Perihematomal Cerebral Tissue Iron Quantification on MRI Following Intracerebral Hemorrhage in Two Human Subjects: Proof of Principle

Abstract

Spontaneous intracranial hemorrhage (ICH) is a common hemorrhagic stroke subtype with significant neurological sequelae. The management of ICH is usually supportive treatment in the neuro-intensive care setting, while the body humors deal with the hematoma. Treatment of the hematoma is usually expectant management unless there is neurological deterioration caused by mass effect from the hemorrhage. Some minimally invasive techniques have been explored for lysing and evacuating the hematoma, but none of them have gained a stronghold in the routine clinical management of this condition. Studies mainly in animal (rodent and porcine) ICH models have shown the role of bound and unbound iron in causing neurotoxicity following an ICH. There is currently no noninvasive method for assessing iron levels in the cerebral tissue following ICH. Our study intends to explore the role of magnetic resonance imaging (MRI) in establishing iron levels in cerebral tissue at the periphery of the hematoma following an ICH. Initially, an MRI phantom was constructed with varying concentrations of liquid iron preparation in a water bath container. Susceptibility weighted sequences were utilized to scan this phantom to generate T2* signal magnitude measurements corresponding to the iron concentration in the phantom. Encouraged by the reliability of the measurements on the phantom, patients with ICH were then recruited into this experimental study once the inclusion criteria were met. One control and two human subjects had their brains scanned in a 3 T MRI scanner utilizing the same susceptibility weighted sequence. We found that ICH perihematomal brain tissue iron susceptibility signal measurements were 4 times higher than those of the baseline control and normal contralateral brain tissue. Three different baseline measurements (one control and two contralateral normal brain) revealed a level of 0.1 mg/ml of iron concentration in the contralateral brain tissue in the identical anatomical location as the hematoma, typically in the basal ganglia region. T2 * signal measurements in the brain tissue at the periphery of the basal ganglia hematoma at day 7 following hemorrhage revealed iron concentration of 0.4 mg/ml (approximately 4 times the baseline/control) in two human subjects included in the study. These measurements mimic those obtained in published animal ICH model studies.

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

“…Neuronal cell death was observed at a concentration of ~1.0 µg/cm 2 (42). The iron concentration of the brain tissue at the periphery of the hematoma has also been shown to be ~400 mg/l in two human subjects (43). The iron concentration in OE (244.4 mg/l) is almost similar to intracerebral hemorrhage (400 mg/l), suggesting that endometriotic cells may face the crisis of death.…”

Hemorrhagic stroke—Pathomechanisms of injury and therapeutic options

“…4 Unfortunately, white matter injury after ICH has not been well studied. 5 In the current issue, Kang Investigators have demonstrated that just like in rat and pig ICH models 9,10 , tissue iron in the periphery of the hematoma can be picked up in the humans too 11 . The concentration of iron in the hematoma is very high but currently there is no reliable measurement of iron concentration can be performed within it.…”

“…This is coming in the form of magnetic resonance imaging (MRI) which can pick up susceptibility from iron in the hemoglobin and otherwise in the intracellular and extracellular environment. Investigators have demonstrated that just like in rat and pig ICH models, tissue iron in the periphery of the hematoma can be picked up in the humans too. The concentration of iron in the hematoma is very high but currently there is no reliable measurement of iron concentration can be performed within it.…”

“…The concentration of iron in the hematoma is very high but currently there is no reliable measurement of iron concentration can be performed within it. On the other hand, in the periphery of the hematoma, such susceptibility compared to the tissue background can be picked up and quantified in the human subjects . The investigators at University of Michigan have also put forth the hypothesis that whether hemoglobin and its degradation products are within or without red blood cells, it dictates the type of signal on MRI .…”

“…On the other hand, in the periphery of the hematoma, such susceptibility compared to the tissue background can be picked up and quantified in the human subjects. 11 The investigators at University of Michigan have also put forth the hypothesis that whether hemoglobin and its degradation products are within or without red blood cells, it dictates the type of signal on MRI. 12 This phenomenon of T2* non-hypointensity, related to early erythrolysis, demonstrated in the animal models, is being investigated in humans with MRI.…”