Application of low field nuclear magnetic resonance technology in life science

Magnetic resonance imaging is widely used in clinic because of its non-invasive, rapid, high resolution and high contrast. Especially in the diagnosis of tumors, the structure and functional images obtained by using different physical properties of diseased tissues and normal tissues have become an indispensable and important basis for the early diagnosis of primary tumors and tumor metastasis. Tumor formation is a complex process of long-term, multi-factor control, multi-step, multi-gene mutations. Most malignant tumors are of monoclonal origin and exhibit uncontrolled growth. Clinically, when a considerable number of patients seek treatment, the disease has entered the middle and late stages, and the optimal treatment time has been lost. This is one of the reasons for the high tumor mortality rate. Although MRI has all of the above advantages, its low sensitivity does not meet the requirements for early diagnosis of tumors. This is because early tumors and normal tissues differ little in physical properties (eg, T1 and T2), and this small difference in physical properties is not sufficient to produce an image contrast between tumor and normal tissue. In order to solve this problem, people use nuclear magnetic resonance contrast agents to enhance the contrast of tumor and normal tissue images to facilitate early diagnosis of tumors.


Principle of magnetic resonance imaging contrast agent
The MRI signal of the hydrogen nucleus is the MRI signal source of various tissues, and the MRI contrast agent does not generate a signal, and its function is to change the relaxation time of the hydrogen nuclear system inside the tissue. Contrast with the surrounding tissue. MRI signal intensity is related to physical and chemical parameters, such as proton density spin-lattice relaxation time T1, spin-spin relaxation time T2. The T1 and T2 parameters control the contrast intensity of the image. The change in hydrogen proton density is small in soft tissue, so T1-weighted imaging and T2-weighted imaging are used in the diagnosis. The function of the contrast agent depends on its concentration in the tissue and the proton density and motion in the tissue.
The MRI contrast agent must be a magnetic substance that interacts magnetically with the hydrogen nucleus. The contrast agent mainly changes the signal intensity by affecting T1 and T2. According to the principle, the contrast agent can be classified into a T1 type preparation and a T2 type preparation. The T1 formulation is an increase in the intensity of the signal in T1-weighted imaging. T2 formulations reduced signal intensity in T2-weighted imaging. Which type of contrast agent is used clinically depends on the characteristics of the tissue. The process of T1 shortening requires that the protons of hydrogen and the magnetic part of the contrast agent act directly, that is, the hydrogen nuclei of the water molecules should be as close as possible to the magnetic particles to achieve relaxation enhancement. For example, liposome-encapsulated Gd-DTPA has a T1 enhancement effect that is weaker than the same concentration of Gd-DTPA, since liposomes limit the proximity of external water molecules to Gd-DTPA. The T2 shortening process is a remote effect that interferes with T2 by the inhomogeneity of the local magnetic environment of the T2 formulation. Inclusion of the T2 formulation into liposomes, T2 relaxation is enhanced because aggregation of the liposomes produces a greater change in the local magnetic environment.
The relationship between T1 and T2 values ​​and contrast agent concentration in the tissue is as follows:


R1 and R2 are the relaxation rates of the contrast agent, and describe the effect of the contrast agent on T1 and T2 in the tissue, and [c] is the concentration of the contrast agent uniformly distributed in the tissue. The reciprocal of equations (1), (2) T1, and T2 has a simple linear relationship with the concentration of the contrast agent. R1 and R2 depend on the structure of the contrast agent. For the T1 type preparation , the contrast agent is mainly close to the water molecule, and the T2 type preparation depends on the concentration of the magnetic substance.

MRI tumor diagnosis
In 1971, Damadian found that the T1 and T2 values ​​of the proton relaxation time of water molecules in tumor tissues were larger than those of normal tissues. In 1978, Mallard, Hutchison and Lauterbur obtained the first human head with NMR equipment of 0.04T~0.085T. , chest and abdomen images. Since then , MRI has been highly valued by the scientific community for its outstanding advantages such as radiation-free damage, non-destructive, reagent-free intrusion and the ability to study living and dynamic processes from the molecular level to the overall organ system. Rapidly, this new medical imaging diagnostic technology has rapidly spread in medical centers and large and medium-sized hospitals in various countries, and has become an important tool for clinical diagnosis.
The principle of MRI diagnostic technology is mainly to use different protons in different tissues of organisms to generate different resonance signals under the influence of external magnetic field. The strength of the signal depends on the content of water in the tissue and the relaxation time of protons in water molecules. It can effectively detect tissue necrosis, ischemia and various malignant lesions (such as tumors) for early diagnosis.

Show results

Rat|| Contrast agent|| Heart, liver|| T1 weighted image|| Coronal plane, cross section|| Layer thickness 3.5mm
The instrument uses the MiniMR-60 NMR rat imaging system. The image is a T1-weighted cross-section and coronal plane. The sampling parameters are as follows: FOV=100mm×100mm, TR=400ms, TE=19ms, layer thickness 3.5mm, layer spacing 1mm, The cumulative number of times 16, K space size is 192 × 256. The imaging results showed that after injection of contrast agent, the heart and liver of the rat became brighter and gradually darkened with the prolongation of metabolic time.

MRI coronal plane before and after angiography in rats (image click to enlarge)

MRI cross section of contrast agent metabolism in rats (click to enlarge)

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