Mechanism of extracellular space changes in cryptococcal brain granuloma revealed by MRI tracer

Nuerbiyemu Abulikemu; Xin Gao; Wei Wang; Qingyuan He; Gang Wang; Tao Jiang; Xiaodong Wang; Yumeng Cheng; Min Chen; Yanran Li; Lulu Liu; Jingjing Zhao; Jin Li; Chunhui Jiang; Yunling Wang; Hongbin Han; Jian Wang

doi:10.3389/fnins.2022.1034091

Mechanism of extracellular space changes in cryptococcal brain granuloma revealed by MRI tracer

Front Neurosci. 2022 Dec 20:16:1034091. doi: 10.3389/fnins.2022.1034091. eCollection 2022.

Authors

Nuerbiyemu Abulikemu^{1

2

3}, Xin Gao⁴, Wei Wang⁵, Qingyuan He^{2

3

6}, Gang Wang^{1

7}, Tao Jiang⁸, Xiaodong Wang⁹, Yumeng Cheng^{2

3}, Min Chen¹⁰, Yanran Li¹, Lulu Liu¹, Jingjing Zhao¹, Jin Li¹, Chunhui Jiang¹, Yunling Wang¹, Hongbin Han^{2

3

6}, Jian Wang^{1

4}

Affiliations

¹ Imaging Center, First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China.
² Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology, Peking University Third Hospital, Beijing, China.
³ Institute of Medical Technology, Peking University Health Science Center, Beijing, China.
⁴ Shanghai Universal Medical Imaging Diagnostic Center, Shanghai University, Shanghai, China.
⁵ Department of Rehabilitation Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
⁶ Department of Radiology, Peking University Third Hospital, Beijing, China.
⁷ Imaging Center, Xi'an Gem Flower Changqing Hospital, Xi'an, China.
⁸ The Animal Experimental Center, Xinjiang Medical University, Ürümqi, China.
⁹ Department of Dermatology, First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China.
¹⁰ Department of Dermatology, Shanghai Key Laboratory of Molecular Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Abstract

Purpose: This study aimed to investigate the changes in extracellular space (ECS) in cryptococcal brain granuloma and its pathological mechanism.

Materials and methods: The animal model of cryptococcal brain granuloma was established by injecting 1 × 10⁶ CFU/ml of Cryptococcus neoformans type A suspension into the caudate nucleus of Sprague-Dawley rats with stereotactic technology. The infection in the brain was observed by conventional MRI scanning on days 14, 21, and 28 of modeling. The tracer-based MRI with a gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a magnetic tracer was performed on the rats with cryptococcal granuloma and the rats in the control group. The parameters of ECS in each area of cryptococcal brain granuloma were measured. The parameters of ECS in the two groups were compared by independent sample t-test, and the changes in ECS and its mechanism were analyzed.

Results: Up to 28 days of modeling, the success rate of establishing the brain cryptococcal granuloma model with 1 × 10⁶ CFU/ml Cryptococcus neoformans suspension was 60%. In the internal area of cryptococcal granuloma, the effective diffusion coefficient D* was significantly higher than that of the control group (t = 2.76, P < 0.05), and the same trend showed in the volume ratio α (t = 3.71, P < 0.05), the clearance rate constant k (t = 3.137, P < 0.05), and the tracer half-life T_1/2 (t = 3.837, P < 0.05). The tortuosity λ decreased compared with the control group (t = -2.70, P < 0.05). At the edge of the cryptococcal granuloma, the D* and α decreased, while the λ increased compared with the control group (D*:t = -6.05, P < 0.05; α: t = -4.988, P < 0.05; λ: t = 6.222, P < 0.05).

Conclusion: The internal area of the lesion demonstrated a quicker, broader, and more extended distribution of the tracer, while the edge of the lesion exhibited a slower and narrower distribution. MRI tracer method can monitor morphological and functional changes of ECS in pathological conditions and provide a theoretical basis for the treatment via ECS.

Keywords: MRI tracer; brain; cryptococcal granuloma; extracellular space; mechanism.