(1) Background: Blood brain barrier (BBB) disruption following traumatic brain injury (TBI) results in a secondary injury by facilitating the entry of neurotoxins to the brain parenchyma without filtration. In the current paper, we aimed to review previous dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies to evaluate the occurrence of BBB disruption after TBI. (2) Methods: In electronic databases (PubMed, Scopus, Embase, and the Cochrane Library), we searched for the following keywords: dynamic contrast-enhanced OR DCE AND brain injury. We included studies in which BBB disruption was evaluated in patients with TBI using DCE-MRI. (3) Results: Four articles were included in this review. To assess BBB disruption, linear fit, Tofts, extended Tofts, or Patlak models were used. $K^{Trans}$ and $v_e$ were increased, and the values of $v_p$ were decreased in the cerebral cortex and predilection sites for diffusion axonal injury. These findings are indicative of BBB disruption following TBI. (4) Conclusions: Our analysis supports the possibility of utilizing DCE-MRI for the detection of BBB disruption following TBI.

Methods to improve drug delivery efficiency through blood-brain barrier disruption (BBBD) based on microbubbles and focused ultrasound (FUS) are continuously being studied. However, most studies are being conducted in preclinical trial environments using small animals. The use of the human skull shows differences between the clinical and preclinical trials. BBBD results from preclinical trials are difficult to represent in clinical trials because various distortions of ultrasound by the human skull are excluded in the former. Therefore, in our study, a clinical validation platform based on a preclinical trial environment, using a human skull fragment and a rat model, was developed to induce BBBD under conditions similar to clinical trials. For this, a human skull fragment was inserted between the rat head and a 250 kHz FUS transducer, and optimal ultrasound parameters for the free field (without human skull fragment) and human skull (with human skull fragment) were derived by 300 mV_pp and 700 mV_pp, respectively. BBBD was analyzed according to each case using magnetic resonance images, Evans blue dye, cavitation, and histology. Although it was confirmed using magnetic resonance images and Evans blue dye that a BBB opening was induced in each case, multiple BBB openings were observed in the brain tissues. This phenomenon was analyzed by numerical simulation, and it was confirmed to be due to standing waves owing to the small skull size of the rat model. The stable cavitation doses (SCD_h and SCD_u) in the human skull decreased by 13.6- and 5.3-fold, respectively, compared to those in the free field. Additionally, the inertial cavitation dose in the human skull decreased by 1.05-fold compared to that of the free field. For the histological analysis, although some extravasated red blood cells were observed in each case, it was evaluated as recoverable based on our previous study results. Therefore, our proposed platform can help deduct optimal ultrasound parameters and BBBD results for clinical trials in the preclinical trials with small animals because it considers variables relevant to the human skull.

Background and Objectives: Petechial cerebral hemorrhages can be caused by various factors, such as traumas, cerebral infarctions, and aging, and is related to the disruption of the blood–brain barrier or the cellular damage of blood vessels. However, there is no animal model that recapitulates cerebral petechial hemorrhages. Materials and Methods: Here, we implemented a petechial hemorrhage using a novel technology, i.e., microbubble-assisted focused ultrasound (MB + FUS). Results: This method increases the permeability of the blood–brain barrier by directly applying mechanical force to the vascular endothelial cells through cavitation of the microbubbles. Microbubble-enhanced cavitation has the advantage of controlling the degree and location of petechial hemorrhages. Conclusions: We thus generated a preclinical rat model using noninvasive focal MB + FUS. This method is histologically similar to actual petechial hemorrhages of the brain and allows the achievement of a physiologically resembling petechial hemorrhage. In the future, this method shall be considered as a useful animal model for studying the pathophysiology and treatment of petechial cerebral hemorrhages.