Image-localized biopsy mapping of brain tumor heterogeneity: A single-center study protocol.

Brain cancers pose a novel set of difficulties due to the limited accessibility of human brain tumor tissue. For this reason, clinical decision-making relies heavily on MR imaging interpretation, yet the mapping between MRI features and underlying biology remains ambiguous. Standard (clinical) tissue sampling fails to capture the full heterogeneity of the disease. Biopsies are required to obtain a pathological diagnosis and are predominantly taken from the tumor core, which often has different traits to the surrounding invasive tumor that typically leads to recurrent disease. One approach to solving this issue is to characterize the spatial heterogeneity of molecular, genetic, and cellular features of glioma through the intraoperative collection of multiple image-localized biopsy samples paired with multi-parametric MRIs. We have adopted this approach and are currently actively enrolling patients for our 'Image-Based Mapping of Brain Tumors' study. Patients are eligible for this research study (IRB #16-002424) if they are 18 years or older and undergoing surgical intervention for a brain lesion. Once identified, candidate patients receive dynamic susceptibility contrast (DSC) perfusion MRI and diffusion tensor imaging (DTI), in addition to standard sequences (T1, T1Gd, T2, T2-FLAIR) at their presurgical scan. During surgery, sample anatomical locations are tracked using neuronavigation. The collected specimens from this research study are used to capture the intra-tumoral heterogeneity across brain tumors including quantification of genetic aberrations through whole-exome and RNA sequencing as well as other tissue analysis techniques. To date, these data (made available through a public portal) have been used to generate, test, and validate predictive regional maps of the spatial distribution of tumor cell density and/or treatment-related key genetic marker status to identify biopsy and/or treatment targets based on insight from the entire tumor makeup. This type of methodology, when delivered within clinically feasible time frames, has the potential to further inform medical decision-making by improving surgical intervention, radiation, and targeted drug therapy for patients with glioma.

Dermal Fat Grafting to Reconstruct the Parotidectomy Defect Normalizes Facial Attention.

OBJECTIVES/HYPOTHESIS: Use validated eye-tracking technology to objectively measure 1) the attentional distraction of facial contour defects after superficial and total parotidectomy and 2) changes in attentional distraction with abdominal dermal fat graft reconstruction. METHODS: Standardized frontal and oblique facial images of 16 patients who had undergone superficial or total parotidectomy with or without fat graft reconstruction; four normal controls were obtained. One hundred casual observers were recruited to view these images, and gaze data were collected using a Tobii Pro eye-tracking system. Gaze durations for predefined facial areas of interest were analyzed using mixed-effects linear regression to test study hypotheses. RESULTS: For frontal images, total parotidectomy increased gaze to the operated parotid area compared to the contralateral nonoperated parotid area (92 milliseconds, 95% confidence interval [CI]: 48-138 milliseconds, P < .001). Fat grafting normalized the attentional distraction, with no difference in gaze time on the operated parotid region compared to normal control faces (P = .414). For oblique images, total parotidectomy increased gaze to the operated parotid area compared to the contralateral nonoperated parotid area (658 milliseconds, 95% CI: 463-854 milliseconds, P < .001). Fat grafting normalized this attentional distraction, with no difference in gaze time on the operated parotid region compared to normal control faces (P = .504). In both views, superficial parotidectomy demonstrated no significant attentional distractions, with or without fat grafting. CONCLUSIONS: This eye-tracking study objectively demonstrates that total parotidectomy results in a facial contour deformity that is distracting to observers, whereas superficial parotidectomy does not. For total parotidectomy, this attentional distraction can be normalized with dermal fat graft reconstruction. LEVEL OF EVIDENCE: 3b Laryngoscope, 131:E124-E131, 2021.

Analysis of Abdominal Dermal-Fat Grafting to Repair Parotidectomy Defects: An 18-Year Cohort Study.

OBJECTIVES: To assess the outcomes of abdominal dermal-fat grafting following superficial and total parotidectomy. METHODS: A retrospective chart review of parotidectomy patients was performed. Patients were divided into four groups based on surgical extent and grafting status: superficial parotidectomy (SP), superficial parotidectomy with grafting (SPg), total parotidectomy (TP), and total parotidectomy with grafting (TPg). Complication rates and operative times were then compared between surgically matched groups (SP vs. SPg, TP vs. TPg). Complications included graft necrosis, gustatory sweating, first-bite syndrome, infection, hematoma, sialocele, and seroma. Data was analyzed via chi-square and two-sample t testing, logistic regression, and one-way analysis of variance. RESULTS: The cohort consisted of 330 patients: 106 SP (32.12%), 61 SPg (18.48%), 82 TP (24.85%), and 81 TPg (24.55%). No donor site complications occurred. TPg resulted in seven graft necroses (8.64%), and 22 reported gustatory sweating (27.20% vs. 10 TP patients (12.2%), P = 0.016); SPg resulted in two necroses (3.28%). There were no other statistically significant differences in complication rates. Graft recipients receiving adjuvant radiation were more likely to develop necrosis (odds ratio [OR] 4.60, 95% confidence interval [CI], 1.16-18.27, P = .0194). Patients who developed gustatory sweating were 8.38 years younger (95% CI 2.66-14.10, P = 0.002, follow-up time > 48 days). Grafting did not increase operative times (TP/TPg: mean = 275.91/263.65 minutes, standard error of the mean = 41.96/33.75, P = 0.822). CONCLUSION: An abdominal dermal-fat graft is an excellent reconstructive choice for a parotidectomy defect and is not associated with increased complication rates or prolonged operative time. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2144-2147, 2020.

Treatment Strategy of a Patient With a Brain Arteriovenous Malformation and Cranial Dural Fistula: 2-Dimensional Operative Video.

We present the case of a 56-yr-old right-handed male, after informed consent was obtained, who presented with acute confusion and agitation, on the background of a remote history of an uncomplicated resection of a left parietal grade 2 glioma. Imaging revealed a large, acute right temporal intracerebral hemorrhage (ICH). Standard vascular workup for the cause of the ICH included catheter angiography. No direct cause of the hemorrhage was revealed; however, a high grade parasagittal dural arteriovenous fistula (DAVF) with cortical venous reflux was noted close to the prior craniotomy site. The venous reflux was towards the left hemisphere, but it was hypothesized that similar reflux on the right side may have been present and was not presently evident due to thrombosis. The DAVF was embolized by endovascular means, followed by evacuation of the hematoma. Follow-up angiogram 7 mo later revealed a high-flow, right superior temporal cortical arteriovenous malformation (AVM). The DAVF unfortunately had also progressed. Endovascular occlusion of both lesions was attempted but was not successful. Subsequently, microsurgical resection for both the vascular malformations was performed with careful pre- and intraoperative planning to obtain a successful clinical and angiographic result. In this video, we summarize diagnostic and therapeutic nuances that have broad implications for the workup of ICH and the strategic management of a unique scenario involving a brain AVM and high-grade cranial dural fistula in the same patient. Prior to each procedure, informed consent was obtained from the patient, which includes consent for publication.

Mathematical Analysis of Glioma Growth in a Murine Model.

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm3 to 62 mm3, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

Awake Surgery for Brain Vascular Malformations and Moyamoya Disease.

OBJECTIVE: Although a significant amount of experience has accumulated for awake procedures for brain tumor, epilepsy, and carotid surgery, its utility for intracranial neurovascular indications remains largely undefined. Awake surgery for select neurovascular cases offers the advantage of precise brain mapping and robust neurologic monitoring during surgery for lesions in eloquent areas, avoidance of potential hemodynamic instability, and possible faster recovery. It also opens the window for perilesional epileptogenic tissue resection with potentially less risk for iatrogenic injury. METHODS: Institutional review board approval was obtained for a retrospective review of awake surgeries for intracranial neurovascular indications over the past 36 months from a prospectively maintained quality database. We reviewed patients' clinical indications, clinical and imaging parameters, and postoperative outcomes. RESULTS: Eight consecutive patients underwent 9 intracranial neurovascular awake procedures conducted by the senior author. A standardized "sedated-awake-sedated" protocol was used in all 8 patients. For the 2 patients with arteriovenous malformations and the 3 patients with cavernoma, awake brain surface and white matter mapping was performed before and during microsurgical resection. A neurological examination was obtained periodically throughout all 5 procedures. There were no intraoperative or perioperative complications. Hypotension was avoided during the 2 Moyamoya revascularization procedures in the patient with a history of labile blood pressure. Postoperative imaging confirmed complete arteriovenous malformation and cavernoma resections. No new neurologic deficits or new-onset seizures were noted on 3-month follow-up. CONCLUSIONS: Awake surgery appears to be safe for select patients with intracranial neurovascular pathologies. Potential advantages include greater safety, shorter length of stay, and reduced cost.