Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke

Abstract

Background: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making.

Methods: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm³ and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma.

Results: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R²=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05).

Conclusions: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.

Keywords: blood coagulation; cerebral hemorrhage; fibrin; magnetic resonance imaging; quantitative phase imaging.

Figure 1.

Summary of image processing steps used to quantify the images. The first row (left to right) is fluid attenuation inversion recovery (FLAIR) b0 of diffusion tensor imaging (DTI), and phase and magnitude (MAG) image of multigradient echo. The second row shows the segmented hematoma, edema, and processed fractional anisotropy (FA), mean diffusivity (MD), and quantitative susceptibility maps (QSMs). The third row shows the T1-weighted image (T1w) registration process to the parametric maps, segmented hematoma, perihematomal edema volumes, and matching contralesional homologous regions. The last row illustrates the FA, MD, and QSM values overlaid on a high-resolution anatomic image.

Figure 2.

Qualitative and quantitative analysis of human blood clots. A, T2*-weighted MRI signal contrast in (left to right) water, 70% red blood cells without (RBC WO) calcium chloride (CaCl₂) liquid blood, coagulated plasma with CaCl₂, and 70% red blood cells with (RBC W) CaCl₂ (coagulated blood), respectively. B, Left to Right, The corresponding quantitative susceptibility map of the tubes in A. Coagulated blood showed pockets of clotted blood distributed throughout the tube with higher susceptibility. C, A 3-µm slice of coagulated blood with Martius Scarlet Blue (MSB)–stained displayed pockets of clots randomly distributed as seen in MRI. A high-resolution (60×) image of the clot with MSB stain (C, middle) showed the presence of fibrin (red), red blood cells (RBCs; yellow), and white blood cells (WBCs; blue), whereas hematoxylin and eosin (H&E; C, right) only showed the RBC and WBC. The coagulated plasma with no RBC (D, left to right) illustrates a 3-µm slice section with no pockets of clotted blood, a high-resolution (40×) MSB, and H&E stained with fibrin only. QSM indicates quantitative susceptibility mapping.

Figure 3.

An illustration of the temporal coagulation within hematoma between hyperacute to acute stages on a representative patient with intracerebral hemorrhage. The first row shows the change in contrast within the hematoma over time on a fluid attenuation inversion recovery (FLAIR) image. The second row displays quantitative susceptibility maps (QSMs) at 3 time intervals with a distinct increase in hypointense negative susceptibility in the surrounding perihematomal edema (PHE) at the last time point. The third row illustrates the change in susceptibilities within hematoma and PHE over time overlaid on a T1-weighted image. The last row is a zoomed hematoma volume showing the susceptibility gradient within the hematoma and changes over time. PPM indicates parts per millions; and ROI, region of interest.

Figure 4.

Quantitative changes in imaging metrics are shown using box and whisker plots in the hematoma and perihematomal edema over time. Quantitative temporal changes in the hematoma volume (Ai), susceptibility (Aii), fractional anisotropy (FA; Aiii), and mean diffusivity (MD; Aiv), with a significant dynamic increase in the susceptibility (P<0.0001) and FA (P<0.01). Quantitative temporal changes in the perihematomal edema volume (Bi), susceptibility (Bii), FA (Biii), and MD (Biv), with a significant increase in volume (P<0.05) and decrease in FA (P<0.05). AU indicates arbitrary unit; and ppm, parts per millions.