A preliminary study on MR amide proton imaging in patients with Alzheimer’s disease and mild cognitive impairment
Rui Wang1, Chunmei Li1, Yongming Dai2, Dantao Peng3, Xuna Zhao4, and Min Chen1

1Radiology, Beijing Hospital, Beijing, China, People's Republic of, 2Philips Heathcare, Shanghai, China, People's Republic of, 3China-Japan Friendship Hospital, Beijing, China, People's Republic of, 4Philips Heathcare, Beijing, China, People's Republic of

Synopsis

The aim of this study is to evaluate the feasibility of MR amide proton transfer (APT) imaging for the detection of cerebral abnormalities in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI), and to explore its clinical utility. Twenty-one AD patients, 11 aMCI patients and 19 normal controls (NC) underwent APT MR imaging. The magnetic resonance ratio asymmetry (MTRasym) values at 3.5ppm of bilateral hippocampi, temporal white matter regions, occipital white matter regions and cerebral peduncles were measured on the oblique APT images. We found that MTRasym(3.5ppm)asym in bilateral hippocampi showed a consistently increasing trend from NC to MCI, to AD. MTRasym(3.5ppm) values of bilateral hippocampi were significantly negatively correlated with MMSE. Our results suggested that APT imaging is a useful tool to diagnose early AD and monitor the disease.

Purpose

AD is known as the leading cause of dementia in elderly. Earlier treatment can hamper the disease process and improve disease prognosis, so the early diagnosis of AD is of a high clinical importance. MCI is an intermediate stage between the expected cognitive decline of normal aging and the more serious decline of AD. APT imaging is a novel molecular MRI technique that detects low-concentration endogenous mobile proteins and peptides in tissue to indirectly reflect intracellular metabolic change and physiological and pathological information in vivo.1 Most current studies about APT focus on tumors and stroke,2 whereas there are few studies in terms of using APT imaging on patients with neurodegenerative disease.3 This study aimed to evaluate the feasibility of using APT imaging to detect cerebral abnormality patients in AD and aMCI at 3 T.

Methods

Twenty-one AD patients (age: 71.3±4.5, M/F:9/12, MMSE: 16.6±6.0, years of education: 9.9±2.9), 11 aMCI patients (age:73.5±4.1, M/F:5/6, MMSE: 25.6±1.4, years of education: 11.2±3.3) and 19 NC(age: 72.3±4.8, M/F:10/9, MMSE: 28.4±1.2, years of education: 10.4±3.2) were enrolled in the study. The MR examinations were performed on a 3T MRI scanner (Achieva TX, Philips Healthcare, Best, The Netherlands), using an eight-channel head coil. APT imaging was based on a single-shot, turbo-spin-echo readout, with the following parameters: repetition time 3000 ms, turbo-spin-echo factor 54, field of view 230mm × 220 mm, matrix 105 × 100; slice thickness 5mm. We used a pseudo-continuous wave, off-resonance RF irradiation (saturation duration 200 ms × 4, inter-pulse delay 10 ms, power level 2 μT) and a multi-offset, multi-acquisition APT imaging protocol. The oblique axial scanning plane is parallel to the long axis of the right hippocampus. The T1-weighted image was used as the anatomical reference to draw regions of interest of bilateral Hippocampi, temporal white matter (TWM), occipital white matter (OWM)and cerebral peduncles (CP) on the oblique axial APT image, as shown in Fig. 1. MTRasym(3.5ppm) were measured for each region. MTRasym(3.5ppm) of cerebral structures among these groups were compared with one-way ANOVA. Controlling for age and years of education, partial correlation analysis was used to investigate the associations between MMSE and the various MR imaging measures among all the subjects.

Results

We found that the compared to normal controls, MTRasym(3.5ppm) values of bilateral hippocampi were increased in aMCI and AD patients, moreover, MTRasym(3.5ppm) in bilateral hippocampi showed a consistently increasing trend from NC to MCI, to AD. In contrast, There was no significant statistically difference in MTRasym(3.5ppm) values of other cerebral structures among three groups (Table 1). MTRasym(3.5ppm) values of bilateral hippocampi were significantly negatively correlated with MMSE (right r= -0.595, P=0.000; left r= -0.552, P=0.000).

Discussion and Conclusions

In the study, MTRasym(3.5 ppm) values of bilateral hippocampi in the patients with aMCI and AD increased, which may be associated with increased abnormal proteins, including Aβ oligomer, Tau, a-synuclein, TDP-43, and so on.4,5 Meanwhile the hippocampus is affected the earliest and most severely in MCI and AD patients.6 No significant elevation of MTRasym(3.5ppm) value in the white matter structures is likely to reflect the regional predilection of AD pathological lesions. In conclusion, the APT imaging, as a non-invasive MRI method, can show sensitively cerebral abnormal metabolite based on increased proteins and peptides in the hippocampus in patients with AD and aMCI, which suggests the technique is a useful tool to diagnose early AD and monitor the disease.

Acknowledgements

No acknowledgement found.

References

1. Zhou J, Payen J, Wilson DA, et al. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nature Med, 2003; 9(8):1085-1090.

2. Zhou J, Tryggestad E, Wen Z, et al. Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nature Med, 2011; 17(1): 130-134.

3. Li C, Peng S, Wang R, et al. Chemical exchange saturation transfer MR imaging of Parkinson's disease at 3 Tesla. Eur Radiol, 2014; 24:2631-9.

4. Larson ME, Lesné SE. Soluble Aβ oligomer production and toxicity. J Neurochem, 2012; 120(Suppl 1): 125-139.

5. Köpke E, Tung YC, Shaikh S, et al. Microtubule-associated protein tau: Abnormal phosphorylation of non-paired helical filament pool n Alzheimer disease. J Biol Chem, 1993; 268: 24374-24384.

6. Du AT, Schuff N, Amend D, et al. Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease. J eurol Neurosurg Psychiatry, 2001; 71: 441-447.

Figures

Figure1. T1WI (A) and APT weighted image (B) were oblique axial planes along the long axis the right hippocampus. Examples of the definition of regions of interest for quantitative analysis. Brown: TWM, purple: OWM, black: CP, red: hippocampus.

Table1. MTRasym(3.5ppm) (mean ± 95% CI) (%) of bilateral hippocampi, TWM, OWM and CP in three groups



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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