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Simple Summary: Diagnosing brain tumors using minimally invasive methods, such as a liquid biopsy, is challenging due to the blood–brain barrier (BBB). The BBB blocks tumor biomarkers from entering the bloodstream. However, a technique called focused ultrasound with microbubbles (FUS-BBBO) can temporarily open the BBB, thereby potentially increasing the tumor biomarkers in the bloodstream. This systematic review collected data on FUS-BBBO-enhanced liquid biopsy for primary brain tumors. The review included five animal studies and two human studies. Animal studies have shown that biomarker levels were higher in groups subjected to FUS-BBBO compared to control groups. Clinical studies involving 14 patients also showed increased biomarker levels after FUS-BBBO treatment. It is worth noting that using stable cavitation during FUS-BBBO appeared promising for liquid biopsy. Overall, this technique has the potential to improve brain tumor diagnosis and disease monitoring. However, further investigation is necessary to ensure its safe and effective use in the clinical setting. The performance of minimally invasive molecular diagnostic tools in brain tumors, such as liquid biopsy, has so far been limited by the blood–brain barrier (BBB). The BBB hinders the release of brain tumor biomarkers into the bloodstream. The use of focused ultrasound in conjunction with microbubbles has been shown to temporarily open the BBB (FUS-BBBO). This may enhance blood-based tumor biomarker levels. This systematic review provides an overview of the data regarding FUS-BBBO-enhanced liquid biopsy for primary brain tumors. A systematic search was conducted in PubMed and Embase databases with key terms "brain tumors", "liquid biopsy", "FUS" and their synonyms, in accordance with PRISMA statement guidelines. Five preclinical and two clinical studies were included. Preclinical studies utilized mouse, rat and porcine glioma models. Biomarker levels were found to be higher in sonicated groups compared to control groups. Both stable and inertial microbubble cavitation increased biomarker levels, whereas only inertial cavitation induced microhemorrhages. In clinical studies involving 14 patients with high-grade brain tumors, biomarker levels were increased after FUS-BBBO with stable cavitation. In conclusion, FUS-BBBO-enhanced liquid biopsy using stable cavitation shows diagnostic potential for primary brain tumors. Further research is imperative before integrating FUS-BBBO for liquid biopsy enhancement into clinical practice. [ABSTRACT FROM AUTHOR]

Medical image registration is an integral part of various clinical applications including image guidance, motion tracking, therapy assessment and diagnosis. We present a robust approach for mono-modal and multi-modal medical image registration. To this end, we propose the novel shape operator based local image distance (SOLID) which estimates the similarity of images by comparing their second-order curvature information. Our similarity metric is rigorously tailored to be suitable for comparing images from different medical imaging modalities or image contrasts. A critical element of our method is the extraction of local features using higher-order shape information, enabling the accurate identification and registration of smaller structures. In order to assess the efficacy of the proposed similarity metric, we have implemented a variational image registration algorithm that relies on the principle of matching the curvature information of the given images. The performance of the proposed algorithm has been evaluated against various alternative state-of-the-art variational registration algorithms. Our experiments involve mono-modal as well as multi-modal and cross-contrast co-registration tasks in a broad variety of anatomical regions. Compared to the evaluated alternative registration methods, the results indicate a very favorable accuracy, precision and robustness of the proposed SOLID method in various highly challenging registration tasks. [ABSTRACT FROM AUTHOR]

Background: Deformable image registration is increasingly used in radiotherapy to adapt the treatment plan and accumulate the delivered dose. Consequently, clinical workflows using deformable image registration require quick and reliable quality assurance to accept registrations. Additionally, for online adaptive radiotherapy, quality assurance without the need for an operator to delineate contours while the patient is on the treatment table is needed. Established quality assurance criteria such as the Dice similarity coefficient or Hausdorff distance lack these qualities and also display a limited sensitivity to registration errors beyond soft tissue boundaries. Purpose: The purpose of this study is to investigate the existing intensity‐based quality assurance criteria structural similarity and normalized mutual information for their ability to quickly and reliably identify registration errors for (online) adaptive radiotherapy and compare them to contour‐based quality assurance criteria. Methods: All criteria were tested using synthetic and simulated biomechanical deformations of 3D MR images as well as manually annotated 4D CT data. The quality assurance criteria were scored for classification performance, for their ability to predict the registration error, and for their spatial information. Results: We found that besides being fast and operator‐independent, the intensity‐based criteria have the highest area under the receiver operating characteristic curve and provide the best input for models to predict the registration error on all data sets. Structural similarity furthermore provides spatial information with a higher gamma pass rate of the predicted registration error than commonly used spatial quality assurance criteria. Conclusions: Intensity‐based quality assurance criteria can provide the required confidence in decisions about using mono‐modal registrations in clinical workflows. They thereby enable automated quality assurance for deformable image registration in adaptive radiotherapy treatments. [ABSTRACT FROM AUTHOR]

Diffuse midline glioma (DMG) is an aggressive brain tumour with high mortality and limited clinical therapeutic options. Although in vitro research has shown the effectiveness of medication, successful translation to the clinic remains elusive. A literature search highlighted the high variability and lack of standardisation in protocols applied for establishing the commonly used HSJD-DIPG-007 patient-derived xenograft (PDX) model, based on animal host, injection location, number of cells inoculated, volume, and suspension matrices. This study evaluated the HSJD-DIPG-007 PDX model with respect to its ability to mimic human disease progression for therapeutic testing in vivo. The mice received intracranial injections of HSJD-DIPG-007 cells suspended in either PBS or Matrigel. Survival, tumour growth, and metastases were assessed to evaluate differences in the suspension matrix used. After cell implantation, no severe side effects were observed. Additionally, no differences were detected in terms of survival or tumour growth between the two suspension groups. We observed delayed metastases in the Matrigel group, with a significant difference compared to mice with PBS-suspended cells. In conclusion, using Matrigel as a suspension matrix is a reliable method for establishing a DMG PDX mouse model, with delayed metastases formation and is a step forward to obtaining a standardised in vivo PDX model. [ABSTRACT FROM AUTHOR]