2. Tissue MR signal: essentials
3. Pulse Sequences
4. Primary intracerebral hemorrhage
5. Ruptured vascular malformation
7. Subdural hematoma
6. Secondary hemorrhage: Infarction, Neoplasia.
1) Short TR, short TE spin echo (or short TI, short TE composite inversion recovery (IR) spin echo) images are used to demonstrate the high signal that develops at some time after the ictus, as early as 10 hours but typically 2-3 days, and persists for a variable length of time, from a few weeks to a few months. The chemical substrate of this signal has been postulated to be methemoglobin, the auto-oxidation product of hemoglobin under certain pH conditions.
2) In the patient suspected of having acute hemorrhage, long TR, long TE images are critical for demonstration of the overall extent of the lesion, including those regions adjacent to the hemorrhage which are abnormally bright because of infarction, neoplasia, gliosis, other primary pathology or secondary acute edema. An acute hematoma may have high, low or mixed signal, depending on its age, its hematocrit, the local pH and oxygen tension, and the field strength of the imaging system. With higher field MR systems (1.0 - 1.5 Tesla), such images have significant signal loss (proportional to the square of the field strength) in portions of the lesion because of the abnormal magnetic susceptibility of hemorrhagic tissue. Magnetic susceptibility is a reflection of local interruptions of the homogeneity of the magnetic field, and such interruptions produced in parts of a hemorrhagic lesion make the image black. Deoxyhemoglobin has been reported to contribute to the increased magnetic susceptibility, but the chemistry of acute hemorrhage is extremely complex and this is reflected in the variability of observed signal changes. Thus, at highest field strengths, the core of the clot may have low signal, due to the presence of deoxyhemoglobin or of intracellular methemoglobin.
Subacute and chronic hemorrhage contains variable amounts of hemosiderin, the intralysosomal crystalline storage form of heme iron. This substance is thought to produce a magnetic susceptibility effect and consequent signal loss on long TR (SE) images. In cases of vascular malformation, the presence of a signal void caused by vascular structures containing flowing blood is a clue to the diagnosis. Such flow voids are best seen on long TR SE images.
3) In order to maximize sensitivity to hemorrhage-induced alterations in magnetic susceptibility, rapid images can be acquired using the GE technique. In this method, the excitation RF pulse is less than 90¡, no refocusing (180¡) pulse is applied, and the echo formed during imaging is a gradient "echo" --brought about by reversal of the read gradient. GE images are essentially maps of T2*, the observed transverse relaxation time. That is, signal intensity is affected by true tissue transverse relaxation (T2) and by inhomogeneities in the magnetic field -- produced by the tissue or the imaging system. GE images have very high sensitivity to acute hemorrhage even at lower field strengths. An important feature of GE images is the very low acquisition time (seconds). This is a significant advantage in cases of acute hemorrhage in which the patient is unable to cooperate; conventional spin-echo images of such patients are often degraded by motion artifact. Moreover, GE images with a very short TE (ca. 12 msec) may be used to produce high signal corresponding to flow, so-called flow-enhanced images. Such phenomena are also responsible for MRA signal.
Time-dependent changes in cerebral hemorrhage are to be expected in regions where changes in the hemoglobin molecule occur due to local alterations in hematocrit, pH, and oxygen tension. Under these conditions, the changing molecular environment produces alterations in the number of unpaired electrons in the heme nucleus as well as chemical changes that make the unpaired electrons more or less accessible to protons. In vivo, extravasated arterial blood, containing mostly oxyhemoglobin, is first deoxygenated, then undergoes auto-oxidation to methemoglobin. As the reticuloendothelial system begins to react to the hemorrhage, hemosiderin, the crystalline storage form of heme iron, begins to accumulate in macrophages and astrocytes. The pace of this process depends on the ability of a given patient's immune system to mobilize and activate cells which provide this scavenger function; over many years, hemosiderin is removed from the brain. The precise correspondence of MR signal changes and chemical changes in this complex process has not yet been verified, and the use of in vitro data to explain MR signals in live patients may not be entirely appropriate. In the future, proper choice of pulse sequences will perhaps reflect an improved understanding of these chemical substrates.
For many years hypertensive hemorrhage was unquestionably the most common cause of primary intracranial bleeding. With improved control of blood pressure, many centers have found this entity to be declining in incidence, with hemorrhage due to amyloid angiopathy (see below) now seen more commonly. Primary hypertensive hemorrhage must be distinguished from cerebral infarction with secondary bleeding on both pathoanatomic and histopathologic grounds --despite the strong association of both with chronic arterial hypertension. Severe, chronic hypertension is associated with microscopic vascular lesions called Charcot- Bouchard or miliary aneurysms. These lesions are the site of vascular rupture in primary hypertensive hemorrhage and are concentrated in the deep grey matter. The common anatomic sites of this type of hemorrhage are, in order of frequency: putamen, thalamus, cerebellum and pons.
The following sequence of events is postulated to occur in hypertensive hemorrhage: A transient elevation of arterial pressure leads to vessel rupture and a very brief period of actual bleeding. Blood dissects through the tissue and accumulates only until rising intracranial pressure results in tamponade of further bleeding, limiting the lesion size. During the period before MR image acquisition, numerous tissue changes occur that have an important impact on the appearance of images ultimately obtained. Brain parenchymal damage and vessel endothelial damage incite edema (cytotoxic and vasogenic) and consequent progressive displacement of adjacent brain structures, as seen in this case. Regions of lowest x-ray attenuation and high MR signal represent high water content in edematous non-hemorrhagic brain. This is best seen with spin-echo images, but is demonstrable with highly T2-weighted GE images as well. A small portion of the lesion, containing the most concentrated blood, is often seen within the hemorrhage. Surrounding this core is usually a mixture of damaged tissue and blood, and MR signal in this region is a combination of high signal from damaged edematous brain and low signal due to diffusion of protons through the local blood-induced field inhomogeneities. The low signal halo seen on T2-weighted SE and GE images represents T2* shortening that is due to local magnetic field gradients (susceptibility differences) produced by abrupt transition from one tissue type (edematous brain) to another (hemorrhagic brain). GE images are quite sensitive to such field inhomogeneities and demonstrate increasing signal loss in the halo with increasing TE.
In the mid-1970's, neuropathologists began to report the strong association of lobar cerebral hemorrhage in elderly patients with the deposition of amyloid in medium-sized cortical and leptomeningeal vessels. Cerebral amyloid angiopathy is now accepted as a major cause of primary intracranial hemorrhage, particularly in those who are normotensive and elderly. Amyloid is a 4200 dalton protein that infiltrates vessel walls, replaces smooth muscle cells in the media, and may make the vessel structurally brittle. It has characteristic staining properties (apple green birefringence with Congo red staining viewed under polarized light) and has been associated with a large number of central nervous system diseases, including Alzheimer's disease, in which it may have a pathogenetic role. Amyloid is also found in brains of normal old people. Hemorrhage due to amyloid angiopathy almost always occurs in the cerebral cortex and subcortical white matter, and lesions often contain a component of subarachnoid blood. The most common anatomic sites are frontal and parietal lobes; the least common are temporal and occipital lobes. These features serve to distinguish amyloid from hypertensive hemorrhage, which usually affects deep grey structures.
CT usually demonstrates a high attenuation region surrounded by a halo of abnormally low attenuation, consistent with acute hemorrhage and secondary edema, respectively. MR images demonstrate a large range of signal intensities, depending on the MR technique employed. For example, the core of the lesion is often a heterogeneous region of very high signal on the short TR, short TE image, an MR characteristic of parenchymal hemorrhage older than a few days; subdural blood can also have this MR appearance in these lesions.
Long TR images show greater signal heterogeneity within the lesion core as a function of increasing TE, probably because of the paramagnetic properties of hemorrhage: the main magnetic field is locally augmented by paramagnetic material and therefore a susceptibility difference is produced. The effect of this phenomenon can be appreciated by comparing the shorter with the longer TE images (e.g.: TE=40 versus TE=80). More proton diffusion through local field inhomogeneity has occurred in the lesion core after 80 ms than after 40 ms, and therefore more of the image contains proton spins that have lost phase coherence, resulting in signal loss. Surrounding the core of the hemorrhage is very high signal consistent with the long T2 of water in edematous tissue.
Serial GE images acquired with increasing TE (e.g.:TE = 12, 30 and 50 msec), will demonstrate progressive signal loss within the lesion core and a change in the subdural signal from high to low. As in the SE images, but to a differing extent, signal intensity reflects the combined contributions of relaxation time and susceptibility difference.
Partly because of high sensitivity to flow in vascular structures, MR represents a significant advance in the non-invasive assessment of patients suspected of vascular malformation. Lesions angiographically both evident and cryptic can be demonstrated by MR in cases with or without clinically documented hemorrhage. A variety of signal profiles may be seen in this disease, depending on the MR technique employed, and the time after ictus.
Acutely (within hours of the ictus), the T1-weighted images usually demonstrate abnormally low signal; the T2-weighted images abnormally high signal. On the GE images, one can often see a black rim that surrounds regions with heterogeneous signal intensity.
To summarize, these are the image features of fresh hematoma: 1) prolongation of bulk T1 and T2 relaxation times within the clot evident usually as high signal on long TR SE images, and 2) edge effects due to differences in magnetic susceptibility within the hemorrhage or between hemorrhage and brain; these effects shorten T2* and are best demonstrated by the GE image. At highest field strengths, the core of the clot may have low signal on T2-weighted images, due to the presence of intracellular methemoglobin or of deoxyhemoglobin. If there is intraventricular bleeding, and if the patient has been maintained in the supine position since the ictus, the clot can form a cast of the lateral ventricles.
Adjacent to the parenchymal hematoma is often the clue to the etiologic diagnosis: a large signal void, and/or several smaller ones nearby, reflect flow in portions of an AVM. These vessels may or may not ultimately be documented at angiography. GE images acquired with very short TE's often have high signal in flow-bearing structures (normal and abnormal blood vessels and the aqueduct of Sylvius), so-called flow enhanced images. Such images are an important source of confirmatory evidence of flow, since signal void seen on long TR images can arise for other reasons, principally calcification. The short TE GE can show a small focus of high signal representing flow within the AVM, a finding that supports the diagnosis.
The angiographically cryptic AVM is often demonstrated by MR. These lesions are known to contain a mixture of abnormal vessels of various sizes, gliotic tissue, and hemosiderin. T1-weighted IR images show a sharply demarcated focus of low signal, while with T2-weighted images, the lesion center is bright, reflecting prolongation of T2 expected in gliotic, hemorrhagic, or edematous tissue; again a black halo can be seen which represents T2* shortening associated with chronic hemorrhage and is postulated to reflect hemosiderin deposition. There is usually no MR evidence for acute edema surrounding theses lesions. Flow in the AVM itself can be seen as a signal void on T2-weighted images. The short TE GE technique, or more recently developed MRA methods, demonstrates flow in arteries, sigmoid sinuses and torcula, and flowing CSF in the upper fourth ventricle. Flow in the AVM itself is not always observed, and when flow effects are not demonstrated, other diagnostic possibilities must be entertained, particularly low-grade glioma.
Pure subdural hematoma (SDH), in which there is rupture of bridging cortical veins and a hematoma not in direct contact with the brain surface, is distinguished pathologically from SDH with adjacent contusion. Acutely, the T1-weighted image demonstrates the hematoma to have signal nearly the same as normal cortex, and an underlying darker irregular band reflecting the acute contusion and edema which has prolonged bulk T1 relaxation. Prolonged T2 relaxation in both regions is reflected in the long TR/TE. These images demonstrate high signal regions usually separated by a narrow strip of very low signal. The narrow strip presumably reflects a boundary between two regions with different magnetic susceptibilities, producing proton dephasing and signal loss as described above. The narrow strip appears wider on the GE than on SE images, a further indication that susceptibility differences are responsible.
Infarction is the most common cause of secondary intracerebral hemorrhage. Its frequency of occurrence as a complication of cerebral infarction (with or without anticoagulant therapy) is not precisely known; MR is more sensitive CT to small hemorrhages, and very small lesions are being seen with increasing frequency. They are thought to result from the reperfusion of necrotic brain after embolic material has migrated distally from the site of occlusion.
Hemorrhage into neoplasm occurs in choreocarcinoma, melanoma, renal cell, bronchogenic carcinoma, pituitary adenoma, glioblastoma multiforme and medulloblastoma. These tumors may present as hemorrhage.