Histologically, an acute hematoma consists of RBCs trapped in a matrix of fibrin interspersed with small pools of serum. This microscopic heterogeneity and clumping of RBCs results in spin dephasing, loss of signal on T2/T2*-weighted images, and restricted diffusion of water molecules. A hematoma is embedded within, and often intermixed with, tissue or fluid from its site of origin. The final MR appearance is thus a weighted sum of contributions from the hematoma itself as well as background tissues.
Hemoglobin and its Derivatives
Hemoglobin is comprised of four subunits, each containing a heme group with an iron (Fe) atom nestled at its center. Each Fe center has one free coordination site to which oxygen and other small molecules may transiently bind.
Molecular binding creates conformational changes in the Hb molecule and alters its electronic configuration. This, in turn, effects its MR imaging properties, especially at high fields.
Four different hemoglobin species are commonly recognized: oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), methemoglobin (met-Hb), and hemichromes, whose structures appear below.
These hemoglobin species typically evolve in the order shown over the first 1-2 weeks after initial hematoma formation. Ultimately, the hemoglobin molecule is enzymatically cleaved into multiple small fragments. Iron atoms are released, but coalesce by the thousands into large, chunky metallo-protein complexes known as ferritin and hemosiderin. Ferritin and hemosiderin are engulfed by invading macrophages and ultimately deposit along the walls of old hematoma cavities.
(< 12 hours)
When arterial blood extravasates to form a hyperacute hematoma, over 95% of the hemoglobin is in the oxyhemoglobin (oxy-Hb) state. Oxy-Hb has no unpaired electrons, and like most tissues, is weakly diamagnetic. At this stage the MR signal is primarily determined by the microstructural properties of the clot rather than magnetic effects of hemoglobin, with isointensity on T1-weighted images and slight hyperintensity on T2-weighted images. Diffusion is restricted in the center of the clot due to increase in viscosity and reduction in extracellular space secondary to packed erythrocytes.
(12 hours - 2 days)
Within a few hours, oxygen begins to to dissociate from the clot's hemoglobin, with increasing formation of deoxyhemoglobin (deoxy-Hb). This begins at the periphery of the hematoma and gradually spreads inward. Deoxy-Hb, with 4 unpaired electrons per iron atom, is strongly paramagnetic. Because the deoxy-Hb remains concentrated within RBCs, it produces susceptibility-induced distortions of the local magnetic fields, resulting in dephasing and loss of signal on T2/T2*-weighted images. T1 images remain iso-intense in both the hyperacute and acute stages.
Early Subacute Hematoma
(2 days - 1 week)
Methemoglobin (met-Hb) has 5 unpaired electrons and is even more paramagnetic than its precursor, deoxy-Hb. The configuration of the molecule as a result of iron being in the ferric [Fe(III)] state allows access of water very close to the iron center for the very first time. This allows so-called inner sphere relaxation to occur, resulting in very short T1 values (and corresponding brightness on T1-weighted images). Because met-Hb continues to be compartmentalized intracellularly, however, local magnetic susceptibility effects persist and the hematoma remains dark on T2/T2*-weighted images.
Late Subacute Hematoma
(1 week - 2 months)
Late in the first week lysis of RBCs occurs and met-Hb now spills into the extracellular space. The release of met-Hb from its intracellular compartment eliminates the local susceptibility-induced T2/T2* dephasing, so its signal now becomes bright on T2-weighted images. The molecule itself remains intact, with 5 unpaired electrons, inner-sphere bonding of water and high signal on T1-weighted images.
(> 2 months)
The final stages of hemoglobin degradation include transformation to hemichromes that have lost all paramagnetic properties. Hemichromes, along with other protein fragments and hemoglobin breakdown products are dissolved/suspended in water (with long T1 and T2 values) in the central residual cavity of the old hematoma. Around the periphery of the cavity, thousands of iron atoms are scavenged by macrophages and glial cells into aggregates know as ferritin and hemosiderin. Ferritin and hemosiderin are superparamagnetic, with powerful susceptibility effects resulting in marked shortening of T2 and T2* along the walls of the old hematoma cavity.
Mnemonic devices may be useful to help recall the signal changes at different times after hemorrhage. Although I do not use these myself, I feel obligated to report one that is in common use among US Radiology residents, originated by my colleague Jim Smirniotopoulos:
Advanced Discussion (show/hide)»
The "Iddy Biddy Baby" mnemonic confuses signals at the center from the periphery of chronic hematomas. The center of chronic hematomas usually have high water content, rendering them bright, not dark, on T2-weighted images. The periphery of chronic hematomas contain hemosiderin, rendering them slightly dark on T2-weighted images but profoundly dark on T2*/SW images.
Quick Quiz: Do you remember the difference between plasma and serum?
Answer: Serum is plasma with fibrinogen and other clotting factors removed.
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How does the appearance of subarachnoid hemorrhage differ from parenchymal hemorrhage on MRI?
What are the different forms of hemoglobin and why do they have different magnetic properties?