MRI is very sensitive to the changes of water in tissues, so it is necessary to study the MRI signal characteristics of water.
Water in human tissues is divided into free water and bound water. The so-called free water is the water whose molecules are free and not combined with other tissue molecules. The natural movement frequency of free water is high and significantly higher than the incoming frequency of protons. In the large molecules around the protein is also attached to some water molecules, forming a hydration layer, these water molecules are called bound water, bound water because of the attachment to the large molecules, its natural movement frequency will be significantly lower and closer to the proton inlet frequency. Therefore, the T1 value of free water is very long, while bound water can shorten the T1 value of the tissue.
Tissues with an increased component of free water will show a decrease in signal intensity in T1WI, such as brain edema. If the proportion of bound water increases, it will show a relative increase in signal intensity or even high signal on T1WI, such as cysts containing mucus components and viscous pus in abscesses. In abscesses or some tumors such as astrocytomas, because of the presence of bound water in addition to free water in cystic fluid or pus, the signal intensity will be higher in T1WI to varying degrees than in cerebrospinal fluid, which is basically composed of free water.
Cerebral edema
Brain disorders are a high priority for clinical MRI examinations, and cerebral edema is one of the most common underlying pathological changes in brain disorders and can be seen in a variety of brain tissue disorders. Therefore, it is important to recognize the MRI manifestations of brain edema for the MRI diagnosis of brain diseases.
Pathologically, brain edema is divided into three types, namely vasogenic edema, cytotoxic edema and interstitial brain edema.
1. Angiogenic cerebral edema
Vascular-derived edema is the most common type of brain edema, and the mechanism of occurrence is mainly the disruption of the blood-brain barrier, with plasma leaking out of the blood vessels into the extracellular space. Vascular-derived cerebral edema is commonly seen in a variety of brain disorders such as peri-tumor, perihematoma, inflammation, cerebral infarction, and trauma. Angiogenic edema occurring around tumors or hematomas is mostly seen in the white matter of the brain, while the gray matter of the brain is relatively less prone to interstitial cerebral edema due to its denser structure. However, interstitial cerebral edema caused by inflammation, cerebral infarction and trauma can occur in both the gray matter and white matter of the brain.
Vascular-derived edema is mainly dominated by an increase in free water, and therefore shows low signal on T1WI and high signal on T2WI. T2WI is more sensitive than T1WI in responding to interstitial cerebral edema. The water molecules present in the extracellular space are relatively free to diffuse, so interstitial brain edema does not show high signal on DWI, and the measured ADC values are often higher than those of normal brain tissue.
Sometimes on T1WI and T2WI, the tumor is not easily distinguished completely from the surrounding vascular-derived brain edema, and Gd-DTPA enhancement scans can be performed. Tumors and perivascular-derived edema around hematomas are generally not enhanced because the blood-brain barrier is slightly disrupted and Gd-DTPA generally does not easily pass through the slightly disrupted blood-brain barrier. Inflammation and cerebral infarction can cause more serious blood-brain barrier disruption, and Gd-DTPA can pass through, so there is often enhancement, and it is more often seen in the gray matter area of the brain.
2.Cytotoxic brain edema
Cytotoxic edema is mostly caused by cerebral ischemia and hypoxia. Nerve cells cannot perform anaerobic enzymes and are therefore very sensitive to hypoxia. After a few minutes of ischemia, the ATP production of nerve cells is significantly reduced, and the sodium-potassium pump, which depends on the work of ATP, becomes malfunctioning, sodium will be retained in the cells, the intracellular osmotic pressure will increase, and water molecules in the extracellular space will enter the cells, thus causing cell swelling and narrowing of the extracellular space, which is cytotoxic edema.
Cytotoxic edema is commonly found around hyperacute cerebral infarction or acute or subacute cerebral infarction lesions. In fact, cytotoxic edema and vascular-derived edema often coexist during the development and progression of cerebral infarct lesions, only that one type of edema predominates at different stages of the lesion. In the initial stage of brain tissue ischemia, cytotoxic edema tends to predominate, followed by vasogenic edema, and when cell disintegration and serious disruption of the blood-brain barrier occur, vasogenic edema will predominate, and finally foci of cerebral softening will appear
Early cytotoxic edema may have no significant signal intensity changes in T1WI and T2WI due to only a slight elevation of total water in brain tissue. Sometimes there is only a slight change in signal intensity in acute cerebral infarction, and conventional MRI methods can help in the detection of lesions in two ways.
(1) Although T1WI is not as sensitive as T2WI in response to signal changes, it shows structural changes better than T2WI, and morphological changes such as narrowing of the cerebral sulcus and swelling and blurring of the cerebral gyrus may appear on T1WI before the appearance of signal abnormalities in acute infarcts in the cortex.
(2) T2WI is more sensitive to signal changes caused by edema than T1WI, but the mildly increased signal of cerebral gray matter in early infarction is easily masked by higher signal of cerebrospinal fluid, at which time the signal of cerebrospinal fluid is suppressed if FLAIR sequence is used, which is beneficial to the display of cortical abnormal signal.
The diffusion-weighted imaging of water molecules (DWI) technique, which has been introduced in clinical practice in recent years, is currently the most sensitive method for detecting cytotoxic edema. In cytotoxic edema, the diffusion movement is significantly restricted due to the entry of extracellular water into the cell, while the water molecules inside the cell are bound by the cell membrane and other structures; at the same time, the extracellular space is narrowed due to cell swelling, and the diffusion of water molecules in it is also more restricted to varying degrees compared to normal tissue. The signal attenuation of cytotoxic edema in DWI is significantly less than that of normal brain tissue due to the restricted diffusion of water molecules, thus presenting high signal and significantly lower ADC values. DWI techniques are now widely used for the early diagnosis of acute cerebral ischemia. It should be noted that some other lesions such as partial tumors, hematomas, active multiple sclerotic foci, and partial abscesses can also show high signal on DWI, which should be differentiated by combining medical history and conventional MRI and enhancement scans.
3.Interstitial cerebral edema
Interstitial hydrocephalus is mainly secondary to hydrocephalus caused by various reasons. As a result of increased intracerebroventricular pressure, cerebrospinal fluid enters the white matter around the ventricles through the ventricular canal membrane. Interstitial hydrocephalus is often found in the white matter surrounding the lateral ventricles, with both free and bound water elevated. The signal is lower than that of normal cerebral white matter on T1WI but slightly higher than that of cerebrospinal fluid, and significantly higher than that of normal cerebral white matter on T2WI but slightly lower than that of cerebrospinal fluid. Interstitial cerebral edema does not show high signal on DWI, and ADC values are often mildly to moderately elevated in the lesion area.
Hemorrhage
Hemorrhage can occur in many lesions in the human body, and is more common in central nervous system diseases. Cranial hemorrhage can occur in the intracerebral, subarachnoid, subdural, and epidural spaces and can be caused by vascular sclerosis, vascular malformations, tumors, trauma, inflammation, etc. MRI has unique advantages in demonstrating hemorrhage and determining the timing and cause of hemorrhage. Since intracerebral hematoma is the most common in clinical practice and its signal evolution is more regular, this section will focus on the MRI manifestations of intracerebral hematoma.
1. General evolution of MRI signal of intracerebral hematoma
Generally, intracerebral hematoma can be divided into hyperacute, acute, early subacute, mid subacute, late subacute, and chronic phases.
(1) Hyperacute phase
The hyperacute phase is the immediate stage of hematoma, when the leaked blood has not yet clotted. In fact, this period lasts only a few minutes to tens of minutes and is rarely encountered in clinical practice. The uncoagulated blood in the hyperacute phase exhibits the long T1 and long T2 characteristics of the blood, and therefore appears as a slightly low signal on T1WI and a high signal on T2WI.
(2) Acute phase
It is usually within 2 days after bleeding. In this phase, the cell membrane of erythrocytes remains intact and the intracellular oxygenated hemoglobin releases oxygen to become deoxyhemoglobin. The paramagnetic effect of deoxyhemoglobin causes local magnetic field inhomogeneity and accelerates proton out-of-phase, so the hematoma T2 value is significantly shortened and shows low signal on T2WI or T2*WI. The intracellular deoxyhemoglobin has less influence on the T1 value, so the signal change of the hematoma at this stage is not obvious on T1WI, and it often shows slightly low signal or isosignal.
(3) Subacute early stage
It is usually from day 3 to day 5 after bleeding. The cell membrane of erythrocytes remains intact during this period, and intracellular methemoglobin starts to appear, so this period is also called the intracellular phase of methemoglobin, and the appearance of intracellular methemoglobin generally develops gradually from the periphery to the center of the hematoma. Because of the strong paramagnetic properties of intracellular anhemoglobin, the T1 value of the hematoma is shortened, and therefore the hematoma gradually develops high signal from the periphery to the center on T1WI. The hematoma at this stage does not show high signal on T2WI and generally remains low signal.
(4) Subacute middle stage
It is usually the 6th to 10th day after bleeding. The cell membrane of erythrocytes starts to rupture during this period, and nor-ferric hemoglobin overflows into the extracellular phase, so this period is also called the nor-ferric hemoglobin extracellular phase. The rupture of erythrocytes also generally progresses from the periphery of the hematoma to the center. In this stage, the hematoma still shows high signal on T1WI and gradually spreads from the periphery to the center of the hematoma on T2WI.
(5) Late subacute stage
It is usually 10 days to 3 weeks after bleeding. At this stage, the erythrocytes are completely disintegrated and the hematoma is dominated by ortho-hemoglobin, but macrophages in the periphery of the hematoma engulf the hemoglobin and form iron-containing hemoglobin. The intracellular iron-containing hemoglobin is significantly paramagnetic and will cause local magnetic field inhomogeneity. Therefore, the hematoma in this stage is high signal on T1WI and T2WI, but a low signal ring appears around the hematoma on T2WI.
(6) Chronic phase
This is usually after 3 weeks to several months of bleeding. The hematoma is gradually resorbed or liquefied, and there are obvious deposits of iron-containing heme in the macrophages around the lesion. Therefore, the hematoma gradually evolves into a liquefied foci in this stage, with low signal on T1WI and high signal on T2WI; the surrounding iron-containing hemoglobin shows a low signal ring on T2WI and equal or slightly high signal on T1WI.
2. A few notes on the hemorrhagic MRI signal
What was introduced earlier is the typical pattern of MRI signal evolution of intracerebral hematoma, and the signal changes of intracerebral hemorrhage in some cases in clinical work may not be consistent with it, and the possible reasons are.
(1) individual differences.
(2) the exact time of hemorrhage is difficult to determine.
(3) recurrent bleeding of the lesion.
(4) differences in the size of the lesions.
(5) The MRI signal evolution of the hematoma can vary at different field strengths.
Different physicians may have different opinions on whether CT or MRI should be used for intracerebral hemorrhage. It is generally believed that the MRI presentation of hematoma is complex and the early presentation of hemorrhage is atypical, so CT examination may be preferred for cases with clinical diagnosis of acute intracerebral hemorrhage. For subacute or chronic hematomas, MRI examination is more sensitive than CT and is superior to CT in determining the cause of hemorrhage, and MRI may be preferred.
Iron deposition
Iron is an important metal element that plays an important role in human metabolism. Excessive iron deposition may occur during human metabolism, and iron deposition can be physiological or pathological. MRI is very sensitive to changes in iron content, and this section will briefly introduce the MRI signal characteristics of iron deposition in human tissues. Three main areas are presented.
(1) Iron deposition in the brain.
(2) Hereditary hemochromatosis.
(3) Secondary hemochromatosis.
1. Intracerebral iron deposition
Physiological iron deposition often occurs in the brain, especially in the nucleus accumbens. Studies have shown that there is no obvious iron deposition in the brain tissue of newborns, and as age increases, physiological iron deposition begins in various parts of the brain tissue at different ages. For example, iron deposition in the pallidum begins at 6 months of age, in the substantia nigra at 9-12 months of age, in the red nucleus at 18-24 months of age, and in the dentate nucleus of the cerebellum at 3-7 years of age. The age at which iron deposition begins to appear varies from site to site, and the rate of development also varies; for example, iron deposition in the pallidum begins to be more pronounced, while the shell nucleus begins with a very low iron content, which gradually increases with age and generally does not approach the iron content of the pallidum until about 70 years of age. Physiological iron deposition in the gray matter of the cerebrum and cerebellum is mild, with relatively high levels in the temporal subcortical arcuate fibers, followed by the frontal cerebral white matter and occipital cerebral white matter. In the posterior limb of the internal capsule and the optic radiations, there was almost no iron deposition. The mechanism of this selective iron deposition in brain tissue is currently unknown.
Pathological iron deposition can also occur in some diseases of the brain, such as increased iron deposition in the cerebral cortex of patients with progeria, increased iron deposition in the nucleus accumbens and pallidum in patients with Parkinson’s disease, and increased iron deposition around chronic hematomas.
Iron deposition in brain tissue is mainly intracellular, and intracellular iron mainly causes local magnetic field inhomogeneity, which accelerates proton out-of-phase, and therefore reduces tissue signal on T2WI or T2*WI. The signal change is often insignificant on T1WI or may be slightly high signal, and those with severe iron deposition may also show low signal on T1WI.
It is also important to note that the magnetic susceptibility effect caused by iron deposition is more pronounced in high field strength MRI instruments and therefore easier to show, while minor iron deposition cannot be shown in low field strength MRI instruments.
2. Hereditary hemochromatosis
Hereditary hemochromatosis, also known as primary hemochromatosis, is an autosomal recessive disease. The main problem is that the small intestine mucosa absorbs and transports too much iron into the blood. The iron in the blood accumulates and is gradually deposited as ferritin in liver cells, pancreatic gland epithelial cells, cardiac muscle cells, and joint cartilage cells. It will cause progressive damage to the above cells and eventually can cause cirrhosis, hepatocellular carcinoma, pancreatic insufficiency, cardiomyopathy, joint degeneration and other diseases.
Since the onset of hereditary hemochromatosis is relatively insidious, the clinical manifestations are often already in the middle to late stages. Because of the high intracellular iron content, the liver, pancreas, and myocardium show significantly reduced signal intensity on T1WI and T2WI. The spleen generally has normal signal A few cases may have reduced signal in the spleen. Liver cirrhosis, hepatocellular carcinoma, and cardiac enlargement may also be found.
MRI differentiation between primary hemochromatosis and secondary hemochromatosis
Differentiation points Primary hemochromatosis Secondary iron deposition
Site of iron deposition Liver, pancreas, myocardium Reticuloendothelial system
Liver cirrhosis Often present None
Hepatocellular carcinoma May be present None
Pancreatic signal Decreased Normal
Spleen signal Normal or slightly reduced Significantly reduced
Myocardial signal Reduced May be reduced
Bone marrow signal Normal Decreased
3.Secondary hemochromatosis
Secondary hemochromatosis refers to abnormal iron deposition secondary to chronic hemolytic disease or repeated blood transfusions. In both hemolytic diseases and repeated transfusions, there is a long-term massive destruction of red blood cells, and hemoglobin enters the plasma and is finally phagocytosed and cleared by reticuloendothelial cells in the form of iron-containing hemoglobin. Therefore iron deposition secondary to hemochromatosis occurs mainly in the reticuloendothelial system, such as liver blast cells, spleen, bone marrow, etc., but also in cardiac myocytes. Therefore, the main manifestation is a decreased signal on T1WI and T2WI in the above organs.
The pathogenesis and prognosis of secondary hemochromatosis and primary hemochromatosis are clearly different. Primary hemochromatosis often presents with progressive damage to the involved organs, culminating in functional insufficiency or even tumor development. In secondary hemochromatosis, there is less damage to the iron-deposited organs and the excess iron deposited will be gradually removed after the hemolytic disease improves or the blood transfusion is stopped. The MRI differentiation points between primary and secondary hemochromatosis are listed in Table 4.