Putamen; Cl, Claustrum.

DBS is one of the newly emerging techniques for the treatment of many neurodegenerative diseases, such as Parkinson’s disease, and other unknown origins of pain syndromes. Not only is it a reversible treatment, but it also has many options such as an on-and-off option, depending on the need. There is anecdotal evidence indicating that DBS sometimes leads to more permanent improvement of the disease. In addition, many efforts are underway to determine the basic mechanisms of DBS that could lead to better treatment, along with the further development of this technique. One of the most difficult and unsolved problems associated with DBS is the precise targeting of the electrode to the desired target nuclei or organs, as well as the post-operative follow-up of the positions of the electrodes. Current MRI techniques with low fields, such as 1.5T or 3.0T, are unable to provide an image with sufficient resolution that is able to clearly delineate the desired target nuclei, such as the STN or the surrounding potential targets, e.g., the external capsule or zona inserta. The recent development of ultra-high field 7.0T MRI, with its drastically improved resolution, sensitivity, and contrast, allows surgeons direct identification and targeting to the desired nuclei (Cho et al, 2010). This direct visualization and the possibility of direct targeting of the electrode to the target nuclei will not only benefit the operation as a whole, it will also improve the treatment outcome along with the post-treatment management of the DBS operation. We also believe that similar treatments or brain operations, like the Gamma Knife treatment, would equally benefit from direct targeting once an accurate brain map is available, especially when the target tumors or the nuclei are small or located in delicate sites with other critical elements that are sensitive to radiation. Fig. 4 shows some of the early imaging results obtained using 7.0T MRI with T2* weighted imaging that clearly show the midbrain areas, where therapeutically critical organs, such as the STN and SN, are located.

• References

- Zang-Hee Cho, Young-Bo Kim, Jae-Yong Han, Hoon-Ki Min, Kyoung-Nan Kim, Sang-Han Choi, Eugene Veklerov, Larry A. Shepp. New Brain Atlas-Mapping the Human Brain In Vivo with 7.0T MRI and Comparison with Postmortem Histology: Will These Images Change Modern Medicine? International Journal of Imaging Systems and Technology 18,2-8 (2008).
-Zang-Hee Cho, Hoon-Ki Min, Se-Hong Oh, Jae-Yong Han, Chan-Woong Park, Je-Geun Chi, Young-Bo Kim, Sun-Ha Paek, Andres M. Lozano, Kendall H. Lee. Direct Visualization of Deep Brain Stimulation Targets in Parkinson's Disease with the Use of 7.0 Tesla Magnetic Resonance Imaging. Journal of Neurosugery [In Process] (2010)

• Research Interests

High resolution DTI in 7T MRI
3D Modeling and Shape Analysis of Substantia Nigra
Study of probabilistic method of DTI & Clinical Applications