NS-HGlio: A generalizable and repeatable HGG segmentation and volumetric measurement AI algorithm for the longitudinal MRI assessment to inform RANO in trials and clinics.

Background: Accurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable. Methods: A single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed. Results: IV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed. Conclusion: NS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others.

Volume and Infusion Rate Dynamics of Intraparenchymal Central Nervous System Infusion in a Large Animal Model.

Thalamic infusion of adeno-associated viral (AAV) vectors has been shown to have therapeutic effects in neuronopathic lysosomal storage diseases. Preclinical studies in sheep model of Tay-Sachs disease demonstrated that bilateral thalamic injections of AAV gene therapy are required for maximal benefit. Translation of thalamic injection to patients carries risks in that (1) it has never been done in humans, and (2) dosing scale-up based on brain weight from animals to humans requires injection of larger volumes. To increase the safety margin of this infusion, a flexible cannula was selected to enable simultaneous bilateral thalamic infusion in infants while monitoring by imaging and/or to enable awake infusions for injection of large volumes at low infusion rates. In this study, we tested various infusion volumes (200-800 µL) and rates (0.5-5 µL/min) to determine the maximum tolerated combination of injection parameters. Animals were followed for ∼1 month postinjection with magnetic resonance imaging (MRI) performed at 14 and 28 days. T1-weighted MRI was used to quantify thalamic damage followed by histopathological assessment of the brain. Trends in data show that infusion volumes of 800 µL (2 × the volume required in sheep based on thalamic size) resulted in larger lesions than lower volumes, where the long infusion times (between 13 and 26 h) could have contributed to the generation of larger lesions. The target volume (400 µL, projected to be sufficient to cover most of the sheep thalamus) created the smallest lesion size. Cannula placement alone did result in damage, but this is likely associated with an inherent limitation of its use in a small brain due to the length of the distal rigid portion and lack of stable fixation. An injection rate of 5 µL/min at a volume ∼1/3 of the thalamus (400-600 µL) appears to be well tolerated in sheep both clinically and histopathologically.

Pneumocele of the frontal sinus producing orbital roof defect: case report and review of literature.

Type III frontal recess air cell as a cause of frontal sinus pneumocele has not been previously reported in literature. A 31-year-old woman with chronic history of sinusitis presented with pressure in the left eye on blowing the nose. Computed tomography examination of the orbits and paranasal sinuses with coronal and sagittal reformatted images showed abnormal collection of gas in the soft tissues at the superior aspect of the left orbit contiguous with the overlying left frontal sinus through a large defect in the orbital roof and a type III frontal recess air cell narrowing the left frontal recess.