Structural connectome quantifies tumour invasion and predicts survival in glioblastoma patients.

Glioblastoma is characterized by diffuse infiltration into the surrounding tissue along white matter tracts. Identifying the invisible tumour invasion beyond focal lesion promises more effective treatment, which remains a significant challenge. It is increasingly accepted that glioblastoma could widely affect brain structure and function, and further lead to reorganization of neural connectivity. Quantifying neural connectivity in glioblastoma may provide a valuable tool for identifying tumour invasion. Here we propose an approach to systematically identify tumour invasion by quantifying the structural connectome in glioblastoma patients. We first recruit two independent prospective glioblastoma cohorts: the discovery cohort with 117 patients and validation cohort with 42 patients. Next, we use diffusion MRI of healthy subjects to construct tractography templates indicating white matter connection pathways between brain regions. Next, we construct fractional anisotropy skeletons from diffusion MRI using an improved voxel projection approach based on the tract-based spatial statistics, where the strengths of white matter connection and brain regions are estimated. To quantify the disrupted connectome, we calculate the deviation of the connectome strengths of patients from that of the age-matched healthy controls. We then categorize the disruption into regional disruptions on the basis of the relative location of connectome to focal lesions. We also characterize the topological properties of the patient connectome based on the graph theory. Finally, we investigate the clinical, cognitive and prognostic significance of connectome metrics using Pearson correlation test, mediation test and survival models. Our results show that the connectome disruptions in glioblastoma patients are widespread in the normal-appearing brain beyond focal lesions, associated with lower preoperative performance (P < 0.001), impaired cognitive function (P < 0.001) and worse survival (overall survival: hazard ratio = 1.46, P = 0.049; progression-free survival: hazard ratio = 1.49, P = 0.019). Additionally, these distant disruptions mediate the effect on topological alterations of the connectome (mediation effect: clustering coefficient -0.017, P < 0.001, characteristic path length 0.17, P = 0.008). Further, the preserved connectome in the normal-appearing brain demonstrates evidence of connectivity reorganization, where the increased neural connectivity is associated with better overall survival (log-rank P = 0.005). In conclusion, our connectome approach could reveal and quantify the glioblastoma invasion distant from the focal lesion and invisible on the conventional MRI. The structural disruptions in the normal-appearing brain were associated with the topological alteration of the brain and could indicate treatment target. Our approach promises to aid more accurate patient stratification and more precise treatment planning.

Hair-sparing technique using absorbable intradermal barbed suture versus traditional closure methods in supratentorial craniotomies for tumor.

BACKGROUND: Hair-sparing techniques in cranial neurosurgery have gained traction in recent years and previous studies have shown no difference in infection rates, yet limited data exists evaluating the specific closure techniques utilized during hair-sparing craniotomies. Therefore, it was the intention of this study to evaluate the rate of surgical site infections (SSIs) and perioperative complications associated with using an absorbable intradermal barbed suture for skin closure in hair-sparing supratentorial craniotomies for tumor in order to prove non-inferiority to traditional methods. METHODS: A retrospective review of supratentorial craniotomies for tumor by a single surgeon from 2011 to 2017 was performed. All perioperative adverse events and wound complications, defined as a postoperative infection, wound dehiscence, or CSF leak, were compared between three different groups: (1) hair shaving craniotomies + transdermal polypropylene suture/staples for scalp closure, (2) hair-sparing craniotomies + transdermal polypropylene suture/staples for scalp closure, and (3) hair-sparing craniotomies + absorbable intradermal barbed suture for scalp closure. RESULTS: Two hundred sixty-three patients underwent hair shaving + transdermal polypropylene suture/staples, 83 underwent hair sparing + transdermal polypropylene suture/staples, and 100 underwent hair sparing + absorbable intradermal barbed suture. Overall, 2.9% of patients experienced a perioperative complication and 4.3% developed a wound complication. In multivariable analysis, the use of a barbed suture for scalp closure and hair-sparing techniques was not predictive of any complication or 30-day readmission. Furthermore, the absorbable intradermal barbed suture cohort had the lowest overall rate of wound complications (4%). CONCLUSIONS: Hair-sparing techniques using absorbable intradermal barbed suture for scalp closure are safe and do not result in higher rates of infection, readmission, or reoperation when compared with traditional methods.

Predictors of Successful Discharge of Patients on Postoperative Day 1 After Craniotomy for Brain Tumor.

BACKGROUND: Shorter hospital stays have been associated with decreased complication rates, fewer hospital-acquired infections, and lower costs. We evaluated an optimized treatment paradigm for patients undergoing craniotomy allowing for postoperative day 1 (POD1) discharge if the criteria were met. We compared the complication and readmission rates between the POD1 patients and those with longer stays, and examined the patient and surgical variables for predictors of POD1 discharge. METHODS: We performed a retrospective review of craniotomies performed for tumor from 2011 to 2015. Craniotomies for tumors were included, and laser ablations and biopsies were excluded. RESULTS: A total 424 of patients were included, 132 (31%) of whom had been discharged on POD1. The mean length of stay was 6 days. The POD1 patients had had significantly better preoperative Karnofsky performance scale scores (P < 0.0001) and modified Rankin scale scores (P < 0.0001). Patient frailty, measured using the modified frailty index, was negatively predictive of POD1 discharge (P = 0.0183). Surgical factors predictive of early discharge were awake surgery (P < 0.0001) and supratentorial location (P < 0.0001). No POD1 patients experienced deep venous thrombosis (DVT), pulmonary embolus (PE), or urinary tract infections. However, of the patients with a length of stay >1 day, 4.4% and 2.7% developed DVT or PE (P = 0.0119) and urinary tract infections (P = 0.0202), respectively. Multivariate regression identified patient factors (male gender, low preoperative modified Rankin scale score), tumor factors (right-sided, supratentorial, smaller size), lower modified frailty index score, and operative factors (lack of a cerebrospinal fluid drain, awake surgery) as independent predictors of successful early discharge. CONCLUSIONS: Patients with good functional status can be safely discharged on POD1 after tumor craniotomy if the appropriate postoperative criteria have been met. Patients with early discharge had lower 30-day readmission and DVT/PE rates, likely owing to better baseline health status.

Abiotic-biotic characterization of Pt/Ir microelectrode arrays in chronic implants.

Pt/Ir electrodes have been extensively used in neurophysiology research in recent years as they provide a more inert recording surface as compared to tungsten or stainless steel. While floating microelectrode arrays (FMA) consisting of Pt/Ir electrodes are an option for neuroprosthetic applications, long-term in vivo functional performance characterization of these FMAs is lacking. In this study, we have performed comprehensive abiotic-biotic characterization of Pt/Ir arrays in 12 rats with implant periods ranging from 1 week up to 6 months. Each of the FMAs consisted of 16-channel, 1.5 mm long, and 75 µm diameter microwires with tapered tips that were implanted into the somatosensory cortex. Abiotic characterization included (1) pre-implant and post-explant scanning electron microscopy (SEM) to study recording site changes, insulation delamination and cracking, and (2) chronic in vivo electrode impedance spectroscopy. Biotic characterization included study of microglial responses using a panel of antibodies, such as Iba1, ED1, and anti-ferritin, the latter being indicative of blood-brain barrier (BBB) disruption. Significant structural variation was observed pre-implantation among the arrays in the form of irregular insulation, cracks in insulation/recording surface, and insulation delamination. We observed delamination and cracking of insulation in almost all electrodes post-implantation. These changes altered the electrochemical surface area of the electrodes and resulted in declining impedance over the long-term due to formation of electrical leakage pathways. In general, the decline in impedance corresponded with poor electrode functional performance, which was quantified via electrode yield. Our abiotic results suggest that manufacturing variability and insulation material as an important factor contributing to electrode failure. Biotic results show that electrode performance was not correlated with microglial activation (neuroinflammation) as we were able to observe poor performance in the absence of neuroinflammation, as well as good performance in the presence of neuroinflammation. One biotic change that correlated well with poor electrode performance was intraparenchymal bleeding, which was evident macroscopically in some rats and presented microscopically by intense ferritin immunoreactivity in microglia/macrophages. Thus, we currently consider intraparenchymal bleeding, suboptimal electrode fabrication, and insulation delamination as the major factors contributing toward electrode failure.