fMRI prediction of naming change after adult temporal lobe epilepsy surgery: Activation matters.

OBJECTIVE: We aimed to predict language deficits after epilepsy surgery. In addition to evaluating surgical factors examined previously, we determined the impact of the extent of functional magnetic resonance imaging (fMRI) activation that was resected on naming ability. METHOD: Thirty-five adults (mean age 37.5 ± 10.9 years, 13 male) with temporal lobe epilepsy completed a preoperative fMRI auditory description decision task, which reliably activates frontal and temporal language networks. Patients underwent temporal lobe resections (20 left resection). The Boston Naming Test (BNT) was used to determine language functioning before and after surgery. Language dominance was determined for Broca and Wernicke area (WA) by calculating a laterality index following statistical parametric mapping processing. We used an innovative method to generate anatomic resection masks automatically from pre- and postoperative MRI tissue map comparison. This mask provided the following: (a) resection volume; (b) overlap between resection and preoperative activation; and (c) overlap between resection and WA. We examined postoperative language change predictors using stepwise linear regression. Predictors included parameters described above as well as age at seizure onset (ASO), preoperative BNT score, and resection side and its relationship to language dominance. RESULTS: Seven of 35 adults had significant naming decline (6 dominant-side resections). The final regression model predicted 38% of the naming score change variance (adjusted r2  = 0.28, P = 0.012). The percentage of top 10% fMRI activation resected (P = 0.017) was the most significant contributor. Other factors in the model included WA LI, ASO, volume of WA resected, and WA LI absolute value (extent of laterality). SIGNIFICANCE: Resection of fMRI activation during a word-definition decision task is an important factor for postoperative change in naming ability, along with other previously reported predictors. Currently, many centers establish language dominance using fMRI. Our results suggest that the amount of the top 10% of language fMRI activation in the intended resection area provides additional predictive power and should be considered when planning surgical resection.

Using the Spleen as an In Vivo Systemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy with α-PD-L1.

Indications for immunotherapies are still unclear, and there is a great need for real-time patient immune status monitoring. In this study, we confirmed that the local and systemic immune profiles of an orthotopic osteosarcoma model with or without luciferase transfection were statistically equivalent. Next, we used flow cytometry to describe systemic immune cell populations influenced by osteosarcoma disease progression. When compared to vehicle-inoculated sham mice, it was found that tumor-bearing mice had significant immunophenotype disturbances at approximately 11 weeks after inoculation (at which time 90% of primary tumor-bearing mice have fulminant pulmonary metastases). Percent populations of natural killer cells and T regulatory cells were increased in the spleens of tumor-bearing mice (p < 0.0083) compared to shams. Additionally, T lymphocytes from spleens of tumor-bearing mice showed increased Tim-3/PD-1 exhaustion status (p < 0.0083). There were also increases in the percent populations of myeloid cells and overall M1/M2 macrophage marker expression on tumor-bearing mice spleens versus controls (p < 0.00714). Finally, treatment with 20 µg α-PD-L1 decreased T-cell exhaustion back to sham status, with a corresponding increase in CTLA-4 expression on cytotoxic T cells in the majority of mice tested. Checkpoint inhibition also increased splenic monocyte maturation and returned macrophage M1/M2 marker expression back to sham status. These data suggest that cancer induces systemic immune dysregulation and that these changes may be elucidated and utilized for treatment purposes by sampling the systemic immune environment via the spleen. In addition, treatment with the checkpoint inhibitor α-PD-L1 may neutralize but not overcome the systemic immunological changes induced by a progressing malignancy.