Diagnostic Neuroimaging Research

Theme Leader :
Kenji Ishibashi, M.D., Ph.D.
Vice-Chief Researcher :
Kenji Ishii, M.D.
Researcher :
Kei Wagatsuma, R.T., M.Sci.
Adjunct Researcher :
Keiichi Oda, Ph.D., Yukihisa Suzuki, M.D., Ph.D., Motoki Inaji, M.D., Ph.D., Yasumasa Imai, M.D., Ph.D., Shihori Hayashi, M.D., Hatsumi Endo, R.N.

PET, aging, dementia, Alzheimer's disease, Parkinson's disease, cerebrovascular disorders, epilepsy, movement disorders, cerebral blood flow and metabolism, neuroreceptors.

1. 1.Development of diagnostic methods for early, prodromal, and preclinical dementia
2. 2.Research on amyloid imaging for clinical implementation
3. 3.Application of PET techniques for clinical gerontology research and medicine

1. Development of diagnostic methods for early, prodromal, and preclinical dementia
We construct a large set of brain image database with longitudinal observations, and develop tools to detect fine morphological / functional deviations from estimated normal aging to detect very early change in dementia. We collaborate with Brain Bank group to conduce PET-pathology comparison which enable us to establish clinical significance of PET examinations. We tackle not only Alzheimer's disease, but also non-Alzheimer type dementias such as dementia with Lewy bodies and tauopathies

2. Research on amyloid imaging for clinical implementation
In the mid-term plan of 2013-2017, we strongly promote research on amyloid imaging for the clinical implementations. We participate in multi-center dementia studies of national and international scales such as World Wide ADNI studies and DIAN-Japan study in which we are in charge of Amyloid PET Core. We promote clinical trials of diagnostic and therapeutic pharmaceuticals for dementia, and settle on a clinical guideline of amyloid imaging.

3. Application of PET techniques for clinical gerontology research and medicine
We apply various PET techniques to gerontology research in understanding normal brain function and its aging, and age related brain disorders. We also provide selected PET diagnostic methods as advanced medical service of the hospital.

Visiting Scientists: Naonori Ohno, M.D. (Tokyo Medical and Dental University), Etsuko Imabayashi, M.D., Ph.D. (National Center of Neurology and Psychiatry), Masahiko Suzuki, M.D., Ph.D. (Jikei University), Keiichi Kawasaki (Jikei University), Kazuhiro Ishii, M.D., Ph.D. (Tsukuba University), Tadanori Fukami, Ph.D. (Yamagata University), Toshimitsu Musha, Ph.D. (Brain Functions Laboratory)

Technical and administrative staff: Airin Onishi, R.N., Eisuke Haneda, Ph.D., Mika Tanaka, M.Sci.

Collaborating staff of TMGH: Aya M Tokumaru, M.D., Ph.D., Keigo Shimoji, M.D., Ph.D., Kimiteru Ito, M.D., Ph.D., Naoki Yokokawa, R.T., Tatsufumi Osawa, R.T., Makoto Senoo, Ph.C.

1. 1. Murai H, Suzuki Y, Kiyosawa M, Tokumaru AM, Ishiwata K, Ishii K. Cerebral glucose metabolism in the striate cortex positively correlates with fractional anisotropy values of the optic radiation in patients with glaucoma. Clin Experiment Ophthalmol. 2015 Apr 22. doi: 10.1111/ceo.12543.
2. 2. Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, Senda K, Murayama S, Ishii K, Takao M, Ghetti B, Ironside JW, Catafau AM, Stephens AW, Mueller A, Koglin N, Hoffmann A, Roth K, Reininger C, Schulz-Schaeffer WJ. Florbetaben PET imaging to detect amyloid plaques in Alzheimer disease: Phase 3 study. Alzheimr & Dementia 2015 Mar 28. pii: S1552-5260(15)00060-6. doi: 10.1016/j.jalz.2015.02.004.
3. 3. Ishibashi, K., Onishi, A., Fujiwara, Y., Ishiwata, K., Ishii, K. : Relationship between Alzheimer's disease-like pattern of ¹⁸F-FDG and fasting plasma glucose levels in cognitively normal volunteers. J Nucl Med, J Nucl Med, 2015;56(2):229-33.
4. 4. Hatsuta H, Takao M, Ishii K, Ishiwata K, Saito Y, Kanemaru K, Arai T, Suhara T, Shimada H, Shinotoh H, Tamaoka A, Murayama S. Amyloid β accumulation assessed with ¹¹C-Pittsburgh compound B PET and postmortem neuropathology. Accepted in Curr Alzheimer Res 2015;12(3):278-286.
5. 5. Ohno N, Murai H, Suzuki Y, Kiyosawa M, Tokumaru AM, Ishii K, Ohno-Matsui K. Alteration of the optic radiations using diffusion-tensor MRI in patients with retinitis pigmentosa. Br J Ophthalmol. 2015 Jan 30. pii: bjophthalmol-2014-305809. doi: 10.1136/bjophthalmol-2014-305809.
6. 6. Fukasawa R, Hanyu H, Shimizu S, Kanetaka H, Sakurai H, Ishii K. Identification of diabetes-related dementia: Longitudinal perfusionSPECT and amyloid PET studies. J Neurol Sci 2015;349:45-51
7. 7. Ishibashi, K., Miura, Y., Oda, K., Ishiwata, K., Mizusawa, H. and Ishii, K. : Alzheimer's disease-like pattern of ¹⁸F-FDG uptake during a hyperglycemia state and negative ¹¹C-PiB binding in a patient with mild cognitive impairment. J. Alzheimer's Dis. 2014;42(2):385-9.
8. 8. Ishibashia, K., Ishiwata, K., Toyohara, J., Murayama, S. and Ishii, K. : Regional analysis of striatal and cortical amyloid deposition in patients with Alzheimer's disease. Eur. J. Neurosci. 2014;40(4):2701-6
9. 9. Sakurai, R., Fujiwara, Y., Yasunaga, M., Takeuchi, R., Murayama, Y., Oba, H., Sakuma, N., Suzuki, H., Oda, K., Sakata, M., Toyohara, J., Ishiwata, K., Shinkai, S. and Ishii, K. : Regional cerebral glucose metabolism and gait speed in healthy community-dwelling older women. J. Gerontol. A Biol. Sci. Med. Sci. 2014;69(12):1519-27.
10. 10. Momose T, Nariai T, Kawabe T, Inaji M, Tanaka Y, Watanabe S, Maehara T, Oda K, Ishii K, Ishiwata K, Yamamoto M. Clinical benefit of ¹¹C methionine PET imaging as a planning modality for radiosurgery of previously irradiated recurrent brain metastases. Clin Nucl Med 2014; 39(11):939-943.
11. 11. Piché M, Watanabe N, Sakata M, Oda K, Toyohara J, Ishii K, Ishiwata K, Hotta H. Basal ?-opioid receptor availability in the amygdala predicts the inhibition of pain-related brain activity during heterotopic noxious counter-stimulation. Neurosci Res 2014;81-82: 78-84.
12. 12. Sengoku R, Matsushima S, Murakami Y, Fukuda T, Tokumaru AM, Hashimoto M, Suzuki M, Ishiwata K, Ishii K, Mochioet S. ¹¹C-PiB-PET imaging of encephalopathy associated with cerebral amyloid angiopathy. Int. Med., 2014;53(17):1997-2000.
13. 13. Hiura, M., Nariai, T., Ishii, K., Sakata, M., Oda, K., Toyohara, J. and Ishiwata, K. : Changes in cerebral blood flow during steady-state cycling exercise: a study using oxygen-15-labeled water with PET. J. Cereb. Blood Flow Metab., 2014; 34(3): 389-396.
14. 14. Ishibashi, K., Oda, K., Ishiwata, K. and Ishii, K. : Comparison of dopamine transporter decline in a patient with Parkinson's disease and normal aging effects. J. Neurosci. Res., 2014; 339(1-2): 207-209.
15. 15. Suzuki, Y., Kiyosawa, M., Wakakura, M., Mochizuki, M., Ishiwata, K., Oda, K. and Ishii, K. : Glucose hypermetabolism in the thalamus of patients with drug-induced blepharospasm. Neuroscience 2014; 264: 240-249.
16. 16. Hiraoka, K., Tashiro, M., Grobosch, T., Maurer, M., Oda, O., Toyohara, O., Ishii, K., Ishiwata, K. and Yanai, K. : Brain histamine H1 receptor occupancy measured by PET after oral administration of levocetirizine, a non-sedating antihistamine. Expert Opin Drug Saf 2015;14(2):199-206
17. 17. Imabayashi E, Matsuda H, Tabira T, Arima K, Araki N, Ishii K, Yamashita F, Iwatsubo T & Japanese Alzheimer's Disease Neuroimaging Initiative. Comparison between brain CT and MRI for voxel-based morphometry of Alzheimer's disease. Brain and Behavior 2013; 3(4): 487-493.
18. 18. Nariai, T., Inaji, M., Tanaka, Y., Hiura, M., Hosoda, C., Ishii, K., Ohno, K. : PET molecular imaging to investigate higher brain dysfunction in patients with neurotrauma. Acta Neurochir Suppl., 2013;118: 251-254.
19. 19. Ueda M, Nakajima N, Nagayama H, Nishiyama Y, Ishii K, Katayama Y. Therapeutic response to pramipexole in a patient with multiple system atrophy with predominant Parkinsonism: Positron emission tomography and pharmacokinetic assessments. Intern Med 2013;52(15):1731-1735.
20. 20. Takahashi R, Ishii K, Michio S, Kengo I, Ishii K, Kato T, Makishi Y, Nishio T, Ikari Y, Takeshi I, Japanese Alzheimer's Disease Neuroimaging Initiative. Equal sensitivity of early and late scans after injection of FD for the detection of Alzheimer pattern: an analysis of 3D PET data from J-ADNI, a multi-center study. Ann Nucl Med 2013;27:452-459.
21. 21. Suzuki Y, Kiyosawa M, Wakakura M, Ishiwata K, Oda K, Ishii K. A patients with hemidystonia and blepharospasm following traumatic injury. J Neurol Neurophysiol 2013;4(3):153. dio:10.4172/2155-9562.1000153
22. 22. Watanabe N, Ishii K, Hotta H, Oda K, Sakata M, Toyohara J, Ishiwata K. Differential human brain activity induced by two perceptually indistinguishable gentle cutaneous stimuli. NeuroReport 2013, 24:425-430.
23. 23. Murai H, Suzuki Y, Kiyosawa M, Tokumaru AM, Ishii K, Mochizuki M. Positive correlation between the degree of visual field defect and optic radiation damage in glaucoma patients. Jpn J Ophthalmol 2013;57(3):257-262.
24. 24. Sakurai Y, Ishii K, Sonoo M, Saito Y, Murayama S, Iwata A, Hamada K, Sugimoto I, Tsuji S, Mannen T. Progressive apraxia with micrographia presenting as corticobasal syndrome showing extensive Pittsburgh compound B uptake. J Neurol 2013; 260:1982-1991.
25. 25. Shimada, H., Ishii, K., Ishiwata, K., Oda, K., Suzukawa, M., Makizako, H., Doi, T., Suzuki, T. : Gait adoptability and brain activity during unaccustomed treadmill walking in healthy elderly females. Gait Posture 2013 Jun;38(2):203-8.
26. 26. Saito Y, Ishii K, Sakuma N, Kawasaki K, Oda K, Mizusawa H. Neural Substrates for Semantic Memory of Familiar Songs: Is threre an interface between lyrics and melodies? PLoS ONE 7(9):e46354.
27. 27. Sugimoto, A., Koyama, S., Midorikawa, A., Futamura, A., Ishiwata, K., Ishii, K., Miller, M.W. and Kawamura, M. : Is this a new type of primary prosopagnosia, both progressive apperceptive? Neuropsychiat. Dis. Treat., 2012;8:169-173.
28. 28. Mishina, M., Kimura, Y., Naganawa, M., Ishii, K., Oda, K., Sakata, M., Toyohara, J., Kobayashi, S., Katayama, Y. and Ishiwata, K. : Differential effects of age on human striatal adenosine A₁ and A_A2 receptors. Synapse 2012;66(9):832-839.
29. 29. Villemagne, V.L., Klunk, W.E., Mathis, C.A., Rowe, C.C., Brooks, D.J., Hyman, B.T., Ikonomovic, M.D., Ishii, K., Jack, C.R., Jagust, W.J., Johnson, K.A., Koeppe, R.A., Lowe, V.J., Masters, C.L., Montine, T.J., Morris, J.C., Nordberg, A., Petersen, R.C., Reiman, E.M., Selkoe, D.J., Sperling, R.A., Van Laere, K., Weiner, M.W. and Drzezga, A. : Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer's disease. Eur. J. Nucl. Med. Mol. Imaging, 2012;39:209-219.
30. 30. Shimizu, M., Suzuki, Y., Kiyosawa, M., Wakakura, M., Ishii, K., Ishiwata, K. and Mochizuki, M. Glucose hypermetabolism in the thalamus of patients with hemifacial spasm. Mov. Disord., 2012;27(4):519-525.
31. 31. Morooka, M., Kubota, K., Minamimoto, R., Furuhata, M., Abe, H., Ito, K., Miyata, Y., Okasaki, M., Ishii, K. and Ishiwata K. : ¹⁸F-FDG and ¹¹C-methionine PET/CT findings in a case of anti-NMDA receptor encephalitis. Clin. Nucl. Med., 2012;37(4):400-402.
32. 32. Suzuki, Y., Emoto, H. and Kiyosawa M. : Hemifacial spasm - A review and update. Neuro-ophthalmology Japan, 2012;29:111-118.

33. 33. Catalan, M.J., Ishii, K., Bara-Jimenez, W. and Hallett, M. : Reorganization of human somatosensory cortex in hand dystonia. J. Mov. Disorders, 2012;5:5-8.

34. 34. Koyama, S., Kobayakawa, M., Tachibana, N., Masaoka, Y., Homma, I., Ishii, K. and Kawamura, M. : Neuropsychological and radiological assessments of two cases of apparent idiopathic rapid eye movement sleep behaviour disorder. Eur. Neurol., 2012;67:18-25.

35. 35. Suzuki, Y., Nariai, T., Kiyosawa, M., Mochizuki, M., Kimura, Y., Oda, K., Ishii, K. and Ishiwata, K. : Increased adenosine A₁ receptor levels in hemianopia patients after cerebral injury: an application of PET using ¹¹C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine. Clin. Nucl. Med., 2012;37(12):1146-1151.