Article Introduction

In October 2021, the Hyeonseok Jeong team at St. Mary's Hospital in Incheon, South Korea, first investigated the effects of low-intensity tFUS on Regional Cerebral Metabolic Rate of Glucose (rCMRglu) and cognitive function in AD patients.

Highlights

1. tFUS can improve cognitive function, executive function, and memory in AD patients;
2. After tFUS intervention, the local brain glucose metabolism rate increased in AD patients.

1.Material and method

▲ Figure 1. Experimental flowchart. tFUS， Transcranial focused ultrasound; MRI， Magnetic resonance imaging; CT， Computed tomography; PET， Positron emission tomography; NP， Neuropsychological testing

Parameter settings：The patient lies comfortably on the treatment chair, the operating doctor evenly smears the ultrasonic hydrogel on the contact area between the patient's ultrasonic probe and scalp, and injects 10 μ L/kg of MB into the right hippocampus of the patient within one minute by intravenous catheterization. Immediately afterwards, the patient's hippocampus was stimulated using the following ultrasound parameters: fundamental frequency (f0)=250kHz, pulse duration (TBS)=20ms, pulse repetition frequency (PRF)=2Hz, and duty cycle (DC)=4%. The average intensity of spatial peak pulses (Isppa) is 0.5-3W/cm2, and the average intensity of spatial peak times (Ispta) is 0.02-0.12W/cm2.

Prognosis：Scan the patient's head MRI 30 minutes after the end of treatment to observe changes in the brain. One day after the end of treatment, the patient underwent another MRI scan to evaluate the stimulation target rCMRglu level. Combined with neuropsychological tests, the patient's memory, executive ability, and overall cognitive function were re evaluated. Two weeks after prognosis, PET-CT will be performed on the patient to track and observe for any adverse reactions or events.

2.Experimental result

Neurophysiological tests：The results of neuropsychological tests after tFUS intervention showed that AD patients had slight improvements in overall cognitive function (MMSE), executive function, and memory.

▲ Table 1. MMSE, Mini Mental State Examination; CDR， Clinical Dementia Grading Scale; CDR-SOB, CDR Overall Functional Evaluation Scale; RCFT, Rey complex graphic testing; n/a， Not evaluated, due to the patient's inability to read or cooperate; SVLT-E， Seoul Language Learning Test - Elderly Edition; K-CWST， Korean Strut Color Word Test; COWAT， Controlled oral word association test.

Imaging examination：MRI and PET images showed that after low-intensity tFUS intervention, rCMRglu in the right superior frontal gyrus (6.6%, P<0.001), middle right cingulate gyrus (5.5%, P<0.001), and left fusiform gyrus (5.4%, P<0.001) of patients significantly increased (P=0.001).

▲Figure 2. Changes in local brain glucose metabolism rate (rCMRglu) after tFUS stimulation. Compared to baseline, there was an increase (red yellow) or decrease (blue-green) in rCMRglu in patients during follow-up. a) The coordinate system refers to the coordinate system of the Montreal Institute of Neurology.

3.Conclusion

This article suggests that the use of low-intensity transcranial focused ultrasound stimulation (tFUS) can have beneficial effects on brain glucose metabolism and cognitive function in AD patients. With its high-precision spatial resolution and significant depth penetration capability, tFUS is expected to become a novel non-invasive neural regulatory tool for regulating cortical and deep brain neurons in AD patients.