US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1-4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020.

Vascular and neuronal effects of general anesthesia on the brain: An fMRI study.

BACKGROUND AND PURPOSE: A number of functional magnetic resonance imaging (fMRI) studies rely on application of anesthetic agents during scanning that can modulate and complicate interpretation of the measured hemodynamic blood oxygenation level-dependent (BOLD) response. The purpose of the present study was to investigate the effect of general anesthesia on two main components of BOLD signal including neuronal activity and vascular response. METHODS: Breath-holding (BH) fMRI was conducted in wakefulness and under anesthesia states in 9 patients with drug-resistant epilepsy who needed to get scanned under anesthesia during laser interstitial thermal therapy. BOLD and BOLD cerebrovascular reactivity (BOLD-CVR) maps were compared using t-test between two states to assess the effect of anesthesia on neuronal activity and vascular factors (p < .05). RESULTS: Overall, our findings revealed an increase in BOLD-CVR and decrease in BOLD response under anesthesia in several brain regions. The results proposed that the modulatory mechanism of anesthetics on neuronal and vascular components of BOLD signal may work in different ways. CONCLUSION: This experiment for the first human study showed that anesthesia may play an important role in dissociation between neuronal and vascular responses contributed to hemodynamic BOLD signal using BH fMRI imaging that may assist the implication of general anesthesia and interpretation of outcomes in clinical setting.

Microwave ablation as a primary versus secondary treatment for hepatocellular carcinoma

PURPOSE: The purpose of this study was to analyze and compare the outcomes of percutaneous microwave ablation (MWA) when used as a primary vs. secondary treatment for hepatocellular carcinoma (HCC). METHODS: The clinical data of 192 patients with HCC treated with MWA between January 2012 and July 2021 were reviewed retrospectively, with 152 patients being treatment naïve (primary treatment) vs. 40 who had residual or recurrent disease following previous trans-arterial chemoembolization or trans-arterial radioembolization (secondary treatment). The primary outcomes were primary technical efficacy, 1- and 3-year local recurrence-free survival (RFS) and overall survival (OS), local recurrence rates, and adverse events. Pre- and post-intervention liver function tests were compared using a Wilcoxon signed rank test. Univariate and multivariate analyses were also performed, looking at prognostic factors associated with OS and local RFS. RESULTS: There was no significant difference in 1-year local RFS (primary 93.6% vs. secondary 93.7; P = 0.97) and 3-year local RFS (primary 80.6% vs. secondary 86.5%; P = 0.37) rates. There was no significant difference in 1-year OS (primary 82.4% vs. secondary 86.6%; P = 0.51) and 3-year OS (primary 68.3% vs. secondary 77.4%; P = 0.25) between the two groups. The local recurrence rate (primary 9.8% vs. secondary 14.6%; P = 0.37), primary technical efficacy (primary 96.2% vs. secondary 95%; P = 0.73), and adverse events (primary 8.0% vs. secondary 11.6%; P = 0.45) were also similar between the two groups. CONCLUSION: Microwave ablation is safe and effective as a secondary treatment for patients with HCC in a clinical salvage scenario and should be utilized more frequently.

Characteristic dynamic functional connectivity during sevoflurane-induced general anesthesia.

General anesthesia (GA) during surgery is commonly maintained by inhalational sevoflurane. Previous resting state functional MRI (rs-fMRI) studies have demonstrated suppressed functional connectivity (FC) of the entire brain networks, especially the default mode networks, transitioning from the awake to GA condition. However, accuracy and reliability were limited by previous administration methods (e.g. face mask) and short rs-fMRI scans. Therefore, in this study, a clinical scenario of epilepsy patients undergoing laser interstitial thermal therapy was leveraged to acquire 15 min of rs-fMRI while under general endotracheal anesthesia to maximize the accuracy of sevoflurane level. Nine recruited patients had fMRI acquired during awake and under GA, of which seven were included in both static and dynamic FC analyses. Group independent component analysis and a sliding-window method followed by k-means clustering were applied to identify four dynamic brain states, which characterized subtypes of FC patterns. Our results showed that a low-FC brain state was characteristic of the GA condition as a single featuring state during the entire rs-fMRI session; In contrast, the awake condition exhibited frequent fluctuations between three distinct brain states, one of which was a highly synchronized brain state not seen in GA. In conclusion, our study revealed remarkable dynamic connectivity changes from awake to GA condition and demonstrated the advantages of dynamic FC analysis for future studies in the assessments of the effects of GA on brain functional activities.

Evaluation of Suspected Small Bowel Ischemia Using Contrast-Enhanced Ultrasound with Computed Tomography Fusion.

Small bowel ischemia can lead to fatal complications such as necrosis, perforation, and sepsis. Clinical examinations and laboratory tests are usually inconclusive in critically ill patients. The need for surgical exploration is decided based on imaging, examination, and clinical judgment. The decision to operate is time-critical and can be lifesaving, but surgical intervention has the potential to cause additional morbidity, especially in unstable patients. Contrast-enhanced computed tomography (CECT) is the study of choice in suspected small bowel ischemia but has poor specificity. Contrast-enhanced ultrasound (CEUS) provides real-time visualization of the bowel wall vascularity. In this case report, we used a CEUS with CT fusion examination to rule out small bowel ischemia in a critically ill patient with suspected closed loop small bowel obstruction on CECT and in whom surgical exploration would have not been well tolerated. The patient's condition later improved, and an abdominal CT showed no evidence of obstruction.

Use of Functional MRI in Deep Brain Stimulation in Parkinson's Diseases: A Systematic Review.

Deep brain stimulation (DBS) has been used to modulate aberrant circuits associated with Parkinson's disease (PD) for decades and has shown robust therapeutic benefits. However, the mechanism of action of DBS remains incompletely understood. With technological advances, there is an emerging use of functional magnetic resonance imaging (fMRI) after DBS implantation to explore the effects of stimulation on brain networks in PD. This systematic review was designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to summarize peer-reviewed articles published within the past 10 years in which fMRI was employed on patients with PD-DBS. Search in PubMed database provided 353 references, and screenings resulted in a total of 19 studies for qualitative synthesis regarding study designs (fMRI scan timepoints and paradigm), methodology, and PD subtypes. This review concluded that fMRI may be used in patients with PD-DBS after proper safety test; resting-state and block-based fMRI designs have been employed to explore the effects of DBS on brain networks and the mechanism of action of the DBS, respectively. With further validation of safety use of fMRI and advances in imaging techniques, fMRI may play an increasingly important role in better understanding of the mechanism of stimulation as well as in improving clinical care to provide subject-specific neuromodulation treatments.

Emerging Applications of Ultrasound-Contrast Agents in Radiation Therapy.

Radiation therapy (RT) causes DNA damage through ionization, leading to double-strand breaks. In addition, it generates reactive oxygen species (ROS), which are toxic to tumor cells and the vasculature. However, hypoxic regions in the tumor have been shown to not only decrease treatment response but also increase the likelihood of recurrence and metastasis. Ultrasound-sensitive micro-bubbles are emerging as a useful diagnostic and therapeutic tool within RT. Contrast-enhanced ultrasound (CEUS) has shown great promise in early prediction of tumor response to RT. Ultrasound-triggered micro-bubble cavitation has also been shown to induce bio-effects that can sensitize angiogenic tumor vessels to RT. Additionally, ultrasound can trigger the release of drugs from micro-bubble carriers via localized micro-bubble destruction. This approach has numerous applications in RT, including targeted oxygen delivery before radiotherapy. Furthermore, micro-bubbles can be used to locally create ROS without radiation. Sonodynamic therapy uses focused ultrasound and a sonosensitizer to selectively produce ROS in the tumor region and has been explored as a treatment option for cancer. This review summarizes emerging applications of ultrasound contrast agents in RT and ROS augmentation.

Gray Matter Sampling Differences Between Subdural Electrodes and Stereoelectroencephalography Electrodes.

Objective: Stereoelectroencephalography (SEEG) has seen a recent increase in popularity in North America; however, concerns regarding the spatial sampling capabilities of SEEG remain. We aimed to quantify and compare the spatial sampling of subdural electrode (SDE) and SEEG implants. Methods: Patients with drug-resistant epilepsy who underwent invasive monitoring were included in this retrospective case-control study. Ten SEEG cases were compared with ten matched SDE cases based on clinical presentation and pre-implantation hypothesis. To quantify gray matter sampling, MR and CT images were coregistered and a 2.5mm radius sphere was superimposed over the center of each electrode contact. The estimated recording volume of gray matter was defined as the cortical voxels within these spherical models. Paired t-tests were performed to compare volumes and locations of SDE and SEEG recording. A Ripley's K-function analysis was performed to quantify differences in spatial distributions. Results: The average recording volume of gray matter by each individual contact was similar between the two modalities. SEEG implants sampled an average of 20% more total gray matter, consisted of an average of 17% more electrode contacts, and had 77% more of their contacts covering gray matter within sulci. Insular coverage was only achieved with SEEG. SEEG implants generally consist of discrete areas of dense local coverage scattered across the brain; while SDE implants cover relatively contiguous areas with lower density recording. Significance: Average recording volumes per electrode contact are similar for SEEG and SDE, but SEEG may allow for greater overall volumes of recording as more electrodes can be routinely implanted. The primary difference lies in the location and distribution of gray matter than can be sampled. The selection between SEEG and SDE implantation depends on sampling needs of the invasive implant.

Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences.

Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3-6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time-intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (-38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.

The changing characteristics and molecular profiles of papillary thyroid carcinoma over time: a systematic review.

BACKGROUND: The genetic alterations of papillary thyroid carcinoma (PTC) have been reported to change over the past few decades. We performed this systematic review to further examine the trends and modifications of patient demographic, clinicopathological features and molecular profiles of PTC over time. METHODS: A literature search was performed within six electronic databases to identify relevant articles. The inclusion criteria were published studies investigating BRAF mutations, RET/PTC rearrangements or RAS mutations in PTCs or classical PTCs. Two teams of reviewers independently screened titles and abstracts of all articles. Full texts of potential articles were read and extracted data were listed and stratified into an excel file according to country, city, institution, and surgical time period. Student t test and Pearson Chi-square were used to analyze the trends of demographic and clinicopathological features of PTC patients and the prevalence of each genetic alteration in individual institutions. RESULTS: From 3139 articles, we included 16 articles for final analysis. Our results showed an increasing trend of BRAF and a decreasing trend of RET/PTC prevalence over time in PTCs and classical PTCs, accompanied by an older age of PTC patients, an increase in proportion of PTMC and less aggressive behaviours of tumours. CONCLUSIONS: The demographic and clinicopathological characteristics and molecular profile of PTCs have been changing over the past few decades. These modifications suggest changes in etiologies and risk factors of thyroid cancer that influence the tumorigenesis of PTCs.