Association Between Pseudoprogression of Vestibular Schwannoma After Radiosurgery and Radiological Features of Solid and Cystic Components.

BACKGROUND AND OBJECTIVES: The pathophysiology of vestibular schwannoma (VS) pseudoprogression after Gamma Knife radiosurgery (GKRS) remains unclear. Radiological features in pretreatment magnetic resonance images may help predict VS pseudoprogression. This study used VS radiological features quantified using an automated segmentation algorithm to predict pseudoprogression after GKRS treatment. METHODS: This is a retrospective study comprising 330 patients with VS who received GKRS. After image preprocessing and T2W/contrast-enhanced T1-weighted image (CET1W) image generation, with fuzzy C-means clustering, VSs were segmented into solid and cystic components and classified as solid and cystic. Relevant radiological features were then extracted. The response to GKRS was classified into "nonpseudoprogression" and "pseudoprogression/fluctuation". The Z test for two proportions was used to compare solid and cystic VS for the likelihood of pseudoprogression/fluctuation. Logistic regression was used to assess the correlation between clinical variables and radiological features and response to GKRS. RESULTS: The likelihood of pseudoprogression/fluctuation after GKRS was significantly higher for solid VS compared with cystic VS (55% vs 31%, P < .001). For the entire VS cohort, multivariable logistic regression revealed that a lower mean tumor signal intensity (SI) in T2W/CET1W images was associated with pseudoprogression/fluctuation after GKRS ( P = .001). For the solid VS subgroup, a lower mean tumor SI in T2W/CET1W images ( P = .035) was associated with pseudoprogression/fluctuation after GKRS. For the cystic VS subgroup, a lower mean SI of the cystic component in T2W/CET1W images ( P = .040) was associated with pseudoprogression/fluctuation after GKRS. CONCLUSION: Pseudoprogression is more likely to occur in solid VS compared with cystic VS. Quantitative radiological features in pretreatment magnetic resonance images were associated with pseudoprogression after GKRS. In T2W/CET1W images, solid VS with a lower mean tumor SI and cystic VS with a lower mean SI of cystic component were more likely to have pseudoprogression after GKRS. These radiological features can help predict the likelihood of pseudoprogression after GKRS.

Quantification of tumor response of cystic vestibular schwannoma to Gamma Knife radiosurgery by using artificial intelligence.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is a common treatment modality for vestibular schwannoma (VS). The ability to predict treatment response is important in patient counseling and decision-making. The authors developed an algorithm that can automatically segment and differentiate cystic and solid tumor components of VS. They also investigated associations between the quantified radiological features of each component and tumor response after GKRS. METHODS: This is a retrospective study comprising 323 patients with VS treated with GKRS. After preprocessing and generation of pretreatment T2-weighted (T2W)/T1-weighted with contrast (T1WC) images, the authors segmented VSs into cystic and solid components by using fuzzy C-means clustering. Quantitative radiological features of the entire tumor and its cystic and solid components were extracted. Linear regression models were implemented to correlate clinical variables and radiological features with the specific growth rate (SGR) of VS after GKRS. RESULTS: A multivariable linear regression model of radiological features of the entire tumor demonstrated that a higher tumor mean signal intensity (SI) on T2W/T1WC images (p < 0.001) was associated with a lower SGR after GKRS. Similarly, a multivariable linear regression model using radiological features of cystic and solid tumor components demonstrated that a higher solid component mean SI (p = 0.039) and a higher cystic component mean SI (p = 0.004) on T2W/T1WC images were associated with a lower SGR after GKRS. A larger cystic component proportion (p = 0.085) was associated with a trend toward a lower SGR after GKRS. CONCLUSIONS: Radiological features of VSs on pretreatment MRI that were quantified using fuzzy C-means were associated with tumor response after GKRS. Tumors with a higher tumor mean SI, a higher solid component mean SI, and a higher cystic component mean SI on T2W/T1WC images were more likely to regress in volume after GKRS. Those with a larger cystic component proportion also trended toward regression after GKRS. Further refinement of the algorithm may allow direct prediction of tumor response.

Identifying an unknown compound in flue gas of semiconductor industry - Forensics of a perfluorocarbon.

This study investigated the source of a false positive signal in the measurement of total non-methane organic compounds (TNMOCs) by an on-line analyzer based on flame ionization detection (FID) in the flue gas released from a semiconductor fabrication plant. Since no release of volatile organic compounds (VOCs) into the waste gas stream in acid/base ventilation was assured by the plant authority, the positive detection of VOCs became a subject of dispute. In addition to the TNMOC analysis of 5 samples, the investigation used the method that coupled thermal desorption (TD) with gas chromatography mass spectrometry (GC/MS), dubbed TD-GC/MS, to identify the substance that produced the FID signals of TNMOCs. The waste gas was collected with sampling canisters and analyzed by in-laboratory TD-GC/MS. However, mass scanning from 45 to 250 m/z to remove interference from air matrix of O2, N2 and CO2 forbid detecting any ion fragments smaller than 45 m/z and, thus, led to poor match in mass (MS) library search. As a result, a highly retentive porous layer open tubular (PLOT) capillary column was employed to separate the unknown away from the air peak. The success of acquiring all key ion fragments of 31, 50, 69, and 131 m/z resulted in an excellent match with octafluorocyclobutane (C4F8) in the NIST database. A gas standard was then prepared and injected to confirm the identity of C4F8 by the identical mass spectrum and GC retention time. The concentrations of C4F8 found in the 5 flue gas samples varying from 3.32 to 6.21 ppmv were very close to the NMOC range of 3.48-6.62 ppmv as reported by the TNMOC analyzer, proving that the FID signals observed from TNMOC method were mostly produced from C4F8. Consequently, the method of TD-GC/MS would be an ideal method to pre-screen the presence of PFCs before a non-distinguishable TNMOC analyzer is applied to approximate the VOC level as part of the integrated effort to monitor VOC in flue gas.

Radiomics as prognostic factor in brain metastases treated with Gamma Knife radiosurgery.

PURPOSE: Gamma Knife radiosurgery (GKRS) is a non-invasive procedure for the treatment of brain metastases. This study sought to determine whether radiomic features of brain metastases derived from pre-GKRS magnetic resonance imaging (MRI) could be used in conjunction with clinical variables to predict the effectiveness of GKRS in achieving local tumor control. METHODS: We retrospectively analyzed 161 patients with non-small cell lung cancer (576 brain metastases) who underwent GKRS for brain metastases. The database included clinical data and pre-GKRS MRI. Brain metastases were demarcated by experienced neurosurgeons, and radiomic features of each brain metastasis were extracted. Consensus clustering was used for feature selection. Cox proportional hazards models and cause-specific proportional hazards models were used to correlate clinical variables and radiomic features with local control of brain metastases after GKRS. RESULTS: Multivariate Cox proportional hazards model revealed that higher zone percentage (hazard ratio, HR 0.712; P = .022) was independently associated with superior local tumor control. Similarly, multivariate cause-specific proportional hazards model revealed that higher zone percentage (HR 0.699; P = .014) was independently associated with superior local tumor control. CONCLUSIONS: The zone percentage of brain metastases, a radiomic feature derived from pre-GKRS contrast-enhanced T1-weighted MRIs, was found to be an independent prognostic factor of local tumor control following GKRS in patients with non-small cell lung cancer and brain metastases. Radiomic features indicate the biological basis and characteristics of tumors and could potentially be used as surrogate biomarkers for predicting tumor prognosis following GKRS.

Submicron-bubble-enhanced focused ultrasound for blood-brain barrier disruption and improved CNS drug delivery.

The use of focused ultrasound (FUS) with microbubbles has been proven to induce transient blood-brain barrier opening (BBB-opening). However, FUS-induced inertial cavitation of microbubbles can also result in erythrocyte extravasations. Here we investigated whether induction of submicron bubbles to oscillate at their resonant frequency would reduce inertial cavitation during BBB-opening and thereby eliminate erythrocyte extravasations in a rat brain model. FUS was delivered with acoustic pressures of 0.1-4.5 MPa using either in-house manufactured submicron bubbles or standard SonoVue microbubbles. Wideband and subharmonic emissions from bubbles were used to quantify inertial and stable cavitation, respectively. Erythrocyte extravasations were evaluated by in vivo post-treatment magnetic resonance susceptibility-weighted imaging, and finally by histological confirmation. We found that excitation of submicron bubbles with resonant frequency-matched FUS (10 MHz) can greatly limit inertial cavitation while enhancing stable cavitation. The BBB-opening was mainly caused by stable cavitation, whereas the erythrocyte extravasation was closely correlated with inertial cavitation. Our technique allows extensive reduction of inertial cavitation to induce safe BBB-opening. Furthermore, the safety issue of BBB-opening was not compromised by prolonging FUS exposure time, and the local drug concentrations in the brain tissues were significantly improved to 60 times (BCNU; 18.6 µg versus 0.3 µg) by using chemotherapeutic agent-loaded submicron bubbles with FUS. This study provides important information towards the goal of successfully translating FUS brain drug delivery into clinical use.

In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low-frequency-ultrasound-induced blood-brain barrier opening in swine.

PURPOSE: To verify that low-frequency planar ultrasound can be used to disrupt the BBB in large animals, and the usefulness of MRI to quantitatively monitor the delivery of superparamagnetic iron oxide (SPIO) nanoparticles into the disrupted regions. MATERIALS AND METHODS: Two groups of swine subjected to craniotomy were sonicated with burst lengths of 30 or 100 ms, and one group of experiment was also performed to confirm the ability of 28-kHz sonication to open the BBB transcranially. SPIO nanoparticles were administered to the animals after BBB disruption. Procedures were monitored by MRI; SPIO concentrations were estimated by relaxivity mapping. RESULTS: Sonication for 30 ms created shallow disruptions near the probe tip; 100-ms sonications after craniotomy can create larger and more penetrating openings, increasing SPIO leakage ∼3.6-fold than 30-ms sonications. However, this was accompanied by off-target effects possibly caused by ultrasonic wave reflection. SPIO concentrations estimated from transverse relaxation rate maps correlated well with direct measurements of SPIO concentration by optical emission spectrometry. We have also shown that transcranial low-frequency 28-kHz sonication can induce secure BBB opening from longitudinal MR image follow up to 7 days. CONCLUSION: This study provides valuable information regarding the use low-frequency ultrasound for BBB disruption and suggest that SPIO nanoparticles has the potential to serve as a thernostic agent in MRI-guided ultrasound-enhanced brain drug delivery.