A multi-echo magnetization transfer imaging method for simultaneous detection of iron deposition and neuromelanin

Through the multi-echo magnetization transfer magnetic resonance imaging method, the multi-echo gradient echo sequence is combined with the magnetization transfer sequence, which solves the problem of neuromelanin and iron deposition measurement in the prior art, realizes a comprehensive analysis of the early diagnosis and pathogenesis of PD, and has important clinical application potential.

CN114994584BActive Publication Date: 2025-09-02SHANDONG PROVINCIAL HOSPITAL AFFILIATED TO SHANDONG FIRST MEDICAL UNIVERSITY (SHANDONG PROVINCIAL HOSPITAL)
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Patent Information

Application Number
CN202210666866.0
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-06-13
Publication Date
2025-09-02
Estimated Expiration
2042-06-13

AI Technical Summary

Technical Problem

Existing magnetic resonance imaging technology is difficult to accurately measure neuromelanin and iron deposition simultaneously, and the data collection time is long, which affects the early diagnosis and pathogenesis of PD.

Method used

Multi-echo magnetization transfer magnetic resonance imaging method is used to combine the multi-echo gradient echo sequence with the magnetization transfer sequence to achieve a scan to obtain neuromelanin, iron deposition and quantitative magnetic susceptibility images, reducing scanning time and improving accuracy.

Benefits of technology

Simultaneous detection of neuromelanin and iron deposition is achieved, which reduces scanning time, provides a comprehensive analysis of early diagnosis and pathogenesis of PD, and has important clinical application potential.

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Abstract

The present invention relates to a multi-echo magnetization transfer magnetic resonance imaging (MMT) method for simultaneously detecting iron deposition and neuromelanin content in the substantia nigra and locus coeruleus. By optimizing the existing NM-MRI sequence and employing a multi-echo (6 TE values) MMT method, NM-MRI images, SWI images, and QSM images can be simultaneously obtained. The MMT MMT method innovatively combines a multi-echo gradient echo sequence with a MMT sequence, enabling rapid and efficient acquisition through a single sequence. Simultaneously, it explores two key mechanisms of PD pathogenesis, eliminating the need for image registration and enabling further exploration of the correlation between iron deposition and neuromelanin signals.
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Description

Technical Field

[0001] The invention relates to a multi-echo magnetization transfer imaging method for simultaneously detecting iron deposition and neuromelanin, and belongs to the technical field of magnetic resonance imaging. Background Art

[0002] Neuromelanin is a key intermediate formed during dopamine synthesis by motor neurons in the substantia nigra and is stored in organelles. In normal individuals, neuromelanin levels in the substantia nigra increase annually and stabilize after age 65. Pathological studies have confirmed a high correlation between neuromelanin levels in the substantia nigra and the number of dopaminergic neurons. This means that measuring neuromelanin levels in the substantia nigra zona compacta can indirectly infer the extent of dopaminergic neuron necrosis. Studies have shown that by the time Parkinson's disease (PD) patients develop clinical symptoms, over 30% of the total number of dopaminergic neurons in the substantia nigra have already been apoptotic, while neuromelanin levels are only 50%-60% of those in normal individuals. PD is a chronic, progressive disease. We hypothesize that rapid dopamine neuron apoptosis is already initiated in the preclinical stages, with a corresponding decrease in neuromelanin levels. Therefore, measuring neuromelanin levels in the substantia nigra has the potential to diagnose PD early. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) sequences utilize the short T1 properties of melanin to visually visualize neuromelanin in vivo. Previous studies have shown that neuromelanin levels in the substantia nigra and locus coeruleus are significantly lower in Parkinson's disease patients compared to age- and sex-matched controls, closely associated with decreased dopamine function and noradrenergic function. This research further confirms the potential value of NM-MRI sequences in the early diagnosis and treatment assessment of Parkinson's disease.

[0003] Abnormal iron accumulation is believed to contribute to the pathogenesis of Parkinson's disease (PD). Iron can promote the aggregation of α-synuclein under oxidative stress, thereby inducing the formation of Lewy bodies. Abnormal iron accumulation in the substantia nigra and nigrostriatal regions often indicates degeneration and necrosis of dopaminergic neurons and projection fibers within the nigrostriatal pathway, and is correlated with the onset and severity of PD, as well as drug response. Susceptibility-weighted magnetic resonance imaging (SWI) can noninvasively assess brain tissue iron content, quantitatively analyzing parameters such as phase value, effective transverse relaxation rate, quantitative sensitivity, and QSM.

[0004] NM-MRI and SWI are the two most important magnetic resonance imaging methods currently used to study PD. Current technical methods are relatively mature. For example, Chinese patent document CN 113164063 A discloses an exemplary system, method, and computer-accessible medium for determining a patient's dopamine function. It can measure the content of neuromelanin in the substantia nigra to reflect the degree of apoptosis of dopaminergic neurons, determine the dopamine function in the striatum, and provide an imaging basis for the early diagnosis of PD. Chinese patent document CN 102743173 B discloses a method for non-invasively measuring the iron content of brain tissue. It can non-invasively measure the iron content of different brain regions in brain tissue to reflect the degeneration of neurons in brain tissue. However, the current problem is whether abnormal iron deposition affects the accurate measurement of neuromelanin in the NM-MRI sequence. The relevant research evidence is controversial and the conclusion has not reached a consensus. In addition, it takes a long time to collect data, and the imaging principles of the two sequences are quite different. It is difficult to achieve accurate alignment of the resulting sequence to realize the study of the relationship between the two substances. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention optimizes the existing NM-MRI sequence and employs a multi-echo (6 TE values) magnetization transfer MRI method to simultaneously acquire NM-MRI, SWI, and QSM images. This innovative combination of a multi-echo gradient echo sequence with a magnetization transfer sequence allows for simultaneous investigation of two key mechanisms in the pathogenesis of PD using a single acquisition sequence. The resulting images do not require registration, allowing for further investigation of the correlation between iron deposition and neuromelanin signaling.

[0006] Explanation of terms:

[0007] 1. QSM: Quantitative susceptibility mapping, which stands for quantitative magnetic susceptibility mapping in Chinese, is a relatively new imaging technology. Compared with traditional contrast imaging, QSM's most significant feature is that image contrast is derived entirely from the image phase rather than the amplitude of the magnetic susceptibility signal, and reflects the magnetic susceptibility effect of different substances in a magnetic field.

[0008] 2. Multi-echo magnetization transfer MRI method: It mainly uses a multi-echo gradient echo sequence combined with a magnetization transfer sequence to obtain multiple important parameters such as T2* relaxation, QSM, MTR and different contrast images in a single scan.

[0009] 3. SWI: abbreviation of susceptibility weighted imaging, which means susceptibility-weighted magnetic resonance imaging in Chinese.

[0010] 4. NM-MRI: The abbreviation of neuromelanin sensitive MRI, which means neuromelanin sensitive sequence magnetic resonance imaging in Chinese.

[0011] 5. T1WI: T1weighted image, T1 weighted image.

[0012] The technical solution of the present invention is:

[0013] A multi-echo magnetization transfer imaging method for simultaneously detecting iron deposition and neuromelanin, comprising the steps of:

[0014] 1) Acquire a three-dimensional sagittal T1WI sequence and reconstruct axial and coronal images for positioning in subsequent multi-echo magnetization transfer MRI sequences;

[0015] 2) a multi-echo magnetization transfer MRI sequence was called, and the midbrain region was scanned, positioned perpendicular to the anterior wall of the fourth ventricle;

[0016] 3) After the scan is complete, phase and amplitude maps are acquired for 5-10 echo times (TEs). The echo time corresponding to the best neuromelanin signal in the substantia nigra and locus coeruleus is selected as the shortest echo time, and the resulting amplitude map is used as the neuromelanin-sensitive sequence magnetic resonance imaging (NM-MRI) map. The window width and window position of the amplitude map corresponding to the shortest echo time are adjusted, and signals with signal intensity higher than that in the cerebral peduncle are defined as high signals, i.e., neuromelanin signals. This allows for the observation of neuromelanin signals in the substantia nigra and locus coeruleus, enabling qualitative analysis of the neuromelanin content in these regions.

[0017] Multiple echo times TE are selected to outline the change curve of tissue signal value in different TE, so as to obtain the corresponding QSM diagram and quantitatively analyze the content of iron deposition in different brain regions. Studies have shown that the field map fitted using 5-10 echoes is more accurate, the reconstructed magnetic susceptibility distribution map has a higher signal-to-noise ratio, and better magnetic susceptibility contrast of cranial nuclei can be obtained.

[0018] 4) As the echo time (TE) value increases, the magnetic sensitivity of the obtained image to paramagnetic substances increases. The echo time that best corresponds to the magnetic sensitivity of the substantia nigra corpuscles 1 is selected, and the amplitude map corresponding to this echo time is used as the magnetic susceptibility weighted imaging (SWI) map. Signals with signal intensity lower than that in the cerebral peduncle are defined as signals of iron deposition. This allows for direct observation of the iron deposition content in the substantia nigra and locus coeruleus, enabling qualitative analysis of the iron deposition content in the substantia nigra and locus coeruleus. It also enables qualitative observation of changes in the signal of the substantia nigra corpuscles 1 in the dorsolateral substantia nigra and identification of changes in the swallowtail sign.

[0019] 5) Post-processing the phase and amplitude maps corresponding to different echo times (TE) obtained in step 3) to obtain QSM maps. Post-processing is a well-known technique and mainly includes field pattern fitting, background field removal, and magnetic susceptibility inversion. The QSM map is used to quantitatively calculate the magnetic susceptibility of brain tissue, which reflects the iron deposition content in the substantia nigra and locus coeruleus.

[0020] The existing imaging technology, NM-MRI, can measure the content of neuromelanin in the substantia nigra. However, the existing imaging technology, SWI, has a relatively long scanning time, and the data obtained can only obtain the NM-MRI signal value in the substantia nigra, and cannot simultaneously obtain relevant information on iron deposition. Because during the progression of PD, the apoptosis of dopaminergic neurons also causes corresponding changes in iron content. The apoptosis of neurons reflected by a single neuromelanin content and the degeneration of nerve fibers corresponding to iron deposition are difficult to explain the heterogeneity of clinical symptoms, drug responses, and prognosis of all PD patients. The relationship between the two is crucial for further revealing the pathogenesis of PD. The present invention adopts a multi-echo magnetization transfer magnetic resonance imaging method to achieve a sequence of simultaneous acquisition of data on neuromelanin and iron deposition in the substantia nigra and locus coeruleus, comprehensively analyzing the pathogenesis of PD from two different perspectives and further exploring the relationship between iron deposition and neuromelanin.

[0021] Multi-echo magnetization transfer MRI (MTI) primarily utilizes a multi-echo gradient echo sequence combined with a magnetization transfer sequence to acquire multiple important parameters in a single scan. Magnetization transfer imaging (MTI) selectively saturates macromolecules with significant water-macromolecule interactions using off-resonance saturation pulses. This technique is primarily used to suppress the signal from background tissue in MR angiography (MRA) and enhance T1-weighted images. Another application of MTI is to enhance the signal in diseased tissue, where altered protein-water interactions result in less suppression from the MT pulse. The magnetization transfer ratio (MTR) is the only quantitative parameter of this sequence. Synthetic MRI can generate different contrast-weighted images and quantifications based on tissue property measurements from a single acquisition. The magnetization saturation pulse can be followed by different readout sequences, such as gradient echo and fast spin echo. This invention innovatively combines a multi-echo gradient echo sequence with a magnetization transfer sequence. T2* relaxation, QSM, MTR, and different contrast images can be acquired in a single acquisition. Using this invention, these parameters can be acquired simultaneously in a single scan, thereby reducing scan time.

[0022] According to the preferred embodiment of the present invention, in step 2), the specific imaging parameters used in the multi-echo magnetization transfer magnetic resonance imaging sequence are as follows: repetition time TR is 60ms, field of view FOV is 220mm×220mm, acquisition matrix is ​​328×316, flip angle is 30°, voxel size is 0.66×0.66×2.0mm3 , the layer thickness is 2 mm, the layer interval is 0, the number of layers is 20, the parallel acquisition acceleration factor is 2, and the scanning time is 6 minutes and 14 seconds.

[0023] According to the preferred embodiment of the present invention, in step 3), the six echo times (TEs) are 7.5 ms, 15.5 ms, 23.5 ms, 31.5 ms, 39.5 ms, and 47.5 ms, respectively. Considering that more TE settings increase the time required, we ultimately determined that a TE of six times provides a good balance between spatial and temporal resolution of the sequence.

[0024] Preferably, according to the present invention, in step 3), when the echo time TE is 7.5 ms, the high neuromelanin signal in the substantia nigra and locus coeruleus is best displayed, and the echo time TE of 7.5 ms is set as the shortest echo time.

[0025] Preferably, according to the present invention, in step 4), when the echo time TE is 31.5 ms, the magnetic sensitivity of the substantia nigra corpuscles 1 is optimal.

[0026] Preferably, according to the present invention, in step 3), the content of neuromelanin is quantitatively analyzed by outlining the area of ​​the high signal region, or the relative signal ratio of the substantia nigra and locus coeruleus is measured, where the relative signal ratio of the substantia nigra is substantia nigra signal value / cerebral peduncle signal value; the signal ratio of the locus coeruleus is locus coeruleus signal value / cerebral peduncle signal value.

[0027] Preferably according to the present invention, in step 3), the window width is 300 and the window level is 500.

[0028] The beneficial effects of the present invention are:

[0029] 1. The present invention adopts a multi-echo magnetization transfer MRI method, innovatively combining a multi-echo gradient echo sequence with a magnetization transfer sequence. This allows the acquisition of parameters such as T2* relaxation, QSM, MTR, and different contrast images in a single scan, thereby reducing the scan duration.

[0030] 2. This invention utilizes multi-echo magnetization transfer MRI, which allows for precise registration of images acquired within a single scan without extensive correction. This technology is suitable for studying the relationship between neuromelanin and iron deposition in patients with Parkinson's disease (PD). This technology is readily applicable in clinical practice, and our research has demonstrated its potential value in the early diagnosis, treatment, and prognosis of PD. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is a sequence localization map for the multi-echo magnetization transfer magnetic resonance imaging method;

[0032] Figure 2Amplitude maps of six TEs (7.5 ms, 15.5 ms, 23.5 ms, 31.5 ms, 39.5 ms, and 47.5 ms, respectively) obtained using a multi-echo magnetization transfer MRI sequence in the middle layer of the substantia nigra;

[0033] Figure 3a This is a neuromelanin imaging (NM-MRI) image of the substantia nigra obtained by multi-echo magnetization transfer magnetic resonance imaging in a normal person;

[0034] Figure 3b Susceptibility-weighted imaging (SWI) images of normal subjects obtained under multi-echo magnetization transfer magnetic resonance imaging;

[0035] Figure 3c This is a quantitative susceptibility imaging (QSM) image of a normal person obtained under multi-echo magnetization transfer magnetic resonance imaging;

[0036] Figure 3d This is a neuromelanin imaging (NM-MRI) image of the substantia nigra obtained by multi-echo magnetization transfer magnetic resonance imaging in patients with PD;

[0037] Figure 3e Susceptibility-weighted imaging (SWI) images of PD patients obtained under multi-echo magnetization transfer magnetic resonance imaging;

[0038] Figure 3f Quantitative susceptibility imaging (QSM) images of PD patients obtained under multi-echo magnetization transfer magnetic resonance imaging;

[0039] Figure 4a This is a neuromelanin image of the locus coeruleus obtained in a normal person using multi-echo magnetization transfer magnetic resonance imaging.

[0040] Figure 4b This is a neuromelanin image of the locus coeruleus obtained by multi-echo magnetization transfer magnetic resonance imaging in a PD patient. DETAILED DESCRIPTION

[0041] The present invention will be further described below with reference to the embodiments and the accompanying drawings, but is not limited thereto.

[0042] Example 1

[0043] A multi-echo magnetization transfer imaging method for simultaneously detecting iron deposition and neuromelanin, comprising the steps of:

[0044] 1) After the participant is positioned, a three-dimensional sagittal T1WI sequence is acquired, and axial and coronal images are reconstructed for positioning of the subsequent multi-echo magnetization transfer MRI sequence.

[0045] 2) Invoke a multi-echo magnetization transfer MRI sequence and scan the midbrain region, positioned perpendicular to the anterior wall of the fourth ventricle; e.g. Figure 1 As shown; Figure 1 In the figure, the area between the top and bottom lines is the scanning range, and the middle line is one of the scanning levels.

[0046] 3) After the scan is complete, phase and amplitude maps are acquired for 5-10 echo times (TEs). The echo time corresponding to the best neuromelanin signal in the substantia nigra and locus coeruleus is selected as the shortest echo time, and the resulting amplitude map is used as the neuromelanin-sensitive sequence magnetic resonance imaging (NM-MRI) map. The window width and window position of the amplitude map corresponding to the shortest echo time are adjusted, and signals with signal intensity higher than that in the cerebral peduncle are defined as high signals, i.e., neuromelanin signals. This allows for the observation of neuromelanin signals in the substantia nigra and locus coeruleus, enabling qualitative analysis of the neuromelanin content in these regions.

[0047] Multiple echo times TE are selected to outline the change curve of tissue signal value in different TE, so as to obtain the corresponding QSM map and quantify the iron deposition content in different brain regions. Studies have shown that the field map fitted using 5-10 echoes is more accurate, the reconstructed magnetic susceptibility distribution map has a higher signal-to-noise ratio, and better magnetic susceptibility contrast of cranial nuclei can be obtained.

[0048] 4) As the echo time TE value increases, the magnetic sensitivity of the obtained image to paramagnetic substances increases. The echo time that best corresponds to the observation of the magnetic sensitivity of the substantia nigra corpuscles 1 is selected, and the amplitude map corresponding to the echo time is used as the magnetic susceptibility weighted imaging (SWI) map. The signal with a signal intensity lower than that in the cerebral peduncle area is defined as the signal of iron deposition, thereby directly observing the content of iron deposition in the substantia nigra and locus coeruleus area, realizing the qualitative analysis of the content of iron deposition in the substantia nigra and locus coeruleus area, and being able to qualitatively observe the changes in the signal of the substantia nigra corpuscles 1 in the dorsolateral part of the substantia nigra and identify the changes in the swallowtail sign.

[0049] 5) Post-process the phase and amplitude maps corresponding to different echo times (TEs) obtained in step 3) to obtain QSM maps. This post-processing involves field pattern fitting, background field removal, and magnetic susceptibility inversion. The QSM map is used to quantitatively calculate brain tissue magnetic susceptibility, which is used to reflect the iron deposition content in the substantia nigra and locus coeruleus. Specifically, the brain tissue magnetic susceptibility is determined by locating a specific area and using the signal intensity value within that area. The brain tissue magnetic susceptibility is then used to reflect the iron deposition content in the substantia nigra and locus coeruleus.

[0050] The existing imaging technology, NM-MRI, can measure the content of neuromelanin in the substantia nigra. However, the existing imaging technology, SWI, has a relatively long scanning time, and the data obtained can only obtain the NM-MRI signal value in the substantia nigra, and cannot simultaneously obtain relevant information on iron deposition. Because during the progression of PD, the apoptosis of dopaminergic neurons also causes corresponding changes in iron content. The apoptosis of neurons reflected by a single neuromelanin content and the degeneration of nerve fibers corresponding to iron deposition are difficult to explain the heterogeneity of clinical symptoms, drug responses, and prognosis of all PD patients. The relationship between the two is crucial for further revealing the pathogenesis of PD. The present invention adopts a multi-echo magnetization transfer magnetic resonance imaging method to achieve a sequence of simultaneous acquisition of data on neuromelanin and iron deposition in the substantia nigra and locus coeruleus, comprehensively analyzing the pathogenesis of PD from two different perspectives and further exploring the relationship between iron deposition and neuromelanin.

[0051] Multi-echo magnetization transfer MRI (MTI) primarily utilizes a multi-echo gradient echo sequence combined with a magnetization transfer sequence to acquire multiple important parameters in a single scan. Magnetization transfer imaging (MTI) selectively saturates macromolecules with significant water-macromolecule interactions using off-resonance saturation pulses. This technique is primarily used to suppress the signal from background tissue in MR angiography (MRA) and enhance T1-weighted images. Another application of MTI is to enhance the signal in diseased tissue, where altered protein-water interactions result in less suppression from the MT pulse. The magnetization transfer ratio (MTR) is the only quantitative parameter of this sequence. Synthetic MRI can generate different contrast-weighted images and quantifications based on tissue property measurements from a single acquisition. The magnetization saturation pulse can be followed by different readout sequences, such as gradient echo and fast spin echo. This invention innovatively combines a multi-echo gradient echo sequence with a magnetization transfer sequence. T2* relaxation, QSM, MTR, and different contrast images can be acquired in a single acquisition. Using this invention, these parameters can be acquired simultaneously in a single scan, thereby reducing scan time.

[0052] Example 2

[0053] The multi-echo magnetization transfer imaging method for simultaneously detecting iron deposition and neuromelanin provided in Example 1 is different in that:

[0054] In step 2), the specific imaging parameters used for the multi-echo magnetization transfer MRI sequence are as follows: repetition time TR is 60 ms, field of view FOV is 220 mm × 220 mm, acquisition matrix is ​​328 × 316, flip angle is 30°, and voxel size is 0.66 × 0.66 × 2.0 mm. 3, the layer thickness is 2 mm, the layer interval is 0, the number of layers is 20, the parallel acquisition acceleration factor is 2, and the scanning time is approximately 6 minutes and 14 seconds.

[0055] In step 3), after the scan is completed, phase images and amplitude images of six echo times TE are obtained; wherein the six echo times TE are 7.5 ms, 15.5 ms, 23.5 ms, 31.5 ms, 39.5 ms, and 47.5 ms, respectively.

[0056] The purpose of selecting multiple TEs is to outline the curve of changes in tissue signal values ​​in different TEs, so as to obtain the corresponding QSM diagram and quantify the iron deposition content in different brain regions. Studies have shown that the field map fitted using 5-10 echoes is more accurate, the reconstructed magnetic susceptibility distribution map has a higher signal-to-noise ratio, and better magnetic susceptibility contrast of cranial nuclei can be obtained. However, considering that the more TE settings, the more time it takes, we finally determined that 6 TE times can take into account both the spatial resolution and temporal resolution of the sequence.

[0057] By adjusting the window width and window level, in this embodiment, the window width is 300 and the window level is 500.

[0058] When TE = 7.5ms, neuromelanin in the substantia nigra and locus coeruleus showed obvious high signal as NM-MRI sequence;

[0059] For images with TE=7.5ms, the content of neuromelanin in the substantia nigra and locus coeruleus can be intuitively displayed by adjusting the window width and window position, thereby indirectly reflecting the degree of apoptosis of dopaminergic neurons in the substantia nigra zona compacta and noradrenergic neurons in the locus coeruleus.

[0060] Signal intensity and high signal volume can also be measured using semi-quantitative and fully automated quantitative techniques. In this example, the area of ​​the high signal region is delineated to quantitatively analyze neuromelanin content. Alternatively, the relative signal ratio of the substantia nigra and locus coeruleus can be measured: the substantia nigra relative signal ratio is calculated as substantia nigra signal value / cerebral peduncle signal value; the locus coeruleus relative signal ratio is calculated as locus coeruleus signal value / cerebral peduncle signal value.

[0061] In step 4), when TE = 31.5 ms, the susceptibility weight is high and the paramagnetic material shows a significant low signal, which is used as the susceptibility-weighted imaging (SWI) sequence;

[0062] By using TE = 31.5ms, the deposition of paramagnetic iron in the midbrain region can be visually observed, and changes in the substantia nigra corpuscle 1 signal in the dorsolateral part of the substantia nigra can be qualitatively observed to identify changes in the swallowtail sign, thereby identifying the possibility of Parkinson's syndrome.

[0063] Quantitative susceptibility imaging (QSM) images can be obtained through multiple TE calculations, which are used to quantitatively calculate the magnetic susceptibility of brain tissue, that is, to quantitatively analyze the content of iron deposition in the substantia nigra and locus coeruleus.

[0064] The multi-echo magnetization transfer MRI method can simultaneously obtain data of 6 different TE values ​​in one scan, such as Figure 2 As shown in the figure, according to the directions of the arrows, they are the amplitude diagrams corresponding to 7.5ms, 15.5ms, 23.5ms, 31.5ms, 39.5ms, and 47.5ms.

[0065] When the participants were normal, the obtained substantia nigra multi-echo magnetization transfer MRI was as follows Figure 3a 、 Figure 3b and Figure 3c As shown, Figure 3a (TE=7.5ms) The substantia nigra neuromelanin high signal is full, crescent-shaped, and has clear edges. Figure 3b (TE=31.5ms) The substantia nigra and red nucleus showed obvious low signal, indicating obvious iron deposition. Figure 3c (QSM image) The amount of iron deposits in different brain regions of the midbrain can be quantitatively calculated.

[0066] When the participants were PD patients, the obtained substantia nigra multi-echo magnetization transfer MRI was as follows Figure 3d 、 Figure 3e and Figure 3f As shown in the figure, compared with normal people, the high signal in the substantia nigra of PD patients is significantly reduced, especially in the bilateral lateral part. The degree of iron deposition in the substantia nigra is heavier than that in normal people. SWI shows obvious low signal and higher magnetic susceptibility.

[0067] like Figure 4a As shown, the white arrows indicate the locus coeruleus area. In normal subjects, the bilateral locus coeruleus areas have full signals and clear edges.

[0068] like Figure 4b As shown in the figure, the bilateral locus coeruleus of PD patients has reduced signal and blurred edges, suggesting excessive apoptosis of noradrenergic neurons, which is highly correlated with the non-motor symptoms of PD patients.

[0069] The present application adopts a multi-echo magnetization transfer magnetic resonance imaging method to innovatively combine a multi-echo gradient echo sequence with a magnetization transfer sequence, and can obtain multiple parameters through a single scan acquisition.

[0070] By collecting images corresponding to 6 different TE values, the correlation between iron deposition and neuromelanin signal in the substantia nigra and locus coeruleus was studied.

[0071] By post-processing and analyzing the phase and amplitude maps of the six TE images, a QSM map is obtained, which can be used to quantitatively analyze the iron content in areas such as the substantia nigra and locus coeruleus, thereby inferring the degree of degeneration of neurons and neural pathways.

[0072] The iron deposition and neuromelanin content in the substantia nigra obtained by comprehensive multi-echo magnetization transfer magnetic resonance imaging sequences can be cross-analyzed with information such as Parkinson's disease subtypes, severity, drug response and prognosis, exploring the relationship between the two pathological mechanisms of PD, which is crucial for further clarifying the individual heterogeneity of PD.

Claims

1. A multi-echo magnetization transfer imaging method for simultaneous detection of iron deposition and neuromelanin, characterized in that: Including steps: 1) Acquire a three-dimensional sagittal T1WI sequence and reconstruct axial and coronal images for positioning in subsequent multi-echo magnetization transfer magnetic resonance imaging sequences; 2) a multi-echo magnetization transfer magnetic resonance imaging sequence was called, and the midbrain region was scanned, positioned perpendicular to the anterior wall of the fourth ventricle; 3) After the scan is completed, phase and amplitude maps are obtained for 5-10 echo times (TEs); the echo time corresponding to the best neuromelanin signal display in the substantia nigra and locus coeruleus is selected as the shortest echo time, and the obtained amplitude map is used as the neuromelanin-sensitive sequence magnetic resonance imaging (NM-MRI) map; the window width and window position of the amplitude map corresponding to the shortest echo time are adjusted, and signals with signal intensity higher than that in the cerebral peduncle are defined as high signals, i.e., neuromelanin signals, thereby observing the neuromelanin signals in the substantia nigra and locus coeruleus, and achieving qualitative analysis of the neuromelanin content in the substantia nigra and locus coeruleus; 4) As the echo time (TE) value increases, the magnetic sensitivity of the obtained image to paramagnetic substances increases. The echo time that best corresponds to the magnetic sensitivity of the substantia nigra corpuscles 1 is selected, and the amplitude map corresponding to this echo time is used as the magnetic susceptibility weighted imaging (SWI) map. Signals with signal intensity lower than that in the cerebral peduncle region are defined as signals of iron deposition. This allows for direct observation of the iron deposition content in the substantia nigra and locus coeruleus regions, enabling qualitative analysis of the iron deposition content in the substantia nigra and locus coeruleus regions. It is also possible to qualitatively observe changes in the signal of the substantia nigra corpuscles 1 in the dorsolateral substantia nigra and identify changes in the swallowtail sign. 5) Post-processing the phase and amplitude maps corresponding to different echo times TE obtained in step 3) to obtain QSM maps. The QSM maps are used to quantitatively calculate the magnetic susceptibility of brain tissue, which reflects the content of iron deposition in the substantia nigra and locus coeruleus based on the magnetic susceptibility of brain tissue.

2. The multi-echo magnetization transfer imaging method for simultaneous detection of iron deposition and neuromelanin according to claim 1, characterized in that: In step 2), the specific imaging parameters used in the multi-echo magnetization transfer MRI sequence are as follows: repetition time TR is 60 ms, field of view FOV is 220 mm × 220 mm, acquisition matrix is ​​328 × 316, flip angle is 30°, and voxel size is 0.66 × 0.66 × 2.0 mm 3 , the layer thickness is 2 mm, the layer interval is 0, the number of layers is 20, the parallel acquisition acceleration factor is 2, and the scanning time is 6 minutes and 14 seconds.

3. The multi-echo magnetization transfer imaging method for simultaneous detection of iron deposition and neuromelanin according to claim 1, characterized in that: In step 3), after the scan is completed, the phase diagram and amplitude diagram of 6 echo times TE are obtained, and the 6 echo times TE are 7.5ms, 15.5ms, 23.5ms, 31.5ms, 39.5ms, and 47.5ms respectively.

4. The multi-echo magnetization transfer imaging method for simultaneous detection of iron deposition and neuromelanin according to claim 3, characterized in that: In step 3), when the echo time TE is 7.5 ms, the high signal of neuromelanin in the substantia nigra and locus coeruleus is best displayed, and the echo time TE of 7.5 ms is set as the shortest echo time.

5. The multi-echo magnetization transfer imaging method for simultaneous detection of iron deposition and neuromelanin according to claim 3, characterized in that: In step 4), when the echo time TE is 31.5 ms, the magnetic sensitivity of the substantia nigra corpuscles 1 is optimal.

6. The multi-echo magnetization transfer imaging method for simultaneous detection of iron deposition and neuromelanin according to claim 1, characterized in that: In step 3), the content of neuromelanin is quantitatively analyzed by outlining the area of ​​the high signal region, or the relative signal ratio of the substantia nigra and locus coeruleus is measured. The relative signal ratio of the substantia nigra is the substantia nigra signal value / cerebral peduncle signal value; the signal ratio of the locus coeruleus is the locus coeruleus signal value / cerebral peduncle signal value.

7. The multi-echo magnetization transfer imaging method for simultaneous detection of iron deposition and neuromelanin according to claim 1, characterized in that: In step 3), the window width is 300 and the window level is 500.

Citation Information

Patent Citations

  • Noninvasive method for determining iron content in brain tissue

    CN102743173B

  • System, method and computer-accessible medium for neuromelanin-sensitive magnetic resonance imaging as a non-invasive proxy measure of dopamine function in the human brain

    CN113164063A

  • Neuromelanin image reconstruction method and device, electronic equipment and storage medium

    CN111681184A

  • Parkinson's disease diagnosis apparatus and method

    WO2020055039A1